S

Sacituzumab govitecan (Trodelvy)

Ability to drive, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan has minor influence on the ability to drive and use machines, e.g. dizziness, fatigue

Breast-feeding, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

A risk to breastfed newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with sacituzumab govitecan and for 1 month after the last dose.

Carbamazepine, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Fertility, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Based on findings in animals, sacituzumab govitecan may impair fertility in females of reproductive potential (see section 5.3). No human data on the effect of sacituzumab govitecan on fertility are available.

Ketoconazole, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inhibitors (e.g. propofol, ketoconazole, EGFR tyrosine kinase inhibitors).

Men, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Male patients with female partners of childbearing potential have to use effective contraception during treatment with sacituzumab govitecan and for 3 months after the last dose.

Phenytoin, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Pregnancy, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Based on its mechanism of action, sacituzumab govitecan can cause teratogenicity and/or embryo-foetal lethality when administered during pregnancy. Women who become pregnant must immediately contact their doctor.

Propofol, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inhibitors (e.g. propofol, ketoconazole, EGFR tyrosine kinase inhibitors).

Rifampicin, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Ritonavir, sacituzumab govitecan [2] ---> SmPC of [2] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Sacituzumab govitecan [1], tipranavir ---> SmPC of [1] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Sacituzumab govitecan [1], UGT1A1 inductors ---> SmPC of [1] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inducers (e.g. carbamazepine, phenytoin, rifampicin, ritonavir, tipranavir).

Sacituzumab govitecan [1], UGT1A1 inhibitors ---> SmPC of [1] of EMA

Sacituzumab govitecan should be used with caution in patients receiving UGT1A1 inhibitors (e.g. propofol, ketoconazole, EGFR tyrosine kinase inhibitors).

Sacituzumab govitecan [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential have to use effective contraception during treatment and for 6 months after the last dose.

CONTRAINDICATIONS of Sacituzumab govitecan (Trodelvy)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/trodelvy-epar-product-information_en.pdf 21/08/2025

Sacubitril/Valsartan (Entresto)

Ability to drive, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Sacubitril/valsartan has a minor influence on the ability to drive and use machines. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur.

ACE inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Sacubitril/valsartan must not be started until 36 hours after taking the last dose of ACE inhibitor therapy. ACE inhibitor therapy must not be started until 36 hours after the last dose of sacubitril/valsartan

ACE inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

The concomitant use of Entresto with ACE inhibitors is contraindicated, as the concomitant inhibition of neprilysin (NEP) and ACE may increase the risk of angioedema.

AIIRA, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Entresto contains valsartan, and therefore should not be co-administered with another ARB containing product

Aliskiren, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Combination of Entresto with aliskiren is potentially associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure)

Aliskiren, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

The concomitant use of sacubitril/valsartan with aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or in patients with renal impairment (eGFR <60 ml/min/1.73 m2) (see section 4.3).

Aliskiren, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

The concomitant use of Entresto with aliskiren-containing products is contraindicated in patients with diabetes mellitus or in patients with renal impairment (eGFR <60 ml/min/1.73 m2)

Amiloride, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Concomitant use of potassium-sparing diuretics, mineralocorticoid antagonists, potassium supplements, salt substitutes containing potassium or other agents (such as heparin) may lead to increases in serum potassium, and to increases in serum creatinine.

Angioedema, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

If angioedema occurs, Entresto should be immediately discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred.

Breast-feeding, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

A decision should be made whether to abstain from breast-feeding or to discontinue Entresto while breast-feeding, taking into account the importance of Entresto to the mother.

Cidofovir, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Co-administration of Entresto with inhibitors of OATP1B1, OATP1B3, OAT3 (e.g. rifampicin, ciclosporin), OAT1 (e.g. tenofovir, cidofovir) or MRP2 (e.g. ritonavir) may increase the systemic exposure of LBQ657 or valsartan.

Coxibs, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

In elderly patients, volume-depleted patients (including those on diuretic therapy), or patients with compromised renal function, concomitant use of Entresto and NSAIDs may lead to an increased risk of worsening of renal function.

Cyclosporine, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

CYP450 enzymes, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

In vitro metabolism studies indicate that potential for CYP 450-based drug interactions is low since there is limited metabolism of Entresto via CYP450 enzymes. Entresto does not induce or inhibit CYP450 enzymes.

Direct renin inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

The combination of Entresto with direct renin inhibitors such as aliskiren is not recommended.

Eplerenone, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Fertility, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

There are no available data on the effect of sacubitril/valsartan on human fertility. No impairment of fertility was demonstrated in studies with it in male and female rats (see section 5.3).

Furosemide, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Co-administration of Entresto and furosemide had no effect on the pharmacokinetics of Entresto but reduced Cmax and AUC of furosemide by 50% and 28%, respectively.

Heparin, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Lithium, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

This combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased further.

Metformin, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Co-administration of Entresto with metformin reduced both Cmax and AUC of metformin by 23%. The clinical relevance of these findings is unknown.

Mineralocorticoid antagonists, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

MRP2 inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Nitroglycerine, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Co-administration of nitroglycerin and Entresto was associated with a treatment difference of 5 bpm in heart rate compared to the administration of nitroglycerine alone. In general no dose adjustment is required.

No significant interactions, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

No clinically meaningful drug-drug interaction was observed when Entresto was co-administered with digoxin, warfarin, hydrochlorothiazide, amlodipine, omeprazole, carvedilol or a combination of levonorgestrel/ethinyl estradiol.

NSAID, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

OAT1 inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

OAT3 inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

OATP1B1 inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

OATP1B1 substrates, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

In vitro data indicate that sacubitril inhibits OATP1B1 and OATP1B3 transporters. Entresto may therefore increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins.

OATP1B3 inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

OATP1B3 substrates, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

In vitro data indicate that sacubitril inhibits OATP1B1 and OATP1B3 transporters. Entresto may therefore increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins.

Organic nitrates, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

PDE5 inhibitors, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Caution should be exercised when sildenafil or another PDE5 inhibitor is initiated in patients treated with Entresto.

Potassium, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Pregnancy, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

The use of Entresto is not recommended during the first trimester of pregnancy and is contraindicated during the second and third trimesters of pregnancy

Rifampicin, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Ritonavir, sacubitril/valsartan [2] ---> SmPC of [2] of EMA

Sacubitril/valsartan [1], sildenafil ---> SmPC of [1] of EMA

Caution should be exercised when sildenafil or another PDE5 inhibitor is initiated in patients treated with Entresto.

Sacubitril/valsartan [1], simvastatine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction was observed when simvastatin and Entresto were co-administered.

Sacubitril/valsartan [1], spironolactone ---> SmPC of [1] of EMA

Sacubitril/valsartan [1], statins ---> SmPC of [1] of EMA

In vitro data indicate that sacubitril inhibits OATP1B1 and OATP1B3 transporters. Entresto may therefore increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins.

Sacubitril/valsartan [1], tenofovir ---> SmPC of [1] of EMA

Sacubitril/valsartan [1], triamterene ---> SmPC of [1] of EMA

Sacubitril/valsartan, vericiguat [2] ---> SmPC of [2] of EMA

Co-administration was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of either medicinal product.

CONTRAINDICATIONS of Sacubitril/Valsartan (Entresto)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Concomitant use with ACE inhibitors (see sections 4.4 and 4.5). Entresto must not be administered until 36 hours after discontinuing ACE inhibitor therapy.

- Known history of angioedema related to previous ACE inhibitor or ARB therapy (see section 4.4).

- Hereditary or idiopathic angioedema (see section 4.4).

- Concomitant use with aliskiren-containing medicinal products in patients with diabetes mellitus or in patients with renal impairment (eGFR <60 ml/min/1.73 m2) (see sections 4.4 and 4.5).

- Severe hepatic impairment, biliary cirrhosis and cholestasis (see section 4.2).

- Second and third trimester of pregnancy (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/entresto-epar-product-information_en.pdf 13/01/2026

Safinamide (Xadago)

Ability to drive, safinamide [2] ---> SmPC of [2] of EMA

Somnolence and dizziness may occur during safinamide treatment, therefore patients should be cautioned about using hazardous machines, including motor vehicles, until they are reasonably certain that safinamide does not affect them adversely.

Aciclovir, safinamide [2] ---> SmPC of [2] of EMA

Safinamide inhibits OCT1 in vitro at clinically relevant portal vein concentrations. Therefore, caution is necessary when safinamide is taken concomitantly with medicinal products that are OCT1 substrates and have a tmax similar to safinamide (2 hours)

Amidases, safinamide [2] ---> SmPC of [2] of EMA

There are currently no marketed medicinal products known to cause clinically significant drug-drug interactions through inhibition or induction of amidase enzymes.

Antidepressants, safinamide [2] ---> SmPC of [2] of EMA

In view of the selective and reversible MAO-B inhibitory activity of safinamide, antidepressants may be administered but used at the lowest doses necessary.

BCRP substrates, safinamide [2] ---> SmPC of [2] of EMA

Safinamide may transiently inhibit BCRP in vitro. No precautions are necessary when safinamide is taken with medicinal products that are BCRP substrates (e.g., pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide).

Breast-feeding, safinamide [2] ---> SmPC of [2] of EMA

A risk for the breast-fed child cannot be excluded. Xadago should not be used during breast-feeding.

Ciprofloxacin, safinamide [2] ---> SmPC of [2] of EMA

It is recommended to monitor patients when safinamide is taken with medicinal products that are BCRP substrates (e.g., rosuvastatin, pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide)

CYP450 enzymes, safinamide [2] ---> SmPC of [2] of EMA

It was shown that CYP enzymes play a minor role in the biotransformation of safinamide

Dextromethorphan, non-selective MAO-inhibitors ---> SmPC of [safinamide] of EMA

There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors.

Dextromethorphan, safinamide [2] ---> SmPC of [2] of EMA

There have been reports of medicinal product interactions with the concomitant use of dextromethorphan and non-selective MAO inhibitors. In view of the MAO inhibitory activity of safinamide, the concomitant administration is not recommended,

Diclofenac, safinamide [2] ---> SmPC of [2] of EMA

Dopamine agonists, safinamide [2] ---> SmPC of [2] of EMA

There was no effect on the clearance of safinamide in patients with PD receiving safinamide as adjunct to chronic L-dopa and/or DA-agonists and safinamide treatment did not change the pharmacokinetic profile of co-administered L-dopa.

Ephedrine, safinamide [2] ---> SmPC of [2] of EMA

In view of the MAO inhibitory activity of safinamide, concomitant administration of safinamide and SM, such as those present in nasal and oral decongestants or cold medicinal products containing ephedrine or pseudoephedrine, requires caution

Fertility, safinamide [2] ---> SmPC of [2] of EMA

Animal studies indicate that safinamide treatment is associated with adverse reactions on female rat reproductive performance and sperm quality. Male rat fertility is not affected (see section 5.3).

Fluoxetine, safinamide [2] ---> SmPC of [2] of EMA

The concomitant use of safinamide and fluoxetine should be avoided, this precaution is based on the occurrence of rare serious adverse reactions (e.g. serotonin syndrome) that have occurred when SSRIs have been used with MAO inhibitors.

Fluvoxamine, safinamide [2] ---> SmPC of [2] of EMA

The concomitant use of safinamide and fluvoxamine should be avoided, this precaution is based on the occurrence of rare serious adverse reactions (e.g. serotonin syndrome) that have occurred when SSRIs have been used with MAO inhibitors.

Ganciclovir, safinamide [2] ---> SmPC of [2] of EMA

Glibenclamide, safinamide [2] ---> SmPC of [2] of EMA

IMAOs, pethidine ---> SmPC of [safinamide] of EMA

Serious adverse reactions have been reported with the concomitant use of pethidine and MAO inhibitors. As this may be a class-effect, the concomitant administration of safinamide and pethidine is contraindicated (see section 4.3).

IMAOs, safinamide [2] ---> SmPC of [2] of EMA

Safinamide must not be administered along with other MAO inhibitors (including moclobemide) as there may be a risk of non-selective MAO inhibition that may lead to a hypertensive crisis

IMAOs, SNRIs ---> SmPC of [safinamide] of EMA

Serious adverse reactions have been reported with the concomitant use of selective serotonin norepinephrine reuptake inhibitors (SNRIs) and MAO inhibitors

IMAOs, sympathomimetics ---> SmPC of [safinamide] of EMA

There have been reports of medicinal product interactions with the concomitant use of MAO inhibitors and sympathomimetic medicinal products.

IMAOs, tricyclic antidepressant ---> SmPC of [safinamide] of EMA

Serious adverse reactions have been reported with the concomitant use of tricyclic antidepressants and MAO inhibitors

Ketoconazole, safinamide [2] ---> SmPC of [2] of EMA

Safinamide is eliminated mainly in the urine. In human liver microsomes (HLM), the N-dealkylation step appears to be catalysed by CYP3A4, as safinamide clearance in HLM was inhibited by ketoconazole by 90%.

Levodopa, safinamide [2] ---> SmPC of [2] of EMA

The use of selective MAO-B inhibitors (e.g. rasagiline, selegiline, and safinamide) with levodopa may be associated with orthostatic hypotension. Patients who are taking these medicinal products should be monitored closely.

Metabolized by cytochrome P450, safinamide [2] ---> SmPC of [2] of EMA

CYP enzymes play a minor role in the biotransformation of safinamide

Metformin, safinamide [2] ---> SmPC of [2] of EMA

Methotrexate, safinamide [2] ---> SmPC of [2] of EMA

Moclobemide, safinamide [2] ---> SmPC of [2] of EMA

Safinamide must not be administered along with other MAO inhibitors (including moclobemide) as there may be a risk of non-selective MAO inhibition that may lead to a hypertensive crisis

Nasal decongestants, safinamide [2] ---> SmPC of [2] of EMA

OAT3 inhibitors, safinamide [2] ---> SmPC of [2] of EMA

Medicinal products that are inhibitors of OAT3 given concomitantly with safinamide may reduce clearance of NW-1153, i.e., and thus may increase its systemic exposure.

OCT1 substrates, safinamide [2] ---> SmPC of [2] of EMA

Ophthalmological history, safinamide [2] ---> SmPC of [2] of EMA

Safinamide should not be administered to patients with ophthalmological history that would put them at increased risk for potential retinal effects (e.g., family history of hereditary retinal disease, or history of uveitis) see sections 4.3 and 5.3.

Opicapone [1], safinamide ---> SmPC of [1] of EMA

There is no experience with opicapone when used concomitantly with the MAO-B inhibitor safinamide. Therefore, their concomitant use should be considered with appropriate caution.

Pethidine, safinamide [2] ---> SmPC of [2] of EMA

Pitavastatin, safinamide [2] ---> SmPC of [2] of EMA

Pravastatine, safinamide [2] ---> SmPC of [2] of EMA

Pregnancy, safinamide [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Xadago is not recommended during pregnancy and in women of childbearing potential not using contraception.

Pseudoephedrine, safinamide [2] ---> SmPC of [2] of EMA

Rosuvastatin, safinamide [2] ---> SmPC of [2] of EMA

In drug-drug-interaction studies in human, a weak interaction was observed with rosuvastatin (AUC increase between 1.25 and 2.00 fold) but no significant interaction was found with diclofenac.

Safinamide [1], SNRIs ---> SmPC of [1] of EMA

Serious adverse reactions have been reported with the concomitant use of selective serotonin norepinephrine reuptake inhibitors (SNRIs) and MAO inhibitors

Safinamide [1], SSRI ---> SmPC of [1] of EMA

Serious adverse reactions have been reported with the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and MAO inhibitors

Safinamide [1], sympathomimetics ---> SmPC of [1] of EMA

Safinamide [1], tetracyclic antidepressant ---> SmPC of [1] of EMA

Serious adverse reactions have been reported with the concomitant use of tetracyclic antidepressants and MAO inhibitors

Safinamide [1], topotecan ---> SmPC of [1] of EMA

Safinamide [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Serious adverse reactions have been reported with the concomitant use of tricyclic antidepressants and MAO inhibitors

Safinamide [1], tyramine ---> SmPC of [1] of EMA

Results of several studies with tyramine did not detect any clinically important increase in blood pressure. Safinamide can, therefore, be used safely without any dietary tyramine restrictions.

Safinamide [1], women of childbearing potential ---> SmPC of [1] of EMA

Safinamide should not be given to women of childbearing potential unless adequate contraception is practiced.

CONTRAINDICATIONS of Safinamide (Xadago)

- Hypersensitivity to the active substance or to any of the excipients (see section 6.1).

- Concomitant treatment with other monoamine oxidase (MAO) inhibitors (see sections 4.4 and 4.5).

- Concomitant treatment with pethidine (see sections 4.4 and 4.5).

- Use in patients with severe hepatic impairment (see section 4.2).

- Use in patients with albinism, retinal degeneration, uveitis, inherited retinopathy or severe progressive diabetic retinopathy

https://www.ema.europa.eu/en/documents/product-information/xadago-epar-product-information_en.pdf 26/07/2024

Salbutamol

Antiarrhythmics, salbutamol

The co-administration of salbutamol and antiarrhythmic agents (e.g. digitalis glycoside and quinidine) may increase the risk of adverse effects

Antidiabetics, salbutamol [2] ---> SmPC of [2] of eMC

The administration of beta-agonists is associated with a rise of blood glucose, which can be interpreted as an attenuation of anti-diabetic therapy; therefore individual anti-diabetic therapy may need to be adjusted

Atomoxetine, salbutamol

Atomoxetine should be administered with caution with high dose nebulised or systemically administered (oral/IV) salbutamol (or other ß2-agonists) because the action of salbutamol on the cardiovascular system can be potentiated.

Betablockers, salbutamol [2] ---> SmPC of [2] of eMC

Salbutamol and beta-blocking drugs such as propranolol should not usually be prescribed together.

Breast-feeding, salbutamol [2] ---> SmPC of [2] of eMC

As salbutamol is probably secreted in breast milk its use in nursing mothers requires careful consideration.

Celiprolol, salbutamol

Celiprolol may weaken or antagonise the effect of salbutamol

Corticosteroids, salbutamol [2] ---> SmPC of [2] of eMC

There is an increased risk of hypokalaemia if high doses of corticosteroids are given with higher doses of salbutamol.

Digital glycosides, salbutamol

The co-administration of salbutamol and antiarrhythmic agents (e.g. digitalis glycoside and quinidine) may increase the risk of adverse effects

Digoxin [1], salbutamol ---> SmPC of [1] of eMC

Serum levels of digoxin may be reduced by concomitant administration of salbutamol

Diuretics, salbutamol [2] ---> SmPC of [2] of eMC

Owing to the hypokalaemic effect of beta-agonists, co-administration of serum potassium depleting agents known to exacerbate the risk of hypokalaemia should be administered cautiously after careful evaluation of the benefits and risks

Enflurane, salbutamol

Owing to the additional antihypertensive effect, there is increased uterine inertia with haemorrhage risk; in addition, serious ventricular rhythm disorders due to increased cardiac reactivity have been reported with halogenated anaesthetics.

Ergot derivatives, salbutamol

The co-administration of salbutamol and ergot derivatives (e. g. ergotamine) should be done with caution because it can cause vasoconstrictor and vasodilatator reactions

Etoricoxib [1], salbutamol ---> SmPC of [1] of eMC

It may be prudent to exercise care when administering etoricoxib concurrently with other drugs primarily metabolised by human sulfotransferases

Gliclazide [1], salbutamol ---> SmPC of [1] of eMC

The administration of gliclazide and i.v. salbutamol increases the blood glucose levels due to beta-2 agonist effects

Halogenated anaesthetics, salbutamol [2] ---> SmPC of [2] of eMC

Halothane, salbutamol

Hypokalemia, salbutamol

The co-administration may enhance a hypokaliemia

IMAOs, salbutamol [2] ---> SmPC of [2] of eMC

The effects of salbutamol may be altered by monoamine oxidase inhibitors.

Insulin glargin [1], salbutamol ---> SmPC of [1] of EMA

Reduced blood-glucose-lowering effect

Insulin glargine/lixisenatide [1], salbutamol ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glulisin [1], salbutamol ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin lispro [1], salbutamol ---> SmPC of [1] of EMA

Insulin requirements may be increased by medicinal products with hyperglycaemic activity

Methoxyflurane, salbutamol

The co-administration of salbutamol and halogenated anesthetics may increase the risk of serious heart rhythm disorders and cause hypotension

Nicotine, salbutamol

Decrease of circulating catecholamines. It can be necessary to increase the dose of salbutamol

Nifedipine, salbutamol

The co-administration may enhance the broncholytic effect of salbutamol

Prednisolone, salbutamol

The co-administration may increase the effect and potencial toxicity of salbutamol

Pregnancy, salbutamol [2] ---> SmPC of [2] of eMC

Salbutamol should only be used during pregnancy if it is considered essential by the physician.

Procarbazine, salbutamol

The co-administration of salbutamol and procarbazine may cause hypertensive reactions

Propranolol, salbutamol [2] ---> SmPC of [2] of eMC

Salbutamol and beta-blocking drugs such as propranolol should not usually be prescribed together.

Quinidine, salbutamol

The co-administration of salbutamol and antiarrhythmic agents (e.g. digitalis glycoside and quinidine) may increase the risk of adverse effects

Salbutamol [1], theophylline ---> SmPC of [1] of eMC

There is an increased risk of hypokalaemia if high doses of theophylline are given with higher doses of salbutamol.

Salbutamol [1], xanthines ---> SmPC of [1] of eMC

Salbutamol, sympathomimetics

The co-administration of salbutamol and sympathomimetic agents may enhance the effects of both active principles and increase the risk of adverse effects

Salbutamol, tricyclic antidepressant [2] ---> SmPC of [2] of eMC

The effects of salbutamol may be altered by tricyclic antidepressants

CONTRAINDICATIONS of Salbutamol

1. Salbutamol should not be used for threatened abortion during the first or second trimester of pregnancy.

2. Salbutamol and beta-blocking drugs such as propranolol should not usually be prescribed together.

3. Salbutamol tablets are contraindicated in patients with a history of hypersensitivity to any of their components.

http://www.medicines.org.uk/emc/

Salicylic acid

Acenocoumarol [1], salicylic acid ---> SmPC of [1] of eMC

Drugs altering haemostasis may potentiate the anticoagulant activity and increase the risk of haemorrhage. The use concomitant is not recommended

Breast-feeding, salicylic acid [2] ---> SmPC of [2] of eMC

It should be used with caution or following professional advice.

Calcipotriol, salicylic acid

The co-administration of calcipotriol and salicylic acid may inactivate calcipotriol

Dithranol, salicylic acid

The topical co-administration may increase the dithranol effect

Etoposide, salicylic acid

Displacement of etoposide from its plasma protein binding

Indapamide [1], salicylic acid ---> SmPC of [1] of eMC

High dose salicylic acid (≥3 g/day): Possible reduction in the antihypertensive effect of indapamide. Risk of acute renal failure in dehydrated patients (decreased glomerular filtration).

Methotrexate [1], salicylic acid ---> SmPC of [1] of eMC

NSAIDs should not be administered prior to, or concurrently with, high dose methotrexate as fatal methotrexate toxicity has been reported. Caution is also advised when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate

Nimesulide, salicylic acid

In vitro studies have demonstrated that salicylic acid may displace nimesulide from its plasma protein binding

Pregnancy, salicylic acid [2] ---> SmPC of [2] of eMC

It should be used with caution or following professional advice.

Salicylic acid, sulfonylureas

The systemic absorbed salicylic acid may enhance the hypoglycemic effect of sulfonylurea

Salicylic acid, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products associated with potassium loss and hypokalaemia: These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium

Salicylic acid, topical therapy

Salicylic acid may enhance the permeation of other topical therapies

CONTRAINDICATIONS of Salicylic acid

Contra-indicated in persons with a sensitivity to salicylic acid.

http://www.medicines.org.uk/emc/

Salmeterol

Anticholinergics, salmeterol

Possible additive effect

Atazanavir [1], salmeterol ---> SmPC of [1] of EMA

Concomitant use of salmeterol and REYATAZ may result in increased cardiovascular adverse events associated with salmeterol. Co-administration of salmeterol and REYATAZ is not recommended

Atazanavir/cobicistat [1], salmeterol ---> SmPC of [1] of EMA

Coadministration with EVOTAZ may result in increased concentrations of salmeterol and an increase in salmeterol-associated adverse events. The mechanism of interaction is CYP3A4 inhibition by atazanavir and cobicistat. Coadministration is not recommended

Beta2-adrenergic agonists, salmeterol [2] ---> SmPC of [2] of eMC

Potentially serious hypokalaemia may result from beta2 agonist therapy.

Betablockers, salmeterol [2] ---> SmPC of [2] of eMC

Beta-adrenergic blockers may weaken or antagonise the effect of salmeterol. Both non-selective and selective beta-blockers should be avoided unless there are compelling reasons for their use.

Breast-feeding, salmeterol [2] ---> SmPC of [2] of eMC

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy

Cobicistat [1], salmeterol ---> SmPC of [1] of EMA

Co-administration of salmeterol with cobicistat may result in increased plasma concentrations of salmeterol. Increased plasma concentrations of salmeterol are associated with the potential for serious and/or life-threatening reactions.

Corticosteroids, salmeterol [2] ---> SmPC of [2] of eMC

Particular caution is advised in acute severe asthma as hypokalaemia may be potentiated by concomitant treatment with glucocorticoids.

Darunavir/cobicistat [1], salmeterol ---> SmPC of [1] of EMA

Concomitant use of salmeterol and darunavir/cobicistat is not recommended. The combination may result in increased risk of cardiovascular adverse event with salmeterol, including QT prolongation, palpitations and sinus tachycardia.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], salmeterol ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase salmeterol plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, salmeterol ---> SmPC of [darunavir] of EMA

Concomitant use of salmeterol and darunavir/ritonavir is not recommended. The combination may result in increased risk of cardiovascular adverse event with salmeterol, including QT prolongation, palpitations and sinus tachycardia.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, salmeterol ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Ritonavir is a strong inhibitor of CYP3A. Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events are contraindicated

Diuretics, salmeterol [2] ---> SmPC of [2] of eMC

Particular caution is advised in acute severe asthma as hypokalaemia may be potentiated by concomitant treatment with diuretics.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], salmeterol ---> SmPC of [1] of EMA

Co-administration with Genvoya may result in increased plasma concentrations of salmeterol, which is associated with the potential for serious or life-threatening adverse reactions. Concurrent administration of salmeterol and Genvoya is not recommended.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], salmeterol ---> SmPC of [1] of EMA

Co-administration with Stribild may result in increased plasma concentrations of salmeterol, is associated with the potential for serious and/or life-threatening reactions. Concurrent administration is not recommended.

Erythromycin, salmeterol [2] ---> SmPC of [2] of eMC

Co-administration of erythromycin and salmeterol resulted in a small but non-statistically significant increase in salmeterol exposure. Co-administration with erythromycin was not associated with any serious adverse effects.

Hypokalemia, salmeterol [2] ---> SmPC of [2] of eMC

Idelalisib [1], salmeterol ---> SmPC of [1] of EMA

Concurrent administration of salmeterol and idelalisib is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.

IMAOs, salmeterol

The MAOI may enhance the cardiovascular adverse effects of salmeterol

Itraconazol, salmeterol [2] ---> SmPC of [2] of eMC

The co-administration with strong CYP3A4 inhibitors with salmeterol may significant increase the plasma salmeterol exposure, what may cause a QTc interval prolongation. The co-administration should be avoided

Ketoconazole, salmeterol [2] ---> SmPC of [2] of eMC

Laxatives, salmeterol

Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with laxatives.

Levodopa, salmeterol

Levodopa may enhance the cardiovascular adverse effects of salmeterol

Lopinavir/ritonavir [1], salmeterol ---> SmPC of [1] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase salmeterol plasma concentrations. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol. Therefore, concomitant administration is not recommended

Nelfinavir [1], salmeterol ---> SmPC of [1] of EMA

Concurrent administration of salmeterol with nelfinavir is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.

Ombitasvir/paritaprevir/ritonavir [1], salmeterol ---> SmPC of [1] of EMA

Pregnancy, salmeterol [2] ---> SmPC of [2] of eMC

As a precautionary measure, it is preferable to avoid the use of salmeterol during pregnancy.

QT interval prolonging drugs, salmeterol

Caution is warranted for concomitant use of QT interval prolonging medicines

Quinupristin, salmeterol

Increased risk of toxicity

Ritonavir [1], salmeterol ---> SmPC of [1] of EMA

Ritonavir inhibits CYP3A4 and as a result a pronounced increase in the plasma concentrations of salmeterol is expected. Therefore concomitant use is not recommended.

Salmeterol [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Salmeterol [1], telithromycin ---> SmPC of [1] of eMC

Salmeterol [1], xanthines ---> SmPC of [1] of eMC

Particular caution is advised in acute severe asthma as hypokalaemia may be potentiated by concomitant treatment with xanthine derivatives.

Salmeterol, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir may increase the plasma levels of salmeterol (QT prolongation, palpitations, and sinus tachycardia). Combination not recommended

Salmeterol, telaprevir [2] ---> SmPC of [2] of EMA

Telaprevir, CYP3A4 inhibitor, may increase the plasma levels of salmeterol. Possible prolongation of the QT interval. Co-administration is not recommended

Salmeterol, thyroxine

Thyroxin may enhance the cardiovascular adverse effects of salmeterol

Salmeterol, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

The concurrent administration of tipranavir/ritonavir (inhibition of CYP 3A4 by tipranavir/ritonavir) may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.

Salmeterol, tricyclic antidepressant

The tricyclic antidepressant may enhance the cardiovascular adverse effects of salmeterol

CONTRAINDICATIONS of Salmeterol

Hypersensitivity to salmeterol xinafoate or to any of the excipients

http://www.medicines.org.uk/emc/

Salmeterol/fluticasone propionate (Aerivio Spiromax)

Beta2-adrenergic agonists, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Potentially serious hypokalaemia may result from beta2 agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics.

Betablockers, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Beta adrenergic blockers may weaken or antagonise the effect of salmeterol. Both non-selective and selective betablockers should be avoided unless there are compelling reasons for their use.

Breast-feeding, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breastfeeding or to discontinue Aerivio Spiromax therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

CYP3A4 inhibitors, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided

Diuretics, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Erythromycin, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Co-administration with erythromycin was not associated with any serious adverse effects.

Fertility, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

There are no data in humans. However, animal studies showed no effects of salmeterol or fluticasone propionate on fertility.

Glucose, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

There have been very rare reports of increases in blood glucose levels and this should be considered when prescribing to patients with a history of diabetes mellitus.

Hypokalemia, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Aerivio Spiromax should be used with uncorrected hypokalaemia or patients predisposed to low levels of serum potassium.

Itraconazol, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

There is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g. itraconazole, telithromycin, ritonavir).

Ketoconazole, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

This may lead to an increase in the incidence of other systemic effects of salmeterol treatment (e.g. prolongation of QTc interval and palpitations) compared with salmeterol or ketoconazole treatment alone (see section 4.4).

Moderate CYP3A4 inhibitors, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Co-administration of erythromycin (500 mg orally 3 times a day) and salmeterol (50 micrograms inhaled 2 daily) in 15 healthy subjects for 6 days resulted in a small but non-statistically significant increase in salmeterol exposure

Pregnancy, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

The lowest effective dose of fluticasone propionate needed to maintain adequate asthma control should be used in the treatment of pregnant women.

Pregnancy, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Administration of Aerivio Spiromax to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.

Ritonavir, salmeterol/fluticasone propionate [2] ---> SmPC of [2] of EMA

Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Salmeterol/fluticasone propionate [1], steroids ---> SmPC of [1] of EMA

Salmeterol/fluticasone propionate [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

There is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g. itraconazole, telithromycin, ritonavir).

Salmeterol/fluticasone propionate [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Co-treatment with other potent CYP3A inhibitors, such as itraconazole, and moderate CYP3A inhibitors, such as erythromycin, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic undesirable effects

Salmeterol/fluticasone propionate [1], telithromycin ---> SmPC of [1] of EMA

There is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g. itraconazole, telithromycin, ritonavir).

Salmeterol/fluticasone propionate [1], xanthines ---> SmPC of [1] of EMA

Sympathomimetics, sympathomimetics ---> SmPC of [salmeterol/fluticasone propionate] of EMA

Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination therapy) can have a potentially additive effect.

CONTRAINDICATIONS of Salmeterol/fluticasone propionate (Aerivio Spiromax)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1

https://www.ema.europa.eu/en/documents/product-information/aerivio-spiromax-epar-product-information_en.pdf 15/01/2020 (withdrawn)

Other trade names: Airexar Spiromax, BoPair Spiromax, Seffalair Spiromax,

Samarium lexidronam pentasodium (Quadramet)

Breast-feeding, samarium lexidronam pentasodium [2] ---> SmPC of [2] of EMA

If Quadramet administration is deemed necessary, formula feeding should be substituted for breastfeeding and the expressed feeds discarded.

Chemotherapy, samarium lexidronam pentasodium [2] ---> SmPC of [2] of EMA

Because of the potential for additive effects on bone marrow, the treatment should not be given concurrently with chemotherapy or external beam radiation therapy.

Pregnancy, samarium lexidronam pentasodium [2] ---> SmPC of [2] of EMA

Quadramet is contraindicated in pregnancy. The possibility of pregnancy must strictly be ruled out.

Radiotherapy, samarium lexidronam pentasodium [2] ---> SmPC of [2] of EMA

Because of the potential for additive effects on bone marrow, the treatment should not be given concurrently with chemotherapy or external beam radiation therapy.

Samarium lexidronam pentasodium [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential have to use effective contraception during the treatment and the whole period of follow-up.

CONTRAINDICATIONS of Samarium lexidronam pentasodium (Quadramet)

- Hypersensitivity to the active substance (ethylenediaminetetramethylenephosphonate (EDTMP) or similar phosphonates) or to any of the excipients listed in section 6.1.

- in pregnant women

- in patients having received chemotherapy or hemi-body external radiation therapy in a preceding period of 6 weeks.

- Samarium lexidronam pentasodium is used only as a palliative agent and should not be used concurrently with myelotoxic chemotherapy as this may enhance myelotoxicity.

- It should not be used concurrently with other biphosphonates if an interference is shown on the technetium (99mTc)-labelled biphosphonate bone scans.

https://www.ema.europa.eu/en/documents/product-information/quadramet-epar-product-information_en.pdf 03/06/2015

Sapropterin (Kuvan)

Breast-feeding, sapropterin [2] ---> SmPC of [2] of EMA

It is not known whether sapropterin or its metabolites are excreted in human breast milk. Kuvan should not be used during breast-feeding.

Dihydrofolate reductase inhibitors, sapropterin [2] ---> SmPC of [2] of EMA

Although concomitant administration of inhibitors of dihydrofolate reductase (e.g. methotrexate, trimethoprim) has not been studied, such medicinal products may interfere with BH4 metabolism. Caution is recommended

Fertility, sapropterin [2] ---> SmPC of [2] of EMA

In preclinical studies, no effects of sapropterin on male and female fertility were observed.

Foods, sapropterin [2] ---> SmPC of [2] of EMA

Patients treated with Kuvan must continue a restricted phenylalanine diet and undergo regular clinical assessment (such as monitoring of blood phenylalanine and tyrosine levels, nutrient intake, and psychomotor development).

Foods, sapropterin [2] ---> SmPC of [2] of EMA

The rate and extent of absorption of sapropterin is influenced by food.

Isosorbide dinitrate, sapropterin [2] ---> SmPC of [2] of EMA

Caution is recommended during concomitant use of Kuvan with all medicinal products that cause vasodilation, including those administered topically, by affecting nitric oxide (NO) metabolism or action including classical NO donors

Levodopa, sapropterin [2] ---> SmPC of [2] of EMA

Cases of convulsion, exacerbation of convulsion, increased excitability and irritability have been observed during coadministration of levodopa and sapropterin in BH4-deficient patients.

Methotrexate, sapropterin [2] ---> SmPC of [2] of EMA

Minoxidil, sapropterin [2] ---> SmPC of [2] of EMA

Molsidomine, sapropterin [2] ---> SmPC of [2] of EMA

Nitric oxide donors, sapropterin [2] ---> SmPC of [2] of EMA

Nitroglycerine [1], sapropterin ---> SmPC of [1] of eMC

Treatment with other agents with hypotensive effects may potentiate the hypotensive effect of glyceryl trinitrate.

PDE5 inhibitors, sapropterin [2] ---> SmPC of [2] of EMA

Pregnancy, sapropterin [2] ---> SmPC of [2] of EMA

Caution must be exercised when prescribing to pregnant women.

Sapropterin [1], sodium nitroprusside ---> SmPC of [1] of EMA

Sapropterin [1], trimethoprim ---> SmPC of [1] of EMA

Sapropterin [1], vasodilators ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Sapropterin (Kuvan)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/kuvan-epar-product-information_en.pdf 22/04/2025

Other trade names: Sapropterin Dipharma,

Saquinavir (Invirase)

Ability to drive, saquinavir [2] ---> SmPC of [2] of EMA

Invirase may have a minor influence on the ability to drive and use machines. Dizziness, fatigue and visual impairment have been reported during treatment with Invirase.

Afatinib [1], saquinavir ---> SmPC of [1] of EMA

Increased exposure to afatinib. It is recommended to administer strong P-gp inhibitors using staggered dosing, preferably 6 hours or 12 hours apart from afatinib

Alectinib [1], saquinavir ---> SmPC of [1] of EMA

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inhibitors

Alfentanyl, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of alfentanyl.

Alfentanyl, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of alfentanyl. Contraindicated due to the potential for life threatening cardiac arrhythmia

Alfuzosin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Contraindicated in combination with Invirase/ritonavir due to potential increase in alfuzosin concentration which can result in hypotension and potentially life-threatening cardiac arrhythmia.

Alprazolam, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased benzodiazepine plasma concentrations. Careful monitoring of patients with regard to sedative effects is warranted.

Amiodarone, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Amitriptyline, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Invirase/ritonavir may increase concentrations of tricyclic antidepressants. Contraindicated in combination with Invirase/ritonavir due to potentially life threatening cardiac arrhythmia (see sections 4.3 and 4.4).

Amlodipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Amprenavir [1], saquinavir ---> SmPC of [1] of EMA

No dose adjustment is necessary for either medicinal product when saquinavir is administered in combination with amprenavir.

Astemizole, saquinavir [2] ---> SmPC of [2] of EMA

Possible Increased AUC of astemizole, associated with a prolongation of QTc intervals. Astemizole is contraindicated with boosted or unboosted saquinavir

Astemizole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible Increased AUC of astemizole, associated with a prolongation of QTc intervals. Astemizole is contraindicated with boosted or unboosted saquinavir

Atazanavir, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased ritonavir and saquinavir plasma concentrations. Contraindicated due to the potential for life threatening cardiac arrhythmia

Atorvastatin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

When used with saquinavir/ritonavir, the lowest possible dose of atorvastatin should be administered and the patient should be carefully monitored for signs/symptoms of myopathy

Avacopan [1], saquinavir ---> SmPC of [1] of EMA

Strong CYP3A4 enzyme inhibitors should be used with caution in patients who are being treated with avacopan.

Avanafil [1], saquinavir ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The strong CYP3A4 inhibitors may increase the exposition of avanafil. Co-administration of avanafil with potent CYP3A4 inhibitors is contraindicated

Avapritinib [1], saquinavir ---> SmPC of [1] of EMA

Co-administration with strong or moderate CYP3A inhibitors should be avoided because it may increase the plasma concentration of avapritinib

Axitinib [1], saquinavir ---> SmPC of [1] of EMA

Co-administration of axitinib with strong CYP3A4/5 inhibitors may increase axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 inhibition potential is recommended.

Bepridil, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Bosentan, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The plasma concentrations of bosentan may increase und the plasma concentrations of saquinavir/ritonavir may decrease

Bosutinib [1], saquinavir ---> SmPC of [1] of EMA

The concomitant use of bosutinib with potent CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, saquinavir [2] ---> SmPC of [2] of EMA

It is recommended that HIV-infected women do not breast feed their infants under any circumstances in order to avoid transmission of HIV

Brigatinib [1], saquinavir ---> SmPC of [1] of EMA

The concomitant use of strong CYP3A inhibitors with Alunbrig should be avoided

Budesonide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant use of saquinavir/ritonavir and budesonide or other glucocorticoids that are metabolised by CYP3A4. Risk of systemic corticosteroid effects.

Buprenorphine [1], saquinavir ---> SmPC of [1] of EMA

CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased Cmax and AUC of buprenorphine and norbuprenorphine.

Cabazitaxel [1], saquinavir ---> SmPC of [1] of EMA

Repeated administration of ketoconazole, a strong CYP3A inhibitor, decreased cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inhibitors should be avoided as an increase of plasma concentrations of cabazitaxel may occur

Calcium antagonists, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Capmatinib [1], saquinavir ---> SmPC of [1] of EMA

Patients should be closely monitored for adverse reactions during co-administration of Tabrecta with strong CYP3A inhibitors

Carbamazepine, saquinavir [2] ---> SmPC of [2] of EMA

Carbamazepine, CYP3A4 inductor, may decrease the plasma levels of saquinavir

Carbamazepine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Interaction with Invirase/ritonavir not studied. These medicinal products will induce CYP3A4 and may therefore decrease saquinavir concentrations. Use with caution. Monitoring of saquinavir plasma concentration is recommended (see section 4.4)

Cariprazine [1], saquinavir ---> SmPC of [1] of EMA

Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4. The co-administration of cariprazine with strong or moderate inhibitors of CYP3A4 is contraindicated

Ceritinib [1], saquinavir ---> SmPC of [1] of EMA

If it is not possible to avoid concomitant use with strong CYP3A inhibitors, reduce the ceritinib dose by approximately one third, rounded to the nearest multiple of the 150 mg dosage strength.

Chlorpromazine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Cisapride, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of cisapride. Contraindicated due to the potential for life threatening cardiac arrhythmia

Clarithromycin [1], saquinavir ---> SmPC of [1] of eMC

Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. The mutual inhibition of CYP3A4 may increase the exposition to saquinavir and clarithromycin

Clarithromycin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Clomipramine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Clozapine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Cobicistat, saquinavir [2] ---> SmPC of [2] of EMA

It is not recommended to coadminister Invirase/ritonavir with cobicistat containing products

Colchicine, saquinavir

The P-glycoprotein and CYP3A4 inhibition by lopinavir/ritonavir may increase the plasma concentrations of colchicine. Concomitant use is not recommended

Colchicine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Because of a potential increase of colchicine-related toxicity (neuromuscular events including rhabdomyolysis), its concomitant use with saquinavir/ritonavir is not recommended, especially in the case of renal or hepatic impairment

Crizotinib [1], saquinavir ---> SmPC of [1] of EMA

Coadministration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations. Therefore, the concomitant use of strong CYP3A inhibitors should be avoided.

Cyclosporine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Careful therapeutic drug monitoring is necessary for immunosuppressants when co-administered with saquinavir/ritonavir.

CYP3A4 and P-glycoprotein-inhibitors, saquinavir [2] ---> SmPC of [2] of EMA

Medicinal products that modify CYP3A4 and/or P-gp activity may modify the pharmacokinetics of saquinavir.

CYP3A4 inductors, saquinavir [2] ---> SmPC of [2] of EMA

Medicinal products that induce CYP3A4 may decrease saquinavir concentrations.

CYP3A4 inhibitors, saquinavir [2] ---> SmPC of [2] of EMA

Medicinal products that modify CYP3A4 activity may modify the pharmacokinetics of saquinavir.

Dabrafenib [1], saquinavir ---> SmPC of [1] of EMA

Dabrafenib is a substrate for the metabolising enzymes CYP3A4. Medicines that are strong inhibitors of CYP3A4 are therefore likely to increase dabrafenib concentrations. Use caution if strong inhibitors are coadministered with dabrafenib.

Dalfopristin, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir concentrations may be increased. Use with caution due to possible cardiac arrhythmias. Monitoring for saquinavir toxicity recommended (see section 4.4).

Dapoxetine [1], saquinavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition may increase the plasma concentrations of dapoxetine. Concomitant use of dapoxetine and potent CYP3A4 inhibitors is contraindicated

Dapsone, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of dapsone.

Dapsone, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of dapsone. Contraindicated due to the potential for life threatening cardiac arrhythmia

Darunavir/ritonavir, saquinavir ---> SmPC of [darunavir] of EMA

It is not recommended to combine darunavir co-administered with low dose ritonavir with saquinavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, saquinavir ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations. The coadministration is contraindicated

Delamanid [1], saquinavir ---> SmPC of [1] of EMA

Treatment with delamanid should not be initiated in patients with risk factors like taking medicinal products that are known to prolong the QTc interval, unless the possible benefit is considered to outweigh the potential risks.

Delavirdine, saquinavir [2] ---> SmPC of [2] of EMA

Increased saquinavir AUC. Hepatocellular changes should be monitored frequently if this combination is prescribed.

Delavirdine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased saquinavir AUC. Hepatocellular changes should be monitored frequently if this combination is prescribed.

Dexamethasone, saquinavir [2] ---> SmPC of [2] of EMA

Dexamethasone induces CYP3A4 and may decrease saquinavir concentrations. Use with caution.

Dextromethorphan/quinidine [1], saquinavir ---> SmPC of [1] of EMA

Concomitant administration of medicines that inhibit CYP3A4 can be expected to increase plasma levels of quinidine, which could increase risk relating to QTc prolongation. Strong and moderate CYP3A4 inhibitors should be avoided during treatment.

Diazepam, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased benzodiazepine plasma concentrations. Careful monitoring of patients with regard to sedative effects is warranted.

Didanosine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Decreased saquinavir exposition. No dosage adjustment necessary.

Digoxin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Large increments of digoxin may be expected when saquinavir/ritonavir is introduced in patients already treated with digoxin.

Dihydroergotamine, saquinavir [2] ---> SmPC of [2] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Dihydroergotamine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Diltiazem, saquinavir

Careful monitoring of therapeutic and adverse effects is recommended.

Diltiazem, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Diphemanil, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Dipotassium clorazepate, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased benzodiazepine plasma concentrations. Careful monitoring of patients with regard to sedative effects is warranted.

Disopyramide, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of disopyramide.

Disopyramide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of disopyramide. Contraindicated due to the potential for life threatening cardiac arrhythmia

Docetaxel [1], saquinavir ---> SmPC of [1] of EMA

In case of combination of docetaxel with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism

Dofetilide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Droperidol [1], saquinavir ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Drugs primarily metabolised by CYP3A4, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir might modify the pharmacokinetics of other medicinal products that are substrates for CYP3A4

Drugs primarily metabolised by CYP3A4, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Co-administration of saquinavir/ritonavir with medicinal products that are mainly metabolised by CYP3A4 pathway may result in elevated plasma concentrations of these medicinal products.

Duvelisib [1], saquinavir ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Efavirenz [1], saquinavir ---> SmPC of [1] of EMA

May decrease the plasma levels of saquinavir. Use of efavirenz in combination with saquinavir as the sole protease inhibitor is not recommended.

Efavirenz [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

May decrease the plasma levels of saquinavir. Use of efavirenz in combination with saquinavir as the sole protease inhibitor is not recommended.

Elbasvir/grazoprevir [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

Combination of mechanisms including CYP3A inhibition. Co-administration is contraindicated.

Eliglustat [1], saquinavir ---> SmPC of [1] of EMA

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

Eluxadoline [1], saquinavir ---> SmPC of [1] of EMA

Co-administration of OATP1B1 inhibitors with eluxadoline may increase exposure to eluxadoline. Eluxadoline should not be administered concomitantly with such medicinal products

Enfortumab vedotin [1], saquinavir ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Enfuvirtide [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

Co-administration of ritonavir (potent CYP3A4 inhibitor) or saquinavir in combination with a booster dose of ritonavir or rifampicin (potent CYP3A4 inducer) did not result in clinically significant changes of the pharmacokinetics of enfuvirtide.

Enfuvirtide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

No clinically significant interaction was noted. No dose adjustment required.

Entrectinib [1], saquinavir ---> SmPC of [1] of EMA

Co-administration of strong and moderate CYP3A inhibitors (including, but not limited to, ritonavir, saquinavir, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit or Seville oranges) should be avoided.

Enzyme inductors, saquinavir

The enzymatic inductor may decrease the plasma levels of saquinavir

Eplerenone [1], saquinavir ---> SmPC of [1] of eMC

Moderate CYP3A4 inhibitors may increase the AUC of eplerenone. Eplerenone dosing should not exceed 25 mg when moderate inhibitors of CYP3A4 are co-administered with eplerenone

Eravacycline [1], saquinavir ---> SmPC of [1] of EMA

A drug-drug interaction in vivo cannot be excluded and co-administration of eravacycline and other medicinal products that inhibit gp-P, OATP1B1 y OATP1B3 transporters may increase the eravacycline plasma concentration.

Ergonovine, saquinavir [2] ---> SmPC of [2] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Ergonovine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Ergot derivatives, saquinavir [2] ---> SmPC of [2] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Ergot derivatives, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Ergotamine, saquinavir [2] ---> SmPC of [2] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Ergotamine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Eribulin [1], saquinavir ---> SmPC of [1] of EMA

The inhibition of hepatic transport proteins may increase the plasma concentrations of eribulin. Co-administration is not recommended

Erythromycin, saquinavir [2] ---> SmPC of [2] of EMA

Increased exposition to saquinavir. No dose adjustment required.

Erythromycin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Esomeprazole [1], saquinavir ---> SmPC of [1] of EMA

For saquinavir (with concomitant ritonavir), increased serum levels (80-100%) have been reported during concomitant omeprazole treatment (40 mg qd).

Estazolam, saquinavir

Saquinavir may increase the effect of estazolam

Estrogens, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Alternative or additional contraceptive measures should be used when oestrogen-based oral contraceptives are co-administered.

Ethinyl estradiol, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible decreased plasma concentrations of ethinyl estradiol. Alternative or additional contraceptive measures should be used when oestrogen-based oral contraceptives are co-administered.

Etravirine [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

The co-administration may decrease the plasma levels of etravirine. The combination can be used without dose adjustments

Everolimus [1], saquinavir ---> SmPC of [1] of EMA

Large increase in everolimus concentration is expected. Concomitant treatment of everolimus and potent CYP3A4 inhibitors is not recommended.

Felodipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Fentanyl, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of fentanyl.

Fentanyl, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of fentanyl. Contraindicated due to the potential for life threatening cardiac arrhythmia

Fesoterodine [1], saquinavir ---> SmPC of [1] of EMA

The maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors

Flecainide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Fluconazole [1], saquinavir ---> SmPC of [1] of eMC

Fluconazole increases the AUC and Cmax of saquinavir with approximately 50% and 55% respectively, due to inhibition of saquinavir's hepatic metabolism by CYP3A4 and inhibition of P-glycoprotein.

Fluconazole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Fluconazole is CYP3A4 inhibitors and may increase the plasma concentration of saquinavir. Use with caution due to possible cardiac arrhythmias. Monitoring for saquinavir toxicity recommended

Flurazepam, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased benzodiazepine plasma concentrations. Careful monitoring of patients with regard to sedative effects is warranted.

Fluticasone, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant use of saquinavir/ritonavir and budesonide or other glucocorticoids that are metabolised by CYP3A4. Risk of systemic corticosteroid effects.

Fluvastatin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Metabolism of fluvastatin is not dependent on CYP3A4. Interaction via effects on transport proteins cannot be excluded.

Foods, saquinavir [2] ---> SmPC of [2] of EMA

Take this medication with food.

Fosamprenavir, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Decreased saquinavir concentration. No dose adjustment required for Invirase/ritonavir.

Fosamprenavir/ritonavir, saquinavir ---> SmPC of [fosamprenavir] of EMA

No dose recommendations can be given.

Foscarnet [1], saquinavir ---> SmPC of [1] of eMC

Abnormal renal function has been reported in connection with the use of foscarnet in combination with saquinavir

Fostamatinib [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

Concomitant use of fostamatinib with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions.

Fusidic acid, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Co-administration of fusidic acid and saquinavir/ritonavir can cause increased plasma concentration of both fusidic acid and saquinavir/ritonavir.

Garlic, saquinavir [2] ---> SmPC of [2] of EMA

Patients on saquinavir treatment must not take garlic capsules due to the risk of decreased plasma concentrations and loss of virological response and possible resistance to one or more components of the antiretroviral regimen.

Glucocorticoids metabolized by CYP3A4, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant use of saquinavir/ritonavir and budesonide or other glucocorticoids that are metabolised by CYP3A4. Risk of systemic corticosteroid effects.

Grapefruit juice, saquinavir [2] ---> SmPC of [2] of EMA

Increase of saquinavir exposition not thought to be clinically relevant. No dose adjustment required.

Grapefruit juice, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increase of saquinavir exposition not thought to be clinically relevant. No dose adjustment required.

Guanfacin [1], saquinavir ---> SmPC of [1] of EMA

Co-administration of Intuniv with moderate and strong CYP3A4/5 inhibitors elevates plasma guanfacine concentrations and increases the risk of adverse reactions such as hypotension, bradycardia, and sedation.

Halofantrine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Haloperidol, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Hydroquinidine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Ibrutinib [1], saquinavir ---> SmPC of [1] of EMA

Concomitant use of IMBRUVICA and medicinal products that strongly or moderately inhibit CYP3A4 can increase ibrutinib exposure and strong CYP3A4 inhibitors should be avoided.

Ibutilide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Imatinib [1], saquinavir ---> SmPC of [1] of EMA

Substances that inhibit the cytochrome P450 isoenzyme CYP3A4 activity could decrease metabolism and increase imatinib concentrations. Caution should be taken when administering imatinib with inhibitors of the CYP3A4 family.

Imipramine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Indinavir [1], saquinavir ---> SmPC of [1] of EMA

The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

Indinavir, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Low dose ritonavir increases the concentration of indinavir. Increased concentrations of indinavir may result in nephrolithiasis.

Indinavir/ritonavir, saquinavir ---> SmPC of [indinavir] of EMA

Indinavir with or without ritonavir should not be administered with medicinal products with narrow therapeutic ranges and which are CYP3A4 substrates. The elevated plasma concentrations of these medicines may cause serious or life-threatening reactions.

Irinotecan [1], saquinavir ---> SmPC of [1] of EMA

Co-administration of ONIVYDE with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE.

Isavuconazole [1], saquinavir ---> SmPC of [1] of EMA

No dose adjustment of CRESEMBA is necessary when co-administered with strong CYP3A4/5 inhibitors, however caution is advised as adverse drug reactions may increase

Isradipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Itraconazol, saquinavir [2] ---> SmPC of [2] of EMA

Itraconazole is a moderately potent inhibitor of CYP3A4. An interaction is possible. Monitoring for saquinavir toxicity recommended.

Ixabepilone, saquinavir

The strong CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. The coadministration should be avoided

Ketoconazole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

No dose adjustment required when saquinavir/ritonavir combined with ≤ 200 mg/day ketoconazole. High doses of ketoconazole (> 200 mg/day) are not recommended.

Lamivudine/raltegravir [1], saquinavir ---> SmPC of [1] of EMA

Less potent UGT1A1 inhibitors (e.g., indinavir, saquinavir) may also increase plasma levels of raltegravir, but to a lesser extent compared with atazanavir.

Lapatinib [1], saquinavir ---> SmPC of [1] of EMA

Lapatinib is predominantly metabolised by CYP3A. The strong CYP3A4 inhibition increases the exposition to lapatinib. Co-administration of lapatinib with strong inhibitors of CYP3A4 should be avoided.

Larotrectinib [1], saquinavir ---> SmPC of [1] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A inhibitors, P-gp and BCRP inhibitors may increase larotrectinib plasma concentrations (see section 4.2).

Lidocaine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination with systemic lidocaine is contraindicated due to the potential for life threatening cardiac arrhythmia

Loperamide, saquinavir

Concomitant use of loperamide and saquinavir may significantly decrease Cmax and AUC of saquinavir

Lopinavir/ritonavir [1], saquinavir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Lopinavir/ritonavir, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Lovastatine, saquinavir [2] ---> SmPC of [2] of EMA

Plasma concentrations highly dependent on CYP3A4 metabolism. Increased concentrations of simvastatin and lovastatin have been associated with rhabdomyolysis. These medicinal products are contraindicated for use with Invirase/ritonavir

Lovastatine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Plasma concentrations highly dependent on CYP3A4 metabolism. Increased concentrations of lovastatin have been associated with rhabdomyolysis. Lovastatin is contraindicated for use with saquinavir/ritonavir

Lurasidone [1], saquinavir ---> SmPC of [1] of EMA

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inhibitors

Macitentan [1], saquinavir ---> SmPC of [1] of EMA

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

Maprotiline, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Maprotiline's metabolism appears to involve the isozymes CYP2D6 and CYP 1A2 Associated with a prolongation of QTc intervals Contraindicated in combination with Invirase/ritonavir due to potentially life threatening cardiac arrhythmia

Maraviroc, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

No dose adjustment of saquinavir/ritonavir is required. Dose of maraviroc should be decreased to 150 mg bid with monitoring.

Mesoridazine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Methadone, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Contraindicated combination due to the potential for life threatening cardiac arrhythmia

Methylergonovine, saquinavir [2] ---> SmPC of [2] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Methylergonovine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination may increase ergot alkaloid exposure and increase the potential for acute ergotism. Concomitant use is contraindicated

Miconazole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Miconazol is CYP3A4 inhibitors and may increase the plasma concentration of saquinavir. Use with caution due to possible cardiac arrhythmias. Monitoring for saquinavir toxicity recommended

Midazolam [1], saquinavir ---> SmPC of [1] of EMA

Co-administration with protease inhibitors may cause a large increase in the concentration of midazolam.

Midazolam, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of midazolam. Midazolam oral: contraindicated; parenteral: close clinical monitoring

Mizolastine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Moxifloxacin [1], saquinavir ---> SmPC of [1] of eMC

The co-administration may have an additive effect on the QT interval prolongation. This might lead to an increased risk of ventricular arrhythmias, including torsade de pointes. The combination is contraindicated.

Naldemedine [1], saquinavir ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A inhibitors should be avoided. If use with strong CYP3A inhibitors is unavoidable, monitor for adverse reactions

Naloxegol [1], saquinavir ---> SmPC of [1] of EMA

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. Concomitant use of naloxegol with strong CYP3A4 inhibitors is contraindicated

Nefazodone, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Nefazodone inhibits CYP3A4. Saquinavir concentrations may be increased. Combination not recommended.

Nelfinavir [1], saquinavir ---> SmPC of [1] of EMA

Increased AUC of saquinavir.

Nelfinavir, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Increased AUC of saquinavir. Combination not recommended.

Neratinib [1], saquinavir ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4/Pgp inhibitors should be avoided.

Nevirapine [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

Saquinavir/ritonavir and nevirapine can be co-administered without dose adjustments

Nevirapine, saquinavir [2] ---> SmPC of [2] of EMA

No dose adjustment required.

Nicardipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Nifedipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Nimodipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Nisoldipine, saquinavir

The co-administration of nisoldipine with medicinal products that inhibit the cytochrome P450 3A4-system may increase the bioavailability of nisoldipine. Concomitant use is contraindicated

Nisoldipine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Nitrazepam, saquinavir

Saquinavir may increase the effect of nitrazepam

Olaparib [1], saquinavir ---> SmPC of [1] of EMA

CYP3A4/5 are the isozymes predominantly responsible for the metabolic clearance of olaparib. It is recommended that known strong inhibitors of these isozymes should be avoided with olaparib

Ombitasvir/paritaprevir/ritonavir [1], saquinavir ---> SmPC of [1] of EMA

Omeprazole, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant use may increase the plasma concentrations of saquinavir. Combination not recommended.

Oral anticoagulants, saquinavir

The co-administration may enhance the anticoagulant effect and increase the bleeding risk

Oral contraceptives, saquinavir [2] ---> SmPC of [2] of EMA

Because concentration of ethinyl estradiol may be decreased when coadministered with Invirase/ritonavir, alternative or additional contraceptive measures should be used when oestrogen-based oral contraceptives are co-administered

Oxycodone, saquinavir

The CYP3A4 inhibitors may decrease the oxycodone clearance, which may increase the plasma concentrations of oxycodone. It can be necessary adjust the dose of oxycodone

P-glycoprotein and CYP3A4 inhibitors, saquinavir [2] ---> SmPC of [2] of EMA

Medicinal products that modify CYP3A4 and/or P-gp activity may modify the pharmacokinetics of saquinavir.

P-glycoprotein substrates, saquinavir

Saquinavir, P-glycoprotein inhibitor, may increase the exposition of P-glycoprotein substrates

Paclitaxel [1], saquinavir ---> SmPC of [1] of EMA

Caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 because toxicity of paclitaxel may be increased due to higher paclitaxel exposure.

Palbociclib [1], saquinavir ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

Panobinostat [1], saquinavir ---> SmPC of [1] of EMA

In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, the dose of panobinostat should be reduced

Pazopanib [1], saquinavir ---> SmPC of [1] of EMA

Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to pazopanib

Pentamidine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Phenobarbital [1], saquinavir ---> SmPC of [1] of eMC

Phenobarbital possibly reduces plasma levels of saquinavir

Phenobarbital, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Phenothiazines, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Phenprocoumon, saquinavir

The co-administration may enhance the anticoagulant effect and increase the bleeding risk

Phenytoin, saquinavir [2] ---> SmPC of [2] of EMA

Phenytoin, CYP3A4 inductor, may decrease the plasma levels of saquinavir

Phenytoin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Pimozide [1], saquinavir ---> SmPC of [1] of eMC

Potent inhibitors of the CYP3A4 will inhibit the metabolism of pimozide, resulting in markedly elevated pimozide plasma levels. Concomitant use of pimozide with drugs known to be inhibitors of cytochrome CYP3A4 is contraindicated

Pimozide, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concentrations of pimozide may be increased when co-administered with saquinavir/ritonavir. Due to a potential for life threatening cardiac arrhythmias, saquinavir/ritonavir is contra-indicated in combination with pimozide

Piperaquine, saquinavir ---> SmPC of [piperaquine/artenimol] of EMA

The combination of piperaquine with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Piperaquine/artenimol [1], saquinavir ---> SmPC of [1] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Pixantrone [1], saquinavir ---> SmPC of [1] of EMA

The inhibition of the transporters of the P-glycoprotein has the potential to decrease hepatic uptake and excretion efficiency of pixantrone.

Polatuzumab vedotin [1], saquinavir ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Ponatinib [1], saquinavir ---> SmPC of [1] of EMA

Caution should be exercised and a reduction of the starting dose should be considered with concurrent use of ponatinib with strong CYP3A inhibitors (modest increases in ponatinib systemic exposure are possible)

PR interval prolonging drugs, saquinavir [2] ---> SmPC of [2] of EMA

The coadministration of saquinavir with other medicinal products which prolong the PR-interval is contra-indicated

PR interval prolonging drugs, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The coadministration of ritonavir-boosted saquinavir with other medicinal products which prolong the PR-interval is contra-indicated

Pralsetinib [1], saquinavir ---> SmPC of [1] of EMA

Therefore, co-administration of pralsetinib with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided. If co-administration cannot be avoided, reduce the current dose of pralsetinib

Pravastatine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Metabolism of pravastatine is not dependent on CYP3A4. Interaction via effects on transport proteins cannot be excluded.

Pregnancy, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus

Primidone, saquinavir

The co-administration may decrease the plasma levels of protease inhibitor

Propafenone, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Protease inhibitors, saquinavir

Generally, dual therapy with protease inhibitors is not recommended

Proton pump inhibitors, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

No data are available on the concomitant administration. The coadministration is not recommended

QT interval prolonging drugs, saquinavir [2] ---> SmPC of [2] of EMA

The coadministration of saquinavir with other medicinal products which prolong the QT-interval is contra-indicated

QT interval prolonging drugs, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The coadministration of ritonavir-boosted saquinavir with other medicinal products which prolong the QT-interval is contra-indicated

Quetiapine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant administration of Invirase and quetiapine is contraindicated as it may increase quetiapine-related toxicity. Increased plasma concentrations of quetiapine may lead to coma

Quinidine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Quinine, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of quinine.

Quinine, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Quinupristin, saquinavir [2] ---> SmPC of [2] of EMA

Saquinavir concentrations may be increased. Use with caution due to possible cardiac arrhythmias. Monitoring for saquinavir toxicity recommended (see section 4.4).

Raltegravir [1], saquinavir ---> SmPC of [1] of EMA

The inhibition of UGT1A1 may increase plasma levels of raltegravir

Ranitidine, saquinavir [2] ---> SmPC of [2] of EMA

Increased saquinavir AUC. Increase not thought to be clinically relevant. No dose adjustment of saquinavir recommended.

Rapamycin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Careful therapeutic drug monitoring is necessary for immunosuppressants when co-administered with saquinavir/ritonavir.

Ribociclib [1], saquinavir ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Rifabutin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Possible increase in exposure to rifabutin. Monitoring of neutropenia and liver enzyme levels is recommended

Rifampicin, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Rifampicin is contraindicated in combination with Invirase/ritonavir. Risk of severe hepatocellular toxicity

Rilpivirine [1], saquinavir/ritonavir ---> SmPC of [1] of EMA

Not studied. Concomitant use of rilpivirine with ritonavir-boosted PIs (inhibition of CYP3A enzymes) causes an increase in the plasma concentrations of rilpivirine, but no dose adjustment is required.

Rilpivirine, saquinavir [2] ---> SmPC of [2] of EMA

Switching directly from a rilpivirine containing regimen to Invirase/ritonavir is contraindicated as is concomitant use due to the potential for life threatening cardiac arrhythmia (see sections 4.3 and 4.4).

Ritonavir [1], saquinavir ---> SmPC of [1] of EMA

Ritonavir increases the serum levels of saquinavir as a result of CYP3A4 inhibition. Saquinavir should only be given in combination with ritonavir.

Ruxolitinib [1], saquinavir ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase ruxolitinib exposition. When co-administering with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced

Salmeterol, saquinavir/ritonavir ---> SmPC of [saquinavir] of EMA

Combination not recommended as may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia (see section 4.4).

Saquinavir [1], simvastatine ---> SmPC of [1] of EMA

Saquinavir [1], St. John's wort ---> SmPC of [1] of EMA

Plasma levels of saquinavir can be reduced by concomitant use of the herbal preparation St. John's wort (Hypericum perforatum). This is due to induction of drug metabolising enzymes and/or transport proteins by St. John's wort.

Saquinavir [1], streptogramins ---> SmPC of [1] of EMA

Saquinavir concentrations may be increased. Use with caution due to possible cardiac arrhythmias. Monitoring for saquinavir toxicity recommended (see section 4.4).

Saquinavir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Medicinal products that induce CYP3A4 may decrease saquinavir concentrations.

Saquinavir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Medicinal products that modify CYP3A4 activity may modify the pharmacokinetics of saquinavir.

Saquinavir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Medicinal products that modify P-gp activity may modify the pharmacokinetics of saquinavir.

Saquinavir [1], substrates of CYP3A and P-gp ---> SmPC of [1] of EMA

Saquinavir might modify the pharmacokinetics of other medicinal products that are substrates for CYP3A4 or P-gp.

Saquinavir [1], terfenadine ---> SmPC of [1] of EMA

Increased AUC of terfenadine, associated with a prolongation of QTc intervals. Terfenadine is contraindicated with boosted or unboosted saquinavir

Saquinavir [1], triazolam ---> SmPC of [1] of EMA

Concomitant use of saquinavir with triazolam is contraindicated due to the potential for prolonged or increased sedation, respiratory depression

Saquinavir [1], zalcitabine ---> SmPC of [1] of EMA

Interaction with zalcitabine is unlikely due to different routes of metabolism and excretion. No dose adjustment required.

Saquinavir, selpercatinib [2] ---> SmPC of [2] of EMA

If strong CYP3A and/or P-gp inhibitors, e. g. ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, telithromycin, posaconazole and nefazodone, have to be coadministered, the dose of selpercatinib should be reduced

Saquinavir, sildenafil [2] ---> SmPC of [2] of EMA

Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at steady state (1200 mg three times a day) with sildenafil (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC.

Saquinavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Saquinavir, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inhibitors of CYP3A4 can increase sonidegib concentrations significantly. The sonidegib dose should be reduced to 200 mg every other day

Saquinavir, tacrolimus [2] ---> SmPC of [2] of EMA

Contraindicated in combination with Invirase/ritonavir due to the potential for life threatening cardiac arrhythmia (see sections 4.3 and 4.4).

Saquinavir, tadalafil [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing tadalafil to patients using potent CYP3A4 inhibitors as increased tadalafil exposure (AUC) has been observed if the medicinal products are combined

Saquinavir, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong P-gp inhibitors during treatment with talazoparib should be avoided.

Saquinavir, telithromycin [2] ---> SmPC of [2] of EMA

Concomitant administration of telithromycin with medicinal products that prolong the QT interval and are CYP3A4 substrates is contraindicated

Saquinavir, tepotinib [2] ---> SmPC of [2] of EMA

Concomitant use of TEPMETKO with dual strong CYP3A and P-gp inhibitors (e.g. itraconazole, ketoconazole, ritonavir, saquinavir, nelfinavir) should be avoided.

Saquinavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Saquinavir, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

Saquinavir, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant use of vardenafil with HIV protease inhibitors is contraindicated, as they are very potent inhibitors of CYP3A4

Saquinavir, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Saquinavir, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Saquinavir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Saquinavir, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that voriconazole may inhibit the metabolism of HIV protease inhibitors and the metabolism of voriconazole may also be inhibited by HIV protease inhibitors.

Saquinavir, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Saquinavir/ritonavir, sertindole ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, sildenafil ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of sildenafil. Contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Saquinavir/ritonavir, simvastatine ---> SmPC of [saquinavir] of EMA

Plasma concentrations highly dependent on CYP3A4 metabolism. Increased concentrations of simvastatin have been associated with rhabdomyolysis. Simvastatin is contraindicated for use with saquinavir/ritonavir

Saquinavir/ritonavir, sirolimus ---> SmPC of [saquinavir] of EMA

Careful therapeutic drug monitoring is necessary for immunosuppressants when co-administered with saquinavir/ritonavir.

Saquinavir/ritonavir, sotalol ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, sparfloxacin ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, strong CYP3A4 inductors ---> SmPC of [saquinavir] of EMA

Medicinal products that induce CYP3A4 may decrease saquinavir concentrations.

Saquinavir/ritonavir, sultopride ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, tacrolimus ---> SmPC of [saquinavir] of EMA

Contraindicated in combination with Invirase/ritonavir due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, tadalafil ---> SmPC of [saquinavir] of EMA

Saquinavir may increase the plasma concentrations of tadalafil. Contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, tenofovir disoproxil ---> SmPC of [saquinavir] of EMA

No dose adjustment required.

Saquinavir/ritonavir, terfenadine ---> SmPC of [saquinavir] of EMA

Increased AUC of terfenadine, associated with a prolongation of QTc intervals. Terfenadine is contraindicated with boosted or unboosted saquinavir

Saquinavir/ritonavir, thioridazine ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, tipranavir/ritonavir ---> SmPC of [saquinavir] of EMA

Concomitant use of boosted saquinavir and tipranavir, co-administered with low dose ritonavir in a dual-boosted regimen, results in a significant decrease in saquinavir plasma concentration.

Saquinavir/ritonavir, trazodone ---> SmPC of [saquinavir] of EMA

Plasma concentrations of trazodone may increase. Adverse events of nausea, dizziness, hypotension and syncope have been observed. Contraindicated in combination with Invirase/ritonavir due to potentially life threatening cardiac arrhythmia

Saquinavir/ritonavir, triazolam ---> SmPC of [saquinavir] of EMA

Increased triazolam plasma concentrations. Triazolam is contraindicated in combination with saquinavir/ritonavir, due to the risk of potentially prolonged or increased sedation and respiratory depression

Saquinavir/ritonavir, tricyclic antidepressant ---> SmPC of [saquinavir] of EMA

Saquinavir/ritonavir, vardenafil ---> SmPC of [saquinavir] of EMA

Saquinavir may increase the plasma concentrations of vardenafil. Contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, verapamil ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Saquinavir/ritonavir, vincamine ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Saquinavir/ritonavir, warfarin ---> SmPC of [saquinavir] of EMA

Concentrations of warfarin may be affected when co-administered with Invirase/ritonavir. INR monitoring recommended

Saquinavir/ritonavir, zalcitabine ---> SmPC of [saquinavir] of EMA

Interaction with zalcitabine is unlikely due to different routes of metabolism and excretion. No dose adjustment required.

Saquinavir/ritonavir, zidovudine ---> SmPC of [saquinavir] of EMA

For zidovudine (200 mg every 8 hours) a 25 % decrease in AUC was reported when combined with ritonavir (300 mg every 6 hours). No dose adjustment required.

Saquinavir/ritonavir, ziprasidone ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

CONTRAINDICATIONS of Saquinavir (Invirase)

Invirase is contraindicated in patients with:

- hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- decompensated liver disease

- congenital or documented acquired QT prolongation

- electrolyte disturbances, particularly uncorrected hypokalaemia

- clinically relevant bradycardia

- clinically relevant heart failure with reduced left-ventricular ejection fraction

- previous history of symptomatic arrhythmias

- concurrent therapy with any of the following drugs, which may interact and result in potentially life-threatening undesirable effects:

- drugs that prolong the QT and/or PR interval

- midazolam administered orally (for caution on parenterally administered midazolam, see section 4.5), triazolam (potential for prolonged or increased sedation, respiratory depression)

- simvastatin, lovastatin (increased risk of myopathy including rhabdomyolysis)

- ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine, and methylergonovine) (potential for acute ergot toxicity)

- rifampicin (risk of severe hepatocellular toxicity).

- quetiapine (risk of coma)

- lurasidone (potential for serious and/or life-threatening reactions, see section 4.5)

https://www.ema.europa.eu/en/documents/product-information/invirase-epar-product-information_en.pdf. 25/09/2023

Sarilumab (Kevzara)

Biological DMARD, sarilumab [2] ---> SmPC of [2] of EMA

However, no clinical data was collected. Sarilumab has not been investigated in combination with Janus kinase (JAK) inhibitors or biological DMARDs such as Tumor Necrosis Factor (TNF) antagonists.

Blockade of IL-6 signalling, sarilumab [2] ---> SmPC of [2] of EMA

Blockade of IL-6 signalling by IL-6Ralfa antagonists such as sarilumab might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered medicinal products concentrations.

Breast-feeding, sarilumab [2] ---> SmPC of [2] of EMA

Because IgG1 are excreted in human milk, a decision should be made whether to discontinue breast-feeding or to discontinue sarilumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

CYP3A4 substrates, sarilumab [2] ---> SmPC of [2] of EMA

Kevzara may reverse the inhibitory effect of IL-6 and restore CYP3A4 activity, leading to decreased exposure and activity of CYP3A4 substrate.

CYP450 substrates, sarilumab [2] ---> SmPC of [2] of EMA

The modulation of IL-6 effect on CYP enzymes by sarilumab may be clinically relevant for CYP substrates with a narrow therapeutic index, where the dose is individually adjusted.

Cytochrome P450, sarilumab [2] ---> SmPC of [2] of EMA

Various in vitro and limited in vivo human studies have shown that cytokines and cytokine modulators can influence the expression and activity of specific cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2C19, and CYP3A4)

Fertility, sarilumab [2] ---> SmPC of [2] of EMA

No data are available on the effect of sarilumab on human fertility. Animal studies showed no impairment of male or female fertility (see section 5.3).

Interleukin-6, sarilumab [2] ---> SmPC of [2] of EMA

Elevated levels of interleukin-6 (IL-6) may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA.

Methotrexate, sarilumab [2] ---> SmPC of [2] of EMA

Sarilumab exposure was not affected when coadministered with MTX based on the population pharmacokinetic analyses and across study comparisons. MTX exposure is not expected to be changed by sarilumab coadministration;

Oral contraceptives, sarilumab [2] ---> SmPC of [2] of EMA

Kevzara may reverse the inhibitory effect of IL-6 and restore CYP3A4 activity, leading to decreased exposure and activity of CYP3A4 substrate.

Pregnancy, sarilumab [2] ---> SmPC of [2] of EMA

Kevzara should not be used during pregnancy unless the clinical condition of the woman requires treatment with sarilumab.

Sarilumab [1], statins ---> SmPC of [1] of EMA

Kevzara may reverse the inhibitory effect of IL-6 and restore CYP3A4 activity, leading to decreased exposure and activity of CYP3A4 substrate.

Sarilumab [1], theophylline ---> SmPC of [1] of EMA

Therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., theophylline) should be performed and the individual dose of the medicinal product should be adjusted as needed.

Sarilumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Avoid concurrent use of live vaccines as well as live attenuated vaccines during treatment with Kevzara as clinical safety has not been established.

Sarilumab [1], warfarin ---> SmPC of [1] of EMA

Therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., theophylline) should be performed and the individual dose of the medicinal product should be adjusted as needed.

Sarilumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception during and up to 3 months after treatment.

CONTRAINDICATIONS of Sarilumab (Kevzara)

- Hypersensitivity to the active substance or any of the excipients listed in section 6.1.

- Active, severe infections (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/kevzara-epar-product-information_en.pdf 28/03/2025

Satralizumab (Enspryng)

Azathioprine, satralizumab [2] ---> SmPC of [2] of EMA

Population pharmacokinetic (PK) analyses did not detect any effect of azathioprine (AZA), oral corticosteroids (OCs) or mycophenolate mofetil (MMF) on the clearance of satralizumab.

Breast-feeding, satralizumab [2] ---> SmPC of [2] of EMA

Which is decreasing to low concentrations soon afterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period. Afterwards, use of Enspryng could be considered during breast-feeding only if clinically needed.

Carbamazepine, satralizumab [2] ---> SmPC of [2] of EMA

Caution should be exercised when starting or discontinuing satralizumab treatment in patients also receiving substrates of CYP450 3A4, 1A2, 2C9 or 2C19, particularly those with a narrow therapeutic index

CYP1A2 substrates with narrow therapeutic index, satralizumab [2] ---> SmPC of [2] of EMA

CYP2C19 substrates with narrow therapeutic index, satralizumab [2] ---> SmPC of [2] of EMA

CYP2C9 substrates with narrow therapeutic index, satralizumab [2] ---> SmPC of [2] of EMA

Cytokine, satralizumab [2] ---> SmPC of [2] of EMA

Both in vitro and in vivo studies have shown that the expression of specific hepatic CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, and CYP3A4) is suppressed by cytokines such as IL-6.

Drugs primarily metabolised by CYP1A2, satralizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C19, satralizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C9, satralizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, satralizumab [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, satralizumab [2] ---> SmPC of [2] of EMA

Fertility, satralizumab [2] ---> SmPC of [2] of EMA

No clinical data are available on the effect of satralizumab on human fertility. Animal studies showed no impairment of male or female fertility (see section 5.3).

Half life, satralizumab [2] ---> SmPC of [2] of EMA

Given the prolonged terminal half-life of satralizumab, the effect of satralizumab may persist for several weeks after stopping treatment.

Phenytoin, satralizumab [2] ---> SmPC of [2] of EMA

Pregnancy [1], satralizumab ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Enspryng during pregnancy.

Satralizumab [1], theophylline ---> SmPC of [1] of EMA

Satralizumab [1], vaccinations ---> SmPC of [1] of EMA

Live and live-attenuated vaccines should not be given concurrently with satralizumab as clinical safety has not been established.

Satralizumab [1], warfarin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Satralizumab (Enspryng)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/enspryng-epar-product-information_en.pdf 30/09/2024

Saxagliptin (Onglyza)

Ability to drive, saxagliptin [2] ---> SmPC of [2] of EMA

When driving or using machines, it should be taken into account that dizziness has been reported in studies with saxagliptin.

ACE inhibitors, saxagliptin ---> SmPC of [perindopril] of eMC

Increased risk of angio-oedema, due to dipeptidyl peptidase IV (DPP-IV) decreased activity by the gliptin, in patients co-treated with an ACE inhibitor.

Breast-feeding, saxagliptin [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy to the woman.

Cabozantinib [1], saxagliptin ---> SmPC of [1] of EMA

Cabozantinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp. Subjects should be cautioned regarding taking a P-gp substrate while receiving cabozantinib.

Capmatinib [1], saxagliptin ---> SmPC of [1] of EMA

Caution should be exercised during co-administration of Tabrecta with P-gp (digoxin, dabigatran etexilate, colchicine, sitagliptin, saxagliptin and posaconazole)

Carbamazepine, saxagliptin [2] ---> SmPC of [2] of EMA

The co-administration of saxagliptin and CYP3A4/5 inducers may result in decreased plasma concentration of saxagliptin and increased concentration of its major metabolite. Glycaemic control should be carefully assessed

Dexamethasone, saxagliptin [2] ---> SmPC of [2] of EMA

Diltiazem, saxagliptin [2] ---> SmPC of [2] of EMA

Coadministration of saxagliptin with the moderate inhibitor of CYP3A4/5 diltiazem, increased the Cmax and AUC of saxagliptin by 63% and 2.1-fold, respectively, and the corresponding values for the active metabolite were decreased by 44% and 34%.

Insulin, saxagliptin [2] ---> SmPC of [2] of EMA

Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, a lower dose of sulphonylurea or insulin may be required to reduce the risk of hypoglycaemia when used in combination with Onglyza.

Ketoconazole, saxagliptin [2] ---> SmPC of [2] of EMA

Concomitant administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold, respectively, and the corresponding values for the active metabolite were decreased by 95% and 88

Lomitapide [1], saxagliptin ---> SmPC of [1] of EMA

Coadministration of Lojuxta with P gp may increase the absorption of P gp substrates. Dose reduction of the P gp substrate should be considered when used concomitantly with Lojuxta.

Moderate CYP3A4 inhibitors, saxagliptin [2] ---> SmPC of [2] of EMA

Perindopril [1], saxagliptin ---> SmPC of [1] of eMC

Increased risk of angio-oedema, due to dipeptidyl peptidase IV (DPP-IV) decreased activity by the gliptin, in patients co-treated with an ACE inhibitor.

Pharmacokinetics, saxagliptin

Saxagliptin did not meaningfully alter the pharmacokinetics of metformin, glibenclamide, pioglitazone, digoxin, simvastatin, the active components of a combined oral contraceptive (ethinyl estradiol and norgestimate), diltiazem or ketoconazole.

Pharmacokinetics, saxagliptin

In in vitro studies, saxagliptin and its major metabolite neither inhibited CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4, nor induced CYP1A2, 2B6, 2C9, or 3A4.

Pharmacokinetics, saxagliptin

The effects of smoking, diet, herbal products, and alcohol use on the pharmacokinetics of saxagliptin have not been specifically studied.

Pharmacokinetics, saxagliptin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin and its major metabolite, were meaningfully altered by metformin, glibenclamide, pioglitazone, digoxin, simvastatin, omeprazole, antacids or famotidine.

Phenobarbital, saxagliptin [2] ---> SmPC of [2] of EMA

Phenytoin, saxagliptin [2] ---> SmPC of [2] of EMA

Pregnancy, saxagliptin [2] ---> SmPC of [2] of EMA

Onglyza should not be used during pregnancy unless clearly necessary.

Rifampicin, saxagliptin [2] ---> SmPC of [2] of EMA

The exposure of the active metabolite and the plasma DPP4 activity inhibition over a dose interval were not influenced by rifampicin (see section 4.4).

Rifampicin, saxagliptin [2] ---> SmPC of [2] of EMA

Concomitant administration of saxagliptin with the potent CYP3A4/5 inducer rifampicin, reduced Cmax and AUC of saxagliptin by 53% and 76%, respectively.

Saxagliptin [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Saxagliptin [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Saxagliptin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the AUC of saxagliptin and decrease those of the principal metabolite

Saxagliptin [1], sulfonylureas ---> SmPC of [1] of EMA

Saxagliptin, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib is an in vitro inhibitor of P-gp and BCRP. Caution should be used when taking a P-gp substrate (e.g., fexofenadine, dabigatran etexilate, digoxin, colchicine, saxagliptin)

Saxagliptin, somatropin

Somatropin may antagonize the hypoglycemic effect of saxagliptin.

CONTRAINDICATIONS of Saxagliptin (Onglyza)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or history of a serious hypersensitivity reaction, including anaphylactic reaction, anaphylactic shock, and angioedema, to any dipeptidyl peptidase-4 (DPP4) inhibitor

https://www.ema.europa.eu/en/documents/product-information/onglyza-epar-product-information_en.pdf 13/05/2024

Saxagliptin/dapagliflozin (Qtern)

Ability to drive, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

When driving or using machines, it should be taken into account that dizziness has been reported in studies with combined use of saxagliptin and dapagliflozin.

Alcohol, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

The effects of smoking, diet, herbal products and alcohol use on the pharmacokinetics of saxagliptin, dapagliflozin or fixed dose combination tablet have not been studied.

Antacids, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Breast-feeding, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Qtern should not be used while breast-feeding.

Bumetanide, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Dapagliflozin did not meaningfully alter the pharmacokinetic

Carbamazepine, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Dexamethasone, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Digoxin, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Saxagliptin did not meaningfully alter the pharmacokinetics (PK) of dapagliflozin, metformin, glibenclamide, pioglitazone, digoxin, diltiazem or simvastatin. These medicinal products did not alter the PK of saxagliptin or its major active metabolite.

Diltiazem, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

The pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.

Drugs with high protein binding, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Dapagliflozin is approximately 91 % protein bound. Protein binding was not altered in various disease states (e.g. renal or hepatic impairment).

Famotidine, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Fertility, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In male and female rats, dapagliflozin showed no effects on fertility at any dose tested. Effects on fertility were observed using saxagliptin in male and female rats at high doses producing overt signs of toxicity

Glibenclamide, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glimepiride, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Dapagliflozin did not meaningfully alter the pharmacokinetic

Hydrochlorothiazide, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Dapagliflozin did not meaningfully alter the pharmacokinetic

Insulin secretagogues, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

If this medicinal product is used in combination with insulin secretagogue (sulphonylurea), a reduction in the dose of sulphonylurea may be required to minimise the risk of hypoglycaemia (see section 4.4).

Ketoconazole, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

The pharmacokinetic effects are not clinically meaningful and do not require dose adjustment.

Loop diuretics, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension

Mefenamic acid, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Following coadministration of dapagliflozin with mefenamic acid (an inhibitor of UGT1A9), a 55 % increase in dapagliflozin systemic exposure was seen, but with no clinically meaningful effect on 24-hour urinary glucose excretion.

Metformin, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Omeprazole, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

In studies conducted in healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite were meaningfully altered

Pharmacokinetics, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Dapagliflozin did not meaningfully alter the pharmacokinetics (PK) of saxagliptin, metformin, pioglitazone, sitagliptin, glimepiride, voglibose, HCT, bumetanide, valsartan, or simvastatin. These medications did not alter the PK of dapagliflozin.

Phenobarbital, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Phenytoin, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Pioglitazone, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Pregnancy, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Qtern should not be used during pregnancy. If pregnancy is detected, treatment with Qtern should be discontinued.

Rifampicin, saxagliptin/dapagliflozin [2] ---> SmPC of [2] of EMA

Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent CYP3A4/5 inducer.

Saxagliptin/dapagliflozin [1], simvastatine ---> SmPC of [1] of EMA

Saxagliptin/dapagliflozin [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Using CYP3A4 inducers may reduce the glycaemic lowering effect of Qtern. Glycaemic control should be assessed when it is used concomitantly with a potent CYP3A4/5 inducer

Saxagliptin/dapagliflozin [1], sulfonylureas ---> SmPC of [1] of EMA

Saxagliptin/dapagliflozin [1], test ---> SmPC of [1] of EMA

Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors.

Saxagliptin/dapagliflozin [1], thiazides ---> SmPC of [1] of EMA

Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension

Saxagliptin/dapagliflozin [1], valsartan ---> SmPC of [1] of EMA

Dapagliflozin did not meaningfully alter the pharmacokinetic

Saxagliptin/dapagliflozin [1], voglibose ---> SmPC of [1] of EMA

Dapagliflozin did not meaningfully alter the pharmacokinetic

CONTRAINDICATIONS of Saxagliptin/dapagliflozin (Qtern)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or history of a serious hypersensitivity reaction, including anaphylactic reaction, anaphylactic shock, and angioedema, to any dipeptidyl peptidase-4 (DPP-4) inhibitor or to any sodium-glucose co-transporter 2 (SGLT2) inhibitor

https://www.ema.europa.eu/en/documents/product-information/qtern-epar-product-information_en.pdf 07/02/2024

Saxagliptin/metformin (Komboglyze)

Ability to drive, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Dizziness has been reported in studies with saxagliptin. In addition, patients should be alerted to the risk of hypoglycaemia when Komboglyze is used in combination with other antidiabetic medicinal products known to cause hypoglycaemia

ACE inhibitors, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis. When starting or using such products in combination with metformin, close monitoring of renal function is necessary.

AIIRA, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Alcohol, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in the case of fasting, malnutrition or hepatic impairment due to the metformin. Consumption of alcohol and medicinal products containing alcohol should be avoided

Beta2-adrenergic agonists, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Beta-2 agonists have intrinsic hyperglycaemic activity. Should be more frequent blood glucose monitoring performed

Breast-feeding, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

This medicinal product must not be used in women who are breastfeeding

Carbamazepine, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Cationic substances eliminated by renal tubular secretion, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Cationic active substances that are eliminated by renal tubular secretion may interact with metformin by competing for common renal tubular transport systems and hence delay the elimination of metformin

Cationic substances eliminated by renal tubular secretion, tubular secretion ---> SmPC of [saxagliptin/metformin]

Therefore, close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when cationic medicinal products that are eliminated by renal tubular secretion are co-administered.

Cimetidine, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Coxibs, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Dexamethasone, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Diltiazem, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the moderate inhibitor of CYP3A4/5 diltiazem, increased the Cmax and AUC of saxagliptin by 63% and 2.1-fold, respectively, and the corresponding values for the active metabolite were decreased by 44% and 34%.

Diuretics, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Diuretics may increase the risk of lactic acidosis due to their potential to decrease renal function. Diuretics have also intrinsic hyperglycaemic activity.

Fertility, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

The effect of saxagliptin on fertility in humans has not been studied. Effects on fertility were observed in male and female rats at high doses producing overt signs of toxicity. For metformin, studies in animals have not shown reproductive toxicity

Foods, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Komboglyze should be given twice daily with meals to reduce the gastrointestinal adverse reactions associated with metformin.

Glucocorticoids, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Glucocorticoids have intrinsic hyperglycaemic activity. Should be more frequent blood glucose monitoring performed

Insulin, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Insulin and sulphonylureas are known to cause hypoglycaemia. Therefore, a lower dose of insulin or sulphonylurea may be required to reduce the risk of hypoglycaemia when used in combination with Komboglyze.

Iodinated contrast media, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Komboglyze must be discontinued prior to, or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable (see sections 4.2 and 4.4).

Iodinated contrast media, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

The intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis.

Ketoconazole, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Co-administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold, respectively, and the corresponding values for the active metabolite were decreased by 95% and 88%.

Moderate CYP3A4 inhibitors, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

NSAID, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Pharmacokinetics, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

In in vitro studies, saxagliptin and its major metabolite neither inhibited CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4, nor induced CYP1A2, 2B6, 2C9, or 3A4.

Phenobarbital, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Phenytoin, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Pregnancy, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

This medicinal product should not be used during pregnancy. If the patient wishes to become pregnant, or if a pregnancy occurs, treatment with this medicinal product should be discontinued and switched to insulin treatment as soon as possible.

Rifampicin, saxagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant administration of saxagliptin with the potent CYP3A4/5 inducer rifampicin, reduced Cmax and AUC of saxagliptin by 53% and 76%, respectively.

Saxagliptin/metformin [1], smoking ---> SmPC of [1] of EMA

The effects of smoking, diet, herbal products, and alcohol use on the pharmacokinetics of saxagliptin have not been specifically studied.

Saxagliptin/metformin [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Saxagliptin/metformin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Coadministration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold, respectively, and the corresponding values for the active metabolite were decreased by 95% and 88%.

Saxagliptin/metformin [1], sulfonylureas ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Saxagliptin/metformin (Komboglyze)

- Diabetic ketoacidosis, diabetic pre-coma;

- Moderate and severe renal impairment (creatinine clearance < 60 ml/min) (see section 4.4);

- Acute conditions with the potential to alter renal function such as: - dehydration,

- severe infection,

- shock;

- Acute or chronic disease which may cause tissue hypoxia such as:

- cardiac or respiratory failure,

- recent myocardial infarction,

- shock;

- Hepatic impairment (see sections 4.2 and 5.2);

- Acute alcohol intoxication, alcoholism (see section 4.5);

- Breast-feeding (see section 4.6).

https://www.ema.europa.eu/en/documents/product-information/komboglyze-epar-product-information_en.pdf 09/04/2024

Selpercatinib (Retsevmo)

Ability to drive, selpercatinib [2] ---> SmPC of [2] of EMA

Patients should be advised to be cautious when driving or using machines in case they experience fatigue or dizziness during treatment with Retsevmo

Alfentanyl, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Antihypertensive, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib should be discontinued permanently if medically significant hypertension cannot be controlled with antihypertensive therapy.

Avanafil, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Breast-feeding, selpercatinib [2] ---> SmPC of [2] of EMA

Breast-feeding should be discontinued during treatment with Retsevmo and for at least one week after the last dose.

Buprenorphine, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased the Cmax and AUC of repaglinide (a substrate of CYP2C8) by approximately 91% and 188% respectively. Therefore, coadministration with sensitive CYP2C8 substrates should be avoided.

Buspirone, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Carbamazepine, selpercatinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Cerivastatin, selpercatinib [2] ---> SmPC of [2] of EMA

Colchicine, selpercatinib [2] ---> SmPC of [2] of EMA

Therefore, caution should be used when taking a sensitive P-gp substrate (e.g., fexofenadine, dabigatran etexilate, colchicine, saxagliptin), and particularly those with a narrow therapeutic index (e.g., digoxin) (see section 5.2).

Conivaptan, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Dabigatran etexilate, selpercatinib [2] ---> SmPC of [2] of EMA

Darifenacin, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Darunavir, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Dasabuvir, selpercatinib [2] ---> SmPC of [2] of EMA

Digoxin, selpercatinib [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C8, selpercatinib [2] ---> SmPC of [2] of EMA

Ebastine, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Electrolyte imbalance, selpercatinib [2] ---> SmPC of [2] of EMA

Patients should have a QTcF interval of ≤470 ms and serum electrolytes within normal range before starting selpercatinib treatment.

Enzalutamide, selpercatinib [2] ---> SmPC of [2] of EMA

Fertility, selpercatinib [2] ---> SmPC of [2] of EMA

Male and female fertility may be compromised by treatment with Retsevmo. Both men and women should seek advice on fertility preservation before treatment.

Fexofenadine, selpercatinib [2] ---> SmPC of [2] of EMA

H2 antagonists, selpercatinib [2] ---> SmPC of [2] of EMA

Retsevmo should be administered 2 hours before or 10 hours after H2 receptor antagonists

Hypocalcemia, selpercatinib [2] ---> SmPC of [2] of EMA

Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiating selpercatinib and during treatment.

Hypokalemia, selpercatinib [2] ---> SmPC of [2] of EMA

Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiating selpercatinib and during treatment.

Hypomagnesemia, selpercatinib [2] ---> SmPC of [2] of EMA

Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiating selpercatinib and during treatment.

Itraconazol, selpercatinib [2] ---> SmPC of [2] of EMA

Ketoconazole, selpercatinib [2] ---> SmPC of [2] of EMA

Levothyroxine, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib could inhibit D2 deiodinase and thereby decrease the conversion of levothyroxine (T4) to triiodothyronine (T3).

Lomitapide, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Lovastatine, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

MATE1 inhibitors, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib inhibits the renal transporter multidrug and toxin extrusion protein 1 (MATE1). In vivo interactions of selpercatinib with clinically relevant substrates of MATE1, such as creatinine, may occur

MATE1 substrates, selpercatinib [2] ---> SmPC of [2] of EMA

In vivo interactions of selpercatinib with clinically relevant substrates of MATE1, such as creatinine, may occur (see section 5.2).

Midazolam, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Montelukast, selpercatinib [2] ---> SmPC of [2] of EMA

Naloxegol, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Nefazodone, selpercatinib [2] ---> SmPC of [2] of EMA

Nisoldipine, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Omeprazole, selpercatinib [2] ---> SmPC of [2] of EMA

Co-administration with multiple daily doses of omeprazole did not significantly change the selpercatinib AUC0-INF and Cmax when Retsevmo was administered with food.

Paclitaxel, selpercatinib [2] ---> SmPC of [2] of EMA

Phenobarbital, selpercatinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Phenytoin, selpercatinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Posaconazole, selpercatinib [2] ---> SmPC of [2] of EMA

Pregnancy, selpercatinib [2] ---> SmPC of [2] of EMA

Retsevmo is not recommended during pregnancy and in women of childbearing potential not using contraception. It should only be used during pregnancy if the potential benefit justifies the potential risk to the foetus.

Proton pump inhibitors, selpercatinib [2] ---> SmPC of [2] of EMA

Retsevmo must be accompanied by a meal if used concomitantly with a proton pump inhibitor

QT interval prolonging drugs, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib should be used with caution in patients with such conditions as congenital long QT syndrome or acquired long QT syndrome or other clinical conditions that predispose to arrhythmias.

Ranitidine, selpercatinib [2] ---> SmPC of [2] of EMA

No clinically significant differences in selpercatinib pharmacokinetics were observed when co-administered with multiple daily doses of ranitidine (H2 receptor antagonist) given 2 hours after the selpercatinib dose.

Repaglinide, selpercatinib [2] ---> SmPC of [2] of EMA

Rifabutin, selpercatinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Rifampicin, selpercatinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Ritonavir, selpercatinib [2] ---> SmPC of [2] of EMA

Rosiglitazone, selpercatinib [2] ---> SmPC of [2] of EMA

Saquinavir, selpercatinib [2] ---> SmPC of [2] of EMA

Saxagliptin, selpercatinib [2] ---> SmPC of [2] of EMA

Selexipag, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib [1], simvastatine ---> SmPC of [1] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Selpercatinib [1], sorafenib ---> SmPC of [1] of EMA

Selpercatinib [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Selpercatinib [1], strong CYP3A4 and P-glycoprotein-inhibitors ---> SmPC of [1] of EMA

Selpercatinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of selpercatinib

Selpercatinib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Selpercatinib [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Selpercatinib [1], telithromycin ---> SmPC of [1] of EMA

Selpercatinib [1], tipranavir ---> SmPC of [1] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Selpercatinib [1], torasemid ---> SmPC of [1] of EMA

Selpercatinib [1], triazolam ---> SmPC of [1] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Selpercatinib [1], vardenafil ---> SmPC of [1] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Selpercatinib [1], voriconazole ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Selpercatinib (Retsevmo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/retsevmo-epar-product-information_en.pdf 27/09/2024

Solutions for sealant (Evicel)

Alcohol, solutions for sealant [2] ---> SmPC of [2] of EMA

Similar to comparable products or thrombin solutions, the product may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g., antiseptic solutions).

Antiseptics, solutions for sealant [2] ---> SmPC of [2] of EMA

Similar to comparable products or thrombin solutions, the product may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g., antiseptic solutions).

Breast-feeding, solutions for sealant [2] ---> SmPC of [2] of EMA

Therefore, the product should be administered to pregnant and breast-feeding women only if clearly needed.

Iodine, solutions for sealant [2] ---> SmPC of [2] of EMA

Similar to comparable products or thrombin solutions, the product may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g., antiseptic solutions).

Pregnancy, solutions for sealant [2] ---> SmPC of [2] of EMA

Therefore, the product should be administered to pregnant and breast-feeding women only if clearly needed.

Solutions containing heavy metals, solutions for sealant [2] ---> SmPC of [2] of EMA

Similar to comparable products or thrombin solutions, the product may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g., antiseptic solutions).

CONTRAINDICATIONS of Solutions for sealant (Evicel)

- EVICEL must not be applied intravascularly.

- Hypersensitivity to the active substances or to any of the excipients listed in Section 6.1.

- Spray application of EVICEL should not be used in endoscopic procedures. For laparoscopy, see Section 4.4.

- EVICEL must not be used for sealing the suture line in dura mater if there are gaps of greater than 2 mm after suturing.

- EVICEL must not be used as a glue for the fixation of dural patches.

- EVICEL must not be used as a sealant when the dura mater cannot be sutured.

https://www.ema.europa.eu/en/documents/product-information/evicel-epar-product-information_en.pdf 06/08/2024 (withdrawn)

Sebelipase alfa (Kanuma)

Breast-feeding, sebelipase alfa [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sebelipase alfa therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility, sebelipase alfa [2] ---> SmPC of [2] of EMA

There are no clinical data on the effects of sebelipase alfa on fertility. Animal studies show no evidence of impaired fertility (see section 5.3).

Metabolized by cytochrome P450, sebelipase alfa [2] ---> SmPC of [2] of EMA

Because it is a recombinant human protein, sebelipase alfa is an unlikely candidate for cytochrome P450 mediated or other drug-drug interactions.

Pregnancy, sebelipase alfa [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid use of sebelipase alfa during pregnancy.

CONTRAINDICATIONS of Sebelipase alfa (Kanuma)

Life-threatening hypersensitivity (anaphylactic reaction) to the active substance when attempts to rechallenge are unsuccessful, or to egg or any of the excipients listed in section 6.1

https://www.ema.europa.eu/en/documents/product-information/kanuma-epar-product-information_en.pdf. 25/08/2023

Sebetralstat (Ekterly)

Ability to drive, sebetralstat [2] ---> SmPC of [2] of EMA

Dizziness has been reported following the use of Ekterly. This symptom may also occur as a result of an attack of HAE. Patients should be advised not to drive or use machines if they feel dizzy.

Antacids, sebetralstat [2] ---> SmPC of [2] of EMA

Caution should be used when co-administering Ekterly with gastric pH modifying agents such as antacids, proton-pump inhibitors, and histamine 2 receptor antagonists.

Breast-feeding, sebetralstat [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue/abstain from Ekterly therapy, or to discontinue breast-feeding for 24 hours after taking Ekterly, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Carbamazepine, sebetralstat [2] ---> SmPC of [2] of EMA

In patients taking strong or moderate CYP3A4 inducers (e.g. rifampicin, efavirenz, carbamazepine, phenytoin, phenobarbital), it is recommended that an HAE attack is treated with a dose of 900 mg (3 x 300 mg tablets).

Cimetidine, sebetralstat [2] ---> SmPC of [2] of EMA

Co-administration with the weak CYP3A4 inhibitor cimetidine caused no change in the exposure of sebetralstat. No dose adjustment is required when taking CYP3A4 inhibitors.

Clarithromycin, sebetralstat [2] ---> SmPC of [2] of EMA

In patients with moderate hepatic impairment who are taking a strong CYP3A4 inhibitor (e.g. erythromycin, clarithromycin, itraconazole, ketoconazole, ritonavir) a single dose of 300 mg is recommended when treating an HAE attack.

Cyclosporine, sebetralstat [2] ---> SmPC of [2] of EMA

Co-administration of sebetralstat with transporters which have a narrow therapeutic index should be avoided unless clinically warranted given the risk of increased pharmacokinetic exposure of these co-administered drugs and thus of toxicity.

CYP3A4 inductors, sebetralstat [2] ---> SmPC of [2] of EMA

Co-administration with the weak CYP3A4 inducer modafinil caused no clinically relevant change in the exposure of sebetralstat. No dose adjustment is required when taking weak CYP3A4 inducers.

CYP3A4 inhibitors, sebetralstat [2] ---> SmPC of [2] of EMA

Co-administration with the weak CYP3A4 inhibitor cimetidine caused no change in the exposure of sebetralstat. No dose adjustment is required when taking CYP3A4 inhibitors.

Efavirenz, sebetralstat [2] ---> SmPC of [2] of EMA

The moderate CYP3A4 inducer efavirenz reduced the Cmax of sebetralstat by 63% and the AUC by 79%.

Erythromycin, sebetralstat [2] ---> SmPC of [2] of EMA

Fertility, sebetralstat [2] ---> SmPC of [2] of EMA

There are no data regarding the effects of Ekterly on human fertility. No effect on fertility was observed in animal studies (see section 5.3).

Gastric pH increasing medication, sebetralstat [2] ---> SmPC of [2] of EMA

No dedicated in vivo drug-drug interaction (DDI) study with gastric acid reducing agents was performed. Thus, the effect of gastric acid reducing agents on the pharmacokinetics of sebetralstat is unknown.

H2 antagonists, sebetralstat [2] ---> SmPC of [2] of EMA

Caution should be used when co-administering Ekterly with gastric pH modifying agents such as antacids, proton-pump inhibitors, and histamine 2 receptor antagonists.

Itraconazol, sebetralstat [2] ---> SmPC of [2] of EMA

Itraconazole, a strong CYP3A4 inhibitor, increased the Cmax of sebetralstat by 135% and the AUC by 420%.

Ketoconazole, sebetralstat [2] ---> SmPC of [2] of EMA

Laryngeal attack, sebetralstat [2] ---> SmPC of [2] of EMA

Following treatment of laryngeal attacks, patients should seek immediate medical attention. If laryngeal attack symptoms worsen after treatment, patients should be managed in an appropriate medical institution.

Liver insufficiency, sebetralstat [2] ---> SmPC of [2] of EMA

Modafinil, sebetralstat [2] ---> SmPC of [2] of EMA

Co-administration with the weak CYP3A4 inducer modafinil caused no clinically relevant change in the exposure of sebetralstat. No dose adjustment is required when taking weak CYP3A4 inducers.

Moderate CYP3A4 inductors, sebetralstat [2] ---> SmPC of [2] of EMA

Mycophenolic acid, sebetralstat [2] ---> SmPC of [2] of EMA

Phenobarbital, sebetralstat [2] ---> SmPC of [2] of EMA

Phenytoin, sebetralstat [2] ---> SmPC of [2] of EMA

Phenytoin, a strong CYP3A4 inducer, reduced the Cmax of sebetralstat by 66% and the AUC by 83%.

Pregnancy, sebetralstat [2] ---> SmPC of [2] of EMA

Ekterly should be used during pregnancy only if the potential benefit justifies the potential risk for the fetus (e.g. for treatment of potentially life-threatening laryngeal attacks).

Proton pump inhibitors, sebetralstat [2] ---> SmPC of [2] of EMA

Caution should be used when co-administering Ekterly with gastric pH modifying agents such as antacids, proton-pump inhibitors, and histamine 2 receptor antagonists.

QT interval prolonging drugs, sebetralstat [2] ---> SmPC of [2] of EMA

Caution is warranted on the risk of QT prolongation in these patients, especially in patients who have more than one risk factor (see section 5.1).

Rifampicin, sebetralstat [2] ---> SmPC of [2] of EMA

Ritonavir, sebetralstat [2] ---> SmPC of [2] of EMA

Sebetralstat [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Sebetralstat [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Sebetralstat [1], tacrolimus ---> SmPC of [1] of EMA

Sebetralstat [1], verapamil ---> SmPC of [1] of EMA

The moderate CYP3A4 inhibitor verapamil increased the Cmax of sebetralstat by 76% and the AUC by 102%.

Sebetralstat [1], warfarin ---> SmPC of [1] of EMA

Sebetralstat [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment with Ekterly and for a period of 24 hours after the last dose.

CONTRAINDICATIONS of Sebetralstat (Ekterly)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/ekterly-epar-product-information_en.pdf 08/10/2025

Secukinumab (Cosentyx)

Breast-feeding, secukinumab [2] ---> SmPC of [2] of EMA

Because of the potential for adverse reactions in nursing infants from secukinumab, a decision on whether to discontinue breast-feeding during treatment and up to 20 weeks after treatment or to discontinue therapy with Cosentyx

Corticosteroids, secukinumab [2] ---> SmPC of [2] of EMA

No interaction was seen when secukinumab was administered concomitantly with methotrexate (MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and axial spondyloarthritis).

Fertility, secukinumab [2] ---> SmPC of [2] of EMA

The effect of secukinumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Immunosuppressives, secukinumab [2] ---> SmPC of [2] of EMA

Caution should be exercised when considering concomitant use of other immunosuppressants and secukinumab (see also section 4.5).

Immunosuppressives, secukinumab [2] ---> SmPC of [2] of EMA

In psoriasis studies, the safety and efficacy of secukinumab in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated.

Infection, secukinumab [2] ---> SmPC of [2] of EMA

Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur.

Methotrexate, secukinumab [2] ---> SmPC of [2] of EMA

Midazolam, secukinumab [2] ---> SmPC of [2] of EMA

In a study in adult subjects with plaque psoriasis, no interaction was observed between secukinumab and midazolam (CYP3A4 substrate).

Pregnancy, secukinumab [2] ---> SmPC of [2] of EMA

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Cosentyx during pregnancy.

Secukinumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Live vaccines should not be given concurrently with secukinumab

Secukinumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment.

CONTRAINDICATIONS of Secukinumab (Cosentyx)

- Severe hypersensitivity reactions to the active substance or to any of the excipients listed in section 6.1.

- Clinically important, active infection (e.g. active tuberculosis; see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/cosentyx-epar-product-information_en.pdf 16/10/2025

Lyvdelzi (previously Seladelpar Gilead)

Bile-acid sequestrants, seladelpar [2] ---> SmPC of [2] of EMA

Bile acid binding resins may reduce the absorption of other medicinal products administered concurrently. Patients should take seladelpar at least 4 hours before or 4 hours after taking a bile acid binding resin.

Breast-feeding, seladelpar [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from seladelpar therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Carbamazepine, seladelpar [2] ---> SmPC of [2] of EMA

The carbamazepine (a strong CYP3A and weak CYP2C9 inducer) dose was escalated from 100 mg to 300 mg over 7 days.

Cholestyramine, seladelpar [2] ---> SmPC of [2] of EMA

Colesevelam, seladelpar [2] ---> SmPC of [2] of EMA

Colestipol, seladelpar [2] ---> SmPC of [2] of EMA

Cyclosporine, seladelpar [2] ---> SmPC of [2] of EMA

Concomitant administration of seladelpar with dual or multiple clinical inhibitors of drugs transporters including BCRP, OATP1B1, OATP1B3 and OAT3 (e.g cyclosporine) may result in an increase of seladelpar exposure.

CYP2C9 inducers and strong CYP3A4 inducers, seladelpar [2] ---> SmPC of [2] of EMA

Concomitant administration of seladelpar with medicines that are CYP2C9 inducers and strong CYP3A4 inducers (e.g. rifampicin, a strong CYP3A4 and moderate CYP2C9 inducer) can decrease seladelpar exposure.

Dual moderate CYP2C9 and moderate-to-strong CYP3A4 inhibitors, seladelpar [2] ---> SmPC of [2] of EMA

The concomitant administration may result in an increase in seladelpar exposure. Patients should be closely monitored for adverse effects.

Fertility, seladelpar [2] ---> SmPC of [2] of EMA

Animal studies do not indicate any direct or indirect effects on fertility or the ability to reproduce.

Fluconazole, seladelpar [2] ---> SmPC of [2] of EMA

The concomitant administration may result in an increase in seladelpar exposure. Patients should be closely monitored for adverse effects.

Mifepristone, seladelpar [2] ---> SmPC of [2] of EMA

The concomitant administration may result in an increase in seladelpar exposure. Patients should be closely monitored for adverse effects.

Pregnancy, seladelpar [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of seladelpar during pregnancy.

Probenecide, seladelpar [2] ---> SmPC of [2] of EMA

Concomitant administration of seladelpar with probenecid (an OAT1, OAT3 and OATP1B1-inhibitor) is not recommended (see section 4.4).

Rifampicin, seladelpar [2] ---> SmPC of [2] of EMA

Seladelpar [1], strong CYP2C9 inhibitors ---> SmPC of [1] of EMA

The concomitant administration may result in an increase in seladelpar exposure. Patients should be closely monitored for adverse effects.

CONTRAINDICATIONS of Lyvdelzi (previously Seladelpar Gilead)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/lyvdelzi-epar-product-information_en.pdf 16/05/2025

Selegiline

Ability to drive, selegiline [2] ---> SmPC of [2] of eMC

Selegiline has major influence (e.g may cause dizziness) on the ability to drive and use machines, therefore patients should avoid these activities.

Alcohol, selegiline [2] ---> SmPC of [2] of eMC

Concomitant use of selegiline and alcohol should be avoided.

Amantadine, selegiline [2] ---> SmPC of [2] of eMC

Concomitant administration of selegiline and amantadine can lead to an increased occurrence of side-effects.

Anticholinergics, selegiline [2] ---> SmPC of [2] of eMC

Concomitant administration of selegiline and anticholinergic drugs can lead to an increased occurrence of side-effects.

Anticoagulants, selegiline [2] ---> SmPC of [2] of eMC

In view of the high degree of binding to plasma proteins by selegiline particular attention must be given to patients who are being treated with medicines with a narrow therapeutic margin

Breast-feeding, selegiline [2] ---> SmPC of [2] of eMC

Physico-chemical data on selegiline point to excretion in breast milk and a risk to the suckling child cannot be excluded. Selegiline should not be used during breast-feeding.

Citalopram [1], selegiline ---> SmPC of [1] of eMC

The concomitant use of citalopram and selegiline (in doses above 10 mg daily) is contraindicated

CNS depressants, selegiline [2] ---> SmPC of [2] of eMC

Concomitant use selegiline and central suppressant drugs and should be avoided.

Dextromethorphan, selegiline

Concomitant use may cause a serotoninergic syndrome. Concomitant use should be avoided within 14 day after taking selegiline

Digital glycosides, selegiline [2] ---> SmPC of [2] of eMC

In view of the high degree of binding to plasma proteins by selegiline particular attention must be given to patients who are being treated with medicines with a narrow therapeutic margin

Drugs with a narrow therapeutic window, selegiline [2] ---> SmPC of [2] of eMC

In view of the high degree of binding to plasma proteins by selegiline particular attention must be given to patients who are being treated with medicines with a narrow therapeutic margin

Entacapone [1], selegiline ---> SmPC of [1] of EMA

Entacapone may be used with selegiline (a selective MAO-B inhibitor), but the daily dose of selegiline should not exceed 10 mg.

Escitalopram [1], selegiline ---> SmPC of [1] of eMC

In combination with selegiline (irreversible MAO-B inhibitor), caution is required due to the risk of developing serotonin syndrome.

Ethinylestradiol/norgestimate [1], selegiline ---> SmPC of [1] of eMC

Combination hormonal contraceptives with selegiline may increase plasma levels (due to CYP inhibition) of selegiline

Fluoxetine [1], selegiline ---> SmPC of [1] of eMC

The co-administration may increase the risk of serotoninergic syndrome. Clinical monitoring is recommended.

Hypertensive drugs, selegiline [2] ---> SmPC of [2] of eMC

Concomitant use selegiline and hypertensive drugs and should be avoided.

Hypnotics, selegiline [2] ---> SmPC of [2] of eMC

Concomitant use selegiline and central suppressant drugs and should be avoided.

IMAOs, selegiline [2] ---> SmPC of [2] of eMC

Selegiline should not be given in conjunction with non-specific MAO inhibitors, e.g. linezolid. Concomitant administration of selegiline and MAO inhibitors may cause central nervous and cardiovascular system disorders

Ioflupane [1], selegiline ---> SmPC of [1] of EMA

Medicines shown during clinical trials not to interfere with DaTSCAN imaging include amantadine, trihexyphenidyl, budipine, levodopa, metoprolol, primidone, propranolol and selegiline.

Levodopa, selegiline [2] ---> SmPC of [2] of eMC

As selegiline potentiates the levodopa effect, the side-effects of levodopa (restlessness, hyperkinesia, dyskinesia, agitation, confusion, hallucination, postural hypotension, cardiac arrhythmias) may be emphasised unless the levodopa dosage is reduced.

Levodopa/benserazide [1], selegiline ---> SmPC of [1] of eMC

It should not be given in conjunction with, or within 2 weeks of withdrawal of, monoamine oxidase (MAO) inhibitors, except selective MAO-B inhibitors (e.g. selegiline) or selective MAO-A inhibitors (e.g. moclobemide)

Levodopa/carbidopa [1], selegiline ---> SmPC of [1] of EMA

Numient can be taken concomitantly with the recommended dose of an MAO inhibitor, which is selective for MAO inhibitor type B such as selegiline and rasagiline.

Linezolid [1], selegiline ---> SmPC of [1] of eMC

Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B or within 2 weeks of taking any such medicinal product.

Moclobemide [1], selegiline ---> SmPC of [1] of eMC

Co-administration of moclobemide with selegiline is contraindicated

Nevirapine, selegiline

The CYP3A and CYP2B6 inductions may decrease the plasma levels of selegiline

Opiates, selegiline

The co-administration is contraindicated and during and until 14 days after treatment with a MAOI

Opicapone [1], selegiline ---> SmPC of [1] of EMA

Concomitant use of opicapone and MAO inhibitors for the treatment of Parkinson's disease, e.g. rasagiline (up to 1 mg/day) and selegiline (up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation), is permissible

Oral contraceptives, selegiline ---> SmPC of [ethinylestradiol/norgestimate] of eMC

Combination hormonal contraceptives with selegiline may increase plasma levels (due to CYP inhibition) of selegiline

Pethidine, selegiline [2] ---> SmPC of [2] of eMC

Because of the risk of hypertension, co-administration of selegiline and sympathomimetics, including nasal decongestants is contraindicated.

Pregnancy, selegiline [2] ---> SmPC of [2] of eMC

As a precautionary measure, it is preferable to avoid the use of selegiline in pregnancy.

Pseudoephedrine, selegiline

Hypertensive crisis may occur if pseudoephedrine is co-administered with MAOIs. Concomitant use of, or within 14 days following the administration of, monoamine oxidase inhibitors (MAOI) with pseudoephedrine should be avoided with MAOIs

Psychostimulants, selegiline [2] ---> SmPC of [2] of eMC

Concomitant use selegiline and psychostimulants drugs and should be avoided.

Sedatives, selegiline [2] ---> SmPC of [2] of eMC

Concomitant use selegiline and central suppressant drugs and should be avoided.

Selegiline [1], SNRIs ---> SmPC of [1] of eMC

Because of the risk of confusion, hypomania, hallucination and manic episodes, agitation, myoclonus, hyperreflexia, etc., which can be part of the serotonin syndrome, concomitant administration of selegiline and SNRIs is contraindicated.

Selegiline [1], SSRI ---> SmPC of [1] of eMC

Selegiline [1], sympathomimetics ---> SmPC of [1] of eMC

Because of the risk of hypertension, co-administration of selegiline and sympathomimetics, including nasal decongestants is contraindicated.

Selegiline [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Severe CNS toxicity has been reported in patients with the combination of tricyclic antidepressants and selegiline. The co-administration is contraindicated

Selegiline, serotonin agonists [2] ---> SmPC of [2] of eMC

The co-administration may increase the serotoninergic effects. The co-administration is contraindicated

Selegiline, sertraline [2] ---> SmPC of [2] of EMA

Combination contraindicated. Sertraline should not be administrated within at least 7 days BEFORE initia. nor 14 days AFTER discontin. a therapy with irreversible MAOI

Selegiline, tiapride

Concomitant use of tiapride and dopaminergic agonists, except levodopa, is not recommended in patients with Parkinson disease due to mutual antagonism between dopaminergic agonists and neuroleptics

Selegiline, tryptophan

The co-administration can cause serotoninergic syndrome. The combination is contraindicated

Selegiline, vortioxetine [2] ---> SmPC of [2] of EMA

The combination should be administered with caution. Close monitoring for serotonin syndrome is necessary if used concomitantly

CONTRAINDICATIONS of Selegiline

- Hypersensitivity to the active substance or to any of the excipients.

- Patients receiving treatment with serotonin-agonists (e.g. sumatriptan, naratriptan, zolmitriptan and rizatriptan).

- Patients with phenylketonuria due to the content of aspartame, a source of phenylalanine.

- Concomitant use with pethidine and other opioids.

- Patients with other extrapyramidal disorders not related to dopamine deficiency.

- Patients with active duodenal or gastric ulcer.

- Patients who are being treated with antidepressant drugs, including tricyclic antidepressants, MAO inhibitors and selective serotonin reuptake inhibitors (SSRIs), e.g citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and serotonin noradrenaline reuptake inhibitors (SNR) (e.g. venlafaxine).

- Concomitant use with sympathomimetics or monoamine oxidase inhibitors, e.g. linezolid.

- Combination with levodopa is contra-indicated in severe cardiovascular disease, arterial hypertension, hyperthyroidism, phaeochromocytoma, narrow-angle glaucoma, prostatic adenoma with appearance of residual urine, tachycardia, arrhythmias, severe angina pectoris, psychoses, advanced dementia and thyrotoxicosis.

- The contraindications which apply to levodopa must be taken into account.

http://www.medicines.org.uk/emc/

Selexipag (Uptravi)

Ability to drive, selexipag [2] ---> SmPC of [2] of EMA

The clinical status of the patient and the adverse reaction profile of selexipag (such as headache or hypotension) should be kept in mind when considering the patient's ability to drive and use machines.

Breast-feeding, selexipag [2] ---> SmPC of [2] of EMA

A risk to the suckling child cannot be excluded. Uptravi should not be used during breast-feeding.

Carbamazepine, selexipag [2] ---> SmPC of [2] of EMA

Dose adjustment of selexipag may be required with concomitant administration of inducers of CYP2C8 (e.g., rifampicin, carbamazepine, phenytoin).

Clopidogrel, selexipag [2] ---> SmPC of [2] of EMA

The total daily dose of Uptravi should be decreased by reducing each dose to half when co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide).

Coumarin anticoagulants, selexipag [2] ---> SmPC of [2] of EMA

Selexipag is an inhibitor of platelet aggregation in vitro. In the Phase 3 placebo-controlled study in patients with PAH, no increased risk of bleeding was detected with selexipag compared to placebo

CYP3A4 inductors, selexipag [2] ---> SmPC of [2] of EMA

No effect of inducers of CYP3A4 on the pharmacokinetics of the active metabolite is expected.

CYP3A4 inhibitors, selexipag [2] ---> SmPC of [2] of EMA

Since a strong inhibitor of CYP3A4 did not affect the pharmacokinetics of the active metabolite, indicating that the CYP3A4 pathway is not important in the elimination of the active metabolite

CYP3A4 substrates, selexipag [2] ---> SmPC of [2] of EMA

Concomitant administration of selexipag with CYP3A4 substrates does not require dose adjustment.

Cytochrome P450, selexipag [2] ---> SmPC of [2] of EMA

Selexipag and its active metabolite do not inhibit (are not expected to induce) cytochrome P450 enzymes at clinically relevant concentrations. Selexipag and its active metabolite do not inhibit transport proteins.

Deferasirox, selexipag [2] ---> SmPC of [2] of EMA

The total daily dose of Uptravi should be decreased by reducing each dose to half when co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide).

Endothelin receptor antagonist, selexipag [2] ---> SmPC of [2] of EMA

In the Phase 3 placebo-controlled trial in patients with PAH, the use of selexipag in combination with both an ERA and a PDE-5 inhibitor resulted in a 30% lower exposure to the active metabolite.

Fertility, selexipag [2] ---> SmPC of [2] of EMA

There are no clinical data available. In rat studies, selexipag at high doses caused transient disturbances in oestrus cycles that did not affect fertility (see section 5.3). The relevance for humans is not known.

Fluconazole, selexipag [2] ---> SmPC of [2] of EMA

The effect of strong inhibitors of UGT1A3 and UGT2B7 (valproic acid, probenecid, and fluconazole) on the exposure to selexipag has not been studied. A potential pharmacokinetic interaction with strong inhibitors of UGT1A3 and UGT2B7 cannot be excluded.

Foods, selexipag [2] ---> SmPC of [2] of EMA

To improve tolerability, it is recommended to take Uptravi with food and, at the beginning of each up-titration phase, to take the first increased dose in the evening.

Gemfibrozil, selexipag [2] ---> SmPC of [2] of EMA

The exposure to the active metabolite, the major contributor to efficacy, increased approximately 11-fold. Concomitant administration of Uptravi with strong inhibitors of CYP2C8 (e.g., gemfibrozil) is contraindicated (see section 4.3).

Heparin, selexipag [2] ---> SmPC of [2] of EMA

Selexipag is an inhibitor of platelet aggregation in vitro. In the Phase 3 placebo-controlled study in patients with PAH, no increased risk of bleeding was detected with selexipag compared to placebo

Hormonal contraceptives, selexipag [2] ---> SmPC of [2] of EMA

Since selexipag did not affect the exposure to the CYP3A4 substrate R-warfarin or to the CYP2C9 substrate S-warfarin, reduced efficacy of hormonal contraceptives is not expected.

Lopinavir/ritonavir, selexipag [2] ---> SmPC of [2] of EMA

Given that the majority of the pharmacological effect is driven by the active metabolite, this effect is not clinically relevant.

Lopinavir/ritonavir, selexipag [2] ---> SmPC of [2] of EMA

In the presence of 400/100 mg lopinavir/ritonavir twice daily, a strong CYP3A4 inhibitor, exposure to selexipag increased approximately 2-fold, whereas the exposure to the active metabolite of selexipag did not change.

Midazolam, selexipag [2] ---> SmPC of [2] of EMA

Concomitant administration of selexipag with CYP3A4 substrates does not require dose adjustment.

Moderate inhibitors of CYP2C8, selexipag [2] ---> SmPC of [2] of EMA

The total daily dose of Uptravi should be decreased by reducing each dose to half when co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide).

PDE5 inhibitors, selexipag [2] ---> SmPC of [2] of EMA

In the Phase 3 placebo-controlled trial in patients with PAH, the use of selexipag in combination with both an ERA and a PDE-5 inhibitor resulted in a 30% lower exposure to the active metabolite.

Phenytoin, selexipag [2] ---> SmPC of [2] of EMA

Dose adjustment of selexipag may be required with concomitant administration of inducers of CYP2C8 (e.g., rifampicin, carbamazepine, phenytoin).

Pirtobrutinib [1], selexipag ---> SmPC of [1] of EMA

Since pirtobrutinib can increase the plasma concentrations of CYP2C8 substrates, caution is advised when co-administering with CYP2C8 substrates (e.g. repaglinide, dasabuvir, selexipag, rosiglitazone, pioglitazone, and montelukast).

Platelet aggregation inhibitors, selexipag [2] ---> SmPC of [2] of EMA

Selexipag is an inhibitor of platelet aggregation in vitro. In the Phase 3 placebo-controlled study in patients with PAH, no increased risk of bleeding was detected with selexipag compared to placebo

Pregnancy, selexipag [2] ---> SmPC of [2] of EMA

Uptravi is not recommended during pregnancy and in women of childbearing potential not using contraception.

Probenecide, selexipag [2] ---> SmPC of [2] of EMA

Rifampicin, selexipag [2] ---> SmPC of [2] of EMA

Dose adjustment of selexipag may be required with concomitant administration of inducers of CYP2C8 (e.g., rifampicin, carbamazepine, phenytoin).

Selexipag [1], strong CYP2C8 inductors ---> SmPC of [1] of EMA

Dose adjustment of selexipag may be required with concomitant administration of inducers of CYP2C8 (e.g., rifampicin, carbamazepine, phenytoin).

Selexipag [1], strong CYP2C8 inhibitors ---> SmPC of [1] of EMA

Selexipag [1], strong UGT1A3 inductors ---> SmPC of [1] of EMA

Caution is required when administering these medicinal products concomitantly with Uptravi. A potential pharmacokinetic interaction with strong inhibitors or inducers of these enzymes cannot be excluded.

Selexipag [1], strong UGT1A3 inhibitors ---> SmPC of [1] of EMA

Selexipag [1], strong UGT2B7 inductors ---> SmPC of [1] of EMA

Selexipag [1], strong UGT2B7 inhibitors ---> SmPC of [1] of EMA

Selexipag [1], teriflunomide ---> SmPC of [1] of EMA

The total daily dose of Uptravi should be decreased by reducing each dose to half when co-administered with moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide).

Selexipag [1], valproic acid ---> SmPC of [1] of EMA

Selexipag [1], warfarin ---> SmPC of [1] of EMA

The pharmacokinetics of selexipag and its active metabolite are not affected by warfarin. Selexipag did not influence the pharmacodynamic effect of warfarin on the international normalised ratio.

Selexipag [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should practise effective contraception while taking selexipag (see section 4.6).

Selexipag, selpercatinib [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Selexipag (Uptravi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Severe coronary heart disease or unstable angina.

- Myocardial infarction within the last 6 months.

- Decompensated cardiac failure if not under close medical supervision.

- Severe arrhythmias.

- Cerebrovascular events (e.g., transient ischaemic attack, stroke) within the last 3 months.

- Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.

- Concomitant use of strong inhibitors of CYP2C8 (e.g., gemfibrozil; see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/uptravi-epar-product-information_en.pdf 15/05/2024

Selumetinib (Koselugo)

Ability to drive, selumetinib [2] ---> SmPC of [2] of EMA

Fatigue, asthenia and visual disturbances have been reported during treatment with selumetinib and patients who experience these symptoms should observe caution when driving or using machines.

Anticoagulants, selumetinib [2] ---> SmPC of [2] of EMA

Patients should avoid taking supplemental vitamin E and anticoagulant assessments should be performed more frequently in patients taking concomitant anticoagulant or antiplatelet medicinal products

Antiplatelet therapy, selumetinib [2] ---> SmPC of [2] of EMA

Patients should avoid taking supplemental vitamin E and anticoagulant assessments should be performed more frequently in patients taking concomitant anticoagulant or antiplatelet medicinal products

Breast-feeding, selumetinib [2] ---> SmPC of [2] of EMA

Selumetinib and its active metabolite are excreted in the milk of lactating mice (see section 5.3). A risk to the breast-fed child cannot be excluded, therefore breast-feeding should be discontinued during treatment with Koselugo.

Carbamazepine, selumetinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with Koselugo should be avoided.

Clarithromycin, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided.

Digoxin, selumetinib [2] ---> SmPC of [2] of EMA

TPGS is a P-gp inhibitor in vitro and it cannot be excluded that it may cause clinically relevant drug interactions with substrates of P-gp (e.g. digoxin or fexofenadine).

Erythromycin, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are moderate inhibitors of CYP3A4 (e.g., erythromycin and fluconazole) and CYP2C19 (e.g., omeprazole) should be avoided.

Fertility, selumetinib [2] ---> SmPC of [2] of EMA

Selumetinib had no impact on fertility and mating performance in male and female mice, although a reduction in embryonic survival was observed in female mice

Fexofenadine, selumetinib [2] ---> SmPC of [2] of EMA

TPGS is a P-gp inhibitor in vitro and it cannot be excluded that it may cause clinically relevant drug interactions with substrates of P-gp (e.g. digoxin or fexofenadine).

Fluconazole, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are moderate inhibitors of CYP3A4 (e.g., erythromycin and fluconazole) and CYP2C19 (e.g., omeprazole) should be avoided.

Foods, selumetinib [2] ---> SmPC of [2] of EMA

Koselugo is for oral use. It can be taken with or without food (see section 5.2).

Furosemide, selumetinib [2] ---> SmPC of [2] of EMA

The potential for a clinically relevant effect on the pharmacokinetics of concomitantly administered substrates of OAT3 (e.g., methotrexate and furosemide) cannot be excluded

Grapefruit juice, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided.

H2 antagonists, selumetinib [2] ---> SmPC of [2] of EMA

Selumetinib capsules do not exhibit pH dependent dissolution. Koselugo can be used concomitantly with gastric pH modifying agents without restrictions, except for omeprazole which is a CYP2C19 inhibitor.

Itraconazol, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with a strong CYP3A4 inhibitor (200 mg itraconazole twice daily for 4 days) increased selumetinib Cmax by 19% (90% CI 4, 35) and AUC by 49% (90% CI 40, 59) in healthy adult subjects.

Ketoconazole, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided.

Men, selumetinib [2] ---> SmPC of [2] of EMA

Both male and female patients (of reproductive potential) should be advised to use effective contraception during and for at least 1 week after completion of treatment with Koselugo.

Methotrexate, selumetinib [2] ---> SmPC of [2] of EMA

The potential for a clinically relevant effect on the pharmacokinetics of concomitantly administered substrates of OAT3 (e.g., methotrexate and furosemide) cannot be excluded

Moderate CYP2C19 inhibitors, selumetinib [2] ---> SmPC of [2] of EMA

If a strong or moderate CYP3A4 or CYP2C19 inhibitor must be co-administered, the recommended Koselugo dose reduction

Moderate CYP3A4 inhibitors, selumetinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with Koselugo should be avoided.

OAT3 substrates, selumetinib [2] ---> SmPC of [2] of EMA

The potential for a clinically relevant effect on the pharmacokinetics of concomitantly administered substrates of OAT3 (e.g., methotrexate and furosemide) cannot be excluded

Omeprazole, selumetinib [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are moderate inhibitors of CYP3A4 (e.g., erythromycin and fluconazole) and CYP2C19 (e.g., omeprazole) should be avoided.

Oral contraceptives, selumetinib [2] ---> SmPC of [2] of EMA

The effect of selumetinib on the exposure of oral contraceptives has not been evaluated. Therefore, use of an additional barrier method should be recommended to women using hormonal contraceptives

P-glycoprotein substrates, selumetinib [2] ---> SmPC of [2] of EMA

TPGS is a P-gp inhibitor in vitro and it cannot be excluded that it may cause clinically relevant drug interactions with substrates of P-gp (e.g. digoxin or fexofenadine).

Phenytoin, selumetinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with Koselugo should be avoided.

Pregnancy, selumetinib [2] ---> SmPC of [2] of EMA

If a female patient or a female partner of a male patient receiving Koselugo becomes pregnant, she should be apprised of the potential risk to the foetus.

Pregnancy, selumetinib [2] ---> SmPC of [2] of EMA

Koselugo is not recommended during pregnancy and in women of childbearing potential not using contraception.

Proton pump inhibitors, selumetinib [2] ---> SmPC of [2] of EMA

Rifampicin, selumetinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with Koselugo should be avoided.

Selumetinib [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with Koselugo should be avoided.

Selumetinib [1], strong CYP2C19 inhibitors ---> SmPC of [1] of EMA

Concomitant use of strong or moderate CYP3A4 or CYP2C19 inhibitors is not recommended and alternative agents should be considered.

Selumetinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine, St. John's Wort) or moderate CYP3A4 inducers with Koselugo should be avoided.

Selumetinib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Concomitant use of strong or moderate CYP3A4 or CYP2C19 inhibitors is not recommended and alternative agents should be considered.

Selumetinib [1], ticlopidine ---> SmPC of [1] of EMA

Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided.

Selumetinib [1], vitamin E ---> SmPC of [1] of EMA

Patients should avoid taking supplemental vitamin E and anticoagulant assessments should be performed more frequently in patients taking concomitant anticoagulant or antiplatelet medicinal products

Selumetinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to avoid becoming pregnant while receiving Koselugo. It is recommended that a pregnancy test should be performed on women of childbearing potential prior to initiating treatment.

CONTRAINDICATIONS of Selumetinib (Koselugo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Severe hepatic impairment (see sections 4.2 and 5.2).

https://www.ema.europa.eu/en/documents/product-information/koselugo-epar-product-information_en.pdf 09/01/2024

Selinexor (Nexpovio)

Ability to drive, selinexor [2] ---> SmPC of [2] of EMA

Selinexor can cause fatigue, confusional state and dizziness. Patients should be advised not to drive or operate machines if they experience any of these symptoms.

Breast-feeding, selinexor [2] ---> SmPC of [2] of EMA

It is unknown whether selinexor or its metabolites are excreted in human milk. A risk to breast-fed children cannot be excluded. Breast-feeding

Clarithromycin, selinexor [2] ---> SmPC of [2] of EMA

No clinically significant differences in selinexor pharmacokinetics were observed when co-administered with a strong CYP3A4 inhibitor, clarithromycin (500 mg PO twice daily for 7 days).

Fertility, selinexor [2] ---> SmPC of [2] of EMA

Based on findings in animals, selinexor may impair fertility in females and males

Men, selinexor [2] ---> SmPC of [2] of EMA

Women of childbearing potential and male patients of reproductive potential should be advised to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with selinexor and for at least 1 week following t

Paracetamol, selinexor [2] ---> SmPC of [2] of EMA

No clinically significant differences in selinexor pharmacokinetics were observed when co-administered with up to 1000 mg daily dose of paracetamol.

Pregnancy test, selinexor [2] ---> SmPC of [2] of EMA

A pregnancy test is recommended for women of childbearing potential prior to initiating selinexor treatment.

Pregnancy, selinexor [2] ---> SmPC of [2] of EMA

Selinexor is not recommended during pregnancy and in women of childbearing potential not using contraception.

Selinexor [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inducer might lead to lower exposure of selinexor.

Selinexor [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to avoid becoming pregnant or abstain from sexual intercourse while being treated with selinexor and for at least 1 week following the last dose of selinexor.

CONTRAINDICATIONS of Selinexor (Nexpovio)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/nexpovio-epar-product-information_en.pdf 17/08/2023

Semaglutide (Ozempic)

Ability to drive, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide has no or negligible influence on the ability to drive or use machines. When it is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines

Atorvastatin, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide did not change the overall exposure of atorvastatin following a single dose administration of atorvastatin (40 mg). Atorvastatin Cmax was decreased by 38%. This was assessed not to be clinically relevant.

Breast-feeding, semaglutide [2] ---> SmPC of [2] of EMA

In lactating rats, semaglutide was excreted in milk. As a risk to a breast-fed child cannot be excluded, semaglutide should not be used during breast-feeding.

Coumarin anticoagulants, semaglutide [2] ---> SmPC of [2] of EMA

However, upon initiation of semaglutide treatment in patients on warfarin or other coumarin derivatives, frequent monitoring of INR is recommended.

Delayed gastric emptying, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide delays gastric emptying and has the potential to impact the absorption rate of co-administered oral medicines. It should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption.

Digoxin, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide did not change the overall exposure or Cmax of digoxin following a single dose of digoxin (0.5 mg).

Fertility, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide did not affect male fertility in rats. In female rats, an increase in oestrous length and a small reduction in number of ovulations were observed at doses associated with maternal body weight loss (see section 5.3).

Metformin, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide did not change the overall exposure or Cmax of metformin following dosing of 500 mg twice daily over 3.5 days.

Oral contraceptives, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide is not anticipated to decrease the effect of oral contraceptives as semaglutide did not change the overall exposure of ethinylestradiol and levonorgestrel to a clinically relevant degree

Paracetamol, semaglutide [2] ---> SmPC of [2] of EMA

Semaglutide delays the rate of gastric emptying as assessed by paracetamol pharmacokinetics during a standardised meal test. No dose adjustment of paracetamol is necessary when administered with semaglutide.

Pregnancy, semaglutide [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). There are limited data from the use of semaglutide in pregnant women. Therefore, semaglutide should not be used during pregnancy.

Semaglutide [1], warfarin ---> SmPC of [1] of EMA

However, upon initiation of semaglutide treatment in patients on warfarin or other coumarin derivatives, frequent monitoring of INR is recommended.

Semaglutide [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential are recommended to use contraception when treated with semaglutide.

CONTRAINDICATIONS of Semaglutide (Ozempic)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/ozempic-epar-product-information_en.pdf 27/01/2026

Other trade names: Rybelsus, Wegovy,

Sepiapterin (Sephience)

Breast-feeding, sepiapterin [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Sephience therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Dihydrofolate reductase inhibitors, sepiapterin [2] ---> SmPC of [2] of EMA

Caution and more frequent monitoring of blood Phe are required in patients when sepiapterin is co-administered with a DHFR inhibitor, such as trimethoprim, methotrexate, pemetrexed, pralatrexate, and trimetrexate (see section 4.4).

Fertility, sepiapterin [2] ---> SmPC of [2] of EMA

No clinical studies on the effect on human fertility have been conducted for sepiapterin. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Isosorbide dinitrate, sepiapterin [2] ---> SmPC of [2] of EMA

Caution is recommended during concomitant use of Sephience with medicinal products that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors

Levodopa, sepiapterin [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing Sephience to patients receiving treatment with levodopa to monitor neurological disorders such as exacerbation of convulsion, increased excitability and irritability, seizures, and exacerbation of seizures.

Methotrexate, sepiapterin [2] ---> SmPC of [2] of EMA

Minoxidil, sepiapterin [2] ---> SmPC of [2] of EMA

Caution is recommended during concomitant use of Sephience with phosphodiesterase type 5 (PDE-5) inhibitors (e.g. sildenafil, vardenafil, or tadalafil), and minoxidil.

Molsidomine, sepiapterin [2] ---> SmPC of [2] of EMA

Caution is recommended during concomitant use of Sephience with medicinal products that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors

Nitroglycerine, sepiapterin [2] ---> SmPC of [2] of EMA

Caution is recommended during concomitant use of Sephience with medicinal products that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors

PDE5 inhibitors, sepiapterin [2] ---> SmPC of [2] of EMA

Caution is recommended during concomitant use of Sephience with phosphodiesterase type 5 (PDE-5) inhibitors (e.g. sildenafil, vardenafil, or tadalafil), and minoxidil.

Pemetrexed, sepiapterin [2] ---> SmPC of [2] of EMA

Pregnancy, sepiapterin [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of Sephience during pregnancy.

Sepiapterin [1], sildenafil ---> SmPC of [1] of EMA

Caution is recommended during concomitant use of Sephience with phosphodiesterase type 5 (PDE-5) inhibitors (e.g. sildenafil, vardenafil, or tadalafil), and minoxidil.

Sepiapterin [1], sodium nitroprusside ---> SmPC of [1] of EMA

Caution is recommended during concomitant use of Sephience with medicinal products that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors

Sepiapterin [1], SR inhibitor ---> SmPC of [1] of EMA

Co-administration of a SR inhibitor is expected to have minimal effect on biotransformation of sepiapterin due to the compensatory effect of carbonyl reductase.

Sepiapterin [1], tadalafil ---> SmPC of [1] of EMA

Caution is recommended during concomitant use of Sephience with phosphodiesterase type 5 (PDE-5) inhibitors (e.g. sildenafil, vardenafil, or tadalafil), and minoxidil.

Sepiapterin [1], trimethoprim ---> SmPC of [1] of EMA

Sepiapterin [1], vardenafil ---> SmPC of [1] of EMA

Caution is recommended during concomitant use of Sephience with phosphodiesterase type 5 (PDE-5) inhibitors (e.g. sildenafil, vardenafil, or tadalafil), and minoxidil.

Sepiapterin [1], vasodilators ---> SmPC of [1] of EMA

Caution is recommended during concomitant use of Sephience with medicinal products that cause vasodilation by affecting nitric oxide (NO) metabolism or action, including classical NO donors

CONTRAINDICATIONS of Sepiapterin (Sephience)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/sephience-epar-product-information_en.pdf 28/07/2025

Serplulimab (Hetronifly)

Ability to drive, serplulimab [2] ---> SmPC of [2] of EMA

Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that serplulimab does not adversely affect them.

Breast-feeding, serplulimab [2] ---> SmPC of [2] of EMA

Afterwards, serplulimab could be used during breast-feeding if clinically needed.

Breast-feeding, serplulimab [2] ---> SmPC of [2] of EMA

Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon; consequently, a risk to the breast-fed infant cannot be excluded during this short period.

Corticosteroids, serplulimab [2] ---> SmPC of [2] of EMA

The use of systemic corticosteroids or immunosuppressants before starting serplulimab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy.

Cytochrome P450, serplulimab [2] ---> SmPC of [2] of EMA

Inhibition, or induction of these metabolising enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetics of HETRONIFLY.

Fertility, serplulimab [2] ---> SmPC of [2] of EMA

Studies to evaluate fertility have not been performed. Thus, the effect of serplulimab on male and female fertility is unknown.

Pregnancy, serplulimab [2] ---> SmPC of [2] of EMA

Serplulimab is not recommended during pregnancy and in women of childbearing potential not using contraception.

Serplulimab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use effective contraception during treatment and for at least 6 months after the last dose of serplulimab.

CONTRAINDICATIONS of Serplulimab (Hetronifly)

- Hypersensitivity to active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/hetronifly-epar-product-information_en.pdf 12/01/2026

Sertaconazole

Breast-feeding, sertaconazole

As a precautionary measure, it is preferable to avoid the use of sertaconazole during breastfeeding.

Latex, sertaconazole

Decreased breaking strength

Pregnancy, sertaconazole

As a precautionary measure, it is preferable to avoid the use of sertaconazole during pregnancy.

Sertindole

Ability to drive, sertindole

Patients should be advised not to drive or operate machinery until their individual susceptibility is known.

Astemizole, sertindole

Increases in the QT interval related to sertindole treatment may be exacerbated by the co-administration of other drugs known to significantly increase the QT interval. Co-administration of such drugs is therefore contraindicated

Azole antifungals, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Breast-feeding, sertindole

It is expected that sertindole will be excreted in breast milk. If treatment with sertindole is considered necessary, discontinuation of breast-feeding should be considered.

Carbamazepine, sertindole

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Cimetidine, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Cisapride, sertindole

Clarithromycin, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Class IA antiarrhythmic agents, sertindole

Class III antiarrhythmic agents, sertindole

Darunavir/cobicistat [1], sertindole ---> SmPC of [1] of EMA

Co-administration of darunavir/cobicistat with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sertindole ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/ritonavir, sertindole ---> SmPC of [darunavir] of EMA

Co-administration of darunavir boosted with ritonavir, with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious and/or life-threatening events is contraindicated

Delamanid [1], sertindole ---> SmPC of [1] of EMA

Diltiazem, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Dopamine agonists, sertindole

Neuroleptics may inhibit the effects of dopamine agonists. Sertindole should be use with caution in patients with Parkinson's disease

Droperidol [1], sertindole ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Enzyme inductors, sertindole

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Erythromycin, sertindole [2] ---> SmPC of [2] of eMC

The concomitant use is contraindicated due to the risk of QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsades de pointes.

Fluoxetine, sertindole

The plasma concentration of sertindole is increased in patients concurrently taking potent CYP2D6 inhibitors; sertindole should therefore only be used concomitantly with CYP2D6 inhibitors with extreme caution.

Gatifloxacin, sertindole

Haloperidol [1], sertindole ---> SmPC of [1] of eMC

Concomitant use of haloperidol with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Therefore concomitant use of these products is not recommended

Indinavir, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Interferon, sertindole

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Itraconazol [1], sertindole ---> SmPC of [1] of eMC

The co-administration of itraconazole with CYP3A4 metabolised substrates that can prolong the QT-interval is contraindicated

Ivabradine [1], sertindole ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Ketoconazole [1], sertindole ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with substances that may have their plasma concentrations increased and have QT prolonging potential is contraindicated

Levacetylmethadol [1], sertindole ---> SmPC of [1] of EMA

The co-administration of levacetylmethadol with medicinal products that prolong the interval QT is contraindicated

Lithium, sertindole

Miconazole [1], sertindole ---> SmPC of [1] of eMC

Oral miconazole is contraindicated with the coadministration of substrates known to prolong the QT-interval that are subject to metabolism by CYP3A4

Moxifloxacin [1], sertindole ---> SmPC of [1] of eMC

Nortriptyline, sertindole

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Paroxetine, sertindole

Pasireotide [1], sertindole ---> SmPC of [1] of EMA

Pasireotide should be used with caution in patients who are concomitantly receiving medicinal products that prolong the QT interval

Phenobarbital, sertindole

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Phenytoin, sertindole

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Pimozide [1], sertindole ---> SmPC of [1] of eMC

Concomitant use of pimozide with drugs known to prolong the QT interval is contra-indicated

Piperaquine/artenimol [1], sertindole ---> SmPC of [1] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Pregnancy, sertindole

Sertindole should not be used during pregnancy.

Promazine [1], sertindole ---> SmPC of [1] of eMC

Concomitant use of promazine with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Therefore, concomitant use of these products is not recommended.

Protease inhibitors, sertindole

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

QT interval prolonging drugs, sertindole

Quinidine, sertindole

Quinidine, strong CYP2D6 inhibitor, may increase the plasma levels of sertindole and significantly prolong the QT interval. The co-administration is contraindicated

Rifampicin, sertindole

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Saquinavir/ritonavir, sertindole ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Sertindole, sotalol

Sertindole, strong CYP2D6 inhibitors

Sertindole, strong CYP3A4 inductors

The metabolism of sertindole may be significantly enhanced by agents known to induce CYP isozymes, which can decrease the plasma concentrations of sertindole

Sertindole, strong CYP3A4 inhibitors

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Sertindole, terfenadine

Sertindole, thioridazine

Sertindole, tiapride

Tiapride should not be combined with drugs that prolong the QT interval. These drugs (with the exception of anti-infectious) should be discontinued, if possible, if they induce torsades de pointes

Sertindole, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Co-administration of tipranavir with low dose ritonavir, with active substances that are highly dependent on CYP3A for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events, is contraindicated.

Sertindole, toremifene [2] ---> SmPC of [2] of EMA

An additive effect on QT interval prolongation between toremifene and medicinal products that may prolong the QTc interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias. Co-administration is contraindicated

Sertindole, triamterene [2] ---> SmPC of [2] of eMC

Hypokalaemia caused by diuretics increases risk of ventricular arrhythmias with sertindole

Sertindole, verapamil

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Sertindole, ziprasidone

Additive QT-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Sertraline

Ability to drive, sertraline [2] ---> SmPC of [2] of EMA

Psychotropic drugs may impair the mental or physical abilities required for the performance of potentially hazardous

Acenocoumarol, sertraline

The co-administration may enhance the anticoagulant effect and increase the bleeding risk.

Acetylsalicylic acid, sertraline [2] ---> SmPC of [2] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Acetylsalicylic acid, SSRI ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Alcohol, sertraline [2] ---> SmPC of [2] of EMA

The concomitant use of sertraline and alcohol is not recommended.

Alprazolam, sertraline

Concomitant use of alprazolam and strong CYP3A4 inhibitors should be done with caution a significant dose reduction should be considered

Amitriptyline, sertraline

The CYP2D6 inhibition may increase the plasma concentrations of amitriptyline. Concomitant use should be avoided

Anticoagulants, sertraline [2] ---> SmPC of [2] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Anticoagulants, SNRIs ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Bictegravir/emtricitabine/tenofovir alafenamide [1], sertraline ---> SmPC of [1] of EMA

No dose adjustment is required upon co-administration.

Breast-feeding, sertraline [2] ---> SmPC of [2] of EMA

Use in nursing mothers is not recommended unless, in the judgment of the physician, the benefit outweighs the risk.

Cimetidine, sertraline [2] ---> SmPC of [2] of EMA

Co-administration with cimetidine caused a substantial decrease in sertraline clearance.

Class IC antiarrhythmic agents, sertraline [2] ---> SmPC of [2] of EMA

Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index, especially at higher sertraline dose levels.

Clomipramine [1], sertraline ---> SmPC of [1] of eMC

SSRIs which are inhibitors of CYP2D6, such as fluoxetine, paroxetine, or sertraline, and of others including CYP1A2 and CYP2C19 (e.g. fluvoxamine), may increase plasma concentrations of clomipramine, with corresponding adverse effects.

Clozapine [1], sertraline ---> SmPC of [1] of eMC

Concomitant administration of substances known to inhibit the activity of some cytochrome P450 isozymes (CYP2D6) may increase the levels of clozapine, and the dose of clozapine may need to be reduced to prevent undesirable effects.

CYP3A4 and CYP2B6 inductors, sertraline

The CYP3A and CYP2B6 inductions may decrease the plasma levels of sertraline

Darunavir/cobicistat [1], sertraline ---> SmPC of [1] of EMA

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sertraline ---> SmPC of [1] of EMA

If this anti-depressant is to be used with Symtuza clinical monitoring is recommended and a dose adjustment of the anti-depressant may be needed.

Darunavir/ritonavir, sertraline ---> SmPC of [darunavir] of EMA

The co-administration may decrease the plasma levels of sertraline

Diuretics, sertraline [2] ---> SmPC of [2] of EMA

The co-administration increases the risk of hyponatremia

Dopamine antagonists, sertraline

The co-administration increases the risk of serotonin syndrome and of neuroleptic malignant syndrome. The combination should be avoided

Droperidol [1], sertraline ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Drugs primarily metabolised by CYP2D6 with narrow therapeutic index, sertraline [2] ---> SmPC of [2] of EMA

Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index, especially at higher sertraline dose levels.

Drugs primarily metabolised by CYP2D6, sertraline [2] ---> SmPC of [2] of EMA

Sertraline, moderate CYP2D6 inhibitor, may increase the plasma concentrations of the medicinal products metabolised by CYP2D6

Drugs with high protein binding, sertraline

An interaction with other plasma protein bound active substances is generally possible

Efavirenz [1], sertraline ---> SmPC of [1] of EMA

The CYP3A4 induction by efavirenz decreases the plasma concentrations of sertraline

Efavirenz/emtricitabine/tenofovir disoproxil [1], sertraline ---> SmPC of [1] of EMA

CYP3A4 induction. When co-administered with Atripla, sertraline dose increases should be guided by clinical response.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], sertraline ---> SmPC of [1] of EMA

Concentrations of sertraline are not affected upon co-administration with Genvoya. No dose adjustment is required upon co-administration.

Emtricitabine/tenofovir alafenamide [1], sertraline ---> SmPC of [1] of EMA

No dose adjustment of sertraline is required. Dose Descovy according to the concomitant antiretroviral

Felodipine/metoprolol, sertraline

CYP2D6 inhibitors may increase the plasma levels of metoprolol

Fenfluramine, sertraline [2] ---> SmPC of [2] of EMA

Co-administration of sertraline with other drugs which enhance the effects of serotonergic neurotransmission should be undertaken with caution and avoided whenever possible due to the potential for a pharmacodynamic interaction

Ferric citrate coordination complex [1], sertraline ---> SmPC of [1] of EMA

Any medicinal product that has the potential to interact with Fexeric, should be taken at least 2 hours before or after Fexeric.

Flecainide, sertraline [2] ---> SmPC of [2] of EMA

Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index, especially at higher sertraline dose levels.

Fosphenytoin [1], sertraline ---> SmPC of [1] of eMC

Concomitant use of sertraline with phenytoin may lower the seizure threshold.

Frovatriptan [1], sertraline ---> SmPC of [1] of eMC

Potential risk of hypertension, coronary vasoconstriction or serotonin syndrome. Strict adherence to the recommended dose is an essential factor to prevent this syndrome.

Haloperidol [1], sertraline ---> SmPC of [1] of eMC

Inhibition of the CYP2D6 by another drug may result in increased haloperidol concentrations and an increased risk of adverse events, including QT-prolongation.

IMAOs, sertraline

Combination (contraindicated) may cause serious and sometimes fatal reactions. After discontinuing MAOI, wait (depending on IMAO) 5/2 weeks or 1 day before administering SSRI

Imipramine, sertraline

Co-medication of SSRIs and imipramine may lead to additive effects on the serotonergic system.

Insulin, sertraline

Sertraline may alter glycaemic control

Ioflupane [1], sertraline ---> SmPC of [1] of EMA

Ioflupane binds to the dopamine transporter. Medicines that bind to the dopamine transporter with high affinity may therefore interfere with ioflupane diagnosis.

Irreversible MAO-inhibitors, sertraline [2] ---> SmPC of [2] of EMA

Combination contraindicated. Sertraline should not be administrated within at least 7 days BEFORE initia. nor 14 days AFTER discontin. a therapy with irreversible MAOI

Irreversible selective MAO-A inhibitors, sertraline [2] ---> SmPC of [2] of EMA

Combination contraindicated. Sertraline should not be administrated within at least 7 days BEFORE initiation nor 14 days AFTER discontinuing a therapy with irreversible MAOI

Irreversible selective MAO-B inhibitors, sertraline [2] ---> SmPC of [2] of EMA

Combination contraindicated. Sertraline should not be administrated within at least 7 days BEFORE initia. nor 14 days AFTER discontin. a therapy with irreversible MAOI

Levomepromazine [1], sertraline ---> SmPC of [1] of eMC

Co-administration of levomepromazine and drugs primarily metabolised by the CYP2D6 may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic or adverse effects of those drugs.

Levothyroxine [1], sertraline ---> SmPC of [1] of eMC

Effects of Levothyroxine may be decreased by concomitant sertraline.

Linezolid, sertraline [2] ---> SmPC of [2] of EMA

The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients treated with sertraline

Liothyronine, sertraline

Decreased effect of liothyronine and increased plasma levels of TSH

Lithium, sertraline [2] ---> SmPC of [2] of EMA

The co-administration may increase the incidence of tremor

Lumacaftor/ivacaftor [1], sertraline ---> SmPC of [1] of EMA

A higher dose of this antidepressant may be required to obtain the desired clinical effect. Lumacaftor/ivacaftor may decrease the exposures of this antidepressant, which may reduce its efficacy.

Methadone, sertraline

Methadone clearance is decreased when co-administered with drugs which inhibit CYP3A4 activity, since the metabolism of methadone is mediated by the CYP3A4 isoenzyme.

Metoprolol, sertraline ---> SmPC of [felodipine/metoprolol] of EMA

CYP2D6 inhibitors may increase the plasma levels of metoprolol

Moclobemide, sertraline [2] ---> SmPC of [2] of EMA

Contraindicated (serotonin syndrome risk). Sertraline should not be administrated within at least 7 days BEFORE initiating/14 days AFTER suspending a reversible selective MAOI

Neuroleptics, sertraline [2] ---> SmPC of [2] of EMA

Nevirapine, sertraline

The CYP3A and CYP2B6 inductions may decrease the plasma levels of sertraline

NSAID, sertraline [2] ---> SmPC of [2] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

NSAID, SSRI ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Oral antidiabetics, sertraline

Sertraline may alter glycaemic control

Phenothiazines, sertraline [2] ---> SmPC of [2] of EMA

Caution is advised in patients taking SSRIs, particularly in concomitant use with drugs known to affect platelet function

Phenytoin, sertraline [2] ---> SmPC of [2] of EMA

Some case reports have emerged of high phenytoin exposure in patients using sertraline. In addition, co-administration of phenytoin may cause a reduction of sertraline plasma levels.

Pimozide, sertraline [2] ---> SmPC of [2] of EMA

Increased plasma levels of pimozide. Due to the narrow therapeutic index of pimozide, concomitant administration of sertraline and pimozide is contraindicated

Platelet aggregation inhibitors, sertraline [2] ---> SmPC of [2] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Platelet aggregation inhibitors, SSRI ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Pregnancy, sertraline [2] ---> SmPC of [2] of EMA

Sertraline is not recommended in pregnancy, unless the clinical condition of the woman is such that the benefit of the treatment is expected to outweigh the potential risk.

Propafenone, sertraline [2] ---> SmPC of [2] of EMA

Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index, especially at higher sertraline dose levels.

Reversible selective MAO-A inhibitors, sertraline [2] ---> SmPC of [2] of EMA

Contraindicated (serotonin syndrome risk). Sertraline should not be administrated within at least 7 days BEFORE initiating/14 days AFTER suspending a reversible selective MAOI

Ritonavir [1], sertraline ---> SmPC of [1] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine or sertraline.

Selegiline, sertraline [2] ---> SmPC of [2] of EMA

Combination contraindicated. Sertraline should not be administrated within at least 7 days BEFORE initia. nor 14 days AFTER discontin. a therapy with irreversible MAOI

Serotonergic medicines, sertraline [2] ---> SmPC of [2] of EMA

Sertraline [1], St. John's wort ---> SmPC of [1] of EMA

Sertraline [1], ticlopidine ---> SmPC of [1] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

Sertraline [1], tramadol ---> SmPC of [1] of EMA

Sertraline [1], tricyclic antidepressant ---> SmPC of [1] of EMA

Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index, especially at higher sertraline dose levels.

Sertraline [1], triptans ---> SmPC of [1] of EMA

Sertraline [1], tryptophan ---> SmPC of [1] of EMA

Sertraline [1], typical neuroleptics ---> SmPC of [1] of EMA

Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index, especially at higher sertraline dose levels.

Sertraline [1], warfarin ---> SmPC of [1] of EMA

The co-administration may increase the prothrombin time

Sertraline, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol is an inhibitor of the enzymes CYP2D6 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions

Sertraline, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP2B6 substrates (e.g. valproic acid, bupropion, sertraline) by decreasing their systemic exposure.

Sertraline, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or sertraline is required.

Sertraline, tetrabenazine [2] ---> SmPC of [2] of eMC

Inhibitors of CYP2D6 may result in increased plasma concentrations of the active metabolite dihydrotetrabenazine, why they should only be combined with caution. A reduction of the tetrabenazine dose may be necessary.

Sertraline, ticagrelor [2] ---> SmPC of [2] of EMA

Due to reports of cutaneous bleeding abnormalities with SSRIs, caution is advised when administering SSRIs with ticagrelor as this may increase the risk of bleeding.

Sertraline, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Sertraline, triazolam

Caution is advised when combining triazolam with sertraline

Sertraline, triiodthyronine

Decreased effect of liothyronine and increased plasma levels of TSH

Sertraline, triptorelin [2] ---> SmPC of [2] of eMC

Drugs which raise prolactin levels should not be prescribed concomitantly as they reduce the level of GnRH receptors in the pituitary.

SSRI, ticlopidine ---> SmPC of [sertraline] of EMA

The risk of bleeding may be increased when medicines acting on platelet function or other medicines that might increase bleeding risk are concomitantly administered with SSRIs

CONTRAINDICATIONS of Sertraline

- Hypersensitivity to the active substance or any of the excipients.

- Concomitant treatment with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia. Sertraline must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI. Sertraline must be discontinued for at least 7 days before starting treatment with an irreversible MAOI

- Concomitant intake of pimozide is contraindicated

- Sertraline concentrate for oral solution is contraindicated with the use of disulfiram due to the alcohol content of the oral concentrate

http://www.ema.europa.eu/

Setmelanotide (Imcivree)

Benzyl alcohol, setmelanotide [2] ---> SmPC of [2] of EMA

Patients who are pregnant or breastfeeding should be advised of the potential risk from the excipient benzyl alcohol (see section 4.4).

Breast-feeding, setmelanotide [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from IMCIVREE therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.

Cytochrome P450, setmelanotide [2] ---> SmPC of [2] of EMA

In vitro studies showed that setmelanotide has low potential for pharmacokinetic interactions related to cytochrome P450 (CYP) transporters and plasma protein binding.

Fertility, setmelanotide [2] ---> SmPC of [2] of EMA

No human data on the effect of setmelanotide on fertility are available. Animal studies did not indicate harmful effects with respect to fertility.

Pregnancy, setmelanotide [2] ---> SmPC of [2] of EMA

As a precautionary measure, IMCIVREE should not be started during pregnancy or while attempting to get pregnant as weight loss during pregnancy may result in foetal harm.

CONTRAINDICATIONS of Setmelanotide (Imcivree)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/imcivree-epar-product-information_en.pdf 15/05/2024

Sevelamer carbonate (Renvela)

Antiarrhythmics, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Possible reduction in absorption cannot be excluded. The anti-arrhythmic medical product should be taken at least one hour before or three hours after Renvela, and blood monitoring can be considered.

Antiepileptics, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Possible reduction in absorption cannot be excluded. The anti-arrhythmic medical product should be taken at least one hour before or three hours after Renvela, and blood monitoring can be considered.

Bioavailability, sevelamer carbonate [2] ---> SmPC of [2] of EMA

When administering any medicine where a reduction in the bioavailability could have a clinically significant effect on safety/efficacy, the medicine should be administered at least 1 hour before or 3 hours after sevelamer carbonate

Bioavailability, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Sevelamer carbonate is not absorbed and may affect the bioavailability of other medicinal products.

Breast-feeding, sevelamer carbonate [2] ---> SmPC of [2] of EMA

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy should be made

Ciprofloxacin, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Decreased the bioavailability of ciprofloxacin by approximately 50% when coadministered with sevelamer hydrochloride in a single dose study. Consequently, sevelamer carbonate should not be taken simultaneously with ciprofloxacin.

Cyclosporine, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant patients when co-administered with sevelamer hydrochloride without any clinical consequences (e.g., graft rejection).

Dialysis, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Interaction studies have not been conducted in patients on dialysis.

Digoxin, sevelamer carbonate [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, had no effect on the bioavailability of digoxin, warfarin, enalapril or metoprolol.

Elbasvir/grazoprevir [1], sevelamer carbonate ---> SmPC of [1] of EMA

No dose adjustment is required.

Enalapril, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Fat-soluble vitamins, sevelamer carbonate [2] ---> SmPC of [2] of EMA

It cannot be excluded that Renvela can bind fat-soluble vitamins contained in ingested food. In patients not taking supplemental vitamins but on sevelamer, serum vitamin A, D, E and K status should be assessed regularly.

Fertility, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Studies in animals have shown that sevelamer did not impair fertility in male or female rats at exposures at a human equivalent dose 2 times the maximum clinical trial dose of 13 g/day, based on a comparison of relative BSA.

Foods, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Tablets should be swallowed intact and should not be crushed, chewed, or broken into pieces prior to administration. Renvela should be taken with food and not on an empty stomach.

Levothyroxine, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Very rare cases of hypothyroidism have been reported in patients co-administered sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, and levothyroxine.

Metoprolol, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Mycophenolate [1], sevelamer carbonate ---> SmPC of [1] of EMA

The possibility of an interaction cannot be excluded and a close monitoring of blood concentrations of ciclosporin, mycophenolate mofetil and tacrolimus should be considered during the use of combination and after its withdrawal.

Pregnancy, sevelamer carbonate [2] ---> SmPC of [2] of EMA

Sevelamer carbonate should only be given to pregnant women if clearly needed and after a careful risk/benefit analysis has been conducted for both the mother and the foetus.

Proton pump inhibitors, sevelamer carbonate [2] ---> SmPC of [2] of EMA

During post-marketing experience, very rare cases of increased phosphate levels have been reported in patients taking proton pump inhibitors co-administered with sevelamer carbonate.

Roxadustat [1], sevelamer carbonate ---> SmPC of [1] of EMA

Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations

Sevelamer carbonate [1], tacrolimus ---> SmPC of [1] of EMA

Sevelamer carbonate [1], warfarin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Sevelamer carbonate (Renvela)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypophosphatemia

- Bowel obstruction

https://www.ema.europa.eu/en/documents/product-information/renvela-epar-product-information_en.pdf 08/01/2025

Other trade names: Sevelamer carbonate Winthrop (previously Sevelamer carbonate Zentiva),

Sevelamer hydrochloride (Renagel)

Antiarrhythmics, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Patients taking anti-arrhythmic medicinal products for the control of arrhythmias and anti-seizure medicinal products for the control of seizure disorders were excluded from clinical trials. Caution should be exercised

Antiepileptics, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Bioavailability, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Renagel is not absorbed and may affect the bioavailability of other medicinal products.

Breast-feeding, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Renagel should only be given to breast-feeding women if clearly needed and after a careful risk/benefit analysis has been conducted for both the mother and the infant (see section 5.3).

Ciprofloxacin, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride decreased the bioavailability of ciprofloxacin by approximately 50% when co-administered with Renagel in a single dose study.

Cyclosporine, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Reduced levels of ciclosporin, mycophenolate mofetil and tacrolimus have been reported in transplant patients when coadministered with sevelamer hydrochloride without any clinical consequences (i.e graft rejection).

Dialysis, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Interaction studies have not been conducted in patients on dialysis.

Digoxin, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride had no effect on the bioavailability of digoxin

Enalapril, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride had no effect on the bioavailability of enalapril

Fertility, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Levothyroxine, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

During post marketing experience, very rare cases of increased thyroid stimulating hormone (TSH) levels have been reported in patients co-administered sevelamer hydrochloride and levothyroxine.

Metoprolol, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride had no effect on the bioavailability of metoprolol

Mycophenolate mofetil, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Pregnancy, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

Renagel should only be given to pregnant women if clearly needed and after a careful risk/benefit analysis has been conducted for both the mother and the foetus (see section 5.3).

Proton pump inhibitors, sevelamer hydrochloride [2] ---> SmPC of [2] of EMA

During post-marketing experience, very rare cases of increased phosphate levels have been reported in patients taking proton pump inhibitors co-administered with sevelamer hydrochloride.

Sevelamer hydrochloride [1], tacrolimus ---> SmPC of [1] of EMA

Sevelamer hydrochloride [1], warfarin ---> SmPC of [1] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride had no effect on the bioavailability of warfarin

CONTRAINDICATIONS of Sevelamer hydrochloride (Renagel)

- Hypersensitivity to sevelamer or to any of the excipients listed in section 6.1.

- Hypophosphatemia

- Bowel obstruction

https://www.ema.europa.eu/en/documents/product-information/renagel-epar-product-information_en.pdf 22/01/2025

Other trade names: Tasermity,

Sevoflurane

Ability to drive, sevoflurane [2] ---> SmPC of [2] of eMC

As with other agents, patients should be advised that performance of activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, may be impaired for some time after general anaesthesia

Adrenaline, sevoflurane [2] ---> SmPC of [2] of eMC

Sevoflurane is similar to isoflurane in the sensitisation of the myocardium to the arrhythmogenic effect of exogenously administered adrenaline.

Alcohol, sevoflurane [2] ---> SmPC of [2] of eMC

Medicinal products and compounds that increase the activity of isoenzyme CYP2E1 may increase the metabolism of sevoflurane and lead to significant increases in plasma fluoride concentrations.

Alfentanyl, sevoflurane [2] ---> SmPC of [2] of eMC

Opioids are expected to decrease the MAC of sevoflurane. Opioids, when combined with sevoflurane, may lead to a synergistic fall in heart rate, blood pressure and respiratory rate.

Amphetamine, sevoflurane [2] ---> SmPC of [2] of eMC

There is a risk of acute hypertensive episode with the concomitant use of sevoflurane and indirect-acting sympathomimetics products

Atracurium, sevoflurane [2] ---> SmPC of [2] of eMC

When used to supplement alfentanil-N2O anaesthesia, sevoflurane potentiates neuromuscular block induced with atracurium.

Benzodiazepines, sevoflurane [2] ---> SmPC of [2] of eMC

Benzodiazepines are expected to decrease the MAC of sevoflurane in the same manner as with other inhalational anaesthetics.

Betablockers, sevoflurane [2] ---> SmPC of [2] of eMC

Sevoflurane may increase the negative inotropic, chronotropic and dromotropic effects of beta blockers (by blocking cardiovascular compensatory mechanisms).

Breast-feeding, sevoflurane [2] ---> SmPC of [2] of eMC

Due to the absence of documented experience, women should be advised to skip breast-feeding for 48 hours after administration of sevoflurane and discard milk produced during this period.

CYP2E1 inductors, sevoflurane [2] ---> SmPC of [2] of eMC

Medicinal products and compounds that increase the activity of isoenzyme CYP2E1 may increase the metabolism of sevoflurane and lead to significant increases in plasma fluoride concentrations.

Ephedrine, sevoflurane [2] ---> SmPC of [2] of eMC

There is a risk of acute hypertensive episode with the concomitant use of sevoflurane and indirect-acting sympathomimetics products

Epinephrine, sevoflurane [2] ---> SmPC of [2] of eMC

Sevoflurane is similar to isoflurane in the sensitisation of the myocardium to the arrhythmogenic effect of exogenously administered adrenaline.

Esketamine, sevoflurane

Enhancement of anesthetic effect

Fentanyl, sevoflurane [2] ---> SmPC of [2] of eMC

Opioids are expected to decrease the MAC of sevoflurane. Opioids, when combined with sevoflurane, may lead to a synergistic fall in heart rate, blood pressure and respiratory rate.

Halogenated anaesthetics, St. John's wort ---> SmPC of [sevoflurane] of eMC

Severe hypotension and delayed emergence from anaesthesia with halogenated inhalational anaesthetics have been reported in patients treated long-term with St John's Wort.

Indirect sympathomimetics, sevoflurane [2] ---> SmPC of [2] of eMC

There is a risk of acute hypertensive episode with the concomitant use of sevoflurane and indirect-acting sympathomimetics products

Isoniazid, sevoflurane [2] ---> SmPC of [2] of eMC

Concomitant use of sevoflurane and isoniazid can potentiate the hepatotoxic effects of isoniazid.

Mivacurium [1], sevoflurane ---> SmPC of [1] of eMC

The neuromuscular block produced by mivacurium may be increased by the concomitant use of inhalational anaesthetics

Muscle relaxants (non-depolarizing), sevoflurane [2] ---> SmPC of [2] of eMC

As with other inhalational anaesthetic agents, sevoflurane affects both the intensity and duration of neuromuscular blockade by non-depolarising muscle relaxants.

Nitrous oxide, sevoflurane [2] ---> SmPC of [2] of eMC

As with other halogenated volatile anaesthetics, the MAC of sevoflurane is decreased when administered in combination with nitrous oxide.

Opiates, sevoflurane [2] ---> SmPC of [2] of eMC

Opioids are expected to decrease the MAC of sevoflurane. Opioids, when combined with sevoflurane, may lead to a synergistic fall in heart rate, blood pressure and respiratory rate.

Pancuronium, sevoflurane [2] ---> SmPC of [2] of eMC

When used to supplement alfentanil-N2O anaesthesia, sevoflurane potentiates neuromuscular block induced with pancuronium.

Pregnancy, sevoflurane [2] ---> SmPC of [2] of eMC

Sevoflurane should be used during pregnancy only if clearly needed.

QT interval prolonging drugs, sevoflurane [2] ---> SmPC of [2] of eMC

Isolated reports of QT prolongation, very rarely associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients.

Sevoflurane [1], St. John's wort ---> SmPC of [1] of eMC

Severe hypotension and delayed emergence from anaesthesia with halogenated inhalational anaesthetics have been reported in patients treated long-term with St John's Wort.

Sevoflurane [1], sufentanil ---> SmPC of [1] of eMC

Opioids are expected to decrease the MAC of sevoflurane. Opioids, when combined with sevoflurane, may lead to a synergistic fall in heart rate, blood pressure and respiratory rate.

Sevoflurane [1], suxamethonium ---> SmPC of [1] of eMC

The effect of sevoflurane on succinylcholine and the duration of depolarising neuromuscular blockade has not been studied.

Sevoflurane [1], vecuronium ---> SmPC of [1] of eMC

When used to supplement alfentanil-N2O anaesthesia, sevoflurane potentiates neuromuscular block induced with vecuronium.

Sevoflurane [1], verapamil ---> SmPC of [1] of eMC

Impairment of atrioventricular conduction was observed when verapamil and sevoflurane were administered at the same time.

CONTRAINDICATIONS of Sevoflurane

- Sevoflurane should not be used in patients with known or suspected sensitivity to sevoflurane or other halogenated anaesthetics (e.g. history of liver function disorder, fever or leucocytosis of unknown cause after anaesthesia with one of these agents).

- Sevoflurane is also contraindicated in patients with known or suspected genetic susceptibility to malignant hyperthermia.

- Sevoflurane is contraindicated in patients in whom general anaesthesia is contraindicated.

http://www.medicines.org.uk/emc/

Sibutramine

Ability to drive, sibutramine [2] ---> SmPC of [2] of eMC

Any centrally-acting drug may impair judgement, thinking or motor skills.

Adrenaline, sibutramine

The effects of adrenaline may be potentiated by noradrenergic-serotoninergic antidepressants.

Alcohol, sibutramine [2] ---> SmPC of [2] of eMC

The consumption of alcohol is not compatible with the recommended dietary measures as a general rule.

Antidepressants, sibutramine [2] ---> SmPC of [2] of eMC

Concomitant use, or use during the past 2 weeks, of other centrally-acting drugs for the treatment of psychiatric disorders (such as antidepressants, antipsychotics) or for weight reduction is contraindicated

Breast-feeding, sibutramine [2] ---> SmPC of [2] of eMC

It is not known whether sibutramine is excreted in human breast milk and therefore administration of Sibutramine is contraindicated during lactation.

Carbamazepine, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Clarithromycin, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Cyclosporine, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Dexamethasone, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Dextromethorphan, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Dihydroergotamine, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Ephedrine, sibutramine [2] ---> SmPC of [2] of eMC

Paroxysmal hypertension with possibility of arrhythmias (inhibition of adrenaline or noradrenaline entry in sympathetic fibers)

Epinephrine, sibutramine

The effects of adrenaline may be potentiated by noradrenergic-serotoninergic antidepressants.

Erythromycin, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Fentanyl, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

IMAOs, sibutramine [2] ---> SmPC of [2] of eMC

Two weeks should elapse between stopping sibutramine and starting monoamine oxidase inhibitors.

Itraconazol, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Ketoconazole, sibutramine [2] ---> SmPC of [2] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Miconazole, sibutramine

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Neuroleptics, sibutramine [2] ---> SmPC of [2] of eMC

Oral contraceptives, sibutramine

Sibutramine doesn't impair the efficacy of oral contraceptives.

Pentazocine, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Pethidine, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Phenobarbital, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Phenytoin, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Pregnancy, sibutramine [2] ---> SmPC of [2] of eMC

Sibutramine should not be used during pregnancy.

Pseudoephedrine, sibutramine [2] ---> SmPC of [2] of eMC

Concomitant use of Sibutramine with other drugs which may raise the blood pressure or heart rate has not been systematically evaluated. Caution should be used when prescribing sibutramine to patients who use these medicines.

Rifampicin, sibutramine [2] ---> SmPC of [2] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Serotonergic medicines, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Serotonin reuptake inhibitors, sibutramine [2] ---> SmPC of [2] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Sibutramine [1], SSRI ---> SmPC of [1] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Sibutramine [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Rifampicin, phenytoin, carbamazepine, phenobarbital and dexamethasone are CYP3A4 enzyme inducers and may accelerate sibutramine metabolism, although this has not been studied experimentally.

Sibutramine [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Sibutramine [1], sumatriptan ---> SmPC of [1] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

Sibutramine [1], sympathomimetics ---> SmPC of [1] of eMC

Sibutramine [1], troleandomycin ---> SmPC of [1] of eMC

Caution should be exercised on concomitant administration of sibutramine with drugs which affect CYP3A4 enzyme activity (increased plasma concentrations (AUC) of sibutramine active metabolites)

Sibutramine [1], tryptophan ---> SmPC of [1] of eMC

Concomitant use, or use during the past 2 weeks, of tryptophan for sleep disturbances is contraindicated

Sibutramine [1], xylometazoline ---> SmPC of [1] of eMC

Sibutramine, tranylcypromine

Tranylcypromine should not be used together with drugs with marked serotonin-reuptake inhibition. Risk of serotonin syndrome with symptoms like hypertension, irritability, hyperthermia with possible fatal outcome

Sibutramine, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Sibutramine, yohimbine

The co-administration may cause tachycardia and hypertension

Sildenafil (Vizarsin)

Ability to drive, sildenafil [2] ---> SmPC of [2] of EMA

As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware of how they react to Vizarsin, before driving or operating machinery.

ACE inhibitors, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as angiotensin converting enzyme inhibitors

Acetylsalicylic acid, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil did not potentiate the increase in bleeding time caused by acetyl salicylic acid

Alcohol, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/dl.

Alfa-adrenergic receptor blockers, sildenafil [2] ---> SmPC of [2] of EMA

Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals.

Allopurinol/lesinurad [1], sildenafil ---> SmPC of [1] of EMA

Patients using lipid lowering or anti-hypertensive medicinal products that were CYP3A substrates required concomitant medicinal product change when treated with lesinurad 200 mg in combination with a xanthine oxidase inhibitor

Alpha-blockers, sildenafil [2] ---> SmPC of [2] of EMA

Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals.

Aluminium hydroxide, sildenafil [2] ---> SmPC of [2] of EMA

Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.

Ambrisentan [1], sildenafil ---> SmPC of [1] of EMA

Co-administration of ambrisentan with a phosphodiesterase inhibitor, either sildenafil or tadalafil (both substrates of CYP3A4) in healthy volunteers did not significantly affect the pharmacokinetics of the phosphodiesterase inhibitor or ambrisentan

Amiodarone [1], sildenafil ---> SmPC of [1] of eMC

Amiodarone, CYP3A4 inhibitor, may increase the plasma concentrations of sildenafil

Amlodipine, sildenafil [2] ---> SmPC of [2] of EMA

In a specific interaction study, where sildenafil (100 mg) was co-administered with amlodipine in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 8 mmHg.

Amprenavir/ritonavir, sildenafil ---> SmPC of [amprenavir] of EMA

Amprenavir/ritonavir, CYP3A4 inhibitors, may increase plasma concentrations of sildenafil, which is contraindicated for the treatment of pulmonary arterial hypertension

Antacids, sildenafil [2] ---> SmPC of [2] of EMA

Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.

Atazanavir [1], sildenafil ---> SmPC of [1] of EMA

Atazanavir, CYP3A4 inhibitor, may increase the plasma levels of sildenafil. Combination contraindicated if sildenafil is used to treat PAH

Atazanavir/cobicistat [1], sildenafil ---> SmPC of [1] of EMA

Co-administration with EVOTAZ may result in increased concentrations of the PDE5 inhibitor. The mechanism of interaction is CYP3A4 inhibition by atazanavir. Sildenafil, when used for the treatment of pulmonary arterial hypertension, is contraindicated

Azithromycin, sildenafil [2] ---> SmPC of [2] of EMA

). In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, tmax, elimination rate constant, or subsequent half-life of sildenafil or its principal circulating metabolite.

Barbiturates, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2D6 inhibitors inducers of CYP450 metabolism (such as rifampicin, barbiturates).

Betablockers, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as beta-adrenoreceptor antagonists

Bosentan, sildenafil [2] ---> SmPC of [2] of EMA

In healthy male volunteers, sildenafil at steady state (80 mg t.i.d.) resulted in a 49.8% increase in bosentan AUC and a 42% increase in bosentan Cmax (125 mg b.i.d.).

Breast-feeding, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil is not indicated for use by women.

Bunazosin, sildenafil

The co-administration may cause hypotension or syncopes

Calcium antagonists, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as calcium channel blockers

Cimetidine, sildenafil [2] ---> SmPC of [2] of EMA

Cimetidine (800 mg), a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to healthy volunteers.

Ciprofloxacin [1], sildenafil ---> SmPC of [1] of eMC

Cmax and AUC of sildenafil were increased approximately twofold in healthy subjects after an oral dose of 50 mg given concomitantly with 500 mg ciprofloxacin.

Clarithromycin, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors

Cobicistat [1], sildenafil ---> SmPC of [1] of EMA

Co-administration with cobicistat may result in increased sildenafil plasma concentrations, which may result in PDE-5 inhibitor-associated adverse reactions. Co-administration for the treatment of pulmonary arterial hypertension is contraindicated

CYP2C9 inhibitors, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors

CYP2D6 inhibitors, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2D6 inhibitors

CYP3A4 inductors, sildenafil [2] ---> SmPC of [2] of EMA

Therefore, concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

CYP3A4 inhibitors, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance

CYP450 inductors, sildenafil [2] ---> SmPC of [2] of EMA

Darunavir/cobicistat [1], sildenafil ---> SmPC of [1] of EMA

Darunavir/cobicistat (CYP3A inhibition) is expected to increase sildenafil plasma concentrations. Co-administration of darunavir/cobicistat and sildenafil when used for the treatment of pulmonary arterial hypertension is contraindicated

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sildenafil ---> SmPC of [1] of EMA

Co-administration is contraindicated (sildenafil - when used for the treatment of pulmonary arterial hypertension) due to the potential for serious and/or life-threatening adverse reactions

Darunavir/ritonavir, sildenafil ---> SmPC of [darunavir] of EMA

Co-administration of darunavir/ritonavir and sildenafil when used for the treatment of pulmonary arterial hypertension is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sildenafil ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of E

The strong CYP3A inhibition by ritonavir may increase the plasma levels of sildenafil. Concomitant use is contraindicated when sildenafil used for the treatment of pulmonary arterial hypertension

Dipyridamole, sildenafil [2] ---> SmPC of [2] of EMA

There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Diuretics, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as thiazide and related diuretics, loop and potassium sparing diuretics

Dolutegravir/rilpivirine [1], sildenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Doxazosin, sildenafil [2] ---> SmPC of [2] of EMA

Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals.

Drugs primarily metabolised by CYP2C9, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin).

Duvelisib [1], sildenafil ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], sildenafil ---> SmPC of [1] of EMA

Co-administration of Genvoya and some medicinal products that are primarily metabolised by CYP3A may increase plasma concentrations of these products, which are associated with the potential for serious/life-threatening adverse reactions. Contraindicated

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], sildenafil ---> SmPC of [1] of EMA

Co-administration of Stribild and other medicinal products primarily metabolised by CYP3A such as amiodarone, quinidine, cisapride, pimozide, alfuzosin and sildenafil for pulmonary arterial hypertension is contraindicated

Emtricitabine/rilpivirine/tenofovir alafenamide [1], sildenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], sildenafil ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Erythromycin, sildenafil [2] ---> SmPC of [2] of EMA

When a single 100 mg dose of sildenafil was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC).

Etravirine [1], sildenafil ---> SmPC of [1] of EMA

Concomitant use of PDE-5 inhibitors with etravirine may require dose adjustment of the PDE-5 inhibitor to attain the desired clinical effect.

Fosamprenavir/ritonavir, sildenafil ---> SmPC of [fosamprenavir] of EMA

Fosamprenavir/ritonavir, CYP3A4 inhibitors, may increase plasma concentrations of sildenafil, which is contraindicated for the treatment of pulmonary arterial hypertension

Glycerol trinitrate, sildenafil

The co-administration may enhance the hypotensive effect. The combination is contraindicated

Grapefruit juice, sildenafil [2] ---> SmPC of [2] of EMA

Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give rise to modest increases in plasma levels of sildenafil.

Idelalisib [1], sildenafil ---> SmPC of [1] of EMA

The co-administration of idelalisib with sildenafil may increase sildenafil serum concentrations. For pulmonary arterial hypertension: Idelalisib should not be co-administered with sildenafil. For erectile dysfunction: Particular caution must be used

Indinavir [1], sildenafil ---> SmPC of [1] of EMA

Coadministration of indinavir with sildenafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.

Indinavir/ritonavir, sildenafil ---> SmPC of [indinavir] of EMA

Coadministration of indinavir with sildenafil is likely to result in an increase of sildenafil by competitive inhibition of metabolism.

Isosorbide dinitrate [1], sildenafil ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide mononitrate [1], sildenafil ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Itraconazol, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors

Ivabradine [1], sildenafil ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the sildenafil on pharmacokinetics and pharmacodynamics of ivabradine

Ketoconazole, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors

Lenacapavir [1], sildenafil ---> SmPC of [1] of EMA

Use of PDE-5 inhibitors for erectile dysfunction: Sildenafil: A starting dose of 25 mg is recommended.

Lesinurad [1], sildenafil ---> SmPC of [1] of EMA

In interaction studies conducted in healthy subjects with Zurampic and CYP3A substrates, lesinurad reduced the plasma concentrations of sildenafil and amlodipine.

Lopinavir, sildenafil

Lopinavir, strong CYP3A4 inhibitor, increases the plasma concentrations of sildenafil. Contraindicated for the treatment of pulmonary arterial hypertension

Lopinavir/ritonavir [1], sildenafil ---> SmPC of [1] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, increase the plasma concentrations of sildenafil. Contraindicated for the treatment of pulmonary arterial hypertension

Macitentan [1], sildenafil ---> SmPC of [1] of EMA

In a placebo-controlled trial in patients with PAH, the efficacy and safety of macitentan in combination with sildenafil were demonstrated.

Magnesium hydroxide, sildenafil [2] ---> SmPC of [2] of EMA

Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.

Meropenem/vaborbactam [1], sildenafil ---> SmPC of [1] of EMA

Caution should be used when administering meropenem/vaborbactam concomitantly with medicinal products with a narrow therapeutic window that are predominantly metabolised by CYP450 enzymes

Miconazole, sildenafil

Miconazole, strong CYP3A4 inhibitor, may increase the plasma levels of sildenafil. Caution is recommended

Molsidomine, sildenafil

The co-administration is contraindicated due to the risk of pronounced potentiation of hypotensive effects that can cause syncopes and myocardial infarctation

Nelfinavir [1], sildenafil ---> SmPC of [1] of EMA

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated. Combination contraindicated if sildenafil is used to treat pulmonary arterial hypertension

Nicorandil, sildenafil [2] ---> SmPC of [2] of EMA

Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component it has the potential to result in a serious interaction with sildenafil.

Nirmatrelvir/ritonavir [1], sildenafil ---> SmPC of [1] of EMA

Concomitant use for the treatment of erectile dysfunction should be with caution and in no instance should sildenafil doses exceed 25 mg in 48 hours. Concomitant use is contraindicated in pulmonary arterial hypertension patients

Nitric oxide donors, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated

Nitric oxide, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated (see section 4.3).

Nitroglycerine [1], sildenafil ---> SmPC of [1] of eMC

Phosphodiesterase type 5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and coadministration with glyceryl trinitrate is therefore contraindicated

Nitroprussiate, sildenafil [2] ---> SmPC of [2] of EMA

Studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside in vitro.

Ombitasvir/paritaprevir/ritonavir [1], sildenafil ---> SmPC of [1] of EMA

The strong CYP3A inhibition by ritonavir may increase the plasma levels of sildenafil. Concomitant use is contraindicated when sildenafil used for the treatment of pulmonary arterial hypertension

Organic nitrates, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated (see section 4.3).

PDE5 inhibitors, riociguat ---> SmPC of [sildenafil] of EMA

Concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated (see section 4.3).

Phenytoin, sildenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors

Pregnancy, sildenafil [2] ---> SmPC of [2] of EMA

Vizarsin is not indicated for use by women.

Protease inhibitors, sildenafil ---> SmPC of [nelfinavir] of EMA

Co-administration of a PI with sildenafil is expected to substantially increase sildenafil concentration and may result in an increase in sildenafil associated adverse events, including hypotension, visual changes, and priapism.

Ribociclib [1], sildenafil ---> SmPC of [1] of EMA

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Rifampicin, sildenafil [2] ---> SmPC of [2] of EMA

Therefore, concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

Rilpivirine [1], sildenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Riociguat, sildenafil [2] ---> SmPC of [2] of EMA

Concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated (see section 4.3).

Ritonavir [1], sildenafil ---> SmPC of [1] of EMA

Based on these pharmacokinetic results co-administration of sildenafil with ritonavir is not advised (see section 4.4) and in any event the maximum dose of sildenafil should under no circumstances exceed 25 mg within 48 hours.

Sacubitril/valsartan [1], sildenafil ---> SmPC of [1] of EMA

Caution should be exercised when sildenafil or another PDE5 inhibitor is initiated in patients treated with Entresto.

Saquinavir, sildenafil [2] ---> SmPC of [2] of EMA

Sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

Saquinavir/ritonavir, sildenafil ---> SmPC of [saquinavir] of EMA

Saquinavir, CYP3A4 inhibitor, may increase the plasma concentrations of sildenafil. Contraindicated due to the potential for life threatening cardiac arrhythmia

Sildenafil [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

Sildenafil [1], theophylline ---> SmPC of [1] of EMA

There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Sildenafil [1], tolbutamide ---> SmPC of [1] of EMA

No significant interactions were shown when sildenafil (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9.

Sildenafil [1], warfarin ---> SmPC of [1] of EMA

No significant interactions were shown when sildenafil (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9.

Sildenafil, silodosin [2] ---> SmPC of [2] of EMA

Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.

Sildenafil, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors. Mild increases in simeprevir concentrations may occur due to mild inhibition of OATP1B1 by sildenafil.

Sildenafil, sitaxentan [2] ---> SmPC of [2] of EMA

The increasing in sildenafil plasma concentrations were not considered clinically significant. Interaction with sildenafil may be serious if hypotension occurs beyond a safe level.

Sildenafil, tecovirimat [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

Sildenafil, telaprevir [2] ---> SmPC of [2] of EMA

Increased plasma levels of sildenafil. Association contraindicated in the treatment of pulmonary arterial hypertension and not recommended in the treatment of erectile dysfunction

Sildenafil, terazosine [2] ---> SmPC of [2] of eMC

Concomitant use of phosphodiesterase-5-inhibitors and terazosin may lead to symptomatic hypotension in some patients

Sildenafil, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Tipranavir, CYP3A4 inhibitor, may increase sildenafil plasma levels. Increased potential for adverse events (visual disturbances, hypotension, prolonged erection, and syncope). Co-administration to treat pulmonary arterial hypertension is contraindicated

Sildenafil, treprostinil [2] ---> SmPC of [2] of EMA

In a pharmacokinetic study in humans, in which sildenafil (60mg/day) and treprostinil diolamine (oral dose of 2 mg/day) were administered concomitantly, no pharmacokinetic interaction between treprostinil and sildenafil was observed.

Sildenafil, vericiguat [2] ---> SmPC of [2] of EMA

No dose-dependent trend was observed with the different sildenafil doses.

CONTRAINDICATIONS of Sildenafil (Vizarsin)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form is therefore contraindicated.

- The co-administration of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension

- Agents for the treatment of erectile dysfunction, including sildenafil, should not be used in men for whom sexual activity is inadvisable (e.g. patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure).

- Vizarsin is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure

- The safety of sildenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated: severe hepatic impairment, hypotension (blood pressure < 90/50 mmHg), recent history of stroke or myocardial infarction and known hereditary degenerative retinal disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

https://www.ema.europa.eu/en/documents/product-information/vizarsin-epar-product-information_en.pdf. 24/02/2023

Silodosin (Silodyx)

Ability to drive, silodosin [2] ---> SmPC of [2] of EMA

Patients should be informed about the possible occurrence of symptoms related to postural hypotension (such as dizziness) and should be cautioned about driving or operating machines

Alcohol dehydrogenase inductors, silodosin [2] ---> SmPC of [2] of EMA

Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7. Substances that inhibit or induce these enzymes may affect the plasma concentrations of silodosin and its active metabolite.

Alcohol dehydrogenase inhibitors, silodosin [2] ---> SmPC of [2] of EMA

Alfa-adrenergic receptor blockers, silodosin [2] ---> SmPC of [2] of EMA

The concomitant use of other alfa-adrenoreceptor antagonists is not recommended

Antihypertensives, silodosin [2] ---> SmPC of [2] of EMA

Caution should be exercised when starting concomitant use of silodosin with antihypertensives and patients should be monitored for possible adverse reactions.

Barbiturates, silodosin [2] ---> SmPC of [2] of EMA

Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7. Substances that induce these enzymes may affect the plasma concentrations of silodosin and its active metabolite.

Boceprevir/peginterferon alfa/ribavirin [1], silodosin ---> SmPC of [1] of EMA

Victrelis, with peginterferon alfa and ribavirin, is contraindicated in coadministration with medicines that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma levels are associated with serious and/or life-threatening events

Breast-feeding, silodosin [2] ---> SmPC of [2] of EMA

Not applicable as silodosin is intended for male patients only

Carbamazepine, silodosin [2] ---> SmPC of [2] of EMA

Cyclosporine, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

CYP3A4 inductors, silodosin [2] ---> SmPC of [2] of EMA

Digoxin, silodosin [2] ---> SmPC of [2] of EMA

Steady state levels of digoxin, a substrate of P-glycoprotein, were not significantly affected. No dose adjustment is required.

Diltiazem, silodosin [2] ---> SmPC of [2] of EMA

When silodosin was co-administered with a CYP3A4 inhibitor of moderate potency such as diltiazem, an increase in silodosin AUC of approximately 30 % was observed, but Cmax and half-life were not affected.

Fertility, silodosin [2] ---> SmPC of [2] of EMA

In clinical studies, the occurrence of ejaculation with reduced or no semen has been observed during treatment with silodosin (see section 4.8), due to the pharmacodynamic properties of silodosin.

Itraconazol, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Ketoconazole, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Moderate CYP3A4 inhibitors, silodosin [2] ---> SmPC of [2] of EMA

P-gp inductors, silodosin [2] ---> SmPC of [2] of EMA

Silodosin is a substrate for P-glycoprotein. Substances that inhibit or induce these enzymes and transporters may affect the plasma concentrations of silodosin and its active metabolite.

P-gp inhibitors, silodosin [2] ---> SmPC of [2] of EMA

Silodosin is a substrate for P-glycoprotein. Substances that inhibit or induce these enzymes and transporters may affect the plasma concentrations of silodosin and its active metabolite.

PDE5 inhibitors, silodosin [2] ---> SmPC of [2] of EMA

Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.

Phenytoin, silodosin [2] ---> SmPC of [2] of EMA

Pregnancy, silodosin [2] ---> SmPC of [2] of EMA

Not applicable as silodosin is intended for male patients only

Rifampicin, silodosin [2] ---> SmPC of [2] of EMA

Ritonavir, silodosin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Sildenafil, silodosin [2] ---> SmPC of [2] of EMA

Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.

Silodosin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase the plasma levels of silodosin. Concomitant use of silodosin with potent CYP3A4 inhibitors is not recommended

Silodosin [1], tadalafil ---> SmPC of [1] of EMA

Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.

Silodosin [1], UGT2B7 inductors ---> SmPC of [1] of EMA

Silodosin [1], UGT2B7 inhibitors ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Silodosin (Silodyx)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/silodyx-epar-product-information_en.pdf 14/03/2025

Other trade names: Silodosin Recordati, Urorec,

Siltuximab (Sylvant)

Breast-feeding, siltuximab [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or discontinue/abstain from siltuximab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Cyclosporine, siltuximab [2] ---> SmPC of [2] of EMA

Upon initation/discontinuation of siltuximab in patients treated with concomitant medicines CYP450 substrates and have a narrow therapeutic index, monitoring of the level of medicinal product (e.g., cyclosporine or theophylline) is recommended.

CYP450 enzymes, siltuximab [2] ---> SmPC of [2] of EMA

The effect of siltuximab on CYP450 enzyme activity can persist for several weeks after stopping therapy.

CYP450 substrates with narrow therapeutic index, siltuximab [2] ---> SmPC of [2] of EMA

Administering siltuximab with CYP450 substrates that have a narrow therapeutic index has the potential to change therapeutic effects and toxicity of these medicinal products due to alteration in the CYP450 pathways.

CYP450 substrates, siltuximab [2] ---> SmPC of [2] of EMA

Prescribers should exercise caution when siltuximab is co-administered with medicinal products that are CYP3A4 substrates where a decrease in effectiveness would be undesirable (e.g., oral contraceptives)

Cytochrome P450, siltuximab [2] ---> SmPC of [2] of EMA

In non-clinical studies, interleukin-6 (IL-6) is known to decrease the activity of cytochrome P450 (CYP450).

Fertility, siltuximab [2] ---> SmPC of [2] of EMA

Effects of siltuximab on fertility have not been evaluated in humans. Available non-clinical data do not suggest an effect on fertility under siltuximab treatment (see section 5.3).

Gastrointestinal perforation, siltuximab [2] ---> SmPC of [2] of EMA

Siltuximab should be used with caution in patients who may be at increased risk for GI perforation.

Hyperlipemia, siltuximab [2] ---> SmPC of [2] of EMA

Patients should be managed according to current clinical guidelines for management of hyperlipidaemia.

Infection, siltuximab [2] ---> SmPC of [2] of EMA

Consequently, infants born to women treated with siltuximab may be at increased risk of infection, and caution is advised in the administration of live vaccines to these infants (see section 4.4).

Interleukin-6, siltuximab [2] ---> SmPC of [2] of EMA

Binding bioactive IL-6 by siltuximab may result in increased metabolism of CYP450 substrates, because CYP450 enzyme activity will normalise.

Neoplasia, siltuximab [2] ---> SmPC of [2] of EMA

Immunomodulatory medicinal products may increase the risk of malignancy. On the basis of limited

Oral contraceptives, siltuximab [2] ---> SmPC of [2] of EMA

Pregnancy, siltuximab [2] ---> SmPC of [2] of EMA

Siltuximab should be given to a pregnant woman only if the benefit clearly outweighs the risk.

Siltuximab [1], theophylline ---> SmPC of [1] of EMA

Siltuximab [1], transaminases ---> SmPC of [1] of EMA

SYLVANT-treated patients with known hepatic impairment as well as patients with elevated transaminase or bilirubin levels should be monitored.

Siltuximab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Live, attenuated vaccines should not be given concurrently or within 4 weeks before initiating siltuximab as clinical safety has not been established.

Siltuximab [1], warfarin ---> SmPC of [1] of EMA

Upon initation or discontinuation of siltuximab in patients being treated with concomitant medicinal products that are CYP450 substrates and have a narrow therapeutic index, monitoring of the effect (e.g., warfarin) is recommended.

Siltuximab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during and up to 3 months after treatment (see section 4.5).

CONTRAINDICATIONS of Siltuximab (Sylvant)

- Severe hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/sylvant-epar-product-information_en.pdf 24/10/2025

Simeprevir (Olysio)

Abacavir, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Aluminium hydroxide, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Amiodarone, simeprevir [2] ---> SmPC of [2] of EMA

Treatment regimen with sofosbuvir: Use only if no other alternative is available. Close monitoring is recommended if this medicinal product is administered with OLYSIO in combination with sofosbuvir

Amiodarone, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of amiodarone. Mild increases in simeprevir concentrations may occur due to inhibition of CYP3A4 by amiodarone.

Amlodipine, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Amlodipine, CYP3A4 inhibitor, may increase the plasma levels of simeprevir

Amprenavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Amprenavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Antacids, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Astemizole, simeprevir [2] ---> SmPC of [2] of EMA

Astemizole has the potential for cardiac arrhythmias. Mild increases in concentrations of astemizole may be expected (intestinal CYP3A4 enzyme inhibition). It is not recommended to co-administer simeprevir with astemizole

Atazanavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Atazanavir/cobicistat [1], simeprevir ---> SmPC of [1] of EMA

EVOTAZ is expected to increase simeprevir plasma concentrations. Simeprevir may increase atazanavir and/or cobicistat plasma concentrations. The mechanism of interaction is CYP3A inhibition. It is not recommended to coadminister EVOTAZ with simeprevir.

Atazanavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Atorvastatin, simeprevir [2] ---> SmPC of [2] of EMA

The OATP1B1 transporter and/or CYP3A4 enzyme inhibition may increase the exposition to atorvastatin. Increased simeprevir concentrations may occur due to inhibition of OATP1B1 by atorvastatin.

Azithromycin, simeprevir [2] ---> SmPC of [2] of EMA

Based on the elimination pathway of azithromycin, no drug interactions are expected between azithromycin and simeprevir. No dose adjustment is required.

BCRP substrates, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir inhibits BCRP transporters. Co-administration of simeprevir with medicinal products that are substrates for BCRP transport may result in increased plasma concentrations of such medicinal products

Bedaquiline, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Bepridil, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Boceprevir, simeprevir [2] ---> SmPC of [2] of EMA

The HCV protease inhibitor is anticipated to be cross-resistant, and co-administration with simeprevir is not recommended

Boosted protease-inhibitors, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with any HIV PI, with or without ritonavir.

Breast-feeding, simeprevir [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from OLYSIO therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the mother.

Budesonide, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Bulevirtide [1], simeprevir ---> SmPC of [1] of EMA

In vitro an inhibition of OATP1B1/3 transporters by bulevirtide was observed, albeit only at a concentration ≥ 0.5 然. As a precautionary measure, close clinical monitoring is warranted when OATP1B1/3 substrates are co-administered.

Buprenorphine/naloxone, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Caffeine, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Calcium carbonate, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Carbamazepine, simeprevir [2] ---> SmPC of [2] of EMA

Co-administration of simeprevir with moderate or strong inductors of CYP3A4 may significantly reduce the plasma exposure of simeprevir and lead to loss of efficacy. Co-administration of simeprevir with these inductors is not recommended.

Cimetidine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Cisapride, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme inhibition by simeprevir may increase the concentrations of cisapride, which has the potential to cause cardiac arrhythmias.

Clarithromycin, simeprevir [2] ---> SmPC of [2] of EMA

Co-administration of simeprevir with moderate or strong inhibitors of CYP3A4 may significantly increase the plasma exposure of simeprevir. Co-administration of simeprevir with these inhibitors is not recommended.

Cobicistat, simeprevir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 enzyme inhibition can significantly increase plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with cobicistat-containing medicinal products.

Cyclosporine, simeprevir [2] ---> SmPC of [2] of EMA

OATP1B1, P-gp and CYP3A inhibition by ciclosporin may increase simeprevir exposition. It is not recommended to co-administer OLYSIO with ciclosporin.

Daclatasvir [1], simeprevir ---> SmPC of [1] of EMA

No dose adjustment is required

Darunavir/cobicistat [1], simeprevir ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat is expected to increase simeprevir plasma concentrations. Simeprevir may increase darunavir and/or cobicistat plasma concentrations. Co-administration is not recommended

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], simeprevir ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase simeprevir plasma concentrations. Simeprevir may increase darunavir and/or cobicistat plasma concentrations.

Darunavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 enzyme inhibition by may increase the exposition of active principles. It is not recommended to co-administer OLYSIO with darunavir/ritonavir.

Delavirdine, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction [etravirine or nevirapine] or inhibition [delavirdine] altered plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with delavirdine, etravirine or nevirapine.

Dexamethasone, simeprevir [2] ---> SmPC of [2] of EMA

The moderate CYP3A4 enzyme induction by dexamethasone may decrease the plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with systemic dexamethasone

Dexlansoprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Dextromethorphan, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Didanosine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Digoxin, simeprevir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp transporter. Concentrations of digoxin should be monitored and used for titration of digoxin dose to obtain the desired clinical effect.

Diltiazem, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Diltiazem, CYP3A4 inhibitor, may increase the plasma levels of simeprevir

Direct acting antivirals, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir should only be co-administered with other direct acting antiviral medicinal products if the benefits are considered to outweigh the risks based upon available data.

Disopyramide, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of this antiarrhythmic drug.

Dolutegravir, simeprevir [2] ---> SmPC of [2] of EMA

Not studied. No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Dolutegravir/rilpivirine [1], simeprevir ---> SmPC of [1] of EMA

No dose adjustment is required.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, simeprevir [2] ---> SmPC of [2] of EMA

Intestinal CYP3A4 enzyme inhibition. Caution is warranted when this medicinal product with narrow therapeutic index is co-administered with OLYSIO via the oral route.

Drugs primarily metabolised by CYP3A4, simeprevir [2] ---> SmPC of [2] of EMA

Co-administration of simeprevir with medicinal products that are primarily metabolised by CYP3A4 may result in increased plasma concentrations of such medicinal products

Efavirenz, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction by efavirenz may decrease the exposition of simeprevir. It is not recommended to co-administer OLYSIO with efavirenz as co-administration may result in loss of therapeutic effect of simeprevir.

Eltrombopag, simeprevir [2] ---> SmPC of [2] of EMA

Inhibitors of OATP1B1 may result in mild increases in simeprevir plasma concentrations.

Emtricitabine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], simeprevir ---> SmPC of [1] of EMA

No dose adjustment is required.

Erythromycin, simeprevir [2] ---> SmPC of [2] of EMA

The inhibition of CYP3A4 enzymes and P-gp transporter by both erythromycin and simeprevir may increase the exposition to both active principles. It is not recommended to co-administer simeprevir with clarithromycin or telithromycin.

Escitalopram, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Esomeprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Ethinyl estradiol, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Etravirine, simeprevir [2] ---> SmPC of [2] of EMA

Felodipine, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Fertility, simeprevir [2] ---> SmPC of [2] of EMA

There are no data on the effect of simeprevir on human fertility. No effects on fertility were observed in animal studies (see section 5.3).

Flecainide, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of this antiarrhythmic drug.

Fluconazole, simeprevir [2] ---> SmPC of [2] of EMA

Fluticasone, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Fluvastatin, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Foods, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir must be taken with food. The type of food does not affect exposure to simeprevir.

Fosamprenavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Fosamprenavir/ritonavir, simeprevir ---> SmPC of [fosamprenavir] of EMA

Coadministration with fosamprenavir/ritonavir is likely to lead to increased plasma exposures of simeprevir due to CYP3A4 enzyme inhibition. Not recommended

Gemfibrozil, simeprevir [2] ---> SmPC of [2] of EMA

Inhibitors of OATP1B1 may result in mild increases in simeprevir plasma concentrations.

H2 antagonists, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Indinavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Indinavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Itraconazol, simeprevir [2] ---> SmPC of [2] of EMA

Ketoconazole, simeprevir [2] ---> SmPC of [2] of EMA

Lamivudine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Lansoprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Ledipasvir, simeprevir [2] ---> SmPC of [2] of EMA

Concentrations of ledipasvir and simeprevir are increased when simeprevir is co-administered with ledipasvir. Co-administration is not recommended.

Ledipasvir/sofosbuvir [1], simeprevir ---> SmPC of [1] of EMA

Concentrations of ledipasvir, sofosbuvir and simeprevir are increased when simeprevir is co-administered with ledipasvir/sofosbuvir. Co-administration is not recommended.

Letermovir [1], simeprevir ---> SmPC of [1] of EMA

Co-administration of PREVYMIS with medicinal products that are inhibitors of OATP1B1/3 transporters may result in increased letermovir plasma concentrations.

Lopinavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Lopinavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Lovastatine, simeprevir [2] ---> SmPC of [2] of EMA

The OATP1B1 transporter and/or CYP3A4 enzyme inhibition may increase plasma concentrations of lovastatin

Magnesium hydroxide, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Maraviroc, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug drug-interaction is expected. No dose adjustment is required for either drug when OLYSIO is co-administered with maraviroc.

Methadone, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Methylphenidate, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Methylprednisolone, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Mexiletine, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of this antiarrhythmic drug.

Midazolam, simeprevir [2] ---> SmPC of [2] of EMA

Intestinal CYP3A4 enzyme inhibition. Caution is warranted when this medicinal product with narrow therapeutic index is co-administered with OLYSIO via the oral route.

Milk thistle, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme inhibition by milk thistle may increase the plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with milk thistle.

Moderate CYP3A4 inductors, simeprevir [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, simeprevir [2] ---> SmPC of [2] of EMA

Naloxone, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Nelfinavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Nelfinavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Nevirapine, simeprevir [2] ---> SmPC of [2] of EMA

Nicardipine, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Nifedipine, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Nisoldipine, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Nizatidine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Norethindrone, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

OATP1B1 inhibitors, simeprevir [2] ---> SmPC of [2] of EMA

Inhibitors of OATP1B1 may result in mild increases in simeprevir plasma concentrations.

OATP1B1 substrates, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir inhibits OATP1B1/3 transporters. Co-administration of simeprevir with medicinal products that are substrates for OATP1B1/3 transport may result in increased plasma concentrations of such medicinal products

Omeprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Oxcarbazepine, simeprevir [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir inhibits P-gp transporters. Co-administration of simeprevir with medicinal products that are substrates for P-gp transport may result in increased plasma concentrations of such medicinal products

Pantoprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

PDE5 inhibitors, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors.

Phenobarbital, simeprevir [2] ---> SmPC of [2] of EMA

Phenytoin, simeprevir [2] ---> SmPC of [2] of EMA

Pitavastatin, simeprevir [2] ---> SmPC of [2] of EMA

The OATP1B1/3 transporter inhibition may increase the plasma concentrations of pitavastatin

Posaconazole, simeprevir [2] ---> SmPC of [2] of EMA

Pravastatine, simeprevir [2] ---> SmPC of [2] of EMA

The OATP1B1/3 transporter inhibition may increase the plasma concentrations of pravastatin

Prednisone, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Pregnancy, simeprevir [2] ---> SmPC of [2] of EMA

OLYSIO should only be used during pregnancy or in women of childbearing potential if the benefit justifies the risk. Female patients of childbearing potential must use an effective form of contraception.

Propafenone, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of this antiarrhythmic drug.

Protease inhibitors, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with any HIV PI, with or without ritonavir.

Proton pump inhibitors, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Quinidine, simeprevir [2] ---> SmPC of [2] of EMA

Simeprevir, inhibitor of intestinal CYP3A4, may increase the plasma levels of this antiarrhythmic drug.

Rabeprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Raltegravir, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Ranitidine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required

Rifabutin, simeprevir [2] ---> SmPC of [2] of EMA

It is not recommended to co-administer simeprevir with rifabutin (CYP3A4 enzyme induction) as co-administration may result in loss of therapeutic effect of simeprevir.

Rifampicin, simeprevir [2] ---> SmPC of [2] of EMA

It is not recommended to co-administer simeprevir with rifampicin (CYP3A4 enzyme induction) as co-administration may result in loss of therapeutic effect of simeprevir.

Rifapentine, simeprevir [2] ---> SmPC of [2] of EMA

It is not recommended to co-administer simeprevir with rifapentine (CYP3A4 enzyme induction) as co-administration may result in loss of therapeutic effect of simeprevir.

Rilpivirine, simeprevir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The strong CYP3A4 enzyme inhibition by may increase the exposition of active principles. It is not recommended to co-administer OLYSIO with ritonavir.

Rosuvastatin, simeprevir [2] ---> SmPC of [2] of EMA

OATP1B1/3, BCRP transporter inhibition. Titrate the rosuvastatin dose carefully and use the lowest necessary dose while monitoring for safety when co-administered with OLYSIO.

Saquinavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Saquinavir/ritonavir, simeprevir [2] ---> SmPC of [2] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Sildenafil, simeprevir [2] ---> SmPC of [2] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors. Mild increases in simeprevir concentrations may occur due to mild inhibition of OATP1B1 by sildenafil.

Simeprevir [1], simvastatine ---> SmPC of [1] of EMA

The OATP1B1 transporter and/or CYP3A4 enzyme inhibition may increase the exposition to simvastatin.

Simeprevir [1], sirolimus ---> SmPC of [1] of EMA

Mild increased or decreased plasma concentrations of sirolimus may occur. Monitoring of blood concentrations of sirolimus is recommended.

Simeprevir [1], St. John's wort ---> SmPC of [1] of EMA

The CYP3A4 enzyme induction by St John's wort may decrease the plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with products containing St John's wort

Simeprevir [1], stavudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Simeprevir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Simeprevir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Simeprevir [1], sun ---> SmPC of [1] of EMA

Patients should be informed of the risk of photosensitivity reactions and on the importance of applying appropriate sun protective measures during treatment. Excess exposure to sun and use of tanning devices during treatment should be avoided.

Simeprevir [1], tacrolimus ---> SmPC of [1] of EMA

Increased simeprevir concentrations may occur due to inhibition of OATP1B1 by tacrolimus. No dose adjustment is required

Simeprevir [1], tadalafil ---> SmPC of [1] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors.

Simeprevir [1], telaprevir ---> SmPC of [1] of EMA

The HCV protease inhibitor is anticipated to be cross-resistant, and co-administration with simeprevir is not recommended

Simeprevir [1], telithromycin ---> SmPC of [1] of EMA

Simeprevir [1], tenofovir ---> SmPC of [1] of EMA

No dose adjustment is required.

Simeprevir [1], terfenadine ---> SmPC of [1] of EMA

Terfenadine has the potential for cardiac arrhythmias. Mild increases in concentrations of terfenadine may be expected (intestinal CYP3A4 enzyme inhibition). It is not recommended to co-administer simeprevir with terfenadine

Simeprevir [1], tipranavir ---> SmPC of [1] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Simeprevir [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Simeprevir [1], triazolam ---> SmPC of [1] of EMA

Intestinal CYP3A4 enzyme inhibition. Caution is warranted when this medicinal product with narrow therapeutic index is co-administered with OLYSIO via the oral route.

Simeprevir [1], vardenafil ---> SmPC of [1] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors.

Simeprevir [1], verapamil ---> SmPC of [1] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Verapamil, CYP3A4 inhibitor, may increase the plasma levels of simeprevir

Simeprevir [1], vitamin K antagonists ---> SmPC of [1] of EMA

As liver function may change during treatment with OLYSIO, close monitoring of International Normalised Ratio (INR) values is recommended.

Simeprevir [1], voriconazole ---> SmPC of [1] of EMA

Simeprevir [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment is required. However, it is recommended that the international normalised ratio (INR) be monitored.

Simeprevir [1], zidovudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Simeprevir, sofosbuvir [2] ---> SmPC of [2] of EMA

Cases of severe bradycardia and heart block have been observed when sofosbuvir is used in combination with another direct-acting antiviral (DAAs, including daclatasvir, simeprevir and ledipasvir) and concomitant amiodarone

CONTRAINDICATIONS of Simeprevir (Olysio)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/olysio-epar-product-information_en.pdf 23/05/2018 (withdrawn)

Simeticone

Breast-feeding, simeticone [2] ---> SmPC of [2] of eMC

Not applicable

Efavirenz [1], simeticone ---> SmPC of [1] of EMA

Co-administration of efavirenz with medicinal products that alter gastric pH would not be expected to affect efavirenz absorption.

Foods, simeticone

With or after each feed

Fosinopril [1], simeticone ---> SmPC of [1] of eMC

Antacids may impair absorption of fosinopril. Administration of fosinopril sodium and antacids should be separated by at least 2 hours.

Levothyroxine, simeticone [2] ---> SmPC of [2] of eMC

Levothyroxine may bind to simeticone. Absorption of levothyroxine may be impaired if simeticone is given concurrently to infants treated for thyroid disorders.

Nilotinib [1], simeticone ---> SmPC of [1] of EMA

If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of Tasigna.

Pregnancy, simeticone [2] ---> SmPC of [2] of eMC

Not applicable

Ribavirin [1], simeticone ---> SmPC of [1] of EMA

The bioavailability of ribavirin 600 mg was decreased by co-administration with an antacid containing magnesium aluminium and simethicone. This interaction is not considered to be clinically relevant.

CONTRAINDICATIONS of Simeticone

None stated

http://www.medicines.org.uk/emc/

Simoctocog alfa (Nuwiq)

Breast-feeding, simoctocog alfa [2] ---> SmPC of [2] of EMA

Nuwiq should be used during pregnancy and breast-feeding only if clearly indicated.

Fertility, simoctocog alfa [2] ---> SmPC of [2] of EMA

There are no fertility data available.

Pregnancy, simoctocog alfa [2] ---> SmPC of [2] of EMA

Nuwiq should be used during pregnancy and breast-feeding only if clearly indicated.

CONTRAINDICATIONS of Simoctocog alfa (Nuwiq)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/nuwiq-epar-product-information_en.pdf 07/11/2022

Other trade names: Vihuma,

Simvastatine

Ability to drive, simvastatine [2] ---> SmPC of [2] of eMC

When driving vehicles or operating machines, it should be taken into account that dizziness has been reported rarely in post-marketing experiences.

Acenocoumarol [1], simvastatine ---> SmPC of [1] of eMC

The co-administration may enhance the anticoagulant effect of acenocoumarol and increase the bleeding risk

Albiglutide [1], simvastatine ---> SmPC of [1] of EMA

Albiglutide showed no impact on the safety of simvastatin in clinical studies.

Alcohol, simvastatine [2] ---> SmPC of [2] of eMC

Simvastatin should be used with caution in patients who consume substantial quantities of alcohol.

Aliskiren/amlodipine [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone.

Aliskiren/amlodipine/hydrochlorothiazide [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone.

Alitretinoin [1], simvastatine ---> SmPC of [1] of eMC

A 16% reduction of simvastatin plasma levels was observed when co-administered with alitretinoin.

Allopurinol/lesinurad [1], simvastatine ---> SmPC of [1] of EMA

Additional monitoring of lipids is recommended in patients using sensitive CYP3A substrate lipid lowering medicinal products, since their efficacy may be reduced

Amiodarone, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of amiodarone with simvastatin. The dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant medication with amiodarone.

Amlodipine, simvastatine ---> SmPC of [aliskiren/amlodipine] of EMA

Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone.

Amlodipine/valsartan [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of multiple doses of amlodipine with simvastatin resulted in an increase in exposure to simvastatin compared to simvastatin alone. It is recommended to limit the dose of simvastatin to 20 mg daily in patients on amlodipine.

Amlodipine/valsartan/hydrochlorothiazide [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone.

Amprenavir [1], simvastatine ---> SmPC of [1] of EMA

Simvastatin is highly dependent on CYP3A4 for metabolism, thus concomitant use of amprenavir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis.

Amprenavir/ritonavir, simvastatine ---> SmPC of [amprenavir] of EMA

Simvastatin is highly dependent on CYP3A4 for metabolism, thus concomitant use of amprenavir with simvastatin is not recommended due to an increased risk of myopathy, including rhabdomyolysis.

Atazanavir [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of simvastatin or simvastatin with atazanavir is contraindicated due to an increased risk of myopathy including rhabdomyolysis.

Atazanavir/cobicistat [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of medicinal products that are substrates of CYP3A and have narrow therapeutic indexes and for which elevated plasma concentrations are associated with serious and/or life-threatening events are contraindicated with EVOTAZ.

Boceprevir/peginterferon alfa/ribavirin [1], simvastatine ---> SmPC of [1] of EMA

Bosentan [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of bosentan decreased the plasma concentrations of simvastatin (a CYP3A4 substrate) and its active beta-hydroxy acid metabolite

Breast-feeding, simvastatine [2] ---> SmPC of [2] of eMC

Because many medicinal products are excreted in human milk and because of the potential for serious adverse reactions, women taking simvastatine must not breast-feed their infants

Canagliflozin [1], simvastatine ---> SmPC of [1] of EMA

The increases in simvastatin and simvastatin acid exposures are not considered clinically relevant.

Canagliflozin/metformin [1], simvastatine ---> SmPC of [1] of EMA

The increases in simvastatin and simvastatin acid exposures are not considered clinically relevant.

Carbamazepine [1], simvastatine ---> SmPC of [1] of eMC

Carbamazepine may lower the plasma level of simvastatine

Cholestyramine, simvastatine

Concomitant administration decreased the bioavailability of statine. The statine should be taken 1 h before or 4 h after colestyramine

Cilostazol [1], simvastatine ---> SmPC of [1] of EMA

Caution is advised in case of co-administration of cilostazol (CYP3A4 inhibitor) with statins metabolised by CYP3A4

Clarithromycin, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of simvastatine and the risk of myopathy and rhabdomyolysis. The co-administration is contraindicated

Cobicistat [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products which are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated

Colchicine, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

There have been reports of myopathy and rhabdomyolysis with the concomitant administration of colchicine and simvastatin in patients with renal insufficiency.

Coumarin anticoagulants, simvastatine [2] ---> SmPC of [2] of eMC

In two clinical studies, one in normal volunteers and the other in hypercholesterolaemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants

Cyclosporine, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy/rhabdomyolysis is increased by concomitant administration of ciclosporin with simvastatin; therefore, use of simvastatin with ciclosporin is contraindicated

Cyclosporine, statins ---> SmPC of [simvastatine] of eMC

Although the mechanism is not fully understood, ciclosporin has been shown to increase the AUC of HMG-CoA reductase inhibitors. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4 and/or OATP1B1.

CYP2D6 inhibitors, simvastatine

The CYP2D6 inhibition may increase plasma concentrations of simvastatine, which has a narrow therapeutic index

CYP3A4 inhibitors, simvastatine

The CYP3A4 inhibition may increase the plasma concentrations of simvastatin

Cyproterone [1], simvastatine ---> SmPC of [1] of eMC

The risk of statin-associated myopathy or rhabdomyolysis may be increased when those statins which are mainly metabolised by CYP3A4 are co-administered with high therapeutic cyproterone doses, since they share the same metabolic pathway.

Dabrafenib [1], simvastatine ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Daclatasvir [1], simvastatine ---> SmPC of [1] of EMA

Inhibition of OATP 1B1 and/or BCRP by daclatasvir may increase plasma concentration of statin. Caution should be used when daclatasvir is coadministered with rosuvastatin or other substrates of OATP 1B1 or BCRP.

Danazol, ezetimibe/simvastatine ---> SmPC of [simvastatine] of eMC

The risk of myopathy/rhabdomyolysis is increased by concomitant administration of danazol with simvastatin; therefore, use of simvastatin with danazol is contraindicated

Danazol, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with simvastatin; therefore, use with danazol is contraindicated

Darunavir/cobicistat [1], simvastatine ---> SmPC of [1] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], simvastatine ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for serious and/or life-threatening adverse reactions

Darunavir/ritonavir, simvastatine ---> SmPC of [darunavir] of EMA

Dasabuvir with ombitasvir/paritaprevir/ritonavir, simvastatine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Dasatinib [1], simvastatine ---> SmPC of [1] of EMA

In a study in healthy subjects, a dose of dasatinib increased AUC and Cmax exposure to simvastatin, a known CYP3A4 substrate, by 20 and 37% respectively

Deferasirox [1], simvastatine ---> SmPC of [1] of EMA

Due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4

Diltiazem, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with simvastatin 80 mg. The dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant medication with diltiazem.

Dronedarone [1], simvastatine ---> SmPC of [1] of EMA

Dronedarone can increase exposure of statins that are substrates of CYP 3A4 and/or P-gp substrates or transported by OATP. Concomitant use of statins should be undertaken with caution.

Drugs primarily metabolised by CYP3A4, simvastatine [2] ---> SmPC of [2] of eMC

Simvastatin does not have an inhibitory effect on cytochrome P450 3A4. Therefore, simvastatin is not expected to affect plasma concentrations of substances metabolised via cytochrome P450 3A4.

Efavirenz [1], simvastatine ---> SmPC of [1] of EMA

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of statine. Cholesterol levels should be periodically monitored.

Efavirenz/emtricitabine/tenofovir disoproxil [1], simvastatine ---> SmPC of [1] of EMA

Cholesterol levels should be periodically monitored. Dosage adjustments of simvastatine may be required when co-administered with Atripla

Elbasvir/grazoprevir [1], simvastatine ---> SmPC of [1] of EMA

Primarily due to intestinal BCRP inhibition and CYP3A inhibition. The dose of fluvastatin, lovastatin, or simvastatin should not exceed a daily dose of 20 mg when co-administered with ZEPATIER.

Eltrombopag [1], simvastatine ---> SmPC of [1] of EMA

When co-administered with eltrombopag, a reduced dose of statins should be considered and careful monitoring for statin adverse reactions should be undertaken

Eluxadoline [1], simvastatine ---> SmPC of [1] of EMA

Eluxadoline increases the exposure of the co-administered OATP1B1 substrate; rosuvastatin by up to 40% of the total exposure which is usually not considered to be clinically relevant.

Eluxadoline [1], simvastatine ---> SmPC of [1] of EMA

The effect on other statins which are more sensitive OATP1B1 substrates (e.g. simvastatin and atorvastatin), however, may be more pronounced.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], simvastatine ---> SmPC of [1] of EMA

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], simvastatine ---> SmPC of [1] of EMA

Co-administration (contraindicated) of Stribild and simvastatine (primarily metabolised by CYP3A) may result in increased plasma concentrations of simvastatine, which are associated with the potential for serious and/or life-threatening reactions

Enzalutamide [1], simvastatine ---> SmPC of [1] of EMA

Enzalutamide, a strong inducer of CYP3A4, can affect the statins metabolized by CYP3A4

Erythromycin, simvastatine [2] ---> SmPC of [2] of eMC

Concomitant use of erythromycin with simvastatin is contraindicated due to the risk of myopathy and rhabdomyolysis. It is recommended that therapy with simvastatin is suspended during the course of treatment.

Eslicarbazepine [1], simvastatine ---> SmPC of [1] of EMA

Decreased systemic exposure to simvastatin. An increase of the simvastatin dose may be required

Etravirine [1], simvastatine ---> SmPC of [1] of EMA

Simvastatin is CYP3A4 substrate and co-administration with etravirine may result in lower plasma concentrations of the HMG Co-A reductase inhibitor. Dose adjustments for this HMG Co-A reductase inhibitor may be necessary.

Fenofibrate, simvastatine [2] ---> SmPC of [2] of eMC

Caution should be used when prescribing fenofibrate with simvastatin, as either agent can cause myopathy when given alone.

Fibrates, simvastatine [2] ---> SmPC of [2] of eMC

The risk of myopathy, including rhabdomyolysis, is increased during concomitant administration with fibrates.

Fluconazole, simvastatine [2] ---> SmPC of [2] of eMC

Rare cases of rhabdomyolysis associated with concomitant administration of simvastatin and fluconazole have been reported

Fosamprenavir/ritonavir, simvastatine ---> SmPC of [fosamprenavir] of EMA

Concomitant use of amprenavir with simvastatin is contraindicated because of increased plasma concentrations of simvastatin which can increase the risk of myopathy, including rhabdomyolysis

Gemfibrozil, simvastatine [2] ---> SmPC of [2] of eMC

Gemfibrozil increases the AUC of simvastatin acid by 1.9-fold, possibly due to inhibition of the glucuronidation pathway and/or OATP1B1. Concomitant administration with gemfibrozil is contraindicated.

Glecaprevir/pibrentasvir [1], simvastatine ---> SmPC of [1] of EMA

Co-administration with atorvastatin and simvastatin is contraindicated

Grapefruit juice, simvastatine [2] ---> SmPC of [2] of eMC

Grapefruit juice inhibits CYP3A4. Concomitant intake of large quantities (over 1 litre daily) of grapefruit juice and simvastatin resulted in a 7-fold increase in exposure to simvastatin acid. Intake of grapefruit juice should be avoided.

Idelalisib [1], simvastatine ---> SmPC of [1] of EMA

The co-administration of idelalisib with simvastatine may increase the serum concentrations of simvastatine. Idelalisib should not be co-administered with simvastatine.

Indinavir [1], simvastatine ---> SmPC of [1] of EMA

Indinavir inhibits CYP3A4 and as a result is expected to markedly increase the plasma levels of simvastatine, which are highly dependent on CYP3A4 metabolism. Combination contraindicated due to an increased risk of myopathy including rhabdomyolysis.

Indinavir/ritonavir, simvastatine ---> SmPC of [indinavir] of EMA

Interferon, simvastatine

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Itraconazol, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of simvastatine and the risk of myopathy and rhabdomyolysis. The co-administration is contraindicated

Ivabradine [1], simvastatine ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the HMG CoA reductase inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

Ketoconazole [1], simvastatine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with CYP3A4 metabolised HMG-CoA reductase inhibitors is contraindicated due to an increased risk of skeletal muscle toxicity including rhabdomyolysis

Laropiprant/nicotinic acid [1], simvastatine ---> SmPC of [1] of EMA

When simvastatin is combined with nicotinic acid, a modest increase in AUC and Cmax of simvastatin acid (the active form of simvastatin) was observed, which may be devoid of clinical relevance.

Leflunomide [1], simvastatine ---> SmPC of [1] of EMA

For substrates of OATP family, especially statins, concomitant administration with leflunomide should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products

Lercanidipine [1], simvastatine ---> SmPC of [1] of eMC

Increased plasma levels of simvastatin. No interaction is expected when lercanidipine is administered in the morning and simvastatin in the evening, as indicated for such drug.

Lesinurad [1], simvastatine ---> SmPC of [1] of EMA

Additional monitoring of lipids is recommended in patients using sensitive CYP3A substrate lipid lowering medicines (such as lovastatin or simvastatin), since their efficacy may be reduce

Letermovir [1], simvastatine ---> SmPC of [1] of EMA

Letermovir may substantially increase plasma concentrations of these statins. Concomitant use is not recommended with PREVYMIS alone. When PREVYMIS is co-administered with cyclosporine, use of these statins is contraindicated.

Linagliptin [1], simvastatine ---> SmPC of [1] of EMA

Multiple daily doses of linagliptin had a minimal effect on the steady-state pharmacokinetics of simvastatin, a sensitive CYP3A4 substrate, in healthy volunteers.

Linagliptin/metformin [1], simvastatine ---> SmPC of [1] of EMA

Multiple daily doses of linagliptin had a minimal effect on the steady-state pharmacokinetics of simvastatin, a sensitive CYP3A4 substrate, in healthy subjects.

Lomitapide [1], simvastatine ---> SmPC of [1] of EMA

Use of lomitapide is contraindicated in patients treated with high doses of simvastatin (> 40 mg)

Lopinavir/ritonavir [1], simvastatine ---> SmPC of [1] of EMA

Markedly increased plasma concentrations of simvastatine due to CYP3A inhibition by lopinavir/ritonavir. Since increased concentrations of statins may cause myopathy, including rhabdomyolysis, the combination is contraindicated

Miconazole, simvastatine

Miconazole, strong CYP3A4 inhibitor, is contraindicated with medicines that are mainly metabolised by CYP3A4 and also have small therapeutic index

Modafinil [1], simvastatine ---> SmPC of [1] of eMC

The CYP3A4 induction may decrease the plasma levels of simvastatin

Moderate CYP3A4 inhibitors, simvastatine [2] ---> SmPC of [2] of eMC

Patients taking other medicines having a moderate inhibitory effect on CYP3A4 concomitantly with simvastatin, particularly higher simvastatin doses, may have an increased risk of myopathy. A dose adjustment of simvastatin may be necessary.

Nefazodone, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of simvastatine and the risk of myopathy and rhabdomyolysis. The co-administration is contraindicated

Nelfinavir [1], simvastatine ---> SmPC of [1] of EMA

Coadministration of nelfinavir with simvastatin may result in significant increases in simvastatin plasma concentrations and is contraindicated product

Nevirapine, simvastatine

The strong CYP3A4 induction may decrease the plasma concentrations of simvastatin

Niacin, simvastatine [2] ---> SmPC of [2] of eMC

Rare cases of myopathy/rhabdomyolysis have been associated with simvastatin co-administered with lipid-modifying doses (≥ 1 g/day) of niacin

OATP1B1 inhibitors, simvastatine [2] ---> SmPC of [2] of eMC

Simvastatin acid is a substrate of OATP1B1. Concomitant administration of medicinal products that are inhibitors of the transport protein OATP1B1 may lead to increased plasma concentrations of simvastatin acid and an increased risk of myopathy

Olaparib [1], simvastatine ---> SmPC of [1] of EMA

Olaparib inhibits CYP3A4 in vitro and is predicted to be a mild CYP3A inhibitor in vivo. Therefore, caution should be exercised when sensitive CYP3A substrates or substrates with a narrow therapeutic margin are combined with olaparib.

Olmesartan medoxomil/amlodipine [1], simvastatine ---> SmPC of [1] of eMC

Co-administration of multiple doses of amlodipine with simvastatin resulted in increase in exposure to simvastatin compared to simvastatin alone.

Ombitasvir/paritaprevir/ritonavir [1], simvastatine ---> SmPC of [1] of EMA

Osimertinib [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of TAGRISSO with simvastatin (sensitive CYP3A4 substrate) decreased the AUC and Cmax of simvastatin by 9% and 23% respectively. These changes are small and not likely to be of clinical significance.

Padeliporfin [1], simvastatine ---> SmPC of [1] of EMA

The use of medicinal products that are substrates of OATP1B1 or OATP1B3 for which concentration-dependent serious adverse events have been observed should be avoided on the day of TOOKAD infusion and for at least 24 hours after administration.

Pazopanib [1], simvastatine ---> SmPC of [1] of EMA

Concomitant use of pazopanib and simvastatin increases the incidence of ALT elevations.

Phenprocoumon, simvastatine

The co-administration may enhance the anticoagulant effect and increase the bleeding risk

Phenytoin, simvastatine

Phenytoin, CYP3A4-inducer, may decrease the efficacy of the HMG-CoA reductase inhibitors which are CYP3A4 isoenzyme substrate (simvastatin)

Piperaquine/artenimol [1], simvastatine ---> SmPC of [1] of EMA

Piperaquine is metabolised by, and is an inhibitor of CYP3A4. Therefore, it has the potential to increase plasma concentrations of other substrates for this enzyme with the risk of increased toxicity.

Posaconazole [1], simvastatine ---> SmPC of [1] of EMA

Posaconazole may substantially increase plasma levels of statins metabolised by CYP3A4. Treatment with these statins should be discontinued during treatment with posaconazole as increased levels have been associated with rhabdomyolysis

Pregnancy, simvastatine [2] ---> SmPC of [2] of eMC

Simvastatin is contraindicated during pregnancy.

Protease inhibitors, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of simvastatine and the risk of myopathy and rhabdomyolysis. The co-administration is contraindicated

Ranolazine [1], simvastatine ---> SmPC of [1] of EMA

Simvastatin metabolism and clearance are highly dependent on CYP3A4. Ranolazine increased simvastatin plasma levels by about 2 fold. Cases of rhabdomyolysis have been observed in patients receiving ranolazine and simvastatin, in postmarketing experience.

Repaglinide [1], simvastatine ---> SmPC of [1] of EMA

Co-administration of cimetidine, nifedipine, oestrogen, or simvastatin with repaglinide, all CYP3A4 substrates, did not significantly alter the pharmacokinetic parameters of repaglinide.

Ribociclib [1], simvastatine ---> SmPC of [1] of EMA

Concomitant administration of ribociclib at the 600 mg dose this CYP3A4 substrates should be avoided

Rifampicin, simvastatine ---> SmPC of [fenofibrate/simvastatin] of EMA

Because rifampicin is a potent CYP 3A4 inducer that interferes with simvastatin metabolism, patients undertaking long-term rifampicin therapy may experience loss of efficacy of simvastatin.

Ritonavir [1], simvastatine ---> SmPC of [1] of EMA

Since increased concentrations of lovastatin and simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of these medicinal products with ritonavir is contraindicated

Sacubitril/valsartan [1], simvastatine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction was observed when simvastatin and Entresto were co-administered.

Saquinavir [1], simvastatine ---> SmPC of [1] of EMA

Concomitant use of saquinavir with simvastatine is contraindicated due to increased risk of myopathy including rhabdomyolysis

Saquinavir/ritonavir, simvastatine ---> SmPC of [saquinavir] of EMA

Simeprevir [1], simvastatine ---> SmPC of [1] of EMA

The OATP1B1 transporter and/or CYP3A4 enzyme inhibition may increase the exposition to simvastatin.

Simvastatine [1], verapamil ---> SmPC of [1] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of verapamil with simvastatin 40 mg or 80 mg. The dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant medication with verapamil.

Simvastatine, sitagliptin [2] ---> SmPC of [2] of EMA

In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives

Simvastatine, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of statine. St. John's Wort should be avoided

Simvastatine, stiripentol [2] ---> SmPC of [2] of EMA

Decreased hepatic metabolism of statine and increased risk of dose-dependent adverse reactions such as rhabdomyolysis. Undesirable combination (to be avoided unless strictly necessary)

Simvastatine, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma concentrations of simvastatin

Simvastatine, strong CYP3A4 inhibitors ---> SmPC of [fenofibrate/simvastatin] of EMA

The strong CYP3A4 inhibition may increase the plasma concentrations of simvastatine and the risk of myopathy and rhabdomyolysis. The co-administration is contraindicated

Simvastatine, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Data from clinical studies have shown that Velphoro does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin).

Simvastatine, telaprevir [2] ---> SmPC of [2] of EMA

Concomitant administration of telaprevir is contraindicated with active substances that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.

Simvastatine, telithromycin [2] ---> SmPC of [2] of EMA

Concomitant administration with simvastatin, atorvastatin, or lovastatin is contraindicated. Treatment with these agents should be interrupted during telithromycin treatment

Simvastatine, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Co-administration of multiple doses of amlodipine with simvastatin 80 mg resulted in an increase in exposure to simvastatin up to 77 %compared to simvastatin alone.

Simvastatine, telotristat ethyl [2] ---> SmPC of [2] of EMA

Concomitant use of Xermelo may decrease the efficacy of medicinal products that are CYP3A4 substrates (e.g. midazolam, everolimus, sunitinib, simvastatin, ethinyloestradiol, amlodipine, cyclosporine_) by decreasing their systemic exposure

Simvastatine, temsirolimus [2] ---> SmPC of [2] of EMA

It is possible that combined administration of temsirolimus with other amphiphilic agents such as amiodarone or statins could result in an increased risk of amphiphilic pulmonary toxicity.

Simvastatine, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, OATP inhibitor, may increase the AUC of OATP substrate. The co-administration should be undertaken with caution

Simvastatine, ticagrelor [2] ---> SmPC of [2] of EMA

Co-administration of ticagrelor with doses of simvastatin exceeding 40 mg daily could cause adverse effects of simvastatin and should be weighed against potential benefits

Simvastatine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Simvastatine, tocilizumab [2] ---> SmPC of [2] of EMA

In a study in RA patients, levels of simvastatin (CYP3A4) were decreased by 57% one week following a single dose of tocilizumab

Simvastatine, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Increase in serum exposure (and the myopathy and rhabdomyolysis risk) has been reported for simvastatin when concomitantly administered with verapamil. The dose of simvastatin (and other statins also metabolised by CYP3A4) should be adapted accordingly.

Simvastatine, troglitazone

Troglitazone, CYP3A4 inductor, may decrease the plasma concentrations of simvastatine

Simvastatine, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Drug-drug interaction studies in healthy subjects were conducted with amlodipine, ramipril, valsartan and simvastatin. No clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Simvastatine, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Simvastatine, vitamin K antagonists ---> SmPC of [fenofibrate/simvastatin] of EMA

Simvastatin enhances effects of Vitamin K antagonists and may increase the risk of bleeding.

Simvastatine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of statins that are metabolised by CYP3A4 and could lead to rhabdomyolysis.

Simvastatine, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

CONTRAINDICATIONS of Simvastatine

- Hypersensitivity to simvastatin or to any of the excipients listed in section 6.1

- Active liver disease or unexplained persistent elevations of serum transaminases

- Concomitant administration of potent CYP3A4 inhibitors (agents that increase AUC approximately 5 fold or greater) (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and medicinal products containing cobicistat)

- Concomitant administration of gemfibrozil, ciclosporin, or danazol

- In patients with HoFH, concomitant administration of lomitapide with doses > 40 mg Zocor

http://www.medicines.org.uk/emc/

Sipavibart (Kavigale)

Breast-feeding, sipavibart [2] ---> SmPC of [2] of EMA

In humans, excretion of IgG antibodies in milk occurs during the first few days after birth, decreasing to low concentrations soon afterwards.

Cytochrome P450, sipavibart [2] ---> SmPC of [2] of EMA

Sipavibart is not expected to be renally excreted or metabolised by cytochrome P450 enzymes (see section 5.2).

Fertility, sipavibart [2] ---> SmPC of [2] of EMA

There are no data on the effects of sipavibart on human fertility.

Pregnancy, sipavibart [2] ---> SmPC of [2] of EMA

Sipavibart should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the foetus.

CONTRAINDICATIONS of Sipavibart (Kavigale)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/kavigale-epar-product-information_en.pdf 17/10/2025

Siponimod (Mayzent)

Ability to drive, siponimod [2] ---> SmPC of [2] of EMA

Dizziness may occasionally occur when initiating therapy with siponimod. Therefore, patients should not drive or use machines during the first day of treatment initiation with siponimod

Alemtuzumab, siponimod [2] ---> SmPC of [2] of EMA

Due to the characteristics and duration of alemtuzumab immune suppressive effects described in its product information, initiating treatment with siponimod after alemtuzumab is not recommended.

Amiodarone, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Antineoplastics, siponimod [2] ---> SmPC of [2] of EMA

Caution should be exercised during concomitant administration due to the risk of additive immune effects during such therapy and in the weeks after administration of any of these medicinal products is stopped

Betablockers, siponimod [2] ---> SmPC of [2] of EMA

Caution should be exercised when siponimod is initiated in patients receiving beta blockers due to the additive effects on lowering heart rate

Bradycardia-inducing calcium-channel blockers, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Breast-feeding, siponimod [2] ---> SmPC of [2] of EMA

Siponimod should not be used during breast-feeding.

Carbamazepine, siponimod [2] ---> SmPC of [2] of EMA

Siponimod may be combined with most types of CYP2C9 and CYP3A4 inducers. Because of an expected reduction in siponimod exposure, the appropriateness and possible benefit of the treatment

Class IA antiarrhythmic agents, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Class III antiarrhythmic agents, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Digoxin, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Diltiazem, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Drugs inducing bradycardia, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Fertility [1], siponimod ---> SmPC of [1] of EMA

The effect of siponimod on human fertility has not been evaluated. Siponimod had no effect on male reproductive organs in rats and monkeys or on fertility parameters in rats.

Fluconazole, siponimod [2] ---> SmPC of [2] of EMA

In CYP2C9*2*2 patients, a 2.7-fold increase in the AUC of siponimod is expected in the presence of moderate CYP2C9/CYP3A4 inhibitors.

Immunomodulatory agents, siponimod [2] ---> SmPC of [2] of EMA

Immunosuppressives, siponimod [2] ---> SmPC of [2] of EMA

Ivabradine, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Modafinil, siponimod [2] ---> SmPC of [2] of EMA

Siponimod may be combined with most types of CYP2C9 and CYP3A4 inducers. Because of an expected reduction in siponimod exposure, the appropriateness and possible benefit of the treatment

Oral contraceptives, siponimod [2] ---> SmPC of [2] of EMA

An effect of siponimod on the efficacy of oral contraceptives is not expected.

Pregnancy, siponimod [2] ---> SmPC of [2] of EMA

If a woman becomes pregnant while on treatment, siponimod must be discontinued. Medical advice should be given regarding the risk of harmful effects to the foetus associated with treatment and ultrasonography examinations should be performed.

Pregnancy, siponimod [2] ---> SmPC of [2] of EMA

Consequently, siponimod is contraindicated during pregnancy (see section 4.3). Siponimod should be stopped at least 10 days before a pregnancy is planned (see section 4.4).

Procainamide, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Propranolol, siponimod [2] ---> SmPC of [2] of EMA

The negative chronotropic effect of co-administration of siponimod and propranolol was evaluated in a dedicated pharmacodynamic/safety study.

QT-prolonging medicinal products with known arrhythmogenic properties, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Quinidine, siponimod [2] ---> SmPC of [2] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Rifampicin, siponimod [2] ---> SmPC of [2] of EMA

The co-administration of siponimod 2 mg daily in the presence of 600 mg daily doses of rifampin (strong CYP3A4 and moderate CYP2C9 inducer) decreased siponimod AUCtau,ss and Cmax,ss by 57% and 45%, respectively, in CY2C9*1*1 subjects.

Siponimod [1], sotalol ---> SmPC of [1] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Siponimod [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

The use of live attenuated vaccines may carry the risk of infection and should therefore be avoided during siponimod treatment and for up to 4 weeks after treatment (see section 4.4).

Siponimod [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of these substances during treatment initiation may be associated with severe bradycardia and heart block.

Siponimod [1], women of childbearing potential ---> SmPC of [1] of EMA

Due to risk for the foetus, siponimod is contraindicated during pregnancy and in women of childbearing potential not using effective contraception.

CONTRAINDICATIONS of Siponimod (Mayzent)

- Hypersensitivity to the active substance, or to peanut, soya or any of the excipients listed in section 6.1.

- Immunodeficiency syndrome.

- History of progressive multifocal leukoencephalopathy or cryptococcal meningitis.

- Active malignancies.

- Severe liver impairment (Child-Pugh class C).

- Patients who in the previous 6 months had a myocardial infarction (MI), unstable angina pectoris, stroke/transient ischaemic attack (TIA), decompensated heart failure (requiring inpatient treatment), or New York Heart Association (NYHA) class III/IV heart failure (see section 4.4).

- Patients with a history of second-degree Mobitz type II atrioventricular (AV) block, third-degree AV block, sino-atrial heart block or sick-sinus syndrome, if they do not wear a pacemaker (see section 4.4).

- Patients homozygous for CYP2C9*3 (CYP2C9*3*3) genotype (poor metaboliser).

- During pregnancy and in women of childbearing potential not using effective contraception (see sections 4.4 and 4.6).

https://www.ema.europa.eu/en/documents/product-information/mayzent-epar-product-information_en.pdf. 08/01/2024

Sirolimus (Rapamune)

Ability to drive, sirolimus [2] ---> SmPC of [2] of EMA

Rapamune has no known influence on the ability to drive and use machines. No studies on the effects on the ability to drive and use machines have been performed.

Absorption and elimination, sirolimus [2] ---> SmPC of [2] of EMA

Therefore, absorption and the subsequent elimination of sirolimus may be influenced by substances that affect these proteins.

ACE inhibitors, sirolimus [2] ---> SmPC of [2] of EMA

The co-administration of sirolimus and ACE inhibitors has resulted in angioneurotic oedema-type reactions. Increased rates of biopsy confirmed acute rejection (BCAR) have been observed with concomitant use of sirolimus with ACE inhibitors

Aciclovir, sirolimus [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic interaction was observed

Adagrasib [1], sirolimus ---> SmPC of [1] of EMA

Adagrasib is a strong CYP3A4 inhibitor. Co-administration of medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated

Alectinib [1], sirolimus ---> SmPC of [1] of EMA

When Alecensa is co-administered with P-gp substrates (e.g., digoxin, dabigatran etexilate, topotecan, sirolimus, everolimus, nilotinib and lapatinib), appropriate monitoring is recommended.

Aprepitant [1], sirolimus ---> SmPC of [1] of EMA

Caution is advised during concomitant administration of aprepitant and orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range

Atazanavir [1], sirolimus ---> SmPC of [1] of EMA

Concentrations of the immunosuppressant may be increased when co-administered with REYATAZ due to CYP3A4 inhibition.

Atazanavir/cobicistat [1], sirolimus ---> SmPC of [1] of EMA

Concentrations of the immunosuppressant may be increased when co-administered with EVOTAZ. The mechanism of interaction is inhibition of CYP3A4 by atazanavir and cobicistat.

Atorvastatin, sirolimus [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic interaction was observed

Avacopan [1], sirolimus ---> SmPC of [1] of EMA

Avacopan is a weak inhibitor of CYP3A4 in vivo and may increase the plasma exposures of concomitant medicinal products that are CYP3A4 substrates with a narrow therapeutic index

Bexarotene [1], sirolimus ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4 substrates having a narrow therapeutic margin

Boceprevir, sirolimus [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition by boceprevir increases the sirolimus plasma levels. The combination requires significant dose reduction and prolongation of the dosing interval for tacrolimus

Bosentan [1], sirolimus ---> SmPC of [1] of EMA

The co-administration may increase the bosentan plasma concentrations and decrease the levels of sirolimus. The coadministration is not recommended

Breast-feeding, sirolimus [2] ---> SmPC of [2] of EMA

It is unknown whether sirolimus is excreted in human milk. Because of the potential for adverse reactions in breast-fed infants from sirolimus, breast-feeding should be discontinued during treatment with Rapamune.

Brigatinib [1], sirolimus ---> SmPC of [1] of EMA

Coadministration of Alunbrig with CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, fentanyl, quinidine, cyclosporine, sirolimus, tacrolimus) should be avoided as their effectiveness may be reduced.

Bromocriptine, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Bulevirtide [1], sirolimus ---> SmPC of [1] of EMA

As a precautionary measure, close clinical monitoring is warranted for co-administered narrow-therapeutic-index drugs which are sensitive CYP3A4 substrates

Calcineurin inhibitors, sirolimus [2] ---> SmPC of [2] of EMA

The concomitant use of sirolimus with a calcineurin inhibitor may increase the risk of calcineurin inhibitor-induced haemolytic uraemic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy (HUS/TTP/TMA)

Cannabidiol, mTOR inhibitors ---> SmPC of [sirolimus] of EMA

Co-administration of cannabidiol with another orally administered mTOR inhibitor in a healthy volunteer study led to an increase in exposure to the mTOR inhibitor, due to inhibition of intestinal P-gp efflux by cannabidiol.

Cannabidiol, sirolimus [2] ---> SmPC of [2] of EMA

Increases in exposure of other orally administered sensitive P-gp substrates (e.g., sirolimus, tacrolimus, digoxin) may occur on coadministration with cannabidiol.

Carbamazepine, sirolimus [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 may increase the metabolism of sirolimus and decrease sirolimus blood levels

Carboplatin, sirolimus

The co-administration of carboplatin with sirolimus may cause an excessive immunosuppression with risk of lymphoproliferation

Ceritinib [1], sirolimus ---> SmPC of [1] of EMA

Co-administration of ceritinib with substrates primarily metabolised by CYP3A or CYP3A substrates known to have narrow therapeutic indices should be avoided

Chenodeoxycholic acid [1], sirolimus ---> SmPC of [1] of EMA

If administration of ciclosporin or sirolimus is considered necessary, serum and urine bile alcohol levels should be closely monitored and the chenodeoxycholic acid dose adjusted accordingly.

Cimetidine, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Cisapride, sirolimus [2] ---> SmPC of [2] of EMA

Pharmacokinetic interactions may be observed with gastrointestinal prokinetic agents, such as cisapride and metoclopramide.

Clarithromycin, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Clotrimazole, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Cobicistat [1], sirolimus ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of immunosuppressive

Crizotinib [1], sirolimus ---> SmPC of [1] of EMA

Coadministration of crizotinib (moderate inhibitor of CYP3A) with CYP3A substrates with narrow therapeutic indices should be avoided. If the combination is needed, then close clinical monitoring should be exercised.

Cyclosporine, sirolimus [2] ---> SmPC of [2] of EMA

Significant increase in the rate and extent of absorption of sirolimus. It is recommended that sirolimus be administered 4 hours after ciclosporin

Cyclosporine/mycophenolate mofetil, sirolimus

Decreased exposition to mycophenolic acid

CYP3A4 inductors, sirolimus [2] ---> SmPC of [2] of EMA

Inductors of CYP3A4 increase the metabolism of sirolimus and decrease sirolimus levels.

CYP3A4 inhibitors, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 decrease the metabolism of sirolimus and increase sirolimus levels.

Dabrafenib [1], sirolimus ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Daclatasvir [1], sirolimus ---> SmPC of [1] of EMA

No dose adjustment of either medicinal product is required when daclatasvir is coadministered with sirolimus

Danazol, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Darunavir/cobicistat [1], sirolimus ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the immunosuppressant plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sirolimus ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these immunosuppressant plasma concentrations. CYP3A inhibition.

Darunavir/ritonavir, sirolimus ---> SmPC of [darunavir] of EMA

Exposure to the immunosuppressant will be increased when co-administered with boosted darunavir. (CYP3A inhibition)

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sirolimus ---> SmPC of [dasabuvir] of EMA

Concomitant use of sirolimus with dasabuvir + ombitasvir/paritaprevir/ ritonavir is not recommended unless the benefits outweigh the risks (see section 4.4).

Dexibuprofen, sirolimus

Concomitant administration of sirolimus with NSAIDs may increase the risk of nephrotoxicity on account of reduced synthesis of prostaglandins in the kidney. During combination treatment renal function must be closely monitored

Digoxin, sirolimus [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic interaction was observed

Diltiazem, sirolimus [2] ---> SmPC of [2] of EMA

Rapamune oral solution and 120 mg of diltiazem significantly affected the bioavailability of sirolimus. If diltiazem is administered, sirolimus blood levels should be monitored and a dose adjustment may be necessary.

Doravirine [1], sirolimus ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Doravirine/lamivudine/tenofovir disoproxil [1], sirolimus ---> SmPC of [1] of EMA

Caution should be used when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that also have a narrow therapeutic window (e.g., tacrolimus and sirolimus)

Dronedarone [1], sirolimus ---> SmPC of [1] of EMA

Dronedarone could increase the sirolimus plasma levels. Monitoring of the plasma concentrations and appropriate dose adjustment is recommended in case of combination

Duvelisib [1], sirolimus ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Efavirenz [1], sirolimus ---> SmPC of [1] of EMA

Decreased exposure of the immunosuppressant may be expected (CYP3A4 induction). This immunosuppressant is not anticipated to affect exposure of efavirenz.

Elranatamab [1], sirolimus ---> SmPC of [1] of EMA

During this time period, toxicity or medicinal product concentrations should be monitored in patients who are receiving concomitant sensitive CYP substrates with a narrow therapeutic index (e.g., cyclosporine, phenytoin, sirolimus, and warfarin).

Eluxadoline [1], sirolimus ---> SmPC of [1] of EMA

Loss of efficacy can occur, especially when medicinal products with low dose and narrow therapeutic index (e.g. alfentanil, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), are co-administered with Eluxadoline.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], sirolimus ---> SmPC of [1] of EMA

Concentrations of this immunosuppressant agent may be increased when administered with cobicistat. Therapeutic monitoring is recommended upon co-administration with Genvoya.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], sirolimus ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of immunosuppressive

Entrectinib [1], sirolimus ---> SmPC of [1] of EMA

Caution is advised when entrectinib is administered together with sensitive CYP3A4 substrates with a narrow therapeutic range, due to the increased risk of adverse drug reactions.

Eribulin [1], sirolimus ---> SmPC of [1] of EMA

Caution and monitoring for adverse effects is recommended with concomitant use of substances that have a narrow therapeutic window and that are eliminated mainly via CYP3A4-mediated metabolism

Erythromycin, sirolimus [2] ---> SmPC of [2] of EMA

Multiple-dose administration of erythromycin and sirolimus oral solution significantly increased the rate and extent of absorption of both medicinal products. Appropriate dose reductions of both medicinal products should be considered.

Ethinyl estradiol, sirolimus [2] ---> SmPC of [2] of EMA

The results of a single-dose interaction study cannot exclude the possibility of changes in the pharmacokinetics that might affect the efficacy of the oral contraceptive during long-term treatment with sirolimus.

Etravirine [1], sirolimus ---> SmPC of [1] of EMA

Etravirine may decrease the plasma concentrations of sirolimus

Fertility, sirolimus [2] ---> SmPC of [2] of EMA

Impairments of sperm parameters have been observed among some patients treated with Rapamune. These effects have been reversible upon discontinuation of Rapamune in most cases (see section 5.3).

Fibrates, sirolimus [2] ---> SmPC of [2] of EMA

Patients administered an HMG-CoA reductase inhibitor and/or fibrate should be monitored for the possible development of rhabdomyolysis and other adverse reactions, as described in the respective Summary of Product Characteristics of these agents.

Fluconazole, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Fosaprepitant [1], sirolimus ---> SmPC of [1] of EMA

Caution is advised during co-administration of fosaprepitant and orally administered active principles metabolised primarily through CYP3A4 and with a narrow therapeutic range

Glibenclamide, sirolimus

No clinically significant pharmacokinetic interaction was observed

Grapefruit juice, sirolimus [2] ---> SmPC of [2] of EMA

Grapefruit juice affects CYP3A4-mediated metabolism, and should therefore be avoided.

Ibrutinib [1], sirolimus ---> SmPC of [1] of EMA

Caution should be exercised if co-administering ibrutinib with CYP3A4 substrates administered orally with narrow therapeutic range (such as dihydroergotamine, ergotamine, fentanyl, cyclosporine, sirolimus and tacrolimus).

Idebenone [1], sirolimus ---> SmPC of [1] of EMA

CYP3A4 substrates known to have a narrow therapeutic index should be administered with caution in patients receiving idebenone.

Idelalisib [1], sirolimus ---> SmPC of [1] of EMA

The co-administration of idelalisib with sirolimus may increase the serum concentrations of sirolimus. Therapeutic monitoring is recommended.

Imatinib [1], sirolimus ---> SmPC of [1] of EMA

Imatinib inhibits CYP3A4 and may increase plasma concentration of other CYP3A4 metabolised drugs. Caution is recommended when administering imatinib with CYP3A4 substrates with a narrow therapeutic window

Indinavir, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Indinavir/ritonavir, sirolimus ---> SmPC of [indinavir] of EMA

Iptacopan [1], sirolimus ---> SmPC of [1] of EMA

Caution should be exercised if co-administration of iptacopan with sensitive CYP3A4 substrates is required, especially for those with a narrow therapeutic index

Isavuconazole [1], sirolimus ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Ciclosporin, sirolimus, tacrolimus: monitoring of plasma levels and appropriate dose adjustment if required. No CRESEMBA dose adjustment

Itraconazol, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Ivacaftor [1], sirolimus ---> SmPC of [1] of EMA

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index, such as ciclosporin, everolimus, sirolimus or tacrolimus, caution and appropriate monitoring should be used.

Ivacaftor/tezacaftor/elexacaftor [1], sirolimus ---> SmPC of [1] of EMA

When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index such as ciclosporin, everolimus, sirolimus, and tacrolimus, caution and appropriate monitoring should be used.

Ivosidenib [1], sirolimus ---> SmPC of [1] of EMA

Patients should be monitored for loss of substrate efficacy (substrate with a narrow therapeutic index) if use of such medicinal products cannot be avoided (see section 5.2).

Ketoconazole [2], sirolimus ---> SmPC of [2] of EMA

The coadministration the everolimus or sirolimus (also known as rapamycin) with ketoconazole is contraindicated due to an increase of the plasma concentrations of these medicinal products;

Ketoconazole, sirolimus [2] ---> SmPC of [2] of EMA

Multiple-dose ketoconazole administration significantly affected the rate and extent of absorption and sirolimus exposure from Rapamune oral solution. Co-administration of sirolimus and ketoconazole is not recommended (see section 4.4).

Larotrectinib [1], sirolimus ---> SmPC of [1] of EMA

Exercise caution with concomitant use of CYP3A substrates with narrow therapeutic range (e.g. alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, or tacrolimus) in patients taking VITRAKVI.

Letermovir [1], sirolimus ---> SmPC of [1] of EMA

Co-administration of PREVYMIS may result in clinically relevant increases in the plasma concentrations of co-administered CYP3A substrates

Lomitapide [1], sirolimus ---> SmPC of [1] of EMA

Coadministration of Lojuxta with P gp may increase the absorption of P gp substrates. Dose reduction of the P gp substrate should be considered when used concomitantly with Lojuxta.

Lopinavir/ritonavir [1], sirolimus ---> SmPC of [1] of EMA

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of sirolimus. Monitoring is recommended

Lorlatinib [1], sirolimus ---> SmPC of [1] of EMA

Concurrent administration of lorlatinib with CYP3A4/5 substrates with narrow therapeutic indices, should be avoided since the concentration of these medicinal products may be reduced by lorlatinib

Lumacaftor/ivacaftor [1], sirolimus ---> SmPC of [1] of EMA

Concomitant use of lumacaftor/ivacaftor with this immunosuppressant is not recommended. Lumacaftor/ivacaftor will decrease the exposure of the immunosuppressant, which may reduce the efficacy of the immunosuppressant.

Maribavir [1], sirolimus ---> SmPC of [1] of EMA

Frequently monitor cyclosporine, everolimus and sirolimus levels, especially following initiation and after discontinuation of maribavir and adjust dose, as needed.

Meropenem/vaborbactam [1], sirolimus ---> SmPC of [1] of EMA

When coadministering Vaborem with medicinal products that are predominantly metabolised by CYP3A4, there could be a potential risk of interaction which may result in decreased plasma levels of the co-administered medicinal product.

Methylprednisolone, sirolimus [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic interaction was observed between sirolimus and methylprednisolone

Methylthioninium chloride [1], sirolimus ---> SmPC of [1] of EMA

These interactions could have a clinical relevance with narrow therapeutic index medicinal products that are metabolised by one of these enzymes

Metoclopramide, sirolimus [2] ---> SmPC of [2] of EMA

Pharmacokinetic interactions may be observed with gastrointestinal prokinetic agents, such as cisapride and metoclopramide.

Micafungin [1], sirolimus ---> SmPC of [1] of EMA

Patients receiving sirolimus in combination with micafungin should be monitored for sirolimus toxicity and the sirolimus dosage should be reduced if necessary

Mitapivat [1], sirolimus ---> SmPC of [1] of EMA

If co-administration of Pyrukynd with sensitive CYP3A4 substrates is unavoidable, patients should be carefully monitored especially for those substrates with a narrow therapeutic index

Moderate CYP3A4 inhibitors, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 decrease the metabolism of sirolimus and increase sirolimus levels.

Mycophenolate mofetil [1], sirolimus ---> SmPC of [1] of EMA

The risk/benefit ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not been established

Mycophenolate [1], sirolimus ---> SmPC of [1] of EMA

In renal transplant patients, concomitant administration of mycophenolate mofetil and CsA resulted in reduced MPA exposures by 30-50% compared with patients receiving the combination of sirolimus and similar doses of mycophenolate

Neratinib [1], sirolimus ---> SmPC of [1] of EMA

This might be clinically relevant for patients who are treated concomitantly with therapeutic agents with a narrow therapeutic window whose absorption involves P-gp transporters in the gastrointestinal tract

Netupitant/palonosetron [1], sirolimus ---> SmPC of [1] of EMA

Netupitant/palonosetron should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range

Nicardipine, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Nifedipine, sirolimus [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic interaction was observed

Nilotinib [1], sirolimus ---> SmPC of [1] of EMA

Nilotinib is a moderate CYP3A4 inhibitor. Appropriate monitoring and dose adjustment may be necessary for drugs that are CYP3A4 substrates and have a narrow therapeutic index when co-administered with nilotinib.

NSAID, sirolimus ---> SmPC of [dexibuprofen] of eMC

Olaparib [1], sirolimus ---> SmPC of [1] of EMA

Oral contraceptives, sirolimus [2] ---> SmPC of [2] of EMA

P-glycoprotein and CYP3A4 inhibitors, sirolimus

The P-glycoprotein and CYP3A4 inhibition may increase the plasma concentrations of sirolimus (small therapeutic range)

P-gp inhibitors, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of P-gp may decrease the efflux of sirolimus from intestinal cells and increase sirolimus levels.

Palbociclib [1], sirolimus ---> SmPC of [1] of EMA

The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced when coadministered with IBRANCE as IBRANCE may increase their exposure.

Pharmacokinetics, sirolimus [2] ---> SmPC of [2] of EMA

No clinically significant pharmacokinetic interaction was observed between sirolimus and any of the following substances: acyclovir, atorvastatin, digoxin, glibenclamide, methylprednisolone, nifedipine, prednisolone, and trimethoprim/sulfamethoxazole.

Phenobarbital, sirolimus [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 may increase the metabolism of sirolimus and decrease sirolimus blood levels

Phenytoin, sirolimus [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 may increase the metabolism of sirolimus and decrease sirolimus blood levels

Posaconazole [1], sirolimus ---> SmPC of [1] of EMA

Coadministration of posaconazole with sirolimus is not recommended and should be avoided whenever possible.

Prednisolone, sirolimus

No clinically significant pharmacokinetic interaction was observed

Pregnancy, sirolimus [2] ---> SmPC of [2] of EMA

Rapamune should not be used during pregnancy unless clearly necessary. Effective contraception must be used during Rapamune therapy and for 12 weeks after Rapamune has been stopped.

Prokinetics, sirolimus [2] ---> SmPC of [2] of EMA

Pharmacokinetic interactions may be observed with gastrointestinal prokinetic agents, such as cisapride and metoclopramide.

Protease inhibitors, sirolimus

The CYP3A4 inhibition may increase the plasma concentrations of sirolimus

Ranolazine [1], sirolimus ---> SmPC of [1] of EMA

Dose adjustment of CYP3A4 substrates with a narrow therapeutic range may be required as ranolazine may increase plasma concentrations of these drugs.

Ribociclib [1], sirolimus ---> SmPC of [1] of EMA

Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index (see section 4.4). The dose of a sensitive CYP3A4 substrate with a narrow therapeutic index

Rifabutin, sirolimus [2] ---> SmPC of [2] of EMA

Inductors of CYP3A4 increase the metabolism of sirolimus and decrease sirolimus levels. Co-administration of sirolimus with strong inductors of CYP3A4 is not recommended

Rifampicin, sirolimus [2] ---> SmPC of [2] of EMA

Rifampicin increased the clearance of sirolimus by approximately 5.5-fold and decreased AUC and Cmax by approximately 82% and 71%, respectively. Co-administration of sirolimus and rifampicin is not recommended (see section 4.4).

Ritlecitinib [1], sirolimus ---> SmPC of [1] of EMA

Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered.

Ritonavir [1], sirolimus ---> SmPC of [1] of EMA

Ritonavir, CYP3A4 inhibitor, may increase the plasma concentrations of sirolimus. More frequent monitoring is recommended

Rucaparib [1], sirolimus ---> SmPC of [1] of EMA

Caution is advised when co-administering medicinal products that CYP3A substrates with a narrow therapeutic index. Dose adjustments may be considered, if clinically indicated based on observed adverse reactions.

Saquinavir/ritonavir, sirolimus ---> SmPC of [saquinavir] of EMA

Careful therapeutic drug monitoring is necessary for immunosuppressants when co-administered with saquinavir/ritonavir.

Simeprevir [1], sirolimus ---> SmPC of [1] of EMA

Mild increased or decreased plasma concentrations of sirolimus may occur. Monitoring of blood concentrations of sirolimus is recommended.

Sirolimus [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of CYP3A4 may increase the metabolism of sirolimus and decrease sirolimus blood levels

Sirolimus [1], statins ---> SmPC of [1] of EMA

Sirolimus [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Inductors of CYP3A4 increase the metabolism of sirolimus and decrease sirolimus levels. Co-administration of sirolimus with strong inductors of CYP3A4 is not recommended

Sirolimus [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Inhibitors of CYP3A4 decrease the metabolism of sirolimus and increase sirolimus levels. Co-administration of sirolimus with strong inhibitors of CYP3A4 is not recommended

Sirolimus [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Inhibitors of P-gp may decrease the efflux of sirolimus from intestinal cells and increase sirolimus levels.

Sirolimus [1], telaprevir ---> SmPC of [1] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Sirolimus [1], telithromycin ---> SmPC of [1] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Sirolimus [1], troleandomycin ---> SmPC of [1] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Sirolimus [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Immunosuppressants may affect response to vaccination. During treatment with immunosuppressants, vaccination may be less effective. The use of live vaccines should be avoided during treatment with sirolimus.

Sirolimus [1], verapamil ---> SmPC of [1] of EMA

Sirolimus [1], women of childbearing potential ---> SmPC of [1] of EMA

Effective contraception must be used during Rapamune therapy and for 12 weeks after Rapamune has been stopped (see section 4.5).

Sirolimus, sotorasib [2] ---> SmPC of [2] of EMA

Avoid co-administration of LUMYKRAS with CYP3A4 substrates with narrow therapeutic indices. If co-administration cannot be avoided, adjust the CYP3A4 substrate dose in accordance with the current summary of product characteristics.

Sirolimus, stiripentol [2] ---> SmPC of [2] of EMA

Raised blood levels of immunosuppressant (decreased hepatic metabolism). The combination is to be avoided unless strictly necessary

Sirolimus, tabelecleucel [2] ---> SmPC of [2] of EMA

In clinical studies, patients received ciclosporin, tacrolimus, sirolimus and other immunosuppressive therapies at the lowest dose considered clinically safe and appropriate.

Sirolimus, tacrolimus [2] ---> SmPC of [2] of EMA

Co-administration of tacrolimus with a mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, everolimus) may increase the risk of thrombotic microangiopathy (including haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura)

Sirolimus, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of mTOR inhibitors.

Sirolimus, tepotinib [2] ---> SmPC of [2] of EMA

Caution and monitoring for adverse reactions of other P-gp-dependent substances with a narrow therapeutic index (e.g. digoxin, aliskiren, everolimus, sirolimus) is recommended during co-administration with TEPMETKO.

Sirolimus, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

Concentrations of sirolimus cannot be predicted when co-administered with tipranavir/ritonavir. More frequent concentration monitoring of these medicinal products is recommended

Sirolimus, trandolapril

Increased risk of angioedema.

Sirolimus, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of sirolimus thus increasing risk of toxicity

Sirolimus, trimethoprim/sulfamethoxazol

No clinically significant pharmacokinetic interaction was observed

Sirolimus, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

Sirolimus, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Sirolimus, venetoclax [2] ---> SmPC of [2] of EMA

Venetoclax is a P-gp, BCRP and OATP1B1 inhibitor in vitro. Co-administration of narrow therapeutic index P-gp, or BCRP substrates (e.g., digoxin, dabigatran, everolimus, sirolimus) with Venclyxto should be avoided.

Sirolimus, voriconazole [2] ---> SmPC of [2] of EMA

Co-administration of sirolimus (2 mg single dose) with multiple-dose administration of oral voriconazole in healthy subjects increases sirolimus Cmax and AUC by an average of 7-fold and 11-fold, respectively. Co-administration is not recommended

Sirolimus, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of voxelotor with sensitive CYP3A4 substrates with a narrow therapeutic index should be avoided. If concomitant use is unavoidable, consider dose reduction of the sensitive CYP3A4 substrate(s).

Sirolimus, zanubrutinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are metabolised by CYP3A should be used with caution, as zanubrutinib may decrease the plasma exposures of these medicinal products.

CONTRAINDICATIONS of Sirolimus (Rapamune)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Rapamune oral solution contains soya oil. Patients allergic to peanut or soya must not take this medicine.

https://www.ema.europa.eu/en/documents/product-information/rapamune-epar-product-information_en.pdf 01/10/2024

Other trade names: Hyftor,

Sitagliptin (Ristaben)

Ability to drive, sitagliptin [2] ---> SmPC of [2] of EMA

When driving or using machines, it should be taken into account that dizziness and somnolence have been reported.

ACE inhibitors, sitagliptin ---> SmPC of [perindopril] of eMC

Increased risk of angio-oedema, due to dipeptidyl peptidase IV (DPP-IV) decreased activity by the gliptin, in patients co-treated with an ACE inhibitor.

Aliskiren/hydrochlorothiazide [1], sitagliptin ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Breast-feeding, sitagliptin [2] ---> SmPC of [2] of EMA

It is unknown whether sitagliptin is excreted in human breast milk. Animal studies have shown excretion of sitagliptin in breast milk. Ristaben should not be used during breast-feeding.

Cabozantinib [1], sitagliptin ---> SmPC of [1] of EMA

Capmatinib [1], sitagliptin ---> SmPC of [1] of EMA

Caution should be exercised during co-administration of Tabrecta with P-gp (digoxin, dabigatran etexilate, colchicine, sitagliptin, saxagliptin and posaconazole)

Cenobamate [1], sitagliptin ---> SmPC of [1] of EMA

In vitro studies have shown that cenobamate inhibits OAT3. Therefore, concomitant administration of cenobamate and medicinal products transported by OAT3 may result in higher exposure of these medicinal products.

Clarithromycin, sitagliptin [2] ---> SmPC of [2] of EMA

It is possible that potent CYP3A4 inhibitors (i.e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Cyclosporine, sitagliptin [2] ---> SmPC of [2] of EMA

Meaningful interactions would not be expected with p-glycoprotein inhibitors.

CYP450 substrates, sitagliptin [2] ---> SmPC of [2] of EMA

In vitro data suggest that sitagliptin does not inhibit nor induce CYP450 isoenzymes.

Dapagliflozin [1], sitagliptin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Dapagliflozin/metformin [1], sitagliptin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy subjects, using mainly a single-dose design, suggest that the pharmacokinetics of dapagliflozin are not altered

Digoxin, sitagliptin [2] ---> SmPC of [2] of EMA

However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly.

Digoxin, sitagliptin [2] ---> SmPC of [2] of EMA

Sitagliptin had a small effect on plasma digoxin concentrations. No dose adjustment of digoxin is recommended.

Doravirine [1], sitagliptin ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], sitagliptin ---> SmPC of [1] of EMA

No dose adjustment is required.

Dulaglutide [1], sitagliptin ---> SmPC of [1] of EMA

Dulaglutide coadministration with sitagliptin increased dulaglutide exposure and Cmax by approximately 38 %and 27 %. The increased exposure may enhance the effects of dulaglutide on blood glucose levels.

Empagliflozin [1], sitagliptin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics

Empagliflozin/metformin [1], sitagliptin ---> SmPC of [1] of EMA

Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics

Fertility, sitagliptin [2] ---> SmPC of [2] of EMA

Animal data do not suggest an effect of treatment with sitagliptin on male and female fertility. Human data are lacking.

Glyburide, sitagliptin [2] ---> SmPC of [2] of EMA

In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT).

Itraconazol, sitagliptin [2] ---> SmPC of [2] of EMA

Ketoconazole, sitagliptin [2] ---> SmPC of [2] of EMA

Lomitapide [1], sitagliptin ---> SmPC of [1] of EMA

Coadministration of Lojuxta with P gp may increase the absorption of P gp substrates. Dose reduction of the P gp substrate should be considered when used concomitantly with Lojuxta.

Metformin, sitagliptin [2] ---> SmPC of [2] of EMA

Co-administration of multiple twice-daily doses of 1,000 mg metformin with 50 mg sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes.

Oral contraceptives, sitagliptin [2] ---> SmPC of [2] of EMA

P-gp inhibitors, sitagliptin [2] ---> SmPC of [2] of EMA

Meaningful interactions would not be expected with p-glycoprotein inhibitors.

Perindopril [1], sitagliptin ---> SmPC of [1] of eMC

Increased risk of angio-oedema, due to dipeptidyl peptidase IV (DPP-IV) decreased activity by the gliptin, in patients co-treated with an ACE inhibitor.

Pregnancy, sitagliptin [2] ---> SmPC of [2] of EMA

Due to lack of human data, Ristaben should not be used during pregnancy.

Probenecide, sitagliptin [2] ---> SmPC of [2] of EMA

OAT3 mediated transport of sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low.

Ritonavir, sitagliptin [2] ---> SmPC of [2] of EMA

Rosiglitazone, sitagliptin [2] ---> SmPC of [2] of EMA

Simvastatine, sitagliptin [2] ---> SmPC of [2] of EMA

Sitagliptin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Sitagliptin [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Meaningful interactions would not be expected with p-glycoprotein inhibitors.

Sitagliptin, somatropin

May antagonize the hypoglycemic effect

Sitagliptin, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat may increase the AUC of OAT3 substrates when co-administered. Monitor for signs of excessive effects of the co-administered OAT3 substrates such as famotidine, furosemide, methotrexate, olmesartan, sitagliptin, and zidovudine.

Sitagliptin, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Sitagliptin, warfarin [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Sitagliptin (Ristaben)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/ristaben-epar-product-information_en.pdf 30/10/2025

Other trade names:Januvia, Sitagliptin Accord, Sitagliptin SUN, Tesavel, Xelevia,

Sitagliptin/metformin (Efficib)

Ability to drive, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

It should be taken into account that dizziness and somnolence have been reported with sitagliptin. In addition, patients should be alerted to the risk of hypoglycaemia when Efficib is used in combination with a sulphonylurea or with insulin.

ACE inhibitors, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

ACE-inhibitors may decrease the blood-glucose levels. If necessary, the dose of the anti-hyperglycaemic medicinal product should be adjusted during therapy with the other medicinal product and on its discontinuation.

AIIRA, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

There is increased risk of lactic acidosis in acute alcohol intoxication due to the metformin active substance of Efficib. Consumption of alcohol and medicinal products containing alcohol should be avoided

Alcohol, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in cases of fasting, malnutrition or hepatic impairment. Consumption of alcohol and medicinal products containing alcohol should be avoided

Beta2-adrenergic agonists, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Glucocorticoids (given by systemic and local routes) beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood glucose monitoring performed

Breast-feeding, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Metformin is excreted in human milk in small amounts. It is not known whether sitagliptin is excreted in human milk. Efficib must therefore not be used in women who are breast-feeding (see section 4.3).

Cimetidine, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin and may increase the risk for lactic acidosis.

Clarithromycin, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

For this reason, it is possible that potent CYP3A4 inhibitors (i.e., ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the pharmacokinetics of sitagliptin in patients with severe renal impairment or ESRD.

Coxibs, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Cyclosporine, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

The renal clearance of sitagliptin was not meaningfully altered. Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.

CYP450, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

In vitro data suggest that sitagliptin does not inhibit nor induce CYP450 isoenzymes.

Cytochrome P450, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives

Digoxin, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Sitagliptin had a small effect on plasma digoxin concentrations. Patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly

Diuretics, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Dolutegravir, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Fertility, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Animal data do not suggest an effect of treatment with sitagliptin on male and female fertility. Human data are lacking.

Glucocorticoids, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Iodinated contrast media, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Efficib must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable. Concomitant use not recommended

Itraconazol, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Ketoconazole, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Loop diuretics, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

MATE inhibitors, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

NSAID, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Organic cationic transporter-2, sitagliptin/metformin

Close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when such products are co-administered.

Organic cationic transporter-2, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

P-gp inhibitors, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

The renal clearance of sitagliptin was not meaningfully altered. Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.

Pregnancy, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Efficib should not be used during pregnancy. If a patient wishes to become pregnant or if a pregnancy occurs, treatment should be discontinued and the patient switched to insulin treatment as soon as possible.

Probenecide, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

OAT3 mediated transport of sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low. Concomitant administration of OAT3 inhibitors has not been evaluated in vivo.

Ranolazine, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Ritonavir, sitagliptin/metformin [2] ---> SmPC of [2] of EMA

Sitagliptin/metformin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Sitagliptin/metformin [1], vandetanib ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Sitagliptin/metformin (Efficib)

Efficib is contraindicated in patients with:

- hypersensitivity to the active substances or to any of the excipients listed in section 6.1

- diabetic ketoacidosis, diabetic pre-coma;

- moderate and severe renal impairment (creatinine clearance < 60 mL/min)

- acute conditions with the potential to alter renal function such as:

- dehydration,

- severe infection,

- shock,

- intravascular administration of iodinated contrast agents

- acute or chronic disease which may cause tissue hypoxia such as:

- cardiac or respiratory failure,

- recent myocardial infarction,

- shock;

- hepatic impairment;

- acute alcohol intoxication, alcoholism;

- breast-feeding.

https://www.ema.europa.eu/en/documents/product-information/efficib-epar-product-information_en.pdf 28/05/2025

Other trade names: Janumet, Ristfor, Sitagliptin/Metformin hydrochloride Accord, Sitagliptin/Metformin hydrochloride Mylan, Sitagliptin / Metformin hydrochloride Sun, Velmetia,

Sitaxentan (Thelin)

Ability to drive, sitaxentan [2] ---> SmPC of [2] of EMA

A known undesirable effect is dizziness, which could influence the ability to drive or use machines.

Acenocoumarol, sitaxentan [2] ---> SmPC of [2] of EMA

It is expected that an increase in anticoagulant effect will be seen with warfarin analogues

Atorvastatin, sitaxentan [2] ---> SmPC of [2] of EMA

The extent of interaction with other OATP inhibitors (except cyclosporine) is unknown but could result in raised plasma levels of sitaxentan.

Breast-feeding, sitaxentan [2] ---> SmPC of [2] of EMA

Women should not breastfeed while using Thelin.

Cyclosporine, sitaxentan [2] ---> SmPC of [2] of EMA

Co-administration with ciclosporin A, a potent OATP inhibitor, resulted in a 6-fold increase in Cmin and a 67% increase in AUC of sitaxentan therefore the use of sitaxentan in patients receiving systemic ciclosporin A is contraindicated

Drugs primarily metabolised by CYP2C9, sitaxentan [2] ---> SmPC of [2] of EMA

Sitaxentan, CYP2C9 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by CYP2C9

Ethinyl estradiol, sitaxentan [2] ---> SmPC of [2] of EMA

Sitaxentan, CYP3A4 inhibitor, increases exposition of ethinylestradiol

Fluconazole, sitaxentan [2] ---> SmPC of [2] of EMA

Co-administration of sitaxentan and fluconazole had no effect on the clearance of sitaxentan sodium.

Fluindione, sitaxentan [2] ---> SmPC of [2] of EMA

It is expected that an increase in anticoagulant effect will be seen with warfarin analogues

Nelfinavir, sitaxentan [2] ---> SmPC of [2] of EMA

Clinical interaction studies with nelfinavir, a moderately potent OATP inhibitor, did not result in clinically significant changes in sitaxentan plasma levels.

Nifedipine, sitaxentan [2] ---> SmPC of [2] of EMA

The clearance of nifedipine was not clinically significantly changed when given concomitantly with sitaxentan. This was tested for low-dose nifedipine only. Therefore, at higher doses of nifedipine, an increase in exposure cannot be excluded.

Norethindrone, sitaxentan [2] ---> SmPC of [2] of EMA

Sitaxentan, CYP3A4 inhibitor, increases exposition of norethindrone

Omeprazole, sitaxentan [2] ---> SmPC of [2] of EMA

Concomitant administration of sitaxentan with omeprazole increased the omeprazole AUC0-24 by 30%; Cmax was unchanged. The change in AUC was not considered clinically significant.

Oral contraceptives, sitaxentan [2] ---> SmPC of [2] of EMA

Sitaxentan sodium did not affect the anti-ovulatory activity of the oral contraceptive as assessed by the plasma concentrations of follicle stimulating hormone (FSH), luteinising hormone (LH), and progesterone

Phenprocoumon, sitaxentan [2] ---> SmPC of [2] of EMA

It is expected that an increase in anticoagulant effect will be seen with warfarin analogues

Pravastatine, sitaxentan [2] ---> SmPC of [2] of EMA

Clinical interaction studies with pravastatin, a low affinity OATP inhibitor, did not result in clinically significant changes in sitaxentan plasma levels.

Pregnancy, sitaxentan [2] ---> SmPC of [2] of EMA

Thelin should not be used during pregnancy unless clearly needed

Rifamicyn, sitaxentan [2] ---> SmPC of [2] of EMA

The extent of interaction with other OATP inhibitors (except cyclosporine) is unknown but could result in raised plasma levels of sitaxentan.

Ritonavir, sitaxentan [2] ---> SmPC of [2] of EMA

The extent of interaction with other OATP inhibitors (except cyclosporine) is unknown but could result in raised plasma levels of sitaxentan.

Sildenafil, sitaxentan [2] ---> SmPC of [2] of EMA

The increasing in sildenafil plasma concentrations were not considered clinically significant. Interaction with sildenafil may be serious if hypotension occurs beyond a safe level.

Sitaxentan [1], strong OATP inhibitors ---> SmPC of [1] of EMA

The extent of interaction with other OATP inhibitors (except cyclosporine) is unknown but could result in raised plasma levels of sitaxentan.

Sitaxentan [1], vitamin K antagonists ---> SmPC of [1] of EMA

It is expected that an increase in anticoagulant effect will be seen with warfarin analogues

Sitaxentan [1], warfarin ---> SmPC of [1] of EMA

Concomitant treatment with sitaxentan sodium resulted in a 2.4 fold increase in S-warfarin exposure.

CONTRAINDICATIONS of Sitaxentan (Thelin)

- Hypersensitivity to the active substance or to any of the excipients.

- Mild to severe hepatic impairment (Child-Pugh Class A-C).

- Elevated aminotransferases prior to initiation of treatment (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x ULN).

- Elevated direct bilirubin > 2 x ULN prior to initiation of treatment.

- Concomitant administration with ciclosporin A

- Lactation

https://www.ema.europa.eu/en/documents/product-information/thelin-epar-product-information_en.pdf 02/03/2011 (withdrawn)

Sodium cromoglycate

Breast-feeding, sodium cromoglycate [2] ---> SmPC of [2] of eMC

It should only be used in lactation where there is a clear need.

Pregnancy, sodium cromoglycate [2] ---> SmPC of [2] of eMC

It should only be used in pregnancy where there is a clear need.

CONTRAINDICATIONS of Sodium cromoglycate

Hypersensitivity to the active substance or to any of the excipients

http://www.medicines.org.uk/emc/

Sodium fluoride

Algeldrate/magnesium hydroxide, sodium fluoride

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium hydroxide, sodium fluoride

The co-administration of antacids containing aluminium with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium oxide/magnesium hydroxide, sodium fluoride

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium, sodium fluoride

Decreased absorption of sodium fluoride. It is recommended to administer the two substances at least 3 hours apart.

Antacids, sodium fluoride

Decreased absorption of sodium fluoride. It is recommended to administer the two substances at least 3 hours apart.

Breast-feeding, sodium fluoride

Use of this product is not contraindicated during lactation.

Calcium carbonate [1], sodium fluoride ---> SmPC of [1] of eMC

Calcium salts may reduce the absorption of sodium fluoride. It is advisable to allow a minimum period of 4 hours before taking the calcium.

Calcium carbonate/cholecalciferol [1], sodium fluoride ---> SmPC of [1] of eMC

Calcium salts may reduce the absorption of sodium fluoride. It is advisable to allow a minimum period of 4 hours before taking the calcium.

Calcium, sodium fluoride [2] ---> SmPC of [2] of eMC

Calcium salts may reduce the absorption of sodium fluoride. It is advisable to allow a minimum period of 4 hours before taking the calcium.

Hydrotalcite, sodium fluoride

The co-administration of hydrotalcite with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 1-2 hours

Magnesium, sodium fluoride

Decreased absorption of sodium fluoride. It is recommended to administer the two substances at least 3 hours apart.

Milk, sodium fluoride

Decreased absorption of sodium fluoride. It is recommended to administer the two substances at least 3 hours apart.

Pregnancy, sodium fluoride

Use of this product is not contraindicated during pregnancy.

Sodium heparin

ACE inhibitors, sodium heparin [2] ---> SmPC of [2] of eMC

Combined use of heparin with ACE inhibitors or angiotensin II antagonists may increase the risk of hyperkalaemia.

AIIRA, heparin ---> SmPC of [sodium heparin] of eMC

Combined use of heparin with ACE inhibitors or angiotensin II antagonists may increase the risk of hyperkalaemia.

AIIRA, sodium heparin [2] ---> SmPC of [2] of eMC

Combined use of heparin with ACE inhibitors or angiotensin II antagonists may increase the risk of hyperkalaemia.

Anticoagulants, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Anticoagulants, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Antihistamines, sodium heparin

Possible decrease of anticoagulant effect of heparin

Benzodiazepines, heparin ---> SmPC of [sodium heparin] of eMC

Heparin may increase the effect of benzodiazepines

Benzodiazepines, sodium heparin

Heparin may increase the effect of benzodiazepines

Breast-feeding, sodium heparin [2] ---> SmPC of [2] of eMC

Heparin is not excreted in breast milk.

Cefamandol, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system.

Cefamandol, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Cefoperazone, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system.

Cefoperazone, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Corticosteroids, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system.

Dextran, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Dextran, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Digital glycosides, sodium heparin

Possible decrease of anticoagulant effect of heparin

Epoprostenol, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Epoprostenol, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Fibrinolytics, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Fibrinolytics, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Glucocorticoids, heparin ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Glucocorticoids, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

GP IIb/IIIa inhibitors, heparin ---> SmPC of [sodium heparin] of eMC

It is considered unsafe to take NSAIDs in combination with anticoagulants due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Heparin calcium, NSAID ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Heparin, hyperkalemia ---> SmPC of [sodium heparin] of eMC

Medicinal products that increase potassium plasma concentrations, like heparine, should only be used under especially careful medical supervision

Heparin, NSAID ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Heparin, oral anticoagulants ---> SmPC of [sodium heparin] of eMC

It is considered unsafe to take NSAIDs in combination with anticoagulants due to increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Heparin, oral antidiabetics ---> SmPC of [sodium heparin] of eMC

Heparin may increase the effect of oral antidiabetic agents

Heparin, platelet aggregation inhibitors ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system.

Heparin, potassium chloride ---> SmPC of [sodium heparin] of eMC

Medicinal products that increase potassium plasma concentrations, like heparine, should only be used under especially careful medical supervision

Heparin, propranolol ---> SmPC of [sodium heparin] of eMC

Enhanced propranolol effect due to displacement from protein binding sites

Heparin, salicylates ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Heparin, thrombolytics ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Heparin, vitamin K antagonists ---> SmPC of [sodium heparin] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Hyperkalemia, sodium heparin

Medicinal products that increase potassium plasma concentrations, like heparine, should only be used under especially careful medical supervision

Mineralocorticoids, sodium heparin

The co-administration may cause a mutual enhancement of the anticoagulant effect

Nitroglycerine, sodium heparin

The anticoagulant effect of heparin may decrease in patients treated with iv nitroglycerin

NSAID, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Oral antidiabetics, sodium heparin

Heparin may increase the effect of oral antidiabetic agents

Oritavancin [1], sodium heparin ---> SmPC of [1] of EMA

Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours after oritavancin administration

Platelet aggregation inhibitors, sodium heparin [2] ---> SmPC of [2] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Pregnancy, sodium heparin [2] ---> SmPC of [2] of eMC

Because of the known haemorrhagic effect, heparin should be used with caution in pregnant women and only if the benefits outweigh the risks according to the physician's judgement.

Propranolol, sodium heparin

Enhanced propranolol effect due to displacement from protein binding sites

Protamine, sodium heparin

The i.v. injection of protamine abolish fast the heparin effect

Sodium heparin [1], sulfonylureas ---> SmPC of [1] of eMC

Heparin may increase the effect of oral antidiabetic agents

Sodium heparin [1], thrombolytics ---> SmPC of [1] of eMC

The anticoagulant effect of heparin may be enhanced by concomitant medication with other drugs affecting platelet function or the coagulation system

Sodium heparin, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Medicinal products that may increase potassium levels or induce hyperkalaemia: Concomitant use of the these medicinal products may lead to increases in serum potassium and is, therefore, not recommended

Sodium heparin, tetracyclines

Possible decrease of anticoagulant effect of heparin

CONTRAINDICATIONS of Sodium heparin

- Known hypersensitivity to constituents.

- Current or history of heparin-induced thrombocytopenia.

- Generalised or local haemorrhagic tendency, including uncontrolled severe hypertension, severe liver insufficiency, active peptic ulcer, acute or subacute septic endocarditis, intracranial haemorrhage or injuries and operations on the central nervous system, eyes and ears, and in women with abortus imminens.

- Heparin (Mucous) Injection contains 10 mg/ml of the preservative benzyl alcohol. This formulation must not be given to premature babies or neonates

- An epidural anaesthesia during birth in pregnant women treated with heparin is contraindicated

- In patients receiving heparin for treatment rather than prophylaxis, locoregional anaesthesia in elective surgical procedures is contra-indicated because the use of heparin may be very rarely associated with epidural or spinal haematoma resulting in prolonged or permanent paralysis.

http://www.medicines.org.uk/emc/

Sodium oxybate (Xyrem)

Ability to drive, sodium oxybate [2] ---> SmPC of [2] of EMA

For at least 6 hours after taking sodium oxybate, patients must not undertake activities requiring complete mental alertness or motor co-ordination

Alcohol, sodium oxybate [2] ---> SmPC of [2] of EMA

The combined use of alcohol with sodium oxybate may result in potentiation of the central nervous system-depressant effects of sodium oxybate. Patients should be warned against the use of any alcoholic beverages in conjunction with sodium oxybate.

Antidepressants, sodium oxybate [2] ---> SmPC of [2] of EMA

Antidepressants have been used in the treatment of cataplexy. A possible additive effect of antidepressants and sodium oxybate cannot be excluded.

Benzodiazepines, sodium oxybate [2] ---> SmPC of [2] of EMA

Given the possibility of increasing the risk of respiratory depression, the concomitant use of benzodiazepines and sodium oxybate should be avoided.

Breast-feeding, sodium oxybate [2] ---> SmPC of [2] of EMA

Sodium Oxybate should not be used during breastfeeding.

CNS depressants, sodium oxybate [2] ---> SmPC of [2] of EMA

Sodium oxybate should not be used in combination with sedative hypnotics or other CNS depressants.

Diclofenac, sodium oxybate [2] ---> SmPC of [2] of EMA

Co-administration of sodium oxybate and diclofenac in healthy volunteers reduced the attention deficit caused by the administration of Xyrem alone as measured by psychometric tests.

Duloxetine, sodium oxybate [2] ---> SmPC of [2] of EMA

No additional effect on sleepiness was observed when comparing single doses of sodium oxybate alone (2.25 g) and sodium oxybate (2.25 g) in combination with duloxetine (60 mg at steady state).

Ethosuximide, sodium oxybate [2] ---> SmPC of [2] of EMA

Since sodium oxybate is metabolised by GHB dehydrogenase there is a potential risk of an interaction with medicinal products that stimulate or inhibit this enzyme (e.g. valproate, phenytoin or ethosuximide) (see section 4.4).

Fentanyl [1], sodium oxybate ---> SmPC of [1] of EMA

Concomitant use of medicinal products containing sodium oxybate and fentanyl is contraindicated (see section 4.3). The treatment with sodium oxybate should be discontinued before start of treatment with Effentora.

Fertility, sodium oxybate [2] ---> SmPC of [2] of EMA

There is no clinical data available on the effect of sodium oxybate on fertility. Studies in male and female rats at doses up to 1,000 mg/kg/day GHB have shown no evidence of an adverse effect on fertility.

Flurazepam, sodium oxybate [2] ---> SmPC of [2] of EMA

Given the possibility of increasing the risk of respiratory depression, the concomitant use of benzodiazepines and sodium oxybate should be avoided.

GHB dehydrogenase inhibitors, sodium oxybate [2] ---> SmPC of [2] of EMA

Human isoenzymes, sodium oxybate [2] ---> SmPC of [2] of EMA

Studies in vitro with pooled human liver microsomes indicate that sodium oxybate does not significantly inhibit the activities of the human isoenzymes (see section 5.2).

Ibuprofen, sodium oxybate [2] ---> SmPC of [2] of EMA

Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate and ibuprofen.

Lorazepam, sodium oxybate [2] ---> SmPC of [2] of EMA

Increased sleepiness was observed after concomitant administration of sodium oxybate

Lormetazepam, sodium oxybate

Concomitant use of lormetazepam with sodium oxybate may enhance a respiratory depression

Modafinil [1], sodium oxybate ---> SmPC of [1] of EMA

A drug interaction study in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate (single dose of 4.5 g) and modafinil (single dose of 200 mg).

Omeprazole, sodium oxybate [2] ---> SmPC of [2] of EMA

The co-administration of omeprazole has no clinically significant effect on the pharmacokinetics of sodium oxybate.

Opiates, sodium oxybate [2] ---> SmPC of [2] of EMA

When higher doses up to 9 g/d of sodium oxybate are combined with higher doses of opioids (within the recommended dose range) pharmacodynamic interactions associated with symptoms of CNS depression and/or respiratory depression cannot be excluded

Phenytoin, sodium oxybate [2] ---> SmPC of [2] of EMA

Pitolisant [1], sodium oxybate ---> SmPC of [1] of EMA

No clinically relevant pharmacokinetic drug-drug interaction was evidenced either with modafinil or with sodium oxybate.

Pregnancy, sodium oxybate [2] ---> SmPC of [2] of EMA

Sodium oxybate is not recommended during pregnancy.

Proton pump inhibitors [1], sodium oxybate ---> SmPC of [1] of EMA

The dose of sodium oxybate therefore does not require adjustment when given concomitantly with proton pump inhibitors.

Sedative hypnotics, sodium oxybate [2] ---> SmPC of [2] of EMA

When higher doses up to 9 g/d of sodium oxybate are combined with higher doses of hypnotics (within the recommended dose range) pharmacodynamic interactions associated with symptoms of CNS depression and/or respiratory depression cannot be excluded

Sodium oxybate [1], topiramate ---> SmPC of [1] of EMA

There have been clinical observation(s) of coma and increased plasma GHB concentration after co-administration of sodium oxybate with topiramate. Therefore, patients should be warned against the use of topiramate in conjunction with sodium oxybate

Sodium oxybate [1], tramadol ---> SmPC of [1] of EMA

A drug interaction study in healthy adults with sodium oxybate (single dose of 2.25 g) and tramadol (single dose of 100 mg) demonstrated no pharmacokinetic/pharmacodynamic interaction.

Sodium oxybate [1], tricyclic antidepressant ---> SmPC of [1] of EMA

The rate of adverse reactions has increased when sodium oxybate is co-administered with tricyclic antidepressants.

Sodium oxybate [1], valproate ---> SmPC of [1] of EMA

The co-administration of sodium oxybate with valproate resulted in an increase in systemic exposure to sodium oxybate by approximately 25% and no significant change in Cmax. No effect on the pharmacokinetics of valproate was observed.

CONTRAINDICATIONS of Sodium oxybate (Xyrem)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Patients with major depression

- Patients with succinic semialdehyde dehydrogenase deficiency.

- Patients being treated with opioids or barbiturates.

https://www.ema.europa.eu/en/documents/product-information/xyrem-epar-product-information_en.pdf 12/10/2022

Sodium phenylbutyrate (Pheburane)

Ability to drive, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

PHEBURANE has negligible influence on the ability to drive and use machines.

Breast-feeding, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

It is unknown whether sodium phenylbutyrate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Pheburane is contra-indicated during breast-feeding (see section 4.3).

Contraceptives, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

Effective contraceptive measures must be taken by women of child-bearing potential.

Corticosteroids, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

Corticosteroids may cause the breakdown of body protein and thus increase plasma ammonia levels.

Fertility, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

There is no evidence available on the effect of sodium phenylbutyrate on fertility.

Foods, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

PHEBURANE should be administered orally. Because of its slow dissolution, PHEBURANE should not be administered by nasogastric or gastrostomy tubes. The total daily dose should be divided into equal amounts and given with each meal or feeding

Haloperidol, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

There have been published reports of hyperammonaemia being induced by haloperidol and by valproate.

Pregnancy, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

There are no or limited amount of data from the use of sodium phenylbutyrate in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Pheburane is contra-indicated during pregnancy (see section 4.3).

Probenecide, sodium phenylbutyrate [2] ---> SmPC of [2] of EMA

Concurrent administration of probenecid may affect renal excretion of the conjugation product of sodium phenylbutyrate.

Sodium phenylbutyrate [1], valproate ---> SmPC of [1] of EMA

There have been published reports of hyperammonaemia being induced by haloperidol and by valproate.

Sodium phenylbutyrate [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment.

CONTRAINDICATIONS of Sodium phenylbutyrate (Pheburane)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy.

- Breast-feeding.

https://www.ema.europa.eu/en/documents/product-information/pheburane-epar-product-information_en.pdf. 10/01/2024

Other trade names: Ammonaps,

Sodium picosulfate

Amiodarone, sodium picosulfate

Hypokaliemia may be a risk of torsades de pointes in patients treated with antiarrhythmics

Antiarrhythmics, sodium picosulfate

Hypokaliemia may be a risk of torsades de pointes in patients treated with antiarrhythmics

Antibiotics, sodium picosulfate [2] ---> SmPC of [2] of eMC

Concurrent administration of antibiotics may reduce the laxative action of this product.

Bepridil, sodium picosulfate

Hypokaliemia may be a risk of torsades de pointes in patients treated with antiarrhythmics

Breast-feeding, sodium picosulfate [2] ---> SmPC of [2] of eMC

As with all medicines, picosulfate should not be during breast feeding unless the expected benefit is thought to outweigh any possible risk and only on medical advice.

Corticosteroids, sodium picosulfate [2] ---> SmPC of [2] of eMC

The concomitant use of adreno-corticosteroids may increase the risk of electrolyte imbalance if excessive doses of picosulfate are taken.

Digital glycosides, sodium picosulfate [2] ---> SmPC of [2] of eMC

Electrolyte imbalance may lead to increased sensitivity to cardiac glycosides.

Diuretics, sodium picosulfate [2] ---> SmPC of [2] of eMC

The concomitant use of diuretics may increase the risk of electrolyte imbalance if excessive doses of picosulfate are taken.

Glycyrrhiza, sodium picosulfate

The co-administration may increase the risk of electrolyte imbalance

Hypokalemia, sodium picosulfate [2] ---> SmPC of [2] of eMC

The concomitant use may increase the risk of electrolyte imbalance if excessive doses of picosulfate are taken.

Pregnancy, sodium picosulfate [2] ---> SmPC of [2] of eMC

As with all medicines, picosulfate should not be taken in pregnancy, especially the first trimester

Quinidine, sodium picosulfate

Hypokaliemia may be a risk of torsades de pointes in patients treated with antiarrhythmics

Sodium picosulfate [1], thiazides ---> SmPC of [1] of eMC

The concomitant use of diuretics may increase the risk of electrolyte imbalance if excessive doses of picosulfate are taken.

Sodium picosulfate, sotalol

Hypokaliemia may be a risk of torsades de pointes in patients treated with antiarrhythmics

Sodium picosulfate, vincamine

Hypokaliemia may be a risk of torsades de pointes in patients treated with vincamine

CONTRAINDICATIONS of Sodium picosulfate

DULCOLAX PICO is contraindicated in patients with:

- Ileus or intestinal obstruction

- Severe painful and/or feverish acute abdominal conditions (e.g. appendicitis) potentially associated with nausea and vomiting

- Acute inflammatory bowel diseases

- Severe dehydration

- Known hypersensitivity to sodium picosulfate or any other component of the product

- Rare hereditary conditions that may be incompatible with an excipient of the product

http://www.medicines.org.uk/emc/

Sodium valproate

Ability to drive, sodium valproate [2] ---> SmPC of [2] of eMC

Patients should be warned of the risk of transient drowsiness, especially in cases of anticonvulsant polytherapy or association with benzodiazepines

Acetylsalicylic acid, sodium valproate [2] ---> SmPC of [2] of eMC

Acetylsalicylic acid may displace valproic acid from its protein binding sites and increase the free valproic acid plasma levels.

Alcohol, sodium valproate [2] ---> SmPC of [2] of eMC

Alcohol intake is not recommended during treatment with valproate

Antidepressants, sodium valproate [2] ---> SmPC of [2] of eMC

Valproate may potentiate the effect of other psychotropics; therefore, clinical monitoring is advised and the dosage of the other psychotropics should be adjusted when appropriate.

Benperidol [1], sodium valproate ---> SmPC of [1] of eMC

The dosage of anti-convulsants may need to be increased to take account of the lowered seizure threshold.

Benzodiazepines, sodium valproate [2] ---> SmPC of [2] of eMC

Valproate may potentiate the effect of other psychotropics; therefore, clinical monitoring is advised and the dosage of the other psychotropics should be adjusted when appropriate.

Breast-feeding, sodium valproate [2] ---> SmPC of [2] of eMC

Although there appears to be no contra-indication to breastfeeding, consideration should be given to the safety profile, specifically haematological disorders

Carbamazepine, sodium valproate [2] ---> SmPC of [2] of eMC

Antiepileptics with enzyme inducing effect decrease valproic acid plasma concentrations. Valproic acid may potentiate toxic effects of carbamazepine.

Carbapeneme, sodium valproate ---> SmPC of [ertapenem] of EMA

Decreases in valproic acid levels that may fall below the therapeutic range have been reported when valproic acid was co-administered with carbapenem agents. Alternative antibacterial or anti-convulsant therapies should be considered.

Chloroquine, sodium valproate

The co-administration may decrease the seizure threshold. Caution is recommended

Cimetidine, sodium valproate [2] ---> SmPC of [2] of eMC

Valproic acid plasma levels may be increased (as a result of reduced hepatic metabolism) in case of concomitant use with cimetidine

Clarithromycin [1], sodium valproate ---> SmPC of [1] of eMC

There have been spontaneous or published reports of interactions of CYP3A inhibitors, including clarithromycin with drugs not thought to be metabolised by CYP3A (e.g. phenytoin and valproate)

Clomipramine [1], sodium valproate ---> SmPC of [1] of eMC

Concomitant administration of valproate with clomipramine may cause inhibition of CYP2C and/or UGT enzymes resulting in increased serum levels of clomipramine and desmethylclomipramine.

Clonazepam [1], sodium valproate ---> SmPC of [1] of eMC

The enzymatic induction may decrease the plasma levels of clonazepam. The combination of clonazepam and sodium valproate has, rarely, been associated with the development of absence status epilepticus.

Diazepam [1], sodium valproate ---> SmPC of [1] of eMC

Diazepam has been reported to be displaced from protein-binding sites by sodium valproate (increased serum levels: increased risk of drowsiness).

Doripenem [1], sodium valproate ---> SmPC of [1] of EMA

It has been shown that co-administration of doripenem and valproic acid significantly reduces serum valproic acid levels below the therapeutic range.

Doxorubicine [1], sodium valproate ---> SmPC of [1] of eMC

The absorption of anticonvulsants (e.g. carbamazepine, phenytoin, valproate) is decreased when administered in combination with doxorubicin.

Ertapenem [1], sodium valproate ---> SmPC of [1] of EMA

Erythromycin, sodium valproate [2] ---> SmPC of [2] of eMC

Valproic acid plasma levels may be increased (as a result of reduced hepatic metabolism) in case of concomitant use with erythromycin.

Ethosuximide, sodium valproate

Sodium valproate increases the plasma concentrations and the risk of adverse reactions of ethosuximide

Felbamate, sodium valproate [2] ---> SmPC of [2] of eMC

Valproic acid may decrease the felbamate mean clearance by up to 16%. The combination of felbamate and valproate decreases valproic acid clearance by 22% to 50% and consequently increase the valproic acid plasma concentrations.

Ferric citrate coordination complex [1], sodium valproate ---> SmPC of [1] of EMA

Any medicinal product that has the potential to interact with Fexeric, should be taken at least 2 hours before or after Fexeric.

Fluoxetine, sodium valproate

The co-administration may increase the plasma levels of valproate or sometimes decrease them

Hepatotoxic drugs, sodium valproate

The potential hepatotoxic medicinal products may exacerbate the hepatic toxicity of valproate

IMAOs, sodium valproate [2] ---> SmPC of [2] of eMC

Valproate may potentiate the effect of other psychotropics; therefore, clinical monitoring is advised and the dosage of the other psychotropics should be adjusted when appropriate.

Imipenem, sodium valproate

Decreased valproate plasma levels. Concomitant use is not recommended

Imipenem/cilastatin [1], sodium valproate ---> SmPC of [1] of eMC

Decreases in valproic acid levels that may fall below the therapeutic range have been reported when valproic acid was co-administered with carbapenem agents. The lowered valproic acid levels can lead to inadequate seizure control

Lamotrigine [1], sodium valproate ---> SmPC of [1] of eMC

Valproic acid reduces the metabolism of lamotrigine and increases the lamotrigine mean half-life by nearly two fold.

Levocarnitine, sodium valproate

Possible Levocarnitine deficiency

Lithium, sodium valproate [2] ---> SmPC of [2] of eMC

Sodium valproate has no effect on serum lithium levels

Lorazepam [1], sodium valproate ---> SmPC of [1] of eMC

Valproate may inhibit the glucuronidation of lorazepam (increased serum levels: increased risk of drowsiness)

Mefloquine, sodium valproate [2] ---> SmPC of [2] of eMC

Mefloquine and chloroquine increase valproic acid metabolism and may lower the seizure threshold; therefore epileptic seizures may occur in cases of combined therapy.

Mesuximide, sodium valproate

Mesuximide may decrease the plasma levels of valproate

Methadone, sodium valproate

The CYP3A4 inhibition may increase the plasma concentrations of methadone

Neuroleptics, sodium valproate [2] ---> SmPC of [2] of eMC

Valproate may potentiate the effect of other psychotropics; therefore, clinical monitoring is advised and the dosage of the other psychotropics should be adjusted when appropriate.

Nimodipine [1], sodium valproate ---> SmPC of [1] of eMC

The simultaneous administration of nimodipine with the anticonvulsant valproic acid can lead to an increase in the plasma concentration of nimodipine

Oral contraceptives, sodium valproate [2] ---> SmPC of [2] of eMC

Valproate usually has no enzyme-inducing effect; as a consequence, valproate does not reduce efficacy of oestroprogestative agents in women receiving hormonal contraception, including the oral contraceptive pill.

Orlistat [1], sodium valproate ---> SmPC of [1] of EMA

Orlistat may unbalance anticonvulsivant treatment by decreasing the absorption of antiepileptic drugs, leading to convulsions

Oxaliplatin [1], sodium valproate ---> SmPC of [1] of eMC

In vitro, no significant displacement of oxaliplatin binding to plasma proteins has been observed

Paliperidone [1], sodium valproate ---> SmPC of [1] of EMA

Co-administration of paliperidone with divalproex sodium prolonged-release tablets increased the exposure to paliperidone

Paroxetine [1], sodium valproate ---> SmPC of [1] of eMC

Concomitant administration does not seem to show any effect on pharmacokinetic/dynamic profile in epileptic patients.

Phenobarbital, sodium valproate [2] ---> SmPC of [2] of eMC

Antiepileptics with enzyme inducing effect decrease valproic acid plasma concentrations. Valproic acid increases phenobarbital plasma concentrations (due to inhibition of hepatic catabolism)

Phenytoin, sodium valproate [2] ---> SmPC of [2] of eMC

Antiepileptics with enzyme inducing effect decrease valproic acid plasma levels. Valproic acid decreases phenytoin total levels and increases phenytoin free form with possible overdosage symptoms

Pregnancy, sodium valproate [2] ---> SmPC of [2] of eMC

This medicine should not be used during pregnancy and in women of child-bearing potential unless clearly necessary

Primidone, sodium valproate [2] ---> SmPC of [2] of eMC

Valproic acid increases primidone plasma levels with exacerbation of its adverse effects (such as sedation)

Quetiapine, sodium valproate [2] ---> SmPC of [2] of eMC

The pharmacokinetics of sodium valproate and quetiapine were not altered to a clinically relevant extent when co-administered. A retrospective study of children and adolescents found a higher incidence of leucopenia and neutropenia

Rifampicin, sodium valproate [2] ---> SmPC of [2] of eMC

Rifampicin may decrease the valproic acid blood levels resulting in a lack of therapeutic effect. Therefore, valproate dosage adjustment may be necessary when it is co-administered with rifampicin.

Rufinamide [1], sodium valproate ---> SmPC of [1] of EMA

Rufinamide appears not to have clinically relevant effect on valproate steady state concentrations

Seizure-threshold lowering drugs, sodium valproate

The co-administration may decrease the seizure threshold. Caution is recommended

Sodium oxybate [1], sodium valproate ---> SmPC of [1] of EMA

Caution is required in patients who are treated concomitantly with valproate or other GHB dehydrogenase inhibitors as pharmacokinetic and pharmacodynamic interactions have been observed when sodium oxybate is co-administered with valproate

Sodium valproate [1], topiramate ---> SmPC of [1] of eMC

Concomitant administration of valproate and topiramate has been associated with encephalopathy and/or hyperammonaemia.

Sodium valproate [1], vitamin K antagonists ---> SmPC of [1] of eMC

The anticoagulant effect of warfarin and other coumarin anticoagulants may be increased following displacement from plasma protein binding sites by valproic acid.

Sodium valproate [1], warfarin ---> SmPC of [1] of eMC

The anticoagulant effect of warfarin and other coumarin anticoagulants may be increased following displacement from plasma protein binding sites by valproic acid.

Sodium valproate [1], zidovudine ---> SmPC of [1] of eMC

Valproic acid may raise zidovudine plasma concentration leading to increased zidovudine toxicity.

Sodium valproate, St. John's wort

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of valproate (with risk of seizures). St. John's Wort should be avoided

Sodium valproate, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

CONTRAINDICATIONS of Sodium valproate

- Active liver disease

- Personal or family history of severe hepatic dysfunction, especially drug related

- Hypersensitivity to sodium valproate

- Porphyria

http://www.medicines.org.uk/emc/

Sodium zirconium cyclosilicate (Lokelma)

Amlodipine, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Anti-HIV medicine, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Atazanavir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Atorvastatin, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Azole antifungals, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Breast-feeding, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to sodium zirconium cyclosilicate is negligible. Lokelma can be used during breast-feeding.

Clopidogrel, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Cyclosporine, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In the same study, coadministration of Lokelma and cyclosporin did not show a clinically meaningful interaction.

Dabigatran, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate and dabigatran may be co-administered without adjusting the dose of dabigatran.

Dasatinib, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Erlotinib, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Fertility, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

No human data on the effect of sodium zirconium cyclosilicate on fertility are available. In rats, there was no effect on fertility with sodium zirconium cyclosilicate treatment.

Furosemide, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Gastric pH increasing medication, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Glipizide, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Indinavir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Itraconazol, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Ketoconazole, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Ledipasvir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Levothyroxine, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Losartan, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Medicinal products, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

As sodium zirconium cyclosilicate is not absorbed or metabolised by the body, there are no expected effects of other medicinal products on the pharmacologic action of sodium zirconium cyclosilicate.

Nelfinavir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Nilotinib, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

PH dependent bioavailability, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate can be co-administered without spacing of dosing times with oral medicinal products that do not exhibit pH-dependent bioavailability.

PH dependent bioavailability, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Posaconazole, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Pregnancy, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Raltegravir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Rilpivirine, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Ritonavir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Saquinavir, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Sodium zirconium cyclosilicate [1], tacrolimus ---> SmPC of [1] of EMA

Therefore, tacrolimus should be taken at least 2 hours before or after Lokelma.

Sodium zirconium cyclosilicate [1], tyrosine kinase inhibitor ---> SmPC of [1] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Sodium zirconium cyclosilicate [1], warfarin ---> SmPC of [1] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

CONTRAINDICATIONS of Sodium zirconium cyclosilicate (Lokelma)

- Hypersensitivity to the active substance.

https://www.ema.europa.eu/en/documents/product-information/lokelma-epar-product-information_en.pdf 03/09/2025

Sofosbuvir (Sovaldi)

Ability to drive, sofosbuvir [2] ---> SmPC of [2] of EMA

Patients should be informed that fatigue and disturbance in attention, dizziness and blurred vision have been reported during treatment with sofosbuvir in combination with peginterferon alfa and ribavirin

Amiodarone, sofosbuvir [2] ---> SmPC of [2] of EMA

Coadministration of amiodarone with a sofosbuvir containing regimen may result in serious symptomatic bradycardia. Use only if no other alternative is available. Close monitoring is recommended if this medicinal product is administered with Sovaldi

BCRP inhibitors, sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration of Sovaldi with medicinal products that inhibit P-gp and/or BCRP may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration, thus Sovaldi may be co-administered with P-gp and/or BCRP inhibitors.

Boceprevir, sofosbuvir [2] ---> SmPC of [2] of EMA

No drug-drug interaction data exists regarding the co-administration of Sovaldi with boceprevir or telaprevir.

Breast-feeding, sofosbuvir [2] ---> SmPC of [2] of EMA

A risk to newborns/infants cannot be excluded. Therefore, Sovaldi should not be used during breast-feeding.

Carbamazepine, sofosbuvir [2] ---> SmPC of [2] of EMA

Medicinal products that are potent P-gp inducers in the intestine may significantly decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi and thus are contraindicated with Sovaldi

Cyclosporine, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or ciclosporin is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of ciclosporin may be required.

Daclatasvir, sofosbuvir

No dose adjustment of Daklinza or sofosbuvir is required.

Daclatasvir, sofosbuvir [2] ---> SmPC of [2] of EMA

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], sofosbuvir ---> SmPC of [1] of EMA

Based on theoretical considerations, no clinically relevant interaction is expected.

Darunavir/ritonavir, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or darunavir (ritonavir boosted) is required when sofosbuvir and darunavir are used concomitantly

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sofosbuvir ---> SmPC of [dasabuvir] of EMA

No dose adjustment needed for sofosbuvir when co-administered with Exviera + ombitasvir/paritaprevir/ritonavir.

Direct acting antivirals, sofosbuvir [2] ---> SmPC of [2] of EMA

Dolutegravir/rilpivirine [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Drugs inducing bradycardia, sofosbuvir [2] ---> SmPC of [2] of EMA

Cases of severe bradycardia and heart block have been observed when Sovaldi is used in combination with Daklinza and concomitant amiodarone with or without other drugs that lower heart rate. The mechanism is not established.

Efavirenz, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or tacrolimus is required when sofosbuvir and efavirenz are used concomitantly.

Elbasvir/grazoprevir [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or efavirenz is required when sofosbuvir and efavirenz are used concomitantly.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], sofosbuvir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Ethinyl estradiol, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or tacrolimus is required when sofosbuvir and ethinylestradiol are used concomitantly.

Fertility, sofosbuvir [2] ---> SmPC of [2] of EMA

No human data on the effect of Sovaldi on fertility are available. Animal studies do not indicate harmful effects on fertility.

Foods, sofosbuvir [2] ---> SmPC of [2] of EMA

The film-coated tablet should not be chewed or crushed, due to the bitter taste of the active substance. The tablet should be taken with food

Fostemsavir [1], sofosbuvir ---> SmPC of [1] of EMA

Although not studied, temsavir may increase plasma concentrations of other HCV DAAs. No dose adjustment is necessary.

Glecaprevir/pibrentasvir [1], sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Hepatic metabolism, sofosbuvir [2] ---> SmPC of [2] of EMA

The pharmacokinetics of medicinal products that are metabolized by the liver (e.g. immunosuppressive medicinal products such as calcineurin inhibitors) may be impacted by changes in liver function during DAA therapy, related to clearance of HCV.

Ledipasvir/sofosbuvir [1], sofosbuvir ---> SmPC of [1] of EMA

Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir.

Letermovir [1], sofosbuvir ---> SmPC of [1] of EMA

Administration of PREVYMIS may result in a clinically relevant decrease in plasma concentrations of co-administered medicinal products that are significantly transported by Pgp in the intestine such as dabigatran and sofosbuvir.

Methadone, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or methadone is required when sofosbuvir and methadone are used concomitantly

Modafinil, sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration of Sovaldi with modafinil is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Such co-administration is not recommended.

Moderate P-gp inductors, sofosbuvir [2] ---> SmPC of [2] of EMA

Medicinal products that are moderate P-gp inducers in the intestine (e.g. modafinil, oxcarbazepine and rifapentine) may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of Sovaldi.

Monotherapy, sofosbuvir [2] ---> SmPC of [2] of EMA

Sovaldi is not recommended for administration as monotherapy and should be prescribed in combination with other medicinal products for the treatment of hepatitis C infection.

Norgestimate, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of norgestimate/ethinyl estradiol is required when sofosbuvir and norgestimate/ethinyl estradiol are used concomitantly.

Ombitasvir/paritaprevir/ritonavir [1], sofosbuvir ---> SmPC of [1] of EMA

BCRP and P-gp inhibition by paritaprevir, ritonavir and dasabuvir. No dose adjustment needed for sofosbuvir when administered with Viekirax with or without dasabuvir.

Oxcarbazepine, sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration of Sovaldi with oxcarbazepine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Such co-administration is not recommended (see section 4.4).

P-gp inhibitors, sofosbuvir [2] ---> SmPC of [2] of EMA

Phenobarbital, sofosbuvir [2] ---> SmPC of [2] of EMA

Phenytoin, sofosbuvir [2] ---> SmPC of [2] of EMA

Potent P-gp inducers in the intestine, sofosbuvir [2] ---> SmPC of [2] of EMA

Pregnancy, sofosbuvir [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of Sovaldi during pregnancy. However, if ribavirin is co-administered with sofosbuvir, the contraindications regarding use of ribavirin during pregnancy apply

Raltegravir, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or tacrolimus is required when sofosbuvir and raltegravir are used concomitantly.

Rifabutin, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Sovaldi is required when concomitantly used with rifabutin.

Rifampicin, sofosbuvir [2] ---> SmPC of [2] of EMA

Rifapentine, sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration of Sovaldi with rifapentine is expected to decrease the concentration of sofosbuvir, leading to reduced therapeutic effect of Sovaldi. Such co-administration is not recommended (see section 4.4).

Rilpivirine, sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of sofosbuvir or rilpivirine is required when sofosbuvir and rilpivirine are used concomitantly.

Simeprevir, sofosbuvir [2] ---> SmPC of [2] of EMA

Sofosbuvir [1], St. John's wort ---> SmPC of [1] of EMA

Sofosbuvir [1], strong BCRP inhibitors ---> SmPC of [1] of EMA

Co-administration of sofosbuvir with medicinal products that inhibit BCRP may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration, thus sofosbuvir may be co-administered with BCRP inhibitors.

Sofosbuvir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Co-administration of sofosbuvir with medicinal products that inhibit P-gp may increase sofosbuvir plasma concentration without increasing GS-331007 plasma concentration, thus sofosbuvir may be co-administered with P-gp inhibitors.

Sofosbuvir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of sofosbuvir or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.

Sofosbuvir [1], telaprevir ---> SmPC of [1] of EMA

No drug-drug interaction data exists regarding the co-administration of Sovaldi with boceprevir or telaprevir.

Sofosbuvir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

No dose adjustment of sofosbuvir or tenofovir disoproxil is required when sofosbuvir and tenofovir disoproxil are used concomitantly.

Sofosbuvir [1], vitamin K antagonists ---> SmPC of [1] of EMA

Close monitoring of INR is recommended with all vitamin K antagonists. This is due to liver function changes during treatment with Sovaldi.

Sofosbuvir [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential or their male partners must use an effective form of contraception during treatment and for a period of time after the treatment has concluded as recommended in the Summary of Product Characteristics for ribavirin.

Sofosbuvir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or sofosbuvir is required.

CONTRAINDICATIONS of Sofosbuvir (Sovaldi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Medicinal products that are strong P-glycoprotein (P-gp) inducers in the intestine (carbamazepine, phenobarbital, phenytoin, rifampicin and St. John's wort). Co-administration will significantly decrease sofosbuvir plasma concentration and could result in loss of efficacy of Sovaldi (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/sovaldi-epar-product-information_en.pdf 27/09/2023

Sofosbuvir/velpatasvir (Epclusa)

Aluminium hydroxide, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. It is recommended to separate antacid and Epclusa administration by 4 hours.

Amiodarone, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration of amiodarone with a sofosbuvir containing regimen may result in serious symptomatic bradycardia. Use only if no other alternative is available.

Antacids, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. It is recommended to separate antacid and Epclusa administration by 4 hours.

Atazanavir/ritonavir, emtricitabine/tenofovir disoproxil/sofosbuvir/velpatasvir ---> SmPC of [sofosbuvir/velpatasvir

No dose adjustment of Epclusa, atazanavir (ritonavir boosted) or emtricitabine/tenofovir disoproxil fumarate is required.

Atorvastatin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Epclusa or atorvastatin is required.

BCRP inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir or velpatasvir plasma concentrations.

BCRP substrates, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration of Epclusa with medicinal products that are substrates of this transporter may increase the exposure of such medicinal products.

Breast-feeding, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Available pharmacokinetic data in animals have shown excretion of velpatasvir and metabolites of sofosbuvir in milk. A risk to the newborns/infants cannot be excluded. Therefore, Epclusa should not be used during breast-feeding.

Calcineurin inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Calcium carbonate, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. It is recommended to separate antacid and Epclusa administration by 4 hours.

Carbamazepine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Medicinal products that are potent P-glycoprotein or potent cytochrome P450 inducers are contraindicated with Epclusa. Co-administration will significantly decrease sofosbuvir or velpatasvir plasma levels and could result in loss of efficacy of Epclusa

Cimetidine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Cyclosporine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Epclusa or ciclosporin is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of ciclosporin may be required.

CYP2B6 inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Medicinal products that inhibit OATP, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentration of velpatasvir.

CYP2C8 inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Medicinal products that inhibit OATP, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentration of velpatasvir.

CYP3A4 inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Medicinal products that inhibit OATP, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentration of velpatasvir.

Dabigatran etexilate, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp. Clinical monitoring, looking for signs of bleeding and anaemia, is recommended when dabigatran is co-administered with Epclusa. A coagulation test helps to identify patients with an increased bleeding risk

Darunavir/ritonavir, emtricitabine/tenofovir disoproxil/sofosbuvir/velpatasvir ---> SmPC of [sofosbuvir/velpatasvir

No dose adjustment of Epclusa, darunavir (ritonavir boosted) or emtricitabine/tenofovir disoproxil fumarate is required.

Digoxin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration of Epclusa with digoxin may increase the concentration of digoxin. Caution is warranted and therapeutic concentration monitoring of digoxin is recommended when co-administered with Epclusa.

Dolutegravir, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Epclusa or dolutegravir is required.

Dolutegravir/lamivudine [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/rilpivirine [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

Patients receiving doravirine/lamivudine/tenofovir disoproxil concomitantly with sofosbuvir/velpatasvir should be monitored for adverse reactions associated with tenofovir disoproxil.

Efavirenz, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Medicinal products that are moderate P-gp inducers and/or moderate CYP inducers (e.g. efavirenz, modafinil, oxcarbazepine or rifapentine) may decrease sofosbuvir or velpatasvir plasma concentration leading to reduced therapeutic effect of Epclusa.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Epclusa or elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate is required.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment of Epclusa or elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

No dose adjustment is recommended. The increased exposure of tenofovir could potentiate adverse reactions associated with tenofovir disoproxil, including renal disorders. Renal function should be closely monitored (see section 4.4).

Emtricitabine/rilpivirine/tenofovir disoproxil [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

Emtricitabine/tenofovir disoproxil/sofosbuvir/velpatasvir, lopinavir/ritonavir ---> SmPC of [sofosbuvir/velpatasvir

No dose adjustment of Epclusa, lopinavir (ritonavir boosted) or emtricitabine/tenofovir disoproxil fumarate is required.

Emtricitabine/tenofovir disoproxil/sofosbuvir/velpatasvir, raltegravir ---> SmPC of [sofosbuvir/velpatasvir] of EM

No dose adjustment of Epclusa, raltegravir or emtricitabine/tenofovir disoproxil fumarate is required.

Esomeprazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Ethinylestradiol/norgestimate, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of oral contraceptives is required.

Famotidine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Fertility, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No human data on the effect of Epclusa on fertility are available. Animal studies do not indicate harmful effects of sofosbuvir or velpatasvir on fertility.

Foods, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Epclusa can be administered without regard to food.

Gastric pH increasing medication, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Velpatasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease the concentration of velpatasvir.

H2 antagonists, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Hepatic metabolism, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Immunosuppressives, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Ketoconazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp and CYPs. No dose adjustment of Epclusa or ketoconazole is required.

Lansoprazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Magnesium hydroxide, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. It is recommended to separate antacid and Epclusa administration by 4 hours.

Metabolic turnover, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

In vitro, slow metabolic turnover of velpatasvir by CYP2B6, CYP2C8, and CYP3A4 was observed.

Methadone, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Epclusa or methadone is required.

Modafinil, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Moderate CYP inductors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Moderate P-gp inductors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Nizatidine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

OATP inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Medicinal products that inhibit OATP, CYP2B6, CYP2C8, or CYP3A4 may increase plasma concentration of velpatasvir.

OATP1B1 substrates, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration of Epclusa with medicinal products that are substrates of this transporter may increase the exposure of such medicinal products.

OATP1B3 substrates, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration of Epclusa with medicinal products that are substrates of this transporter may increase the exposure of such medicinal products.

Omeprazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Oral contraceptives, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

No dose adjustment of oral contraceptives is required.

Oxcarbazepine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration of Epclusa with medicinal products that are substrates of this transporter may increase the exposure of such medicinal products.

P-gp inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir or velpatasvir plasma concentrations.

Pantoprazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Pharmacokinetic enhancer, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

The safety of tenofovir disoproxil fumarate in the setting of Epclusa and a pharmacokinetic enhancer has not been established.

Phenobarbital, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Phenytoin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Pravastatine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B. No dose adjustment of Epclusa or pravastatin is required.

Pregnancy, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

As a precautionary measure, Epclusa use is not recommended during pregnancy.

Proton pump inhibitors, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Rabeprazole, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

If it is considered necessary to co-administer, then Epclusa should be administered with food and taken 4 hours before proton pump inhibitor at max doses comparable to omeprazole 20 mg.

Ranitidine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Increase in gastric pH. H2-receptor antagonists may be administered simultaneously with or staggered from Epclusa at a dose that does not exceed doses comparable to famotidine 40 mg twice daily.

Rifabutin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Rifampicin, sofosbuvir/velpatasvir

Induction of P-gp and CYPs. Epclusa is contraindicated with rifampicin, a potent P-gp and CYP inducer

Rifampicin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Rifapentine, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Rosuvastatin, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B and BCRP. Co-administration of Epclusa with rosuvastatin increases the concentration of rosuvastatin, which is associated with increased risk of myopathy, including rhabdomyolysis.

Sofosbuvir, sofosbuvir/velpatasvir [2] ---> SmPC of [2] of EMA

Epclusa should not be administered concurrently with other medicinal products containing sofosbuvir.

Sofosbuvir/velpatasvir [1], St. John's wort ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir [1], statins ---> SmPC of [1] of EMA

Interactions cannot be excluded with other HMG-CoA reductase inhibitors. When co-administered with Epclusa, careful monitoring for statin adverse reactions should be undertaken and a reduced dose of statins should be considered if required.

Sofosbuvir/velpatasvir [1], strong CYP2B6 inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir [1], strong CYP2C8 inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir [1], strong P-gp inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of Epclusa or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.

Sofosbuvir/velpatasvir [1], tenofovir disoproxil ---> SmPC of [1] of EMA

Epclusa has been shown to increase tenofovir exposure (P-gp-inhibition).

Sofosbuvir/velpatasvir [1], vitamin K antagonists ---> SmPC of [1] of EMA

As liver function may change during treatment with Epclusa, a close monitoring of International Normalised Ratio (INR) values is recommended.

Sofosbuvir/velpatasvir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or ledipasvir/sofosbuvir is required.

CONTRAINDICATIONS of Sofosbuvir/velpatasvir (Epclusa)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Medicinal products that are strong P-glycoprotein (P-gp) and/or strong cytochrome P450 (CYP) inducers (carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin and St. John's wort) (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/epclusa-epar-product-information_en.pdf 27/09/2023

Sofosbuvir/velpatasvir/voxilaprevir (Vosevi)

Aluminium hydroxide, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. It is recommended to separate antacid and Vosevi administration by 4 hours.

Amiodarone, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Life-threatening cases of severe bradycardia and heart block have been observed when sofosbuvir containing regimens are used in combination with amiodarone. Bradycardia has generally occurred within hours to days,

Antacids, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. It is recommended to separate antacid and Vosevi administration by 4 hours.

Atazanavir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B, P-gp and CYP3A. Co-administration of Vosevi with atazanavir is expected to increase the concentration of voxilaprevir. Co-administration of Vosevi with atazanavir-containing regimens is not recommended.

Atazanavir/ritonavir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Atorvastatin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Atorvastatin may be administered with Vosevi at a dose that does not exceed atorvastatin 20 mg.

BCRP inhibitors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir, velpatasvir or voxilaprevir plasma concentrations.

BCRP substrates, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration of Vosevi with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products.

Bictegravir/emtricitabine/tenofovir alafenamide [1], sofosbuvir/velpatasvir/voxilaprevir ---> SmPC of [1] of EMA

No dose adjustment is required upon co-administration.

Breast-feeding, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Therefore, Vosevi should not be used during breast-feeding.

Calcineurin inhibitors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

The pharmacokinetics of medicinal products that are metabolized by the liver (e.g. immunosuppressive agents such as calcineurin inhibitors) may be impacted by changes in liver function during DAA therapy, related to clearance of HCV.

Calcium carbonate, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. It is recommended to separate antacid and Vosevi administration by 4 hours.

Carbamazepine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Medicinal products that are strong inducers of P-gp or strong inducers of CYP2B6, CYP2C8, or CYP3A4 may decrease plasma levels of sofosbuvir, velpatasvir and/or voxilaprevir. The use of such medicinal products with Vosevi is contraindicated

Cimetidine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. H2-receptor antagonists may be administered simultaneously with or staggered from Vosevi at a dose that does not exceed doses comparable with famotidine 40 mg twice daily.

Contraceptives, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Vosevi is contraindicated with ethinylestradiol-containing medicinal products (see section 4.3). Alternative methods of contraception (e.g. progestin only contraception or non-hormonal methods) should be considered.

Cyclosporine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Medicinal products that are strong OATP1B inhibitors (e.g. ciclosporin) may substantially increase voxilaprevir plasma levels, the safety of which has not been established. Co-administration of strong OATP1B inhibitors with Vosevi is not recommended

Dabigatran etexilate, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Dabigatran etexilate (P-gp substrate) and rosuvastatin (OATP1B and BCRP substrate) are contraindicate with rosuvastatin

Darunavir/ritonavir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B, P-gp, and CYP3A. No dose adjustment of Vosevi, darunavir (ritonavir boosted) or emtricitabine/tenofovir disoproxil fumarate is required.

Digoxin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp. Co-administration of Vosevi with digoxin may increase the concentration of digoxin. Caution is warranted and therapeutic concentration monitoring of digoxin is recommended.

Dolutegravir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

No dose adjustment of Vosevi or dolutegravir is required.

Edoxaban, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B1. Co-administration of Vosevi with edoxaban is not recommended. Should direct Xa inhibitor use be deemed necessary, apixaban or rivaroxaban may be considered.

Efavirenz, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Medicinal products that are moderate P-gp or moderate CYP inducers (e.g. oxcarbazepine, rifapentine, modafinil or efavirenz) may decrease sofosbuvir, velpatasvir and/or voxilaprevir plasma concentrations leading to reduced therapeutic effect of Vosevi.

Efavirenz/emtricitabine/tenofovir disoproxil [1], sofosbuvir/velpatasvir/voxilaprevir ---> SmPC of [1] of EMA

Co-administration of Atripla and sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir is not recommended

Efavirenz/emtricitabine/tenofovir disoproxil, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration of Vosevi with efavirenz/emtricitabine/tenofovir disoproxil fumarate is not recommended (see section 4.4).

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of

Inhibition of OATP1B, P-gp/BCRP and CYP3A. No dose adjustment of Vosevi or elvitegravir/cobicistat/ emtricitabine/tenofovir alafenamide fumarate is required.

Emtricitabine/rilpivirine/tenofovir alafenamide, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

No dose adjustment of Vosevi or emtricitabine/rilpivirine/tenofovir alafenamide is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], sofosbuvir/velpatasvir ---> SmPC of [1] of EMA

Emtricitabine/tenofovir alafenamide [1], sofosbuvir/velpatasvir/voxilaprevir ---> SmPC of [1] of EMA

No dose adjustment of sofosbuvir, velpatasvir or voxilaprevir is required. Dose Descovy according to the concomitant antiretroviral (see section 4.2).

Esomeprazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Ethinyl estradiol, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Ethinylestradiol/norgestimate, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Famotidine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Fertility, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

No human data on the effect of Vosevi on fertility are available. Animal studies do not indicate harmful effects of sofosbuvir, velpatasvir or voxilaprevir on fertility.

Foods, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

The recommended dose of Vosevi is one tablet, taken orally, once daily with food

H2 antagonists, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

HMG-CoA reductase inhibitors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B. Interactions cannot be excluded with other HMG-CoA reductase inhibitors. Co-administration with Vosevi is not recommended.

Immunosuppressives, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Ketoconazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of P-gp and CYP3A. No dose adjustment of Vosevi or ketoconazole is required.

Lansoprazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Lopinavir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B. Co-administration of Vosevi with lopinavir-containing regimens is not recommended.

Lopinavir/ritonavir [1], sofosbuvir/velpatasvir/voxilaprevir ---> SmPC of [1] of EMA

Serum concentrations of sofosbuvir, velpatasvir and voxilaprevir may be increased due to P-glycoprotein, BCRP and OATP1B1/3 inhibition by lopinavir/ritonavir. It is not recommended to co-administer Kaletra and sofosbuvir/velpatasvir/ voxilaprevir.

Magnesium hydroxide, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. It is recommended to separate antacid and Vosevi administration by 4 hours.

Methadone, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

No dose adjustment of Vosevi or methadone is required.

Modafinil, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Moderate CYP inductors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Moderate P-gp inductors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Nizatidine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

OATP1B1 substrates, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration of Vosevi with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products.

OATP1B3 substrates, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration of Vosevi with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products.

Omeprazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Oxcarbazepine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration of Vosevi with medicinal products that are substrates of these transporters may increase the exposure of such medicinal products.

P-gp inhibitors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that inhibit P-gp or BCRP may increase sofosbuvir, velpatasvir or voxilaprevir plasma concentrations.

Pantoprazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Phenobarbital, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Phenytoin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Pravastatine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Inhibition of OATP1B. Pravastatin may be administered with Vosevi at a dose that does not exceed pravastatin 40 mg.

Pregnancy, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

As a precautionary measure, Vosevi use is not recommended during pregnancy.

Proton pump inhibitors, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Rabeprazole, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Increase in gastric pH decreases velpatasvir solubility. Proton pump inhibitors may be administered with Vosevi at a dose that does not exceed doses comparable with omeprazole 20 mg.

Raltegravir, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

No dose adjustment of Vosevi, raltegravir or emtricitabine/tenofovir disoproxil fumarate is required.

Ranitidine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Rifabutin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Rifampicin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Rifapentine, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Rosuvastatin, sofosbuvir/velpatasvir/voxilaprevir [2] ---> SmPC of [2] of EMA

Dabigatran etexilate (P-gp substrate) and rosuvastatin (OATP1B and BCRP substrate) are contraindicate with rosuvastatin

Sofosbuvir/velpatasvir/voxilaprevir [1], St. John's wort ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], statins ---> SmPC of [1] of EMA

Inhibition of OATP1B. Interactions cannot be excluded with other HMG-CoA reductase inhibitors. Co-administration with Vosevi is not recommended.

Sofosbuvir/velpatasvir/voxilaprevir [1], strong CYP2B6 inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], strong CYP2C8 inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], strong OATP1B1 inhibitors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], strong OATP1B3 inhibitors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], strong P-gp inductors ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of Vosevi or tacrolimus is required.

Sofosbuvir/velpatasvir/voxilaprevir [1], tenofovir ---> SmPC of [1] of EMA

Vosevi has been shown to increase tenofovir exposure when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat).

Sofosbuvir/velpatasvir/voxilaprevir [1], vitamin K antagonists ---> SmPC of [1] of EMA

As liver function may change during treatment with Vosevi, close monitoring of International Normalised Ratio (INR) values is recommended.

Sofosbuvir/velpatasvir/voxilaprevir [1], voriconazole ---> SmPC of [1] of EMA

Inhibition of CYP3A. No dose adjustment of Vosevi or voriconazole is required.

CONTRAINDICATIONS of Sofosbuvir/velpatasvir/voxilaprevir (Vosevi)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Concomitant use with medicinal products that are strong P-glycoprotein (P-gp) and/or strong cytochrome P450 (CYP) inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin and St. John's wort) (see section 4.5).

- Concomitant use with rosuvastatin or dabigatran etexilate (see section 4.5).

- Concomitant use with ethinylestradiol-containing medicinal products such as combined oral contraceptives or contraceptive vaginal rings or transdermal patches (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/vosevi-epar-product-information_en.pdf 26/07/2024

Solifenacin

Ability to drive, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin, like other anticholinergics may cause blurred vision, and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected

Anticholinergics, solifenacin [2] ---> SmPC of [2] of eMC

Comedication with other anticholinergic drugs may result in more pronounced therapeutic and undesirable effects. Between solifenacin and other anticholinergic should be an interval of at least 1 week

Breast-feeding, solifenacin [2] ---> SmPC of [2] of eMC

The use of solifenacin should be avoided during breast-feeding

Carbamazepine, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with CYP3A4 inducers

Cholinergic agents, solifenacin [2] ---> SmPC of [2] of eMC

The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists

Cisapride, solifenacin [2] ---> SmPC of [2] of eMC

Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastro-intestinal tract, such as metoclopramide and cisapride

Digoxin, solifenacin [2] ---> SmPC of [2] of eMC

Intake of solifenacin showed no effect on the pharmacokinetics of digoxin.

Diltiazem, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. verapamil, diltiazem)

Dopamine antagonists, solifenacin

Mutual weakening of effect on gastrointestinal motility

Itraconazol, solifenacin [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma levels of solifenacin. Simultaneous treatment of solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment

Ketoconazole, solifenacin [2] ---> SmPC of [2] of eMC

Metoclopramide, solifenacin [2] ---> SmPC of [2] of eMC

Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastro-intestinal tract, such as metoclopramide and cisapride

Nelfinavir, solifenacin [2] ---> SmPC of [2] of eMC

Oral contraceptives, solifenacin [2] ---> SmPC of [2] of eMC

Intake of solifenacin showed no pharmacokinetic interaction of solifenacin on combined oral contraceptives (ethinylestradiol/levonorgestrel).

Phenytoin, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with CYP3A4 inducers

Pregnancy, solifenacin [2] ---> SmPC of [2] of eMC

Caution should be exercised when prescribing to pregnant women.

Prokinetics, solifenacin [2] ---> SmPC of [2] of eMC

Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastro-intestinal tract, such as metoclopramide and cisapride

Rifampicin, solifenacin [2] ---> SmPC of [2] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with CYP3A4 inducers

Ritonavir, solifenacin [2] ---> SmPC of [2] of eMC

Solifenacin [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with CYP3A4 inducers

Solifenacin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of eMC

Solifenacin [1], verapamil ---> SmPC of [1] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. verapamil, diltiazem)

Solifenacin [1], warfarin ---> SmPC of [1] of eMC

Intake of solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.

CONTRAINDICATIONS of Solifenacin

Solifenacin is contraindicated in patients with urinary retention, severe gastro-intestinal condition (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma and in patients at risk for these conditions.

- Patients hypersensitive to the active substance or to any of the excipients listed in 6.1.

- Patients undergoing haemodialysis (see Section 5.2).

- Patients with severe hepatic impairment (see Section 5.2).

- Patients with severe renal impairment or moderate hepatic impairment and who are on treatment with a potent CYP3A4 inhibitor, e.g. ketoconazole

http://www.medicines.org.uk/emc/

Solriamfetol (Sunosi)

Ability to drive, solriamfetol [2] ---> SmPC of [2] of EMA

Dizziness and disturbance in attention may occur following administration of solriamfetol. Patients with abnormal levels of sleepiness who take solriamfetol should be advised that their level of wakefulness may not return to normal.

Breast-feeding, solriamfetol [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Sunosi therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the women.

Dopaminergic drugs, solriamfetol [2] ---> SmPC of [2] of EMA

Medicinal products that increase levels of dopamine or that bind directly to dopamine receptors might result in pharmacodynamic interactions with solriamfetol. Concomitant use of such medicinal products should be used with caution.

Fertility, solriamfetol [2] ---> SmPC of [2] of EMA

The effects of solriamfetol in humans are unknown. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Hypertensive drugs, solriamfetol [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that increase blood pressure and heart rate should be used with caution

IMAOs, solriamfetol [2] ---> SmPC of [2] of EMA

Solriamfetol must not be administered concomitantly with MAOIs or within 14 days after MAOI treatment has been discontinued because it may increase the risk of a hypertensive reaction

Pregnancy, solriamfetol [2] ---> SmPC of [2] of EMA

Sunosi is not recommended during pregnancy and in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Solriamfetol (Sunosi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Myocardial infarction within the past year, unstable angina pectoris, uncontrolled hypertension, serious cardiac arrhythmias and other serious heart problems.

- Concomitant use of monoamine oxidase inhibitors (MAOI) or within 14 days after MAOI treatment has been discontinued (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/sunosi-epar-product-information_en.pdf 25/08/2025

Somapacitan (Sogroya)

Antiepileptics [1], somapacitan ---> SmPC of [1] of EMA

The clearance of compounds metabolised by cytochrome P450 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporine) may be especially increased resulting in lower plasma levels of these compounds.

Breast-feeding, somapacitan [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Sogroya therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Corticosteroids, somapacitan [2] ---> SmPC of [2] of EMA

Cyclosporine, somapacitan [2] ---> SmPC of [2] of EMA

Estrogens, somapacitan [2] ---> SmPC of [2] of EMA

In women on oral oestrogen therapy, a higher dose of somapacitan may be required to achieve the treatment goal

Glucocorticoids, somapacitan [2] ---> SmPC of [2] of EMA

Growth hormone decreases the conversion of cortisone to cortisol and may unmask previously undiscovered central hypoadrenalism or render low glucocorticoid replacement doses ineffective

Hormones, somapacitan [2] ---> SmPC of [2] of EMA

The metabolic effects of somapacitan can also be influenced by concomitant therapy with other hormones, e.g. testosterone and thyroid hormones

Hypoglycemic drugs, somapacitan [2] ---> SmPC of [2] of EMA

Antihyperglycaemic treatment including insulin may require dose adjustment in case of somapacitan co-administration since somapacitan may decrease insulin sensitivity

Insulin, somapacitan [2] ---> SmPC of [2] of EMA

Antihyperglycaemic treatment including insulin may require dose adjustment in case of somapacitan co-administration since somapacitan may decrease insulin sensitivity

Metabolized by cytochrome P450, somapacitan [2] ---> SmPC of [2] of EMA

Pregnancy, somapacitan [2] ---> SmPC of [2] of EMA

Sogroya is not recommended during pregnancy and in women of childbearing potential not using contraception.

Somapacitan [1], steroids ---> SmPC of [1] of EMA

Somapacitan [1], testosterone ---> SmPC of [1] of EMA

The metabolic effects of somapacitan can also be influenced by concomitant therapy with other hormones, e.g. testosterone and thyroid hormones

Somapacitan [1], thyroid hormones ---> SmPC of [1] of EMA

The metabolic effects of somapacitan can also be influenced by concomitant therapy with other hormones, e.g. testosterone and thyroid hormones

CONTRAINDICATIONS of Somapacitan (Sogroya)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Somapacitan must not be used when there is any evidence of activity of a tumour. Intracranial tumours must be inactive and antitumour therapy must be completed prior to starting somapacitan therapy. Treatment should be discontinued if there is evidence of tumour growth, see section 4.4.

- No se debe utilizar somapacitán para estimular el crecimiento longitudinal en niños con epífisis cerrada, ver sección 4.2.

- Patients with acute critical illness suffering from complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions must not be treated with somapacitan (regarding patients undergoing substitution therapy, see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/sogroya-epar-product-information_en.pdf 12/08/2025

Somatorelin

Antithyroid medicines, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Arginine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Atropine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Breast-feeding, somatorelin [2] ---> SmPC of [2] of eMC

In general, there is no indication for administration of somatorelin lactation.

Clonidine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Deflazacort, somatorelin [2] ---> SmPC of [2] of eMC

High levels of glucocorticoids as well as somatostatin or its analogues may inhibit the growth hormone release.

Dopamine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Glucagon, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Glucocorticoids, somatorelin [2] ---> SmPC of [2] of eMC

High levels of glucocorticoids as well as somatostatin or its analogues may inhibit the growth hormone release.

Glucose, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Glycine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Growth hormone, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Insulin, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Levodopa, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Ornithine, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Pregnancy, somatorelin [2] ---> SmPC of [2] of eMC

In general, there is no indication for administration of somatorelin during pregnancy

Propranolol, somatorelin [2] ---> SmPC of [2] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Somatorelin [1], somatostatin ---> SmPC of [1] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Somatorelin [1], somatostatin analogues ---> SmPC of [1] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

CONTRAINDICATIONS of Somatorelin

- Hypersensitivity to somatorelin (human) acetate or to any of the excipients.

http://www.medicines.org.uk/emc/

Somatostatin

Barbiturates, somatostatin

Somatostatin prolongs the hypnotic effect of barbiturates. Co-administration is not recommended

Breast-feeding, somatostatin

Somatostatin is contraindicated during breast-feeding

Fructose, somatostatin

Somatostatin should not be administered in solutions with glucose or fructose

Glucose, somatostatin

Somatostatin should not be administered in solutions with glucose or fructose

Pentetrazol, somatostatin

Somatostatin enhances the effect of pentetrazol. The co-administration is not recommended

Phentolamine, somatostatin

The co-administration of somatostatin and phentolamine may shift to lower values the changes in the blood-glucose concentration associated with somatostatin

Pregnancy, somatostatin

Somatostatin is contraindicated during pregnancy

Propranolol, somatostatin

The co-administration of propranolol and somatostatin may enhance the somatostatin-associated hyperglycemic effect

Protirelin, somatostatin

Reduction of TSH-increase

Somatorelin [1], somatostatin ---> SmPC of [1] of eMC

Concomitant use of somatorelin and substances influencing the release of growth hormone should be avoided.

Somatrogon (Ngenla)

ACTH, somatrogon [2] ---> SmPC of [2] of EMA

Patients with adrenocorticotropic hormone (ACTH) deficiency should have their glucocorticoid replacement therapy carefully adjusted to avoid any inhibitory effect on growth.

Antiepileptics, somatrogon [2] ---> SmPC of [2] of EMA

The clearance of compounds metabolised by CYP3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be increased and could result in lower exposure of these compounds.

Breast-feeding, somatrogon [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from somatrogon therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Corticosteroids, somatrogon [2] ---> SmPC of [2] of EMA

The clearance of compounds metabolised by CYP3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be increased and could result in lower exposure of these compounds.

Cyclosporine, somatrogon [2] ---> SmPC of [2] of EMA

The clearance of compounds metabolised by CYP3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be increased and could result in lower exposure of these compounds.

Cytochrome P450, somatrogon [2] ---> SmPC of [2] of EMA

Somatrogon has been shown to induce CYP3A4 mRNA expression in vitro. The clinical significance of this is unknown.

Drugs primarily metabolised by CYP3A4, somatrogon [2] ---> SmPC of [2] of EMA

The clearance of compounds metabolised by CYP3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be increased and could result in lower exposure of these compounds.

Estrogens, somatrogon [2] ---> SmPC of [2] of EMA

In female patients on oral oestrogen-containing therapy, a higher dose of somatrogon may be required to achieve the treatment goal

Fertility, somatrogon [2] ---> SmPC of [2] of EMA

The risk of infertility in females or males of reproductive potential has not been studied in humans. In a rat study, the fertility in males and females was not affected (see section 5.3).

Glucocorticoids, somatrogon [2] ---> SmPC of [2] of EMA

Concomitant treatment with glucocorticoids may inhibit the growth-promoting effects of somatrogon.

Growth hormone, somatrogon [2] ---> SmPC of [2] of EMA

Treatment with daily growth hormone may unmask previously undiagnosed or subclinical central hypothyroidism.

Hypoglycemic drugs, somatrogon [2] ---> SmPC of [2] of EMA

In patients with diabetes mellitus requiring medicinal product therapy, the dose of insulin and/or oral/injectable hypoglycaemic medicinal products may require adjustment when somatrogon therapy is initiated

Insulin, somatrogon [2] ---> SmPC of [2] of EMA

Pregnancy, somatrogon [2] ---> SmPC of [2] of EMA

Ngenla is not recommended during pregnancy and in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Somatrogon (Ngenla)

- Hypersensitivity to somatrogon (see section 4.4) or to any of the excipients listed in section 6.1.

- Somatrogon must not be used when there is any evidence of activity of a tumour based on experience with daily growth hormone medicinal products. Intracranial tumours must be inactive and antitumour therapy must be completed prior to starting growth hormone (GH) therapy. Treatment should be discontinued if there is evidence of tumour growth (see section 4.4).

- Somatrogon must not be used for growth promotion in children with closed epiphyses.

- Patients with acute critical illness suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions must not be treated with somatrogon (regarding patients undergoing substitution therapy, see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/ngenla-epar-product-information_en.pdf 23/04/2025

Somatropin

Anabolic steroids, somatropin

The co-administration may have an additive effect on bone maturation

Androgens, somatropin

The co-administration may have an additive effect on bone maturation

Breast-feeding, somatropin [2] ---> SmPC of [2] of EMA

Caution should be exercised when this medicinal product is administered to breast-feeding women.

Cloprednol, somatropin

Decreased effect of somatropin

Cyclosporine, somatropin [2] ---> SmPC of [2] of EMA

The clearance of compounds metabolised by cytochrome P450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and cyclosporine) may be increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.

Deflazacort, somatropin

Decreased effect of somatropin

Drugs primarily metabolised by CYP, somatropin [2] ---> SmPC of [2] of EMA

Somatropin administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes.

Drugs primarily metabolised by CYP3A4, somatropin [2] ---> SmPC of [2] of EMA

Estrogens, somatropin [2] ---> SmPC of [2] of EMA

In women taking oral oestrogens, a higher dose of somatropin may be required to achieve the treatment goal

Glucocorticoids, somatropin [2] ---> SmPC of [2] of EMA

Excessive glucocorticoid therapy can inhibit the actions of hGH. Patients receiving concomitant glucocorticoid therapy should have their dose carefully adjusted. Growth hormone decreases the conversion of cortisone to cortisol

Gonadotropins, somatropin

The co-administration may have an additive effect on bone maturation

Insulin glargine/lixisenatide [1], somatropin ---> SmPC of [1] of EMA

This substance may reduce the blood-glucose-lowering effect.

Insulin glulisin [1], somatropin ---> SmPC of [1] of EMA

Possible decrease in blood-glucose-lowering activity

Insulin, somatropin [2] ---> SmPC of [2] of EMA

Patients taking insulin for diabetes mellitus should be carefully monitored during treatment with somatropin. Because hGH may induce a state of insulin resistance, an adjustment of the insulin dose may be required.

Metformin, somatropin

Somatropin may antagonize the hypoglycemic effect of metformin.

Methylprednisolone, somatropin

Decreased effect of somatropin

Oral antidiabetics, somatropin [2] ---> SmPC of [2] of EMA

Prednisolone, somatropin

Prednisolone may decrease the effect of somatropin

Prednisone [1], somatropin ---> SmPC of [1] of eMC

The efficacy of somatropin may be reduced.

Pregnancy, somatropin [2] ---> SmPC of [2] of EMA

Somatropin is not recommended during pregnancy

Rosiglitazone, somatropin

Somatropin may antagonize the hypoglycemic effect of rosiglitazone

Saxagliptin, somatropin

Somatropin may antagonize the hypoglycemic effect of saxagliptin.

Sitagliptin, somatropin

May antagonize the hypoglycemic effect

Somatropin [1], thyroid hormones ---> SmPC of [1] of EMA

Growth hormone increases the extrathyroidal conversion of thyroxin (T4) to triiodothyronine (T3) and may unmask central hypothyroidism. Thyroxine replacement therapy may therefore need to be initiated or adjusted.

Somatropin, triamcinolone

Decreased effect of somatropin

CONTRAINDICATIONS of Somatropin

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Somatropin must not be used when there is any evidence of tumour activity. Intracranial tumours must be inactive and antitumour therapy must be completed prior to the initiation of growth hormone therapy. Treatment should be discontinued if there is evidence of tumour (re)growth.

- Somatropin treatment must not be started in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or to patients having acute respiratory failure or similar conditions.

http://www.ema.europa.eu/

Sonidegib (Odomzo)

BCRP substrates with narrow therapeutic range, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

BCRP substrates, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. Patients concomitantly using BCRP transporters, should be carefully monitored for adverse drug reactions.

Breast-feeding, sonidegib [2] ---> SmPC of [2] of EMA

Because of the potential for serious adverse drug reactions, such as serious developmental defects in breast-fed newborns/infants from sonidegib, women must not breast-feed while taking Odomzo or for 20 months after ending treatment

Bupropion, sonidegib [2] ---> SmPC of [2] of EMA

However, results of a drug-drug interaction study in cancer patients demonstrate that the systemic exposure of bupropion (a CYP2B6 substrate) and warfarin (a CYP2C9 substrate) is not altered when co-administered with sonidegib.

Carbamazepine, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inducers of CYP3A4 can decrease sonidegib concentrations significantly. Concomitant use of strong CYP3A inducers should be avoided

Chloroquine, sonidegib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Drugs primarily metabolised by CYP2B6, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a competitive inhibitor of CYP2B6 and CYP2C9 in vitro, potentially increasing the concentrations of substances metabolised by these enzymes. Patients should be carefully monitored for adverse drug reactions.

Drugs primarily metabolised by CYP2C9, sonidegib [2] ---> SmPC of [2] of EMA

Esomeprazole, sonidegib [2] ---> SmPC of [2] of EMA

This interaction is not expected to be clinically significant.

Fertility, sonidegib [2] ---> SmPC of [2] of EMA

Data from studies in rats and dogs indicate that male and female fertility may be irreversibly compromised by treatment with Odomzo (see section 5.3).

Fibrates, sonidegib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Foods, sonidegib [2] ---> SmPC of [2] of EMA

The bioavailability of sonidegib is increased in the presence of food (see section 5.2). Odomzo must be taken at least two hours after a meal and at least one hour before the following meal.

HMG-CoA reductase inhibitors, sonidegib [2] ---> SmPC of [2] of EMA

No patient taking HMG-CoA reductase inhibitors experienced grade 3/4 CK elevations, as opposed to 6 (9.0%) patients not taking HMG-CoA reductase inhibitors.

Hydroxychloroquine, sonidegib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Irinotecan, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

Itraconazol, sonidegib [2] ---> SmPC of [2] of EMA

Ketoconazole, sonidegib [2] ---> SmPC of [2] of EMA

Men, sonidegib [2] ---> SmPC of [2] of EMA

Male patients, even those who have had a vasectomy, must always use a condom (with spermicide, if available) when having sex with a female partner while taking Odomzo and for 6 months after the final dose.

Men, sonidegib [2] ---> SmPC of [2] of EMA

It is unknown whether sonidegib is contained in semen. Men should not father a child or donate semen while taking Odomzo and for at least 6 months after ending treatment.

Methotrexate, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

Mitoxantrone, sonidegib [2] ---> SmPC of [2] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

Muscular toxicity, sonidegib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored and dose adjustments should be considered if muscle symptoms develop.

Myotoxic medicinal products, sonidegib [2] ---> SmPC of [2] of EMA

Due to overlapping toxicities, patients taking Odomzo who are also taking medicinal products known to increase the risk of muscle-related toxicity may be at increased risk of developing muscle-related adverse events.

Nefazodone, sonidegib [2] ---> SmPC of [2] of EMA

Niacin, sonidegib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Penicillamine, sonidegib [2] ---> SmPC of [2] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Phenobarbital, sonidegib [2] ---> SmPC of [2] of EMA

Phenytoin, sonidegib [2] ---> SmPC of [2] of EMA

Posaconazole, sonidegib [2] ---> SmPC of [2] of EMA

Pravastatine, sonidegib [2] ---> SmPC of [2] of EMA

No patient taking HMG-CoA reductase inhibitors experienced grade 3/4 CK elevations, as opposed to 6 (9.0%) patients not taking HMG-CoA reductase inhibitors.

Pregnancy, sonidegib [2] ---> SmPC of [2] of EMA

If the patient does become pregnant, misses a menstrual period, or suspects for any reason that she may be pregnant, she must notify her treating physician immediately.

Pregnancy, sonidegib [2] ---> SmPC of [2] of EMA

There are no data on the use of sonidegib in pregnant women. Studies in animals have shown teratogenicity and foetotoxicity (see section 5.3). Odomzo is contraindicated during pregnancy.

Rifabutin, sonidegib [2] ---> SmPC of [2] of EMA

Rifampicin, sonidegib [2] ---> SmPC of [2] of EMA

Ritonavir, sonidegib [2] ---> SmPC of [2] of EMA

Rosuvastatin, sonidegib [2] ---> SmPC of [2] of EMA

No patient taking HMG-CoA reductase inhibitors experienced grade 3/4 CK elevations, as opposed to 6 (9.0%) patients not taking HMG-CoA reductase inhibitors.

Saquinavir, sonidegib [2] ---> SmPC of [2] of EMA

Simvastatine, sonidegib [2] ---> SmPC of [2] of EMA

No patient taking HMG-CoA reductase inhibitors experienced grade 3/4 CK elevations, as opposed to 6 (9.0%) patients not taking HMG-CoA reductase inhibitors.

Sonidegib [1], St. John's wort ---> SmPC of [1] of EMA

Sonidegib [1], statins ---> SmPC of [1] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

Sonidegib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

The dose of sonidegib used prior to initiation of the strong inducer should be resumed if the strong inducer is discontinued.

Sonidegib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Patients should be carefully monitored for adverse events if one of these agents is used together with sonidegib.

Sonidegib [1], telithromycin ---> SmPC of [1] of EMA

Sonidegib [1], topotecan ---> SmPC of [1] of EMA

Sonidegib is a breast cancer resistance protein (BCRP) inhibitor. BCRP substrates with narrow therapeutic range (e.g. methotrexate, mitoxantrone, irinotecan, topotecan) should be avoided.

Sonidegib [1], voriconazole ---> SmPC of [1] of EMA

Sonidegib [1], warfarin ---> SmPC of [1] of EMA

Sonidegib [1], women of childbearing potential ---> SmPC of [1] of EMA

Due to the risk of embryofoetal death or severe birth defects caused by sonidegib, women taking Odomzo must not be pregnant or become pregnant during treatment and for 20 months after ending treatment (see section 4.4).

Sonidegib [1], zidovudine ---> SmPC of [1] of EMA

Patients should be closely monitored for muscle-related symptoms if Odomzo is used in combination with certain medicinal products that may increase the potential risk of developing muscle toxicity

CONTRAINDICATIONS of Sonidegib (Odomzo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy and breast-feeding (see sections 4.4 and 4.6).

- Women of childbearing potential who do not comply with the Odomzo Pregnancy Prevention Programme (see sections 4.4 and 4.6).

https://www.ema.europa.eu/en/documents/product-information/odomzo-epar-product-information_en.pdf 26/04/2021

Sorafenib (Nexavar)

Ability to drive, sorafenib [2] ---> SmPC of [2] of EMA

No studies on the effects on the ability to drive and use machines have been performed. There is no evidence that sorafenib affects the ability to drive or to operate machinery.

Antibiotics, sorafenib [2] ---> SmPC of [2] of EMA

Co-administration of neomycin or other antibiotics that cause major ecological disturbances of the gastrointestinal microflora may lead to a decrease in sorafenib bioavailability (see section 4.5).

Binimetinib [1], sorafenib ---> SmPC of [1] of EMA

UGT1A1 inducers (such as rifampicin and phenobarbital) and inhibitors (such as indinavir, atazanavir, sorafenib) should be co-administered with caution.

Breast-feeding, sorafenib [2] ---> SmPC of [2] of EMA

Because sorafenib could harm infant growth and development, women must not breast-feed during sorafenib treatment.

Cabotegravir [1], sorafenib ---> SmPC of [1] of EMA

No dosing adjustments for Vocabria are, therefore, recommended in the presence of UGT1A1 inhibitors (e.g. atazanavir, erlotinib, sorafenib).

Capecitabine, sorafenib [2] ---> SmPC of [2] of EMA

Co-administration of capecitabine (750-1050 mg/m2 twice daily, Days 1-14 every 21 days) and sorafenib (200 or 400 mg twice daily, continuous uninterrupted administration) resulted in no significant change in sorafenib exposure

Carbamazepine, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Carboplatin, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib had no clinically relevant effect on the pharmacokinetics of gemcitabine, cisplatin, carboplatin, oxaliplatin or cyclophosphamide.

Cisplatin, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib had no clinically relevant effect on the pharmacokinetics of gemcitabine, cisplatin, carboplatin, oxaliplatin or cyclophosphamide.

Cyclophosphamide, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib had no clinically relevant effect on the pharmacokinetics of gemcitabine, cisplatin, carboplatin, oxaliplatin or cyclophosphamide.

CYP1A2 inductors, sorafenib [2] ---> SmPC of [2] of EMA

CYP1A2 and CYP3A4 activities were not altered after treatment of cultured human hepatocytes with sorafenib, indicating that sorafenib is unlikely to be an inducer of CYP1A2 and CYP3A4

CYP3A4 and CYP2B6 inductors, sorafenib

The CYP3A and CYP2B6 inductions may decrease the plasma levels of sorafenib

CYP3A4 inductors, sorafenib [2] ---> SmPC of [2] of EMA

CYP1A2 and CYP3A4 activities were not altered after treatment of cultured human hepatocytes with sorafenib, indicating that sorafenib is unlikely to be an inducer of CYP1A2 and CYP3A4

Dexamethasone, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Dextromethorphan, sorafenib [2] ---> SmPC of [2] of EMA

Co-administration of sorafenib and midazolam, dextromethorphan or omeprazole, which are substrates for CYP3A4, CYP2D6 and CYP2C19, did not alter the exposure of these agents. This indicates that sorafenib is neither inhibitor/inducer of these isoenzymes.

Digoxin, sorafenib [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of P-gp substrates such as digoxin cannot be excluded with concomitant treatment with sorafenib.

Docetaxel, sorafenib [2] ---> SmPC of [2] of EMA

Caution is recommended when sorafenib is co-administered with docetaxel

Doxorubicine, sorafenib [2] ---> SmPC of [2] of EMA

Concomitant treatment with sorafenib resulted in a 21 % increase in the AUC of doxorubicin.

Drugs primarily metabolised by UGT1A1, sorafenib [2] ---> SmPC of [2] of EMA

Caution is recommended when administering sorafenib with compounds that are metabolised/eliminated predominantly by the UGT1A1 (e.g. irinotecan) or UGT1A9 pathways

Drugs primarily metabolised by UGT1A9, sorafenib [2] ---> SmPC of [2] of EMA

Caution is recommended when administering sorafenib with compounds that are metabolised/eliminated predominantly by the UGT1A1 (e.g. irinotecan) or UGT1A9 pathways

Electrolyte imbalance, sorafenib [2] ---> SmPC of [2] of EMA

When using sorafenib in these patients, periodic monitoring with on-treatment electrocardiograms and electrolytes (magnesium, potassium, calcium) should be considered.

Fertility, sorafenib [2] ---> SmPC of [2] of EMA

Results from animal studies further indicate that sorafenib can impair male and female fertility (see section 5.3).

Foods, sorafenib [2] ---> SmPC of [2] of EMA

It is recommended that sorafenib should be administered without food or with a low or moderate fat meal.

Gemcitabine, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib had no clinically relevant effect on the pharmacokinetics of gemcitabine, cisplatin, carboplatin, oxaliplatin or cyclophosphamide.

Glucuronidation inductors, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Hypocalcemia, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib has been shown to prolong the QT/QTc interval (see section 5.1), which may lead to an increased risk for ventricular arrhythmias.

Hypokalemia, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib has been shown to prolong the QT/QTc interval (see section 5.1), which may lead to an increased risk for ventricular arrhythmias.

Hypomagnesemia, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib has been shown to prolong the QT/QTc interval (see section 5.1), which may lead to an increased risk for ventricular arrhythmias.

Irinotecan, sorafenib [2] ---> SmPC of [2] of EMA

Caution is recommended when administering sorafenib with compounds that are metabolised/eliminated predominantly by the UGT1A1 (e.g. irinotecan) or UGT1A9 pathways

Ketoconazole, sorafenib [2] ---> SmPC of [2] of EMA

Clinical pharmacokinetic interactions of sorafenib with CYP3A4 inhibitors are unlikely.

Midazolam, sorafenib [2] ---> SmPC of [2] of EMA

Neomycin, sorafenib [2] ---> SmPC of [2] of EMA

Co-administration interferes with the enterohepatic recycling of sorafenib, resulting in decreased sorafenib exposure

Nevirapine, sorafenib

The CYP3A and CYP2B6 inductions may decrease the plasma levels of sorafenib

Omeprazole, sorafenib [2] ---> SmPC of [2] of EMA

Oxaliplatin, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib had no clinically relevant effect on the pharmacokinetics of gemcitabine, cisplatin, carboplatin, oxaliplatin or cyclophosphamide.

P-glycoprotein substrates, sorafenib [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of P-gp substrates such as digoxin cannot be excluded with concomitant treatment with sorafenib.

Paclitaxel+carboplatin, sorafenib [2] ---> SmPC of [2] of EMA

These data indicate no need for dose adjustments when paclitaxel and carboplatin are co-administered with sorafenib with a 3-day break in sorafenib dosing (two days prior to and on the day of paclitaxel/carboplatin administration).

Phenobarbital, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Phenprocoumon, sorafenib [2] ---> SmPC of [2] of EMA

Should be monitored regularly for changes in prothrombin time, INR or clinical bleeding episodes

Phenytoin, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Platinum compounds, sorafenib [2] ---> SmPC of [2] of EMA

Higher mortality has been reported in patients with squamous cell carcinoma of the lung treated with sorafenib in combination with platinum-based chemotherapies.

Pregnancy, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib should not be used during pregnancy unless clearly necessary, after careful consideration of the needs of the mother and the risk to the foetus.

Proteolytic enzymes enriched in bromelain [1], sorafenib ---> SmPC of [1] of EMA

NexoBrid, when absorbed, is an inhibitor of CYP2C8 and CYP2C9. This should be taken into account if it is used in patients receiving CYP2C8 substrates

QT interval prolonging drugs, sorafenib [2] ---> SmPC of [2] of EMA

Sorafenib has been shown to prolong the QT/QTc interval (see section 5.1), which may lead to an increased risk for ventricular arrhythmias.

Rifampicin, sorafenib [2] ---> SmPC of [2] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Selpercatinib [1], sorafenib ---> SmPC of [1] of EMA

Sorafenib [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Sorafenib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Clinical pharmacokinetic interactions of sorafenib with CYP3A4 inhibitors are unlikely.

Sorafenib [1], UGT1A1 inductors ---> SmPC of [1] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

Sorafenib [1], warfarin ---> SmPC of [1] of EMA

Should be monitored regularly for changes in prothrombin time, INR or clinical bleeding episodes

Sorafenib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment.

CONTRAINDICATIONS of Sorafenib (Nexavar)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/nexavar-epar-product-information_en.pdf 28/03/2025

Other trade names: Sorafenib Accord,

Sotagliflozin (Zynquista)

Ability to drive, sotagliflozin [2] ---> SmPC of [2] of EMA

Sotagliflozin has no or negligible influence on the ability to drive and use machines. However, patients should be alerted to the risk of hypoglycaemia as sotagliflozin is used in combination with insulin.

Benzylpenicillin, sotagliflozin [2] ---> SmPC of [2] of EMA

It cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP- substrates resulting in potentially larger increases of exposure than seen for rosuvastatin.

Bosentan, sotagliflozin [2] ---> SmPC of [2] of EMA

It cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP- substrates resulting in potentially larger increases of exposure than seen for rosuvastatin.

Breast-feeding, sotagliflozin [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Sotagliflozin should not be used during breast-feeding.

Digoxin, sotagliflozin [2] ---> SmPC of [2] of EMA

There is an increase in AUC0-inf and Cmax of digoxin (27% and 52% respectively) when co- administered with sotagliflozin 400 mg, due to inhibition of P-gp by sotagliflozin.

Drugs primarily metabolised by CYP1A2, sotagliflozin [2] ---> SmPC of [2] of EMA

Based on in-vitro data, induction of CYP2C9, CYP2B6 and CYP1A2 cannot be ruled out. Substrates of these enzymes should be monitored for decreases in efficacy.

Drugs primarily metabolised by CYP2B6, sotagliflozin [2] ---> SmPC of [2] of EMA

Based on in-vitro data, induction of CYP2C9, CYP2B6 and CYP1A2 cannot be ruled out. Substrates of these enzymes should be monitored for decreases in efficacy.

Drugs primarily metabolised by CYP2C9, sotagliflozin [2] ---> SmPC of [2] of EMA

Based on in-vitro data, induction of CYP2C9, CYP2B6 and CYP1A2 cannot be ruled out. Substrates of these enzymes should be monitored for decreases in efficacy.

Enzyme inductors, sotagliflozin [2] ---> SmPC of [2] of EMA

If an enzyme inducer (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) must be co-administered with sotagliflozin, consider frequent monitoring of glucose level.

Fertility, sotagliflozin [2] ---> SmPC of [2] of EMA

No studies on the effect on human fertility have been conducted for sotagliflozin. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Fexofenadine, sotagliflozin [2] ---> SmPC of [2] of EMA

It cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP- substrates resulting in potentially larger increases of exposure than seen for rosuvastatin.

Furosemide, sotagliflozin [2] ---> SmPC of [2] of EMA

It cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP- substrates resulting in potentially larger increases of exposure than seen for rosuvastatin.

Insulin, sotagliflozin [2] ---> SmPC of [2] of EMA

Insulin may increase the risk of hypoglycaemia. A lower dose of insulin may be required to minimise the risk of hypoglycaemia when used in combination with sotagliflozin

Metformin, sotagliflozin [2] ---> SmPC of [2] of EMA

Interaction studies in healthy volunteers showed that metformin, metoprolol, midazolam, rosuvastatin and oral contraceptives had no clinically relevant effect on the pharmacokinetics of sotagliflozin.

Methotrexate, sotagliflozin [2] ---> SmPC of [2] of EMA

It cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP- substrates resulting in potentially larger increases of exposure than seen for rosuvastatin.

Metoprolol, sotagliflozin [2] ---> SmPC of [2] of EMA

Midazolam, sotagliflozin [2] ---> SmPC of [2] of EMA

Oral contraceptives, sotagliflozin [2] ---> SmPC of [2] of EMA

Paclitaxel, sotagliflozin [2] ---> SmPC of [2] of EMA

It cannot be ruled out that sotagliflozin may interact with other sensitive OAT3, OATP- and/or BCRP- substrates resulting in potentially larger increases of exposure than seen for rosuvastatin.

Phenobarbital, sotagliflozin [2] ---> SmPC of [2] of EMA

If an enzyme inducer (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) must be co-administered with sotagliflozin, consider frequent monitoring of glucose level.

Phenytoin, sotagliflozin [2] ---> SmPC of [2] of EMA

If an enzyme inducer (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) must be co-administered with sotagliflozin, consider frequent monitoring of glucose level.

Pregnancy, sotagliflozin [2] ---> SmPC of [2] of EMA

Sotagliflozin is not recommended during the second and third trimesters of pregnancy. As a precautionary measure, when pregnancy is detected, treatment with sotagliflozin should be discontinued.

Rifampicin, sotagliflozin [2] ---> SmPC of [2] of EMA

The coadministration of a multiple dosing regimen of rifampicin, an inducer of various UGT and CYP metabolizing enzymes, with a single dose of 400 mg sotagliflozin resulted in a decrease in the AUC0-inf (60%) and Cmax (40%) of sotagliflozin.

Ritonavir, sotagliflozin [2] ---> SmPC of [2] of EMA

If an enzyme inducer (e.g., rifampicin, phenytoin, phenobarbital, ritonavir) must be co-administered with sotagliflozin, consider frequent monitoring of glucose level.

Rosuvastatin, sotagliflozin [2] ---> SmPC of [2] of EMA

An increase in total exposure and Cmax of rosuvastatin of ca 1.2- and 1.4-fold, respectively, was demonstrated when co-administered with sotagliflozin and is not deemed clinically relevant.

Rosuvastatin, sotagliflozin [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Sotagliflozin (Zynquista)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/zynquista-epar-product-information_en.pdf 16/08/2022 (withdrawn)

Sotalol

Ability to drive, sotalol [2] ---> SmPC of [2] of eMC

There are no data available, but the occasional occurrence of side-effects such as dizziness and fatigue should be taken into account

Abiraterone [1], sotalol ---> SmPC of [1] of EMA

Since androgen deprivation treatment may prolong the QT interval, caution is advised when administering ZYTIGA with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes

Alcohol, sotalol

The concomitant use of alcohol and sotalol should be avoided due to the possibility of ventricular arrhythmias

Alpha-methyldopa, sotalol

The co-administration of sotalol and alfa-methyldopa may increase the negative chronotropic and dromotropic effects of sotalol

Aluminium hydroxide, sotalol

Concomitant use of aluminium hydroxide may decrease the absorption and effect of betablockers. Separate administration by at least 2-3 hours

Amantadine, sotalol

The co-administration of amantadine with drugs that prolong the QT interval is contraindicated

Ambenonium, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Amiodarone [1], sotalol ---> SmPC of [1] of eMC

Combined therapy of amiodarone with drugs which prolong the QT interval is contra-indicated due to the increased risk of torsades de pointes

Amisulpride [1], sotalol ---> SmPC of [1] of eMC

Caution is advised when prescribing amisulpride with medicines known to prolong the QT interval

Amitriptyline [1], sotalol ---> SmPC of [1] of eMC

There is an increased risk of ventricular arrhythmias associated with concomitant use of sotalol.

Amphotericin, sotalol [2] ---> SmPC of [2] of eMC

With potassium-depleting drugs may occur hypokalaemia, increasing the potential for torsade de pointes

Anticholinesterase, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Antihypertensives, sotalol

The combination may enhance the hypotensive effect

Arsenic trioxide [1], sotalol ---> SmPC of [1] of EMA

Caution is advised when arsenic trioxide is coadministered with other medicinal products known to cause QT/QTc interval prolongation

Astemizole, sotalol [2] ---> SmPC of [2] of eMC

Sotalol should be given with extreme caution in conjunction with other drugs known to prolong the QT-interval. Drugs that prolong the QT-interval may cause torsades de pointes. The co-administration with sotalol is contraindicated

Azithromycin [1], sotalol ---> SmPC of [1] of eMC

Azithromycin should be used with caution in patients currently receiving treatment with other active substances known to prolong QT interval

Baclofen, sotalol

Increased antihypertensive effect

Barbiturates, sotalol

The combination may enhance the hypotensive effect

Bepridil, sotalol [2] ---> SmPC of [2] of eMC

Beta2-adrenergic agonists, sotalol [2] ---> SmPC of [2] of eMC

Patients in need of beta-agonists should not normally receive sotalol. However, if concomitant therapy is necessary beta-agonists may have to be administered in increased dosages.

Betablockers, sotalol

The co-administration enhances the effects of sotalol. The combination is contraindicated

Bosutinib [1], sotalol ---> SmPC of [1] of EMA

Bosutinib should be used with caution in patients who have or may develop prolongation of QT, including those patients taking anti-arrhythmic medicinal products or other medicinal products that may lead to QT prolongation

Breast-feeding, sotalol [2] ---> SmPC of [2] of eMC

Most beta-blockers, particularly lipophilic compounds, will pass into breast milk although to a variable extent. Breast feeding is therefore not recommended during administration of these compounds.

Budipine, sotalol

The co-administration of budipine with drugs known to prolong QT interval is contraindicated

Cardiodepressants, sotalol [2] ---> SmPC of [2] of eMC

Special caution has to be exercised with the co-administration of sotalol witch anaesthetic agents that can cause heart depression

Carteolol, sotalol

The co-administration increases the risk of heart rhythm disorders, particularly torsades de pointes

Centrally-acting antihypertensives, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Ceritinib [1], sotalol ---> SmPC of [1] of EMA

Ceritinib should be used with caution in patients taking other medicinal products that may lead to QT prolongation. Monitoring of the QT interval is indicated in the event of combinations of such medicinal products

Chlorpromazine, sotalol [2] ---> SmPC of [2] of eMC

Cisapride, sotalol [2] ---> SmPC of [2] of eMC

Class IA antiarrhythmic agents, sotalol [2] ---> SmPC of [2] of eMC

Class III antiarrhythmic agents, sotalol [2] ---> SmPC of [2] of eMC

Clomipramine [1], sotalol ---> SmPC of [1] of eMC

The risk of QTc prolongation and Torsade de Pointes is likely to be increased if clomipramine is co-administered with other drugs that can cause QTc prolongation. Therefore concomitant use is not recommended

Clonidine, sotalol

The co-administration of sotalol and clonidine may increase the negative chronotropic and dromotropic effects of sotalol

Corticosteroids, sotalol [2] ---> SmPC of [2] of eMC

With potassium-depleting drugs may occur hypokalaemia, increasing the potential for torsade de pointes

Crizotinib [1], sotalol ---> SmPC of [1] of EMA

Concomitant use of crizotinib (prolongs QT interval) with medicinal products known to prolong QT interval or medicinal products able to induce Torsades de pointes should be carefully considered.

Cyamemazine, sotalol [2] ---> SmPC of [2] of eMC

Cyclopropane, sotalol [2] ---> SmPC of [2] of eMC

Special caution has to be exercised with the co-administration of sotalol witch anaesthetic agents that can cause heart depression

Degarelix [1], sotalol ---> SmPC of [1] of EMA

The combination of degarelix with medicinal products known to prolong the QTc interval or medicinal products able to induce torsades de pointes should be carefully evaluated

Delamanid [1], sotalol ---> SmPC of [1] of EMA

Digital glycosides, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Dihydropyridines, sotalol

The co-administration may increase the risk of hypotension,

Diltiazem, sotalol [2] ---> SmPC of [2] of eMC

Beta-blockers should be avoided in combination with cardiodepressant calcium-channel blockers such as verapamil and diltiazem because of the additive effects on atrioventricular conduction, and ventricular function.

Diphemanil, sotalol [2] ---> SmPC of [2] of eMC

Disopyramide, sotalol [2] ---> SmPC of [2] of eMC

Dofetilide, sotalol [2] ---> SmPC of [2] of eMC

Donepezil, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Dronedarone, sotalol [2] ---> SmPC of [2] of eMC

Droperidol, sotalol [2] ---> SmPC of [2] of eMC

Drugs inducing bradycardia, sotalol [2] ---> SmPC of [2] of eMC

Bradycardia increases the risk of torsades de pointes.

Eliglustat [1], sotalol ---> SmPC of [1] of EMA

Because eliglustat is predicted to cause mild increases in ECG intervals at substantially elevated plasma concentrations, use of eliglustat should be avoided in combination with Class IA and Class III antiarrhythmic medicinal products.

Enalapril/hydrochlorothiazide [1], sotalol ---> SmPC of [1] of eMC

Increased risk of torsades de pointes.

Enzalutamide [1], sotalol ---> SmPC of [1] of EMA

The concomitant use of enzalutamide with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated

Erythromycin, sotalol [2] ---> SmPC of [2] of eMC

Floctafenine, sotalol [2] ---> SmPC of [2] of eMC

Beta-adrenergic blocking agents may impede the compensatory cardiovascular reactions associated with hypotension or shock that may be induced by floctafenine.

Flupentixol [1], sotalol ---> SmPC of [1] of eMC

Increases in the QT interval related to antipsychotic treatment may be exacerbated by the co-administration of other drugs known to significantly increase the QT interval. Co-administration of such drugs should be avoided.

Fluphenazine [1], sotalol ---> SmPC of [1] of eMC

The effect of fluphenazine on the QT interval is likely to be potentiated by concurrent use of other drugs that also prolong the QT interval. Therefore, concurrent use of these drugs and fluphenazine is contraindicated.

Galantamine, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Guanfacin, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Halofantrine, sotalol [2] ---> SmPC of [2] of eMC

Halogenated anaesthetics, sotalol

Sotalol decreases the cardiovascular compensation mechanisms

Haloperidol [1], sotalol ---> SmPC of [1] of eMC

Hydralazine, sotalol

The co-administration may increase the hypotensive effect

Hydrochlorothiazide, sotalol ---> SmPC of [losartan/hydrochlorothiazide] of eMC

Periodic monitoring of serum potassium and ECG is recommended, when hydrochlorothiazide is administered with drugs which may induce torsades de pointes

Hydroquinidine, sotalol [2] ---> SmPC of [2] of eMC

Hydroxyzine [1], sotalol ---> SmPC of [1] of eMC

Co-administration of hydroxyzine with drugs known to prolong the QT interval and/or induce Torsade de Pointes increase the risk of cardiac arrhythmia. Therefore, the combination is contra-indicated

Hypokalemia, sotalol [2] ---> SmPC of [2] of eMC

With potassium-depleting diuretic may occur hypokalaemia or hypomagnesaemia, increasing the potential for torsade de pointes

Ibutilide, sotalol [2] ---> SmPC of [2] of eMC

IMAOs, sotalol

Significant blood pressure increase

Indapamide [1], sotalol ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Insulin, sotalol [2] ---> SmPC of [2] of eMC

Hyperglycaemia may occur, and the dosage of antidiabetic drugs may require adjustment. Symptoms of hypoglycaemia (tachycardia) may be masked by beta-blocking agents.

Isoprenaline, sotalol

The co-administration may require increasing the dose of beta2-adrenergic agonist

Ivabradine [1], sotalol ---> SmPC of [1] of EMA

The concomitant use of cardiovascular and non-cardiovascular QT prolonging medicinal products with ivabradine should be avoided since QT prolongation may be exacerbated by heart rate reduction.

Levomepromazine, sotalol

Lidocaine, sotalol

Increased plasma concentrations of (intravenous) lidocaine with possibly neurological and cardiac adverse reactions (due to decreased hepatic clearance of lidocaine)

Lithium, sotalol

As a precautionary measure, lithium should be avoided in patients concomitantly treated with drugs that are known to prolong the QT interval

Losartan/hydrochlorothiazide [1], sotalol ---> SmPC of [1] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Lurasidone [1], sotalol ---> SmPC of [1] of EMA

Caution is advised when prescribing lurasidone with medicinal products known to prolong the QT interval

Macrolide antibiotics, sotalol [2] ---> SmPC of [2] of eMC

Mequitazine, sotalol

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Mizolastine, sotalol [2] ---> SmPC of [2] of eMC

Moxifloxacin [1], sotalol ---> SmPC of [1] of eMC

Muscle relaxants (non-depolarizing), sotalol [2] ---> SmPC of [2] of eMC

The neuromuscular blockade is prolonged by beta-blocking agents.

Neostigmine, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Nilotinib [1], sotalol ---> SmPC of [1] of EMA

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with medicinal products with a known potential to prolong QT. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

Non-potassium-sparing diuretics, sotalol [2] ---> SmPC of [2] of eMC

With potassium-depleting diuretic may occur hypokalaemia or hypomagnesaemia, increasing the potential for torsade de pointes

Norepinephrine, sotalol

Significant blood pressure increase

Nortriptyline, sotalol

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

NSAID, sotalol

The inhibition of prostaglandin synthesis may decrease the antihypertensive effect of betablocker

Oral antidiabetics, sotalol [2] ---> SmPC of [2] of eMC

Hyperglycaemia may occur, and the dosage of antidiabetic drugs may require adjustment. Symptoms of hypoglycaemia (tachycardia) may be masked by beta-blocking agents.

Paliperidone [1], sotalol ---> SmPC of [1] of EMA

Caution is advised when prescribing paliperidone with medicines known to prolong the QT interval

Panobinostat [1], sotalol ---> SmPC of [1] of EMA

Based on preclinical and clinical data, panobinostat has the potential to prolong the QT interval. Concomitant use of panobinostat and other substances that are known to prolong the QT interval is not recommended.

Pasireotide [1], sotalol ---> SmPC of [1] of EMA

Clinical monitoring of heart rate, notably at the beginning of treatment, is recommended in patients receiving pasireotide concomitantly with bradycardic medicinal products

Pentamidine, sotalol [2] ---> SmPC of [2] of eMC

Phenothiazines, sotalol [2] ---> SmPC of [2] of eMC

Pilocarpine, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Pimozide [1], sotalol ---> SmPC of [1] of eMC

Concomitant use of pimozide with drugs known to prolong the QT interval is contra-indicated

Piperaquine/artenimol [1], sotalol ---> SmPC of [1] of EMA

The combination of piperaquine/dihydroartemisinin with drugs that are known to prolong the QTc interval is contraindicated: additive effect on the QTc interval

Pregnancy, sotalol [2] ---> SmPC of [2] of eMC

Sotalol should be used in pregnancy only if the potential benefits outweigh the possible risk to the foetus.

Promazine [1], sotalol ---> SmPC of [1] of eMC

Propafenone, sotalol

Alterations of contractility, automatism and conduction (inhibition of sympathetic compensatory mechanisms)

Pyridostigmine, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

QT interval prolonging drugs, sotalol [2] ---> SmPC of [2] of eMC

Quinidine, sotalol [2] ---> SmPC of [2] of eMC

Quinolones, sotalol [2] ---> SmPC of [2] of eMC

Ranolazine [1], sotalol ---> SmPC of [1] of EMA

Concomitant administration of class III antiarrhythmics (other than amiodarone) with ranolazine is contraindicated

Reserpine, sotalol

The co-administration of sotalol and reserpine may increase the negative chronotropic and dromotropic effects of sotalol

Risperidone [1], sotalol ---> SmPC of [1] of eMC

Caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval

Rivastigmine, sotalol

Bradycardia-inducing medicinal products enhance the risk of torsades de pointes

Saquinavir/ritonavir, sotalol ---> SmPC of [saquinavir] of EMA

The combination is contraindicated due to the potential for life threatening cardiac arrhythmia

Sertindole, sotalol

Sodium picosulfate, sotalol

Hypokaliemia may be a risk of torsades de pointes in patients treated with antiarrhythmics

Sotalol [1], sparfloxacin ---> SmPC of [1] of eMC

Sotalol [1], stimulant laxatives ---> SmPC of [1] of eMC

With potassium-depleting drugs may occur hypokalaemia, increasing the potential for torsade de pointes

Sotalol [1], sultopride ---> SmPC of [1] of eMC

Sotalol [1], terfenadine ---> SmPC of [1] of eMC

Sotalol [1], thioridazine ---> SmPC of [1] of eMC

Sotalol [1], torsades de pointes inducing drugs ---> SmPC of [1] of eMC

Sotalol [1], trichloroethylene ---> SmPC of [1] of eMC

Special caution has to be exercised with the co-administration of sotalol witch anaesthetic agents that can cause heart depression

Sotalol [1], trifluoperazine ---> SmPC of [1] of eMC

Sotalol [1], verapamil ---> SmPC of [1] of eMC

Sotalol, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sotalol, telithromycin [2] ---> SmPC of [2] of EMA

Telithromycin has been shown to decrease the Cmax by 34 % and AUC of sotalol by 20 % due to decreased absorption.

Sotalol, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Periodic monitoring of serum potassium and ECG is recommended when MicardisPlus is administered with drugs affected by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics) and torsades de pointes inducing medicinal products

Sotalol, tetrabenazine [2] ---> SmPC of [2] of eMC

Tetrabenazine should be used with caution with drugs known to prolong QTc

Sotalol, tiapride [2] ---> SmPC of [2] of eMC

Sotalol, tolterodine [2] ---> SmPC of [2] of eMC

Tolterodine should be used with caution in patients with risk factors for QT-prolongation

Sotalol, toremifene [2] ---> SmPC of [2] of EMA

Sotalol, triamcinolone acetonide

Concomitant use of triamcinolone with class III antiarrhythmics is not recommended

Sotalol, tricyclic antidepressant [2] ---> SmPC of [2] of eMC

Sotalol, vardenafil [2] ---> SmPC of [2] of EMA

Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors, for example concomitant administration of antiarrhythmic medicinal products in Class III

Sotalol, vasodilators

The combination may enhance the hypotensive effect

Sotalol, xipamide

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

Sotalol, zuclopenthixol [2] ---> SmPC of [2] of eMC

CONTRAINDICATIONS of Sotalol

- Sotacor should not be used where there is evidence of sick sinus syndrome;

- second and third degree AV heart block unless a functioning pacemaker is present;

- congenital or acquired long QT syndromes;

- torsades de pointes;

- symptomatic sinus bradycardia;

- uncontrolled congestive heart failure;

- cardiogenic shock;

- anaesthesia that produces myocardial depression;

- untreated phaeochromocytoma;

- hypotension (except due to arrhythmia);

- Raynaud's phenomenon and severe peripheral circulatory disturbances;

- history of chronic obstructive airway disease or bronchial asthma;

- hypersensitivity to any of the components of the formulation;

- metabolic acidosis;

- renal failure (creatinine clearance < 10 ml/min).

http://www.medicines.org.uk/emc/

Sotatercept (Winrevair)

Breast-feeding, sotatercept [2] ---> SmPC of [2] of EMA

A risk to newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment and for 4 months after the last dose of treatment.

Fertility, sotatercept [2] ---> SmPC of [2] of EMA

Based on findings in animals, sotatercept may impair female and male fertility (see section 5.3).

Pregnancy, sotatercept [2] ---> SmPC of [2] of EMA

Winrevair is not recommended during pregnancy and in women of childbearing potential not using contraception.

Sotatercept [1], women of childbearing potential ---> SmPC of [1] of EMA

Pregnancy testing is recommended for these women before starting treatment. Women of childbearing potential should use effective contraception during treatment and for at least 4 months after the last dose if treatment is discontinued (see section 5.3).

CONTRAINDICATIONS of Sotatercept (Winrevair)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pacientes con recuentos de plaquetas constantemente < 50 x 109/l antes de iniciar el tratamiento.

https://www.ema.europa.eu/en/documents/product-information/winrevair-epar-product-information_en.pdf 25/09/2024

Sotorasib (Lumykras)

Alfentanyl, sotorasib [2] ---> SmPC of [2] of EMA

Amlodipine, sotorasib [2] ---> SmPC of [2] of EMA

Antacids, sotorasib [2] ---> SmPC of [2] of EMA

If treatment with an acid-reducing agent is required, LUMYKRAS should be taken 4 hours before or 10 hours after administration of a local antacid (see section 4.2).

BCRP substrates, sotorasib [2] ---> SmPC of [2] of EMA

LUMYKRAS is a weak BCRP inhibitor. Co-administration of LUMYKRAS with a BCRP substrate led to an increase in the plasma concentrations of the BCRP substrate, which may increase the effect of the substrate.

Breast-feeding, sotorasib [2] ---> SmPC of [2] of EMA

It is unknown if sotorasib or its metabolites are excreted in human milk. A risk to breast-fed newborns/infants cannot be excluded. LUMYKRAS should not be used during breast-feeding.

Capivasertib [1], sotorasib ---> SmPC of [1] of EMA

Co-administration of capivasertib with moderate CYP3A4 inducer has the potential to decrease the concentration of capivasertib. This may reduce the efficacy of TRUQAP. Co-administration of moderate CYP3A4 inducers should be avoided

Carbamazepine, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort) with LUMYKRAS is not recommended because they may decrease sotorasib exposure.

Cyclosporine, sotorasib [2] ---> SmPC of [2] of EMA

CYP3A4 substrates with narrow therapeutic index, sotorasib [2] ---> SmPC of [2] of EMA

Digoxin, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of sotorasib with digoxin (a P-glycoprotein [P-gp] substrate) increased digoxin Cmax by 1.9-fold and AUCinf by 1.2-fold of digoxin administered alone.

Dihydroergotamine, sotorasib [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP2B6, sotorasib [2] ---> SmPC of [2] of EMA

In vitro data indicated that sotorasib may have the potential to induce CYP2B6, CYP2C8, CYP2C9 and CYP2C19. When sotorasib is co-administered with medicinal products metabolised by these enzymes, appropriate monitoring is recommended.

Drugs metabolised by CYP2C19, sotorasib [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP2C8, sotorasib [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP2C9, sotorasib [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP2D6, sotorasib [2] ---> SmPC of [2] of EMA

In vitro data indicated that sotorasib may have the potential to inhibit CYP2D6. When LUMYKRAS is co-administered with CYP2D6 substrates (e.g. flecainide, propafenone, metoprolol), appropriate monitoring is recommended.

Drugs primarily metabolised by CYP3A4, sotorasib [2] ---> SmPC of [2] of EMA

Sotorasib is a moderate CYP3A4 inducer. Co-administration of sotorasib with CYP3A4 substrates led to a decrease in their plasma concentrations, which may reduce the efficacy of these substrates.

Elacestrant [1], sotorasib ---> SmPC of [1] of EMA

Concomitant administration of ORSERDU with moderate CYP3A4 inductors should be avoided, which may decrease elacestrant activity

Enzalutamide, sotorasib [2] ---> SmPC of [2] of EMA

Erdafitinib [1], sotorasib ---> SmPC of [1] of EMA

If Balversa is co-administered with a moderate CYP3A4 inducer the dose should be cautiously increased by 1 to 2 mg and adjusted gradually every two to three weeks based on clinical monitoring for adverse reactions, not to exceed 9 mg.

Ergotamine, sotorasib [2] ---> SmPC of [2] of EMA

Famotidine, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of sotorasib with a PPI (omeprazole) or an H2 receptor antagonist (famotidine) led to a decrease in sotorasib concentrations.

Fentanyl, sotorasib [2] ---> SmPC of [2] of EMA

Fertility, sotorasib [2] ---> SmPC of [2] of EMA

There are no clinical studies to evaluate the effect of sotorasib on fertility.

Flecainide, sotorasib [2] ---> SmPC of [2] of EMA

H2 antagonists, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of sotorasib with a PPI (omeprazole) or an H2 receptor antagonist (famotidine) led to a decrease in sotorasib concentrations.

Hormonal contraceptives, sotorasib [2] ---> SmPC of [2] of EMA

Itraconazol, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of multiple dose itraconazole (a strong CYP3A4 and P-gp inhibitor) did not increase sotorasib exposures to a clinically significant extent.

Lapatinib, sotorasib [2] ---> SmPC of [2] of EMA

When LUMYKRAS is co-administered with a BCRP substrate, not limited to lapatinib, methotrexate, mitoxantrone, rosuvastatin and topotecan, monitor for adverse reactions of the BCRP substrate and reduce the BCRP dose in accordance with its current SmPC.

Manidipine, sotorasib [2] ---> SmPC of [2] of EMA

Methotrexate, sotorasib [2] ---> SmPC of [2] of EMA

Metoprolol, sotorasib [2] ---> SmPC of [2] of EMA

Midazolam, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of sotorasib with midazolam (a sensitive CYP3A4 substrate) decreased midazolam Cmax by 48% and AUC by 53%.

Mitotane, sotorasib [2] ---> SmPC of [2] of EMA

Mitoxantrone, sotorasib [2] ---> SmPC of [2] of EMA

Omeprazole, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of sotorasib with a PPI (omeprazole) or an H2 receptor antagonist (famotidine) led to a decrease in sotorasib concentrations.

P-glycoprotein substrates with small therapeutic index, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of LUMYKRAS with P-gp substrates with narrow therapeutic indices is not recommended. If co-administration cannot be avoided, adjust the P-gp substrate dosage in accordance with the current summary of product characteristics.

Phenytoin, sotorasib [2] ---> SmPC of [2] of EMA

Pimozide, sotorasib [2] ---> SmPC of [2] of EMA

Pregnancy, sotorasib [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). LUMYKRAS is not recommended during pregnancy and in women of childbearing potential not using contraception.

Pregnancy, sotorasib [2] ---> SmPC of [2] of EMA

Patients must be informed of the potential hazards to the foetus if LUMYKRAS is used during pregnancy, or if the patient becomes pregnant while taking LUMYKRAS.

Propafenone, sotorasib [2] ---> SmPC of [2] of EMA

Proton pump inhibitors [1], sotorasib ---> SmPC of [1] of EMA

Co-administration of sotorasib with a PPI (omeprazole) or an H2 receptor antagonist (famotidine) led to a decrease in sotorasib concentrations.

Quinidine, sotorasib [2] ---> SmPC of [2] of EMA

Rifampicin, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of sotorasib with multiple doses of a strong CYP3A4 inducer (rifampicin) decreased sotorasib Cmax by 35% and AUC by 51%.

Rosuvastatin, sotorasib [2] ---> SmPC of [2] of EMA

Co-administration of LUMYKRAS with rosuvastatin (a BCRP substrate) increased the rosuvastatin Cmax by 70% and AUC by 34%.

Sirolimus, sotorasib [2] ---> SmPC of [2] of EMA

Sotorasib [1], St. John's wort ---> SmPC of [1] of EMA

Sotorasib [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

No dose adjustment of LUMYKRAS is recommended when co-administered with CYP3A4 inhibitors.

Sotorasib [1], tacrolimus ---> SmPC of [1] of EMA

Sotorasib [1], topotecan ---> SmPC of [1] of EMA

Sotorasib [1], women of childbearing potential ---> SmPC of [1] of EMA

LUMYKRAS may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method and for at least 7 days following the last dose of LUMYKRAS.

CONTRAINDICATIONS of Sotorasib (Lumykras)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/lumykras-epar-product-information_en.pdf 03/12/2024

Sotrovimab (Xevudy)

Breast-feeding, sotrovimab [2] ---> SmPC of [2] of EMA

Administration of sotrovimab while breast-feeding can be considered when clinically indicated.

Cytochrome P450, sotrovimab [2] ---> SmPC of [2] of EMA

Sotrovimab is not renally excreted or metabolised by cytochrome P450 (CYP) enzymes; therefore, interactions with medicinal products that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

Pregnancy, sotrovimab [2] ---> SmPC of [2] of EMA

Sotrovimab should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the foetus.

Remdesivir, sotrovimab [2] ---> SmPC of [2] of EMA

In vitro pharmacodynamic studies showed no antagonism between sotrovimab and remdesivir or bamlanivimab.

CONTRAINDICATIONS of Sotrovimab (Xevudy)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/xevudy-epar-product-information_en.pdf 09/12/2024

Sparsentan (Filspari)

Ability to drive, sparsentan [2] ---> SmPC of [2] of EMA

It should, however, be taken into account that dizziness may occur when taking sparsentan (see section 4.8). Patients with dizziness, should be advised to refrain from driving or using machines until symptoms have subsided.

ACE inhibitors, sparsentan [2] ---> SmPC of [2] of EMA

The use of sparsentan in combination with ACE inhibitors such as enalapril or lisinopril should be done with caution, and blood pressure, potassium, and kidney function should be monitored (see section 4.4).

AIIRA, sparsentan [2] ---> SmPC of [2] of EMA

Concomitant use of sparsentan with ERAs such as bosentan, ambrisentan, macitentan, sitaxentan, ARBs such as irbesartan, losartan, valsartan, candesartan, telmisartan, or renin inhibitors such as aliskiren is contraindicated (see section 4.3).

Aldosterone antagonists, sparsentan [2] ---> SmPC of [2] of EMA

Coadministration of sparsentan with mineralocorticoid (aldosterone) receptor inhibitors such as spironolactone and finerenone is expected to be associated with increased risk of hyperkalaemia.

Alfentanyl, sparsentan [2] ---> SmPC of [2] of EMA

Therefore, initiation of sparsentan as co-medication with a CYP3A4 substrate such as alfentanil, conivaptan, indinavir, cyclosporin and tacrolimus should be done with caution.

Ambrisentan, sparsentan [2] ---> SmPC of [2] of EMA

Amiloride, sparsentan [2] ---> SmPC of [2] of EMA

Concomitant use of potassium supplements, potassium-sparing diuretics such as spironolactone, eplerenone, triamterene or amiloride, or salt substitutes containing potassium may increase the risk of hyperkalaemia and is not recommended.

Antacids, sparsentan [2] ---> SmPC of [2] of EMA

Gastric pH modifying agents such as antacids, proton-pump inhibitors, and histamine 2 receptor agonists can be used concomitantly with sparsentan.

Boceprevir, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration with a strong CYP3A inhibitor such as boceprevir, telaprevir, clarithromycin, indinavir, lopinavir/ritonavir, itraconazole, nefazodone, ritonavir, grapefruit and grapefruit juice is not recommended.

Bosentan, sparsentan [2] ---> SmPC of [2] of EMA

Breast-feeding, sparsentan [2] ---> SmPC of [2] of EMA

Physicochemical data suggest excretion of sparsentan in human milk. A risk to newborns/infants cannot be excluded. Sparsentan should not be used during breastfeeding.

Bupropion, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration of sparsentan at steady state with the CYP2B6 substrate bupropion decreased bupropion Cmax by 1.5-fold and AUC0-inf by 1.5-fold. No dose adjustment is required

Candesartan, sparsentan [2] ---> SmPC of [2] of EMA

Carbamazepine, sparsentan [2] ---> SmPC of [2] of EMA

Concomitant use with a moderate or strong CYP3A inducer decreases sparsentan exposure, which may reduce the efficacy of sparsentan. Therefore, co-administration with a moderate or strong CYP3A inducer is not recommended.

Clarithromycin, sparsentan [2] ---> SmPC of [2] of EMA

Conivaptan, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration with a moderate CYP3A inhibitor such as conivaptan, fluconazole and nelfinavir inhibitor should be done with caution.

Cyclosporine, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration of sparsentan with ciclosporin (moderate inhibitor of CYP3A) increased sparsentan Cmax by 1.4-fold and AUC0-inf by 1.7-fold.

Dexamethasone, sparsentan [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, sparsentan [2] ---> SmPC of [2] of EMA

Therefore, initiation of sparsentan as co-medication with a CYP3A4 substrate such as alfentanil, conivaptan, indinavir, cyclosporin and tacrolimus should be done with caution.

Efavirenz, sparsentan [2] ---> SmPC of [2] of EMA

Enalapril, sparsentan [2] ---> SmPC of [2] of EMA

Eplerenone, sparsentan [2] ---> SmPC of [2] of EMA

Fertility, sparsentan [2] ---> SmPC of [2] of EMA

There are no data on the effects of sparsentan on human fertility. Animal data did not indicate any impairment of male or female fertility (see section 5.3).

Finerenone, sparsentan [2] ---> SmPC of [2] of EMA

Coadministration of sparsentan with mineralocorticoid (aldosterone) receptor inhibitors such as spironolactone and finerenone is expected to be associated with increased risk of hyperkalaemia.

Fluconazole, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration with a moderate CYP3A inhibitor such as conivaptan, fluconazole and nelfinavir inhibitor should be done with caution.

Grapefruit juice, sparsentan [2] ---> SmPC of [2] of EMA

Grapefruit, sparsentan [2] ---> SmPC of [2] of EMA

H2 antagonists, sparsentan [2] ---> SmPC of [2] of EMA

Gastric pH modifying agents such as antacids, proton-pump inhibitors, and histamine 2 receptor agonists can be used concomitantly with sparsentan.

Indinavir, sparsentan [2] ---> SmPC of [2] of EMA

Irbesartan, sparsentan [2] ---> SmPC of [2] of EMA

Itraconazol, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration of sparsentan with itraconazole (strong CYP3A inhibitor) increased sparsentan Cmax by 1.3-fold and AUC0-inf by 2.7-fold.

Lisinopril, sparsentan [2] ---> SmPC of [2] of EMA

Lopinavir/ritonavir, sparsentan [2] ---> SmPC of [2] of EMA

Losartan, sparsentan [2] ---> SmPC of [2] of EMA

Macitentan, sparsentan [2] ---> SmPC of [2] of EMA

Midazolam, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration of sparsentan at steady state with the CYP3A4 substrate midazolam had no effect on the systemic exposure of midazolam. No dose adjustment is required

Moderate CYP3A4 inductors, sparsentan [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration with a moderate CYP3A inhibitor such as conivaptan, fluconazole and nelfinavir inhibitor should be done with caution.

Nefazodone, sparsentan [2] ---> SmPC of [2] of EMA

Nelfinavir, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration with a moderate CYP3A inhibitor such as conivaptan, fluconazole and nelfinavir inhibitor should be done with caution.

OAT3 substrates, sparsentan [2] ---> SmPC of [2] of EMA

However, at a dose of 800 mg, sparsentan does not appear to affect the biomarker 6?-hydroxycortisol (substrate of OAT3), indicating that the clinical effect is most likely limited.

P-glycoprotein substrates, sparsentan [2] ---> SmPC of [2] of EMA

Coadministration of sparsentan with P-gp inhibition substrate should be done with caution if it is known that P-gp inhibition has a significant effect on the absorption.

Phenobarbital, sparsentan [2] ---> SmPC of [2] of EMA

Phenytoin, sparsentan [2] ---> SmPC of [2] of EMA

Pitavastatin, sparsentan [2] ---> SmPC of [2] of EMA

Co-administration of sparsentan with pitavastatin (a substrate of OATP1B1, OATP1B3, and BCRP) decreased pitavastin Cmax by 1.2-fold and AUC0-inf by 1.4-fold. No dose adjustment is required

Potassium, sparsentan [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics, sparsentan [2] ---> SmPC of [2] of EMA

Pregnancy, sparsentan [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (see section 5.3). Filspari is contraindicated during pregnancy (see section 4.3).

Proton pump inhibitors, sparsentan [2] ---> SmPC of [2] of EMA

Gastric pH modifying agents such as antacids, proton-pump inhibitors, and histamine 2 receptor agonists can be used concomitantly with sparsentan.

Renin inhibitors, sparsentan [2] ---> SmPC of [2] of EMA

Rifampicin, sparsentan [2] ---> SmPC of [2] of EMA

Ritonavir, sparsentan [2] ---> SmPC of [2] of EMA

Salt substitutes containing potassium, sparsentan [2] ---> SmPC of [2] of EMA

Sitaxentan, sparsentan [2] ---> SmPC of [2] of EMA

Sparsentan [1], spironolactone ---> SmPC of [1] of EMA

Coadministration of sparsentan with mineralocorticoid (aldosterone) receptor inhibitors such as spironolactone and finerenone is expected to be associated with increased risk of hyperkalaemia.

Sparsentan [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Sparsentan [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Sparsentan [1], tacrolimus ---> SmPC of [1] of EMA

Therefore, initiation of sparsentan as co-medication with a CYP3A4 substrate such as alfentanil, conivaptan, indinavir, cyclosporin and tacrolimus should be done with caution.

Sparsentan [1], telaprevir ---> SmPC of [1] of EMA

Sparsentan [1], telmisartan ---> SmPC of [1] of EMA

Sparsentan [1], triamterene ---> SmPC of [1] of EMA

Sparsentan [1], valsartan ---> SmPC of [1] of EMA

Sparsentan [1], warfarin ---> SmPC of [1] of EMA

Co-administration of sparsentan with a CYP2C9 substrate such as s-warfarin, phenytoin and ibuprofen or CYP2C19 substrates such as omeprazole and phenytoin should be done with caution.

Sparsentan [1], women of childbearing potential ---> SmPC of [1] of EMA

Sparsentan treatment must only be initiated in women of childbearing potential when the absence of pregnancy has been verified. Women of childbearing potential have to use effective contraception during and up to 1 month after treatment has stopped.

CONTRAINDICATIONS of Sparsentan (Filspari)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1

- Pregnancy (see sections 4.4 and 4.6)

- Coadministration of angiotensin receptor blockers (ARBs), endothelin receptor antagonists (ERAs), or renin inhibitors (see sections 4.4 and 4.5)

https://www.ema.europa.eu/en/documents/product-information/filspari-epar-product-information_en.pdf 28/05/2024

Spesolimab (Spevigo)

Breast-feeding, spesolimab [2] ---> SmPC of [2] of EMA

No data are present on excretion of spesolimab in human milk. In humans, excretion of IgG antibodies in milk occurs during the first few days after birth, which is decreasing to low concentrations soon afterwards.

CYP450, spesolimab [2] ---> SmPC of [2] of EMA

For the treatment of GPP flares, spesolimab is not expected to cause cytokine mediated CYP interaction as a perpetrator.

Fertility, spesolimab [2] ---> SmPC of [2] of EMA

Studies in mice using a surrogate, mouse specific anti-IL36R monoclonal antibody, do not indicate direct or indirect harmful effects with respect to fertility from antagonism of IL36R (see section 5.3).

Immunosuppressives, spesolimab [2] ---> SmPC of [2] of EMA

Spesolimab should not be used in combination with other GPP treatments, e.g. systemic immunosuppressants, to treat a flare (see sections 4.4 and 4.5).

Peripheral neuropathy, spesolimab [2] ---> SmPC of [2] of EMA

Cases of peripheral neuropathy have been reported in clinical trials with spesolimab.

Pregnancy, spesolimab [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of spesolimab during pregnancy.

Spesolimab [1], tuberculosis ---> SmPC of [1] of EMA

Spesolimab is contraindicated to patients with active TB infection (see section 4.3).

Spesolimab [1], vaccinations ---> SmPC of [1] of EMA

It is unknown whether spesolimab affects the efficacy of vaccines.

Spesolimab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

The interval between live vaccinations and initiation of spesolimab therapy should be at least 4 weeks. Live vaccines should not be administered for at least 16 weeks after treatment with spesolimab.

CONTRAINDICATIONS of Spesolimab (Spevigo)

- Severe or life-threatening hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 4.4).

- Clinically important active infections (e.g. active tuberculosis, see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/spevigo-epar-product-information_en.pdf 05/02/2026

Spheroids/cm2 implantation suspension (Spherox)

Ability to drive, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

Due to the surgical nature of the underlying procedure, implantation of Spherox has a major influence on the ability to drive and use machines.

Antibiotics, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

Locally applied antibiotics or disinfectants may have potential toxicity on articular cartilage and it is not recommended t that hat Spherox comes into direct contact with those substances.

Breast-feeding, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

As Spherox is used to repair cartilage defects of the joint and is therefore implanted during a surgical procedure, it is not recommended for use in pregnant or breast-feeding women.

Corticosteroids, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

In the pivotal studies of Spherox, patients were excluded if they , were under medical treatment with corticosteroids.

Disinfectant, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

Locally applied antibiotics or disinfectants may have potential toxicity on articular cartilage and it is not recommended t that hat Spherox comes into direct contact with those substances.

Fertility, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

There are no data on possible effects of Spherox treatment on fertility.

Pregnancy, spheroids/cm2 implantation suspension [2] ---> SmPC of [2] of EMA

As Spherox is used to repair cartilage defects of the joint and is therefore implanted during a surgical procedure, it is not recommended for use in pregnant or breast-feeding women.

CONTRAINDICATIONS of Spheroids/cm2 implantation suspension (Spherox)

- Patients with not fully closed epiphyseal growth plate in the affected joint.

- Primary (generalised) osteoarthritis.

- Advanced osteoarthritis of the affected joint (exceeding grade II according to Kellgren and Lawrence).

- Infection with the hepatitits B virus (HBV), hepatitis C virus (HCV) or HIV I/II viruses.

https://www.ema.europa.eu/en/documents/product-information/spherox-epar-product-information_en.pdf 03/03/2025

Spiramycin

Aminophylline [1], spiramycin ---> SmPC of [1] of eMC

Macrolide antibiotics may decrease aminophylline clearance resulting in increased plasma theophylline concentrations and the potential for increased toxicity

Breast-feeding, spiramycin

Spiramycin is excreted into breast milk and should be avoided in lactating mothers

Carbamazepine, spiramycin

Spiramycin may delay the elimination of carbamazepine

Carbidopa, spiramycin

Spiramycin prevents the absorption of carbidopa and so decreases the plasma levels of levodopa

Cephalosporins, spiramycin

Antagonistic effect

Clindamycin, spiramycin

The co-administration of spiramycin and clindamycin may have an antagonistic effect. The combination should be avoided

Coumarin anticoagulants, spiramycin

Spiramycin may delay the elimination of coumarine

Dihydroergotamine, spiramycin

The co-administration of dihydroergotamine or other non-hydrogenated ergot derivate with spiramycin may enhance the vasoconstrictor effect

Ergot derivatives, spiramycin

The co-administration of dihydroergotamine or other non-hydrogenated ergot derivate with spiramycin may enhance the vasoconstrictor effect

Hydroquinidine, spiramycin

Concomitant use of hydroquinidine with drugs that can induce torsades de pointes is contraindicated due to increased risk of heart rhythm disorders (torsades de pointes)

Hypokalemia, spiramycin

In case of hypokaliemia, the use of macrolide antibiotics is not indicated due to possible arrythmias, because they prolong the QT interval

Levodopa/carbidopa, spiramycin

Spiramycin prevents the absorption of carbidopa and so decreases the plasma levels of levodopa

Lincomycin, spiramycin

The co-administration of spiramycin and lincomycin may have an antagonistic effect. The combination should be avoided

Mequitazine, spiramycin

Concomitant use of mequitazine with drugs that prolong the QT interval is contraindicated

Methylprednisolone, spiramycin

Spiramycin may delay the elimination of methylprednisolone

Oral contraceptives, spiramycin

Antibiotic may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Penicillins, spiramycin

The macrolide may antagonize the bactericidal effects of penicillin.

Pregnancy, spiramycin

Spiramycin has been safely administered during years in pregnant women

Spiramycin, theophylline [2] ---> SmPC of [2] of eMC

The macrolide antibiotics reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Spiramycin, tiapride

It is not recommended the combination of cisapride with spiramycin IV due to both active principles can induce torsades de pointes or prolong the QT-interval

Spironolactone (Qaialdo)

Ability to drive, spironolactone [2] ---> SmPC of [2] of EMA

Somnolence and dizziness have been reported to occur in some patients. Caution is advised when driving or operating machinery until the response to initial treatment has been determined.

Abiraterone [1], spironolactone ---> SmPC of [1] of EMA

Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. Use with ZYTIGA is not recommended

Abiraterone, spironolactone [2] ---> SmPC of [2] of EMA

Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels in abiraterone-treated prostate cancer patients. Use with abiraterone is not recommended.

Abiraterone/niraparib [1], spironolactone ---> SmPC of [1] of EMA

Spironolactone binds to the androgen receptor and may increase prostate specific antigen (PSA) levels. Use with Akeega is not recommended

ACE inhibitors, spironolactone [2] ---> SmPC of [2] of EMA

Since ACE inhibitors decrease aldosterone production, they should not routinely be used with spironolactone, particularly in patients with marked renal impairment.

Acetylsalicylic acid, spironolactone [2] ---> SmPC of [2] of EMA

Non-steroidal anti-inflammatory medicinal products may attenuate the natriuretic efficacy of diuretics due to the inhibition of intra-renal synthesis of prostaglandins and have been shown to attenuate the diuretic effect of spironolactone.

AIIRA, potassium-sparing diuretics ---> SmPC of [spironolactone] of eMC

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

AIIRA, spironolactone [2] ---> SmPC of [2] of eMC

Concurrent administration of angiotensin-II receptor antagonists and spironolactone may result in an increase in serum potassium levels.

Alcohol, spironolactone

Alcohol may enhance an orthostatic hypotension

Aldosterone antagonists, spironolactone

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

Amiloride, spironolactone [2] ---> SmPC of [2] of eMC

Spironolactone should not be administered concurrently with other potassium-sparing diuretics as this may induce hyperkalaemia.

Amiloride/hydrochlorothiazide, spironolactone

Concomitant administration of potassium-sparing diuretics or potassium salts may increase the risk of hypercaliemia

Ammonium chloride, spironolactone [2] ---> SmPC of [2] of EMA

Hyperkalaemic metabolic acidosis has been reported in patients given spironolactone concurrently with ammonium chloride or colestyramine.

Anaesthesia, spironolactone [2] ---> SmPC of [2] of EMA

Caution should be exercised in the management of patients subjected to regional or general anaesthesia while they are being treated with spironolactone.

Antihypertensives, spironolactone [2] ---> SmPC of [2] of EMA

The concomitant administration of this preparation with cardiac glycosides or hypotensive agents may necessitate adjustment of those medicinal products (see section 4.5).

Antipyrine, spironolactone [2] ---> SmPC of [2] of EMA

Spironolactone enhances the metabolism of antipyrine.

Barbiturates, spironolactone

Barbiturates may enhance an orthostatic hypotension

Benazepril, spironolactone

Potassium-sparing diuretics potassium supplements or potassium-containing salt substitutes have been shown to increase the risk of hyperkalaemia when used concomitantly with ACE inhibitors.

Betablockers, spironolactone

The concomitant use of spironolactone and betablockers may cause hypercaliemia

Breast-feeding, spironolactone [2] ---> SmPC of [2] of EMA

Canrenone is excreted in human milk. Qaialdo should not be used during breast-feeding.

Calcium antagonists, spironolactone

The co-administration may cause severe hyperkalaemia

Captopril [1], spironolactone ---> SmPC of [1] of eMC

Since ACE inhibitors decrease aldosterone production they should not routinely be used with spironolactone, particularly in patients with marked renal impairment.

Carbenoxolone, spironolactone [2] ---> SmPC of [2] of EMA

Concurrent use with carbenoxolone or lithium salts should be avoided.

Cardiac glycosides, spironolactone [2] ---> SmPC of [2] of EMA

The concomitant administration of this preparation with cardiac glycosides or hypotensive agents may necessitate adjustment of those medicinal products (see section 4.5).

Cholestyramine, spironolactone [2] ---> SmPC of [2] of EMA

Hyperkalaemic metabolic acidosis has been reported in patients given spironolactone concurrently with ammonium chloride or colestyramine.

Cilazapril [1], spironolactone ---> SmPC of [1] of eMC

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.

Corticosteroids, spironolactone

The combination of corticoids with spironolactone may cause electrolyte depletion, particularly hypokalaemia

Cotrimoxazole, spironolactone [2] ---> SmPC of [2] of EMA

In addition, concomitant use of trimethoprim/sulfamethoxazole (co-trimoxazole) with spironolactone may result in clinically relevant hyperkalaemia.

Cyclosporine [1], spironolactone ---> SmPC of [1] of eMC

Caution is required with concomitant use of ciclosporin with potassium-sparing medicinal products or potassium-containing medicinal products since they may lead to significant increases in serum potassium

Digital glycosides, spironolactone

The co-administration may increase or decrease the cardiac glycoside effect

Digitoxin, spironolactone

The co-administration may decrease the positive inotrope effect of digitoxin and promote heart rhythm disorders

Digoxin, spironolactone [2] ---> SmPC of [2] of EMA

Spironolactone has been shown to increase the half-life of digoxin. Spironolactone has been reported to increase serum digoxin concentration and to interfere with certain serum digoxin assays.

Diuretics, spironolactone [2] ---> SmPC of [2] of EMA

Dilution hyponatraemia may occur in combination with other diuretics (see section 4.5).

Enalapril [1], spironolactone ---> SmPC of [1] of eMC

Since ACE inhibitors decrease aldosterone production they should not routinely be used with spironolactone, particularly in patients with marked renal impairment.

Enalapril/hydrochlorothiazide [1], spironolactone ---> SmPC of [1] of eMC

ACE inhibitors attenuate diuretic induced potassium loss. Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.

Epinephrine, spironolactone

Spironolactone reduces vascular responsiveness to adrenaline.

Eplerenone, spironolactone [2] ---> SmPC of [2] of eMC

The co-administration may cause severe hyperkalaemia. The combination is contraindicated

Felodipine/ramipril [1], spironolactone ---> SmPC of [1] of eMC

The combination may increase the serum potassium concentration and requires close monitoring of serum potassium. The combination is not recommended

Fertility, spironolactone [2] ---> SmPC of [2] of EMA

Studies in animals suggest spironolactone may impair fertility (see section 5.3).

Finerenone [1], spironolactone ---> SmPC of [1] of EMA

Kerendia should not be used concomitantly with potassium-sparing diuretics and other MRAs (e.g., eplerenone, esaxerenone, spironolactone, canrenone). It is anticipated that these medicinal products increase the risk for hyperkalaemia (see section 4.4)

Fluorimetry, spironolactone [2] ---> SmPC of [2] of EMA

In fluorimetric assays, spironolactone may interfere with the estimation of compounds with similar fluorescence characteristics.

Glycyrrhiza, spironolactone

The administration of spironolactone with great quantities of liquorice may cause a great loss of potassium with the risk of hypokaliemia

Gonadorelin, spironolactone [2] ---> SmPC of [2] of eMC

Spironolactone may stimulate the gonadotropine secretion

Heparin, spironolactone

The concomitant use of spironolactone and heparin may cause hypercaliemia

Hyperkalemia, spironolactone [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products known to cause hyperkalaemia (such as lisinopril, valsartan, indomethacin) with spironolactone may result in severe hyperkalaemia.

Imidapril [1], spironolactone ---> SmPC of [1] of eMC

Potassium sparing diuretics or supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium (potentially lethal), mainly in conjunction with renal impairment (additive hyperkaliemic effects)

Indapamide [1], spironolactone ---> SmPC of [1] of eMC

Whilst rational combinations are useful in some patients, hypokalaemia or hyperkalaemia (particularly in patients with renal failure or diabetes) may still occur. Plasma potassium and ECG should be monitored and, if necessary, treatment re

Indometacin, spironolactone

Indometacin, spironolactone [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products known to cause hyperkalaemia (such as lisinopril, valsartan, indomethacin) with spironolactone may result in severe hyperkalaemia.

Lisinopril [1], spironolactone ---> SmPC of [1] of EMA

Concomitant use of medicinal products known to cause hyperkalaemia (such as lisinopril, valsartan, indomethacin) with spironolactone may result in severe hyperkalaemia.

Lithium, spironolactone [2] ---> SmPC of [2] of EMA

Concurrent use with carbenoxolone or lithium salts should be avoided.

Losartan [1], spironolactone ---> SmPC of [1] of eMC

Concomitant use of other drugs which retain potassium or may increase potassium levels, potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium. Co-medication is not advisable.

Losartan/hydrochlorothiazide [1], spironolactone ---> SmPC of [1] of eMC

Concomitant use of potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium Co-medication is not advisable.

Low molecular weight heparins, spironolactone

The concomitant use of spironolactone and heparin may cause hypercaliemia

Mefenamic acid, spironolactone [2] ---> SmPC of [2] of EMA

Mesalazine, spironolactone

Possible attenuation of the diuretic effect

Metabolic acidosis, spironolactone [2] ---> SmPC of [2] of EMA

Reversible hyperchloraemic metabolic acidosis, usually in association with hyperkalaemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even when renal function is normal.

Metildigoxin, spironolactone

Increased plasma levels of metildigoxin

Mitotane [1], spironolactone ---> SmPC of [1] of EMA

Mitotane must not be given in combination with spironolactone, since this active substance may block the action of mitotane

Mitotane, spironolactone [2] ---> SmPC of [2] of EMA

Spironolactone may reduce mitotane plasma levels in adrenocortical carcinoma patients treated with mitotane and should not be used concomitantly with mitotane.

Narcotics, spironolactone

Narcotic agents may enhance an orthostatic hypotension

Neomycin, spironolactone

Neomycin may delay the absorption of spironolactone

Noradrenaline, spironolactone [2] ---> SmPC of [2] of EMA

Spironolactone reduces vascular responsiveness to noradrenaline.

NSAID, spironolactone [2] ---> SmPC of [2] of EMA

Olsalazine, spironolactone

The natriuretic effect of spirinolactone may be decreased

Patiromer [1], spironolactone ---> SmPC of [1] of EMA

In vitro studies have shown no potential interaction of patiromer with the other active substances

Perindopril [1], spironolactone ---> SmPC of [1] of eMC

In the treatment of class II-IV heart failure (NYHA) with an ejection fraction < 40%, and previously treated with ACE inhibitors and loop diuretics, risk of hyperkalaemia, potentially lethal

Phenazone, spironolactone

Spironolactone may increase the metabolism of phenazone and decrease its plasma levels

Potassium chloride [1], spironolactone ---> SmPC of [1] of eMC

Combined treatment of potassium chloride with potassium sparing diuretics increase the risk of hyperkalaemia

Potassium, spironolactone

Discontinue or interrupt treatment for serum potassium > 5 mEq/L or for serum creatinine > 4 mg/dL (see section 4.2).

Potassium, spironolactone [2] ---> SmPC of [2] of eMC

Potassium supplements are contraindicated except in cases of initial potassium depletion. If supplementation is considered essential, serum electrolytes should be monitored

Potassium-sparing diuretics, spironolactone [2] ---> SmPC of [2] of EMA

Potassium-sparing diuretics should be used with caution in hypertensive paediatric patients with mild renal insufficiency because of the risk of hyperkalaemia.

Pregnancy, spironolactone [2] ---> SmPC of [2] of EMA

There are no studies of spironolactone in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Qaialdo is not recommended during pregnancy and in women of childbearing potential not using contraception.

Progesterone, spironolactone

The enzymatic inductor may increase the metabolism of progesterone and decrease its plasma levels

Prostaglandin synthesis inhibitors, spironolactone

The co-administration may decrease the spironolactone effect

Protirelin, spironolactone

Enhancement of TSH-increase

Renal insufficiency, spironolactone [2] ---> SmPC of [2] of EMA

Hyperkalaemia may also occur in patients with impaired renal function. Cardiac dysrhythmias, occasionally fatal, may result.

Saccharose, spironolactone [2] ---> SmPC of [2] of EMA

As this medicinal product contains 400 mg sucrose per ml, this has to be taken into consideration in terms of daily intake. This should be taken into account in patients with diabetes mellitus. Qaialdo 10 mg/ml may be harmful to the teeth.

Sacubitril/valsartan [1], spironolactone ---> SmPC of [1] of EMA

Salicylates, spironolactone

The co-administration may decrease the spironolactone effect

Sparsentan [1], spironolactone ---> SmPC of [1] of EMA

Coadministration of sparsentan with mineralocorticoid (aldosterone) receptor inhibitors such as spironolactone and finerenone is expected to be associated with increased risk of hyperkalaemia.

Spironolactone [1], triamterene ---> SmPC of [1] of eMC

Spironolactone should not be administered concurrently with other potassium-sparing diuretics as this may induce hyperkalaemia.

Spironolactone [1], urea ---> SmPC of [1] of EMA

Reversible increases in blood urea may occur during use of spironolactone especially in the presence of impaired renal function.

Spironolactone [1], valsartan ---> SmPC of [1] of EMA

Concomitant use of medicinal products known to cause hyperkalaemia (such as lisinopril, valsartan, indomethacin) with spironolactone may result in severe hyperkalaemia.

Spironolactone, tacrolimus [2] ---> SmPC of [2] of EMA

As tacrolimus treatment may be associated with hyperkalaemia, or may increase pre-existing hyperkalaemia, high potassium intake, or potassium-sparing diuretics (e.g. amiloride, triamterene, or spironolactone) should be avoided (see section 4.4).

Spironolactone, telmisartan [2] ---> SmPC of [2] of EMA

As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may provoke hyperkalaemia. The risk may increase in case of treatment combination with other medicinal products that may also provoke hyperkalaemia

Spironolactone, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium.

Spironolactone, trandolapril [2] ---> SmPC of [2] of eMC

Potassium-sparing diuretics or potassium supplements may increase the risk of hyperkalaemia, particularly in renal failure.

Spironolactone, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Potassium sparing diuretics may lead to significant increases in serum potassium, particularly in the presence of renal function impairment.

Spironolactone, vamorolone [2] ---> SmPC of [2] of EMA

No cases of hyperkalaemia have been observed in patients using vamorolone alone or in combination with eplerenone or spironolactone.

Spironolactone, warfarin

The co-administration may decrease the anticoagulant effect

Spironolactone, xipamide

The co-administration may cause hypokaliemia or hyperkaliemia

Spironolactone, zofenopril

Potassium sparing diuretics, potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Combination is not recommended

CONTRAINDICATIONS of Spironolactone (Qaialdo)

- Spironolactone is contraindicated in adult and paediatric patients with the following:

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Acute renal insufficiency, significant renal compromise (GFR < 30 ml/min), anuria

- Addison's disease

- Hyperkalaemia (> 5.5 mEq/L)

- Concomitant use of eplerenone

- In paediatric patients with moderate to severe renal impairment.

Spironolactone should not be administered concurrently with other potassium-conserving diuretics and potassium supplements should not be given routinely with spironolactone as hyperkalaemia may be induced.

https://www.ema.europa.eu/en/documents/product-information/qaialdo-epar-product-information_en.pdf 20/08/2025

Other trade names: Aldactone, Espironolactona Alter,

Medicated sponge (TachoSil)

Alcohol, medicated sponge [2] ---> SmPC of [2] of EMA

The sealant may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g. antiseptic solutions).

Breast-feeding, medicated sponge [2] ---> SmPC of [2] of EMA

Should be administered to breastfeeding women only if clearly needed.

Iodine, medicated sponge [2] ---> SmPC of [2] of EMA

The sealant may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g. antiseptic solutions).

Medicated sponge [1], pregnancy ---> SmPC of [1] of EMA

Should be administered to pregnant women only if clearly needed.

Medicated sponge [1], solutions containing heavy metals ---> SmPC of [1] of EMA

The sealant may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g. antiseptic solutions).

CONTRAINDICATIONS of Medicated sponge (TachoSil)

- TachoSil must not be applied intravascularly.

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/tachosil-epar-product-information_en.pdf 24/05/2024

St. John's wort

5-aminolevulinic acid [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of medicinal products with known phototoxic or photoallergic potential may enhance the phototoxic reaction to photodynamic therapy.

Abemaciclib [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inducers should be avoided due to the risk of decreased efficacy of abemaciclib.

Ability to drive [1], St. John's wort ---> SmPC of [1] of eMC

In rare cases St John's Wort may make you feel dizzy or sleepy. If affected do not drive or use machines.

Abiraterone [1], St. John's wort ---> SmPC of [1] of EMA

Strong inducers of CYP3A4 (decreased mean plasma AUCinf of abiraterone) during treatment are to be avoided, unless there is no therapeutic alternative.

Acenocoumarol, St. John's wort

St. John's wort may decrease the anticoagulant effect of acenocoumarol

Afatinib [1], St. John's wort ---> SmPC of [1] of EMA

Strong P-gp inducers may decrease exposure to afatinib

Alectinib [1], St. John's wort ---> SmPC of [1] of EMA

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin and St. John's Wort (Hypericum perforatum)).

Aliskiren [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of P-gp might decrease the bioavailability of aliskiren. Caution required with concomitant use

Aliskiren/amlodipine [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Aliskiren/amlodipine/hydrochlorothiazide, St. John's wort ---> SmPC of [aliskiren] of EMA

Inducers of P-gp might decrease the bioavailability of aliskiren. Caution required with concomitant use

Aliskiren/hydrochlorothiazide [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of P-gp might decrease the bioavailability of aliskiren. Caution required with concomitant use

Alitretinoin [1], St. John's wort ---> SmPC of [1] of eMC

Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives

Almotriptan [1], St. John's wort ---> SmPC of [1] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's Wort (Hypericum perforatum ).

Alprazolam, St. John's wort

The co-administration may decrease the effect of alprazolam

Aminophylline [1], St. John's wort ---> SmPC of [1] of eMC

St John's Wort (Hypericum perforatum) may decrease aminophylline clearance resulting in increased plasma theophylline concentrations and the potential for increased toxicity

Amiodarone, St. John's wort

The strong CYP3A4 induction may decrease the plasma concentrations of amiodarone. St. John's Wort should be avoided

Amitriptyline, St. John's wort [2] ---> SmPC of [2] of eMC

The co-administration may increase the serotoninergic effects and the adverse reactions. St. John's Wort should be avoided

Amlodipine, St. John's wort ---> SmPC of [amlodipine/valsartan] of EMA

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Amlodipine/valsartan [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Amlodipine/valsartan/hydrochlorothiazide [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Amprenavir [1], St. John's wort ---> SmPC of [1] of EMA

Herbal preparations containing St John's wort (Hypericum perforatum) must not be used while taking amprenavir due to the risk of decreased plasma concentrations and reduced clinical effects of amprenavir

Amprenavir/ritonavir, St. John's wort ---> SmPC of [amprenavir] of EMA

Antidepressants with serotonergic effect, St. John's wort ---> SmPC of [vortioxetine] of EMA

Concomitant use of antidepressants with serotonergic effect and St. John's wort may result in a higher incidence of adverse reactions including serotonin syndrome

Antidepressants, St. John's wort

The co-administration may increase the serotoninergic effects and the adverse reactions. St. John's Wort should be avoided

Antiepileptics, St. John's wort

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of antiepileptic agent (with risk of seizures). St. John's Wort should be avoided

Apixaban [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of apixaban with strong CYP3A4 and P-gp inducers may lead to reduced apixaban plasma concentrations. No dose adjustment for apixaban (almost always) is required during concomitant therapy with such agents

Apremilast [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of strong CYP3A4 enzyme inducer rifampicin resulted in a reduction of systemic exposure of apremilast. Therefore, the use of strong CYP3A4 enzyme inducers with apremilast is not recommended.

Aprepitant [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant administration of aprepitant with active substances that strongly induce CYP3A4 activity should be avoided as the combination results in reductions of the plasma concentrations of aprepitant that may result in decreased efficacy of aprepitant

Aripiprazole [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant administration of aripiprazole and inducers of CYP3A4 may be expected to reduce the geometric means of Cmax and AUC for aripiprazole. The concomitant use of CYP3A4 inducers with aripiprazole should be avoided

Atazanavir [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of St. John's wort (CYP3A4 induction) with atazanavir may be expected to result in significant reduction in atazanavir plasma levels. Co-administration is contraindicated.

Atazanavir/cobicistat [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration (contraindicated) of EVOTAZ with strong inducers of CYP3A may result in decreased plasma concentrations of atazanavir and/or cobicistat, leading to loss of therapeutic effect and possible development of resistance to atazanavir.

Atorvastatin [1], St. John's wort ---> SmPC of [1] of eMC

Concomitant administration of atorvastatin with inducers of cytochrome P450 3A can lead to variable reductions in plasma concentrations of atorvastatin.

Axitinib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of axitinib with strong CYP3A4/5 inducers may decrease axitinib plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 induction potential is recommended.

Bedaquiline [1], St. John's wort ---> SmPC of [1] of EMA

Bedaquiline exposure may be reduced during co-administration with inducers of CYP3A4. Co-administration of bedaquiline and moderate or strong CYP3A4 inducers used systemically should be avoided.

Bictegravir/emtricitabine/tenofovir alafenamide [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration may decrease bictegravir and tenofovir alafenamide plasma concentrations. Co-administration with St John's wort is contraindicated, due to the effect of St John's wort on the bictegravir component of Biktarvy.

Binimetinib [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of Pgp transport (such as Saint John's wort or phenytoin) may decrease binimetinib exposure, which could result in a decrease of efficacy.

Bortezomib [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of bortezomib with strong CYP3A4 inducers is not recommended, as efficacy may be reduced.

Bosentan [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant administration of bosentan and CYP3A4 inductors is expected to lead to reduced systemic exposure to bosentan. A clinically significant reduction of efficacy cannot be excluded.

Bosutinib [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of bosutinib with strong CYP3A inductors should be avoided, as a decrease in bosutinib plasma levels will occur.

Breast-feeding, St. John's wort

It should not be used during breast-feeding

Brigatinib [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of strong CYP3A inducers with Alunbrig should be avoided

Brivaracetam [1], St. John's wort ---> SmPC of [1] of EMA

Other strong enzyme inducers (such as St John´s wort (Hypericum perforatum)) may also decrease the systemic exposure of brivaracetam. Therefore, starting or ending treatment with St John's wort should be done with caution.

Brotizolam, St. John's wort

The strong CYP3A4 induction may decrease the plasma concentrations of brotizolam

Buspirone [1], St. John's wort ---> SmPC of [1] of eMC

When used buspirone in combination with a potent inducer of CYP3A4, an adjustment of the dosage of buspirone may be necessary to maintain buspirone's anxiolytic effect.

Cabazitaxel [1], St. John's wort ---> SmPC of [1] of EMA

Repeated administration of rifampin, a strong CYP3A inducer, resulted in an increase in cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inducers should be avoided as a decrease of plasma concentrations of cabazitaxel may occur

Cabozantinib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of cabozantinib with strong CYP3A4 inductors (decreased plasma cabozantinib exposure (AUC) should be approached with caution.

Canagliflozin [1], St. John's wort ---> SmPC of [1] of EMA

Enzyme inducers may give rise to decreased exposure of canagliflozin. These decreases in exposure to canagliflozin may decrease efficacy.

Canagliflozin/metformin [1], St. John's wort ---> SmPC of [1] of EMA

Enzyme inducers may give rise to decreased exposure of canagliflozin. These decreases in exposure to canagliflozin may decrease efficacy.

Carbamazepine, St. John's wort [2] ---> SmPC of [2] of eMC

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of carbamazepine (with risk of seizures). St. John's Wort should be avoided

Cariprazine [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of cariprazine with strong and moderate inducers of CYP3A4 may result in a significant decrease in total cariprazine exposure, therefore the co-administration of cariprazine and strong or moderate CYP3A4 inducers is contraindicated

Ceritinib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of ceritinib with strong CYP3A inducers decreases ceritinib plasma concentrations. Concomitant use of strong CYP3A inducers should be avoided.

Cerivastatin, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of statine. St. John's Wort should be avoided

Cilostazol [1], St. John's wort ---> SmPC of [1] of EMA

The effect of CYP3A4 and CYP2C19 inducers on cilostazol pharmacokinetics has not been evaluated. The antiplatelet effect may theoretically be altered

Citalopram, St. John's wort [2] ---> SmPC of [2] of eMC

Dynamic interactions between citalopram and the herbal remedy St John's wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects

Clarithromycin [1], St. John's wort ---> SmPC of [1] of eMC

Drugs that are inducers of CYP3A may induce the metabolism of clarithromycin. This may result in sub-therapeutic levels of clarithromycin leading to reduced efficacy.

Clomipramine, St. John's wort

Concomitant administration of clomipramine with St. John's wort during the treatment may decrease the plasma concentrations of clomipramine.

Cobicistat [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of cobicistat with medicinal products that are strong inducers of CYP3A may result in decreased plasma concentrations of cobicistat. Coadministration is contraindicated

Cobimetinib [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of moderate and strong CYP3A inducers should be avoided. Given that cobimetinib concentrations are likely to be significantly reduced when co-administered with moderate to strong CYP3A inducers, patient's efficacy may be compromised.

Conjugated oestrogens/bazedoxifene [1], St. John's wort ---> SmPC of [1] of EMA

Herbal preparations containing St John's wort (Hypericum perforatum) may induce the metabolism of oestrogens. Clinically, an increased metabolism of oestrogens may lead to decreased effect and changes in the uterine bleeding profile.

Coumarin anticoagulants, St. John's wort

The co-administration decreases the anticoagulant effect (risk of thromboembolias). St. John's Wort should be avoided

Crizotinib [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration of crizotinib with strong CYP3A inducers may decrease crizotinib plasma concentrations. The concurrent use of strong CYP3A inducers should be avoided

Cyclophosphamide, St. John's wort

The CYP3A4 induction may increase the toxicity of cyclophosphamide (prodrug)

Cyclosporine [1], St. John's wort ---> SmPC of [1] of eMC

Decreased cyclosporine plasma levels. The co-administration is contraindicated

Cyproterone [1], St. John's wort ---> SmPC of [1] of eMC

Inducers of CYP3A4 may reduce the levels of cyproterone acetate.

Cyproterone/ethinylestradiol [1], St. John's wort ---> SmPC of [1] of eMC

The enzymatic induction by St. John's wort may decrease the plasma levels of ethinylestradiol. St. John's Wort should be avoided

Dabigatran etexilate [1], St. John's wort ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Dabigatran [1], St. John's wort ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Concomitant administration of a P-gp inducer is expected to result in decreased dabigatran concentrations and should be avoided

Dabrafenib [1], St. John's wort ---> SmPC of [1] of EMA

Dabrafenib is a substrate for the metabolising enzymes CYP3A4. Medicines that are strong inductors of CYP3A4 are therefore likely to decrease dabrafenib concentrations. Avoid coadministration of dabrafenib with potent inducers of CYP3A4.

Daclatasvir [1], St. John's wort ---> SmPC of [1] of EMA

Daclatasvir is contraindicated in combination with medicinal products that strongly induce CYP3A4 and P-gp, and thus may lead to lower exposure and loss of efficacy of daclatasvir.

Dapoxetine [1], St. John's wort ---> SmPC of [1] of eMC

Combination dapoxetine and serotonergic drugs (SD) may lead to incidence of serotonin associated effects. Dapoxetine should not be used with SD or in 14 d. of discontinuing SD. SD should not be given in 7 d. after discontinuing dapoxetine

Darifenacin [1], St. John's wort ---> SmPC of [1] of EMA

Substances that are inducers of CYP3A4 are likely to decrease the plasma concentrations of darifenacin.

Darunavir/cobicistat, St. John's wort ---> SmPC of [darunavir] of EMA

Darunavir and cobicistat are metabolised by CYP3A, and co-administration with CYP3A inducers may result in subtherapeutic plasma exposure to darunavir. Co-administration of darunavir/cobicistat with strong inducers of CYP3A is contraindicated

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration is contraindicated due to the potential for loss of therapeutic effect

Darunavir/ritonavir, St. John's wort ---> SmPC of [darunavir] of EMA

Concomitant use of darunavir/ritonavir with strong CYP3A4 inductors may decrease plasma concentrations of darunavir and ritonavir. Concomitant use of darunavir/ritonavir with strong CYP3A4 inductors is contraindicated

Dasabuvir with ombitasvir/paritaprevir/ritonavir, St. John's wort ---> SmPC of [dasabuvir] of EMA

CYP3A4 induction by St. John's Wort may decrease the plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration (contraindicated) of dasabuvir with medicinal products that are strong or moderate enzyme inducers is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect

Dasatinib [1], St. John's wort ---> SmPC of [1] of EMA

The administration of dasatinib with a strong CYP3A4 inductor may increase metabolism and decrease dasatinib plasma concentrations. Therefore, concomitant use of potent CYP3A4 inducers with dasatinib is not recommended.

Delavirdine, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of non-nucleoside reverse transcriptase inhibitor. St. John's Wort should be avoided

Desogestrel [1], St. John's wort ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

Dextromethorphan/quinidine [1], St. John's wort ---> SmPC of [1] of EMA

Potent CYP3A4 inducers may accelerate the metabolism of quinidine, resulting in lower plasma concentrations and hence decreased inhibition of CYP2D6. This may lead to decreased efficacy of dextromethorphan/quinidine.

Dienogest, St. John's wort

The enzymatic induction may decrease the plasma levels of dienogest

Digoxin, St. John's wort

St. John's wort, inductor of transporters of P-glycoprotein, may decrease the exposure to digoxin. St. John's Wort should be avoided

Diltiazem [1], St. John's wort ---> SmPC of [1] of eMC

Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.

Dolutegravir [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 and UGT1A1 induction may decrease the exposition of dolutegravir.

Dolutegravir/abacavir/lamivudine [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 and UGT1A1 induction may decrease plasma levels of dolutegravir. Co-administration with St. John's wort is discouraged.

Dolutegravir/rilpivirine [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in rilpivirine plasma concentrations. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with St. John's wort is contraindicated

Dronedarone [1], St. John's wort ---> SmPC of [1] of EMA

Rifampicin decreased dronedarone exposure. Therefore, co-administration of rifampicin and other potent CYP3A4 inducers is not recommended as they decrease dronedarone exposure.

Drugs primarily metabolised by CYP1A2, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of the medicinal products primarily metabolised by CYP1A2

Drugs primarily metabolised by CYP3A4, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of the medicinal products primarily metabolised by CYP3A4

Duloxetine [1], St. John's wort ---> SmPC of [1] of EMA

In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if duloxetine is used concomitantly with serotonergic agents

Dydrogesterone/estradiol [1], St. John's wort ---> SmPC of [1] of eMC

Herbal preparations containing St John's wort (Hypericum perforatum) may induce the metabolism of estrogens and progestagens.

Edoxaban [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of edoxaban with P-gp inducers may lead to reduced edoxaban plasma concentrations. Edoxaban should be used with caution when co-administered with P-gp inducers.

Efavirenz [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of efavirenz and St. John's wort is contraindicated. Plasma levels of efavirenz can be reduced by concomitant use of St. John's wort due to induction of drug-metabolising enzymes and/or transport proteins by St. John's wort.

Efavirenz/emtricitabine/tenofovir disoproxil [1], St. John's wort ---> SmPC of [1] of EMA

Compounds or herbal preparations (for example St. John's wort) which induce CYP3A4 may give rise to decreased plasma concentrations of efavirenz. Concomitant use of St. John's wort is contraindicated

Elbasvir/grazoprevir [1], St. John's wort ---> SmPC of [1] of EMA

CYP3A or P-gp induction. Co-administration is contraindicated.

Eletriptan [1], St. John's wort ---> SmPC of [1] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St. John's wort (Hypericum perforatum)

Eliglustat [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant administration of a strong CYP3A4 inducer resulted in a decrease in eliglustat exposure. Use of a strong CYP3A inducer with eliglustat is not recommended in poor, intermediate and extensive metabolisers.

Elvitegravir [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of elvitegravir with medicines that are strong inducers of CYP3A is contraindicated as the expected decrease in elvitegravir plasma levels can lead to loss of therapeutic effect and possible development of resistance to elvitegravir

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of Genvoya and some medicinal products that induce CYP3A may result in significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], St. John's wort ---> SmPC of [1] of EMA

The contraindicated coadministration of Stribild and St. John's wort (CYP3A inducer) may result in significantly decreased cobicistat and elvitegravir plasma concentrations, which may result in loss of therapeutic effect and development of resistance

Emtricitabine/rilpivirine/tenofovir alafenamide [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration may cause significant decreases in the plasma concentrations of rilpivirine (induction of CYP3A) and tenofovir alafenamide (induction of P-gp). Co-administration is contraindicated.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], St. John's wort ---> SmPC of [1] of EMA

Emtricitabine/rilpivirine/tenofovir must not be used in combination with products containing St John's wort as co-administration may cause significant decreases in rilpivirine plasma concentrations.

Emtricitabine/tenofovir alafenamide [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of St. John's wort, a P-gp inducer, may decrease tenofovir alafenamide plasma concentrations, which may result in loss of therapeutic effect and development of resistance.

Encorafenib [1], St. John's wort ---> SmPC of [1] of EMA

A reduction in encorafenib exposure is likely and may result in compromised efficacy. Alternative agents with no or minimal CYP3A induction potential should be considered.

Eplerenone [1], St. John's wort ---> SmPC of [1] of eMC

Due to the risk of decreased eplerenone efficacy, the concomitant use of strong CYP3A4 inducers with eplerenone is not recommended

Erlotinib [1], St. John's wort ---> SmPC of [1] of EMA

Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Potent inducers of CYP3A4 activity increase erlotinib metabolism and significantly decrease erlotinib plasma concentrations.

Erythromycin, St. John's wort

The CYP3A4 induction may increase the metabolism of erythromycin and decrease its plasma concentrations and effect

Escitalopram [1], St. John's wort ---> SmPC of [1] of eMC

Concomitant use of SSRIs and herbal remedies containing St. John's Wort (Hypericum perforatum) may result in an increased incidence of adverse reactions

Esomeprazole [1], St. John's wort ---> SmPC of [1] of EMA

Medicinal products known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort (Hypericum perforatum)) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Estradiol valerate/norgestrel [1], St. John's wort ---> SmPC of [1] of eMC

St John's Wort (Hypericum Perforatum) may induce the metabolism of oestrogens and progestagens. Clinically, an increased metabolism of oestrogens and progestagens may lead to decreased efficacy and changes in uterine bleeding profile

Estradiol [1], St. John's wort ---> SmPC of [1] of eMC

Herbal preparations containing Hypericum perforatum may induce the metabolism of estrogens and progestagens. Clinically, an increased metabolism of estrogens and progestagens may lead to decreased effects and changes in the uterine bleeding profile.

Estradiol/norethisterone [1], St. John's wort ---> SmPC of [1] of eMC

Herbal preparations containing St John's wort (Hypericum perforatum) may induce the metabolism of oestrogens and progestogens.

Estriol [1], St. John's wort ---> SmPC of [1] of eMC

The metabolism of estrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estrogens, St. John's wort ---> SmPC of [estradiol] of eMC

Ethinyl estradiol [1], St. John's wort ---> SmPC of [1] of eMC

The enzymatic induction by St. John's wort may decrease the plasma levels of ethinylestradiol. St. John's Wort should be avoided

Ethinylestradiol/chlormadinone, St. John's wort

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/desogestrel [1], St. John's wort ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

Ethinylestradiol/drospirenone [1], St. John's wort ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/etonogestrel [1], St. John's wort ---> SmPC of [1] of eMC

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/gestodene [1], St. John's wort ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

Ethinylestradiol/norgestimate [1], St. John's wort ---> SmPC of [1] of eMC

Drugs or herbal products that induce enzymes, especially CYP3A4, may decrease the plasma concentrations of contraceptive hormones, and may decrease their effectiveness and/or increase breakthrough bleeding.

Etonogestrel [1], St. John's wort ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, specifically cytochrome P450 enzymes, which can result in increased clearance of sex hormones

Etoposide, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of etoposide. St. John's Wort should be avoided

Etravirine [1], St. John's wort ---> SmPC of [1] of EMA

St John's wort is expected to decrease the plasma concentrations of etravirine. Combination not recommended.

Everolimus [1], St. John's wort ---> SmPC of [1] of EMA

Large decrease in exposure of everolimus expected. Preparations containing St John's Wort should not be used during treatment with everolimus

Exemestane [1], St. John's wort ---> SmPC of [1] of eMC

The co-administration of drugs known to induce CYP3A4 may reduce the efficacy of exemestane.

Ezetimibe/atorvastatin [1], St. John's wort ---> SmPC of [1] of eMC

Concomitant administration of atorvastatin with inducers of cytochrome P450 3A4 (e.g., efavirenz, rifampicin, St. John's Wort) can lead to variable reductions in plasma concentrations of atorvastatin.

Felodipine [1], St. John's wort ---> SmPC of [1] of eMC

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of calcium antagonist. St. John's Wort should be avoided

Felodipine/metoprolol, St. John's wort

It has been shown that inductors of cytochrome P450-3A4 system decrease the plasma concentrations of felodipine. The concomitant use with strong CYP3A4 inductors should be avoided

Felodipine/ramipril [1], St. John's wort ---> SmPC of [1] of eMC

The CYP3A4 induction may decrease the plasma levels of felodipine. The co-administration of felodipine with CYP3A4 inductors should be avoided

Fentanyl [1], St. John's wort ---> SmPC of [1] of EMA

The potent CYP3A4 induction may decrease plasma concentrations of fentanyl. St. John's Wort should be avoided

Fesoterodine [1], St. John's wort ---> SmPC of [1] of EMA

Induction of CYP3A4 may lead to subtherapeutic plasma levels. Concomitant use (of fesoterodine) with CYP3A4 inducers is not recommended

Fingolimod [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of fingolimod with strong CYP3A4 enzyme inducers may reduce the AUC of fingolimod and its metabolite. Concomitant administration with St. John's Wort is not recommended

Fluoxetine [1], St. John's wort ---> SmPC of [1] of eMC

An increase in serotonergic effects, such as serotonin syndrome, may occur when selective serotonin reuptake inhibitors and herbal preparations containing St John's Wort (Hypericum perforatum) are used together.

Fluvoxamine [1], St. John's wort ---> SmPC of [1] of eMC

The serotonergic effects of fluvoxamine may be enhanced when used in combination with other serotonergic agents

Fosamprenavir/ritonavir, St. John's wort ---> SmPC of [fosamprenavir] of EMA

CYP3A4 induction by St. John's wort may decrease exposition of amprenavir. Herbal preparations containing St John's wort must not be combined with fosamprenavir

Fosaprepitant [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 induction may decrease the plasma concentrations of fosaprepitant. Concomitant administration of fosaprepitant with herbal preparations containing St. John's Wort is not recommended.

Fosphenytoin [1], St. John's wort ---> SmPC of [1] of eMC

Serum levels of phenytoin can be reduced by concomitant use of the herbal preparations containing St John's wort

Frovatriptan [1], St. John's wort ---> SmPC of [1] of eMC

As with other triptans the risk of the occurrence of serotonin syndrome may be increased.

Gefitinib [1], St. John's wort ---> SmPC of [1] of EMA

Substances that are inducers of CYP3A4 activity may increase metabolism and decrease gefitinib plasma concentrations and thereby reduce the efficacy of gefitinib. Concomitant medicinal products that induce CYP3A4 should be avoided.

Gestagens, St. John's wort ---> SmPC of [estradiol] of eMC

Glecaprevir/pibrentasvir [1], St. John's wort ---> SmPC of [1] of EMA

Medicinal products that are strong P-gp and CYP3A inducers could significantly decrease glecaprevir or pibrentasvir plasma levels and may lead to reduced therapeutic effect of Maviret or loss of virologic response. Co-administration is contraindicated

Guanfacin [1], St. John's wort ---> SmPC of [1] of EMA

There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. Other CYP3A4 inducers may have a comparable effect

Halogenated anaesthetics, St. John's wort ---> SmPC of [sevoflurane] of eMC

Severe hypotension and delayed emergence from anaesthesia with halogenated inhalational anaesthetics have been reported in patients treated long-term with St John's Wort.

Hemp extract, St. John's wort

The co-administration may decrease the Cmax and THC and CBD.

Hydrocortisone [1], St. John's wort ---> SmPC of [1] of EMA

Potent CYP 3A4 inducers can enhance the metabolic clearance of cortisol, decrease terminal half-life and thus reduce circulating levels and increase fluctuations of cortisol (due to shorter terminal half-life).

Ibrutinib [1], St. John's wort ---> SmPC of [1] of EMA

Preparations containing St. John's Wort are contraindicated during treatment with ibrutinib, as efficacy may be reduced.

Idelalisib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of idelalisib with moderate or strong CYP3A inducers should be avoided as this may result in decreased efficacy

IMAOs, St. John's wort

The co-administration may increase the serotoninergic effects and the adverse reactions. St. John's Wort should be avoided

Imatinib [1], St. John's wort ---> SmPC of [1] of EMA

Substances that are inducers of CYP3A4 activity may significantly reduce exposure to imatinib, potentially increasing the risk of therapeutic failure. Concomitant use of strong CYP3A4 inducers and imatinib should be avoided.

Indinavir [1], St. John's wort ---> SmPC of [1] of EMA

Concurrent use of indinavir with herbal preparations containing St John 's wort (Hypericum perforatum) is contraindicated

Irinotecan [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of ONIVYDE with inducers of CYP3A4 may reduce systemic exposure of ONIVYDE.

Isavuconazole [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of CRESEMBA with potent/moderate CYP3A4/5 inducers is contraindicated, since these medicinal products can significantly decrease plasma concentrations of isavuconazole

Itraconazol [1], St. John's wort ---> SmPC of [1] of eMC

Coadministration of itraconazole with potent enzyme inducers of CYP3A4 may decrease the bioavailability of itraconazole and hydroxy-itraconazole to such an extent that efficacy may be largely reduced.

Ivabradine [1], St. John's wort ---> SmPC of [1] of EMA

The combination of ivabradine 10 mg twice daily with St John's Wort was shown to reduce ivabradine AUC by half. The intake of St John's Wort should be restricted during the treatment with ivabradine.

Ivacaftor [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of ivacaftor with rifampicin, a strong CYP3A inducer, decreased ivacaftor exposure (AUC) and M1 exposure. Co-administration with strong CYP3A inducers is not recommended

Ixabepilone, St. John's wort

The strong CYP3A4 induction may reduce plasma concentrations of ixabepilone

Ixazomib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of ixazomib with rifampicin decreased ixazomib Cmax by 54% and AUC by 74%. Therefore, co-administration of strong CYP3A inducers with ixazomib is not recommended

Ketoconazole, St. John's wort

The strong CYP3A4 induction significantly decreases the bioavailability of ketoconazole. St. John's Wort should be avoided

Lacosamide [1], St. John's wort ---> SmPC of [1] of EMA

The enzymatic induction may decrease plasma concentrations of lacosamide. Starting or ending treatment with enzyme inducers should be done with caution

Lansoprazole [1], St. John's wort ---> SmPC of [1] of eMC

Enzyme inducers affecting CYP2C19 and CYP3A4 can markedly reduce the plasma concentrations of lansoprazole.

Lapatinib [1], St. John's wort ---> SmPC of [1] of EMA

The CYP3A4 and P-glycoprotein induction may decrease the exposure of lapatinib. St. John's Wort should be avoided

Lasofoxifene, St. John's wort

Lasofoxifene clearance may be increased in patients chronically treated with inducers of CYP3A4 and may result in reduced efficacy

Ledipasvir/sofosbuvir [1], St. John's wort ---> SmPC of [1] of EMA

Medicinal products that are potent P-gp inducers may significantly decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of ledipasvir/sofosbuvir and thus are contraindicated with Harvoni

Letermovir [1], St. John's wort ---> SmPC of [1] of EMA

Co-treatment with moderate and strong inducers may give rise to subtherapeutic letermovir exposure

Levonorgestrel [1], St. John's wort ---> SmPC of [1] of eMC

The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers.

Levonorgestrel/ethinylestradiol [1], St. John's wort ---> SmPC of [1] of eMC

Interactions of enzyme inducers with oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure: Women should temporarily use a barrier method in addition to the COC or choose another method of contraception.

Lomitapide [1], St. John's wort ---> SmPC of [1] of EMA

Medicines that induce CYP3A4 would be expected to increase the rate and extent of metabolism of lomitapide. Consequently, this would reduce the effect of lomitapide. Any impact on efficacy is likely to be variable.

Lopinavir/ritonavir [1], St. John's wort ---> SmPC of [1] of EMA

Concentrations of lopinavir may be reduced due to induction of CYP3A by the herbal preparation St John's wort. Herbal preparations containing St John's wort must not be combined with lopinavir and ritonavir.

Lovastatine, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of statine. St. John's Wort should be avoided

Lumacaftor/ivacaftor [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of lumacaftor/ivacaftor with St. John's wort is not recommended. The exposure of ivacaftor will be decreased, which may reduce the efficacy of lumacaftor/ivacaftor.

Lurasidone [1], St. John's wort ---> SmPC of [1] of EMA

Lurasidone and its active metabolite ID-14283 are primarily metabolised by CYP3A4. Lurasidone is contraindicated with strong CYP3A4 inductors

Macitentan [1], St. John's wort ---> SmPC of [1] of EMA

In the presence of strong CYP3A4 inducers reduced efficacy of macitentan could occur. The combination of macitentan with strong CYP3A4 inducers should be avoided

Maraviroc [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of maraviroc with St. John's Wort is expected to substantially decrease maraviroc concentrations and may result in suboptimal levels and lead to loss of virologic response and possible resistance to maraviroc.

Medroxyprogesterone, St. John's wort ---> SmPC of [estradiol] of eMC

Methadone, St. John's wort

The co-administration may decrease the plasma levels and the effect of methadone. St. John's Wort should be avoided

Metildigoxin, St. John's wort

The co-administration may decrease the plasma levels of metildigoxin

Midazolam [1], St. John's wort ---> SmPC of [1] of EMA

St John's Wort decreased plasma concentrations of midazolam by about 20-40% associated with a decrease in terminal half-life of about 15-17%.

Midostaurin [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of Rydapt with strong inducers of CYP3A4 (e.g. carbamazepine, rifampicin, enzalutamide, phenytoin, St. John's Wort [Hypericum perforatum]) is contraindicated

Mifepristone [1], St. John's wort ---> SmPC of [1] of eMC

CYP3A4 inductors may induce mifepristone metabolism (lowering serum levels of mifepristone).

Mirtazapine [1], St. John's wort ---> SmPC of [1] of eMC

Co-administration of mirtazapine with other serotonergic active substances may lead to an incidence of serotonin associated effects (serotonin syndrome). Caution should be advised

Mitotane [1], St. John's wort ---> SmPC of [1] of EMA

Mitotane has been shown to have an inductive effect on cytochrome P450 enzymes. Therefore, the plasma concentrations of the substances metabolised via cytochrome P450 may be modified.

Moclobemide, St. John's wort

The combination of moclobemide and St. John's wort increases the risk of serotoninergic syndrome

Naloxegol [1], St. John's wort ---> SmPC of [1] of EMA

Naloxegol is not recommended in patients who are taking strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John's Wort)

Naproxen/esomeprazole [1], St. John's wort ---> SmPC of [1] of eMC

Drugs known to induce CYP2C19 and CYP3A4 may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Naratriptan [1], St. John's wort ---> SmPC of [1] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's Wort (Hypericum perforatum)

Nateglinide [1], St. John's wort ---> SmPC of [1] of EMA

St John's wort may reduce the hypoglycaemic effect of nateglinide

Nefazodone, St. John's wort

Dynamic interactions between SSRI and the herbal remedy St John's wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects

Nelfinavir [1], St. John's wort ---> SmPC of [1] of EMA

Herbal preparations containing St. John's wort (Hypericum perforatum) must not be used while taking nelfinavir due to the risk of decreased plasma concentrations and reduced clinical effects of nelfinavir

Neratinib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration with this medical product that is strong inducer of the CYP3A4/Pgp isoform of cytochrome P450 is contraindicated

Nevirapine [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration of nevirapine with herbal preparations containing St. John's wort (Hypericum perforatum) is contraindicated due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine

Nilotinib [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent.

Nintedanib [1], St. John's wort ---> SmPC of [1] of EMA

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

Nomegestrol/estradiol [1], St. John's wort ---> SmPC of [1] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

Non-nucleoside reverse transcriptase inhibitors, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of non-nucleoside reverse transcriptase inhibitor. St. John's Wort should be avoided

Norelgestromin/ethinylestradiol [1], St. John's wort ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norethisterone acetate, St. John's wort

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone enantate, St. John's wort [2] ---> SmPC of [2] of eMC

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone, St. John's wort

The enzymatic induction may decrease the plasma levels and the effect of progestagen

Norgestimate, St. John's wort

The CYP3A4 induction may accelerate the norgestimate metabolism and decrease its plasma levels and effect. The induction lasts at least 4 weeks after dose interruption

Norgestrel, St. John's wort

The enzymatic induction may accelerate the metabolism of steroid hormones and decrease their plasma levels and effect.

Nortriptyline, St. John's wort

Saint John's wort may decrease the plasma levels of nortriptyline

Olaparib [1], St. John's wort ---> SmPC of [1] of EMA

Known strong inducers of CYP3A4/5 are not recommended with olaparib, as it is possible that the efficacy of olaparib could be substantially reduced

Olmesartan medoxomil/amlodipine [1], St. John's wort ---> SmPC of [1] of eMC

The concomitant use of amlodipine and CYP3A4 inducers may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.

Ombitasvir/paritaprevir/ritonavir [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration of Viekirax with/without dasabuvir with drugs that are strong or moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma levels and reduce their therapeutic effect. Concomitant use contraindicated

Omeprazole, St. John's wort

Principle actives known to induce CYP2C19 and CYP3A4 may increase the omeprazole metabolism and decrease its plasma levels

Oral contraceptives, St. John's wort [2] ---> SmPC of [2] of eMC

Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's Wort.

Osimertinib [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of St. John's Wort is contraindicated.

Ospemifene [1], St. John's wort ---> SmPC of [1] of EMA

Rifampicin, strong CYP3A/CYP2C9 enzyme inducer, decreased the ospemifene AUC by 58%. Therefore, co-administration of ospemifene with strong enzyme inducers would be expected to decrease the exposure of ospemifene, which may decrease the clinical effect.

P-glycoprotein substrates, St. John's wort

St. John's wort, inductor of transporters of P-glycoprotein, may decrease the exposure to medicinal products that are transported by P-glycoprotein

Palbociclib [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration of CYP3A inducers may lead to decreased palbociclib exposure and consequently a risk for lack of efficacy. Therefore, concomitant use of palbociclib with strong CYP3A4 inducers should be avoided.

Paliperidone [1], St. John's wort ---> SmPC of [1] of EMA

St. John 's wort, inducer of P-gp, may increase in renal clearance of paliperidone

Panobinostat [1], St. John's wort ---> SmPC of [1] of EMA

Strong inducers may reduce the efficacy of panobinostat, therefore the concomitant use of strong CYP3A4 inducers should be avoided.

Paracetamol, St. John's wort

The enzymatic inductor may decrease the plasma levels of paracetamol and increase its hepatotoxicity. St. John's Wort should be avoided

Paroxetine, St. John's wort [2] ---> SmPC of [2] of eMC

As with other SSRIs, co-administration with serotonergic drugs may lead to an incidence of 5-HT associated effects (serotonin syndrome)

Perampanel [1], St. John's wort ---> SmPC of [1] of EMA

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of antiepileptic agent (with risk of seizures). St. John's Wort should be avoided

Phenobarbital, St. John's wort

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of phenobarbital (with risk of seizures). St. John's Wort should be avoided

Phenprocoumon, St. John's wort

Weakening of phenprocoumon effect with the use concomitant or prior of John's Wort

Phenytoin, St. John's wort [2] ---> SmPC of [2] of eMC

Serum levels of phenytoin can be reduced by concomitant use of the herbal preparations containing St John's wort

Photosensitizing agents, St. John's wort

It is possible that concomitant use of St. John's Wort with other photosensitizing medicinal products could increase the potential for phototoxic reactions

Piperaquine/artenimol [1], St. John's wort ---> SmPC of [1] of EMA

Enzyme inducing medicinal products are likely to lead to reduced piperaquine plasma concentrations. The concentration of DHA may also be reduced. Concomitant treatment with such medicinal products is not recommended.

Pitolisant [1], St. John's wort ---> SmPC of [1] of EMA

With St John's Wort (Hypericum Perforatum), due to its strong CYP3A4 inducing effect, caution should be exercised when taken concurrently with pitolisant.

Ponatinib [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration of ponatinib with strong CYP3A4 inducers (decreases in ponatinib exposure are possible) should be avoided, and alternatives to the CYP3A4 inducer should be sought, unless the benefit outweighs the possible risk of ponatinib underexposure

Pregnancy, St. John's wort

It should not be used during pregnancy

Primidone, St. John's wort [2] ---> SmPC of [2] of eMC

St. John's Wort induces the CYP450 enzyme system and may result in a reduction of plasma levels of concomitantly administered primidone and of its major metabolite phenobarbitone.

Progesterone, St. John's wort

The strong CYP3A4 induction may decrease the levels of progesterone

Protease inhibitors, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of protease inhibitor. St. John's Wort should be avoided

Quinidine, St. John's wort

The strong CYP3A4 induction may decrease the levels of quinidine

Ranolazine [1], St. John's wort ---> SmPC of [1] of EMA

The CYP3A4 induction may decrease the plasma levels of ranolazine. During the treatment with CYP3A4 inductors should not be initiated a therapy with ranolazine

Rasagiline [1], St. John's wort ---> SmPC of [1] of EMA

Rasagiline should not be administered along with other MAO inhibitors as there may be a risk of non-selective MAO inhibition that may lead to hypertensive crises

Reboxetine [1], St. John's wort ---> SmPC of [1] of eMC

Low reboxetine serum levels have been reported with the concurrent administration of CYP3A4 inducers

Regorafenib [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 inductor may increase metabolism of regorafenib. The combination of regorafenib with strong CYP3A4 inductors should be avoided

Repaglinide [1], St. John's wort ---> SmPC of [1] of EMA

Rifampicin, a potent inducer of CYP3A4, but also CYP2C8, acts both as an inducer and inhibitor of the metabolism of repaglinide. It cannot be excluded that other inducers may have a similar effect.

Ribociclib [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided

Rilpivirine [1], St. John's wort ---> SmPC of [1] of EMA

Significant decreases in rilpivirine plasma concentrations are expected (induction of CYP3A enzymes). Concomitant use is contraindicated

Rimonabant [1], St. John's wort ---> SmPC of [1] of EMA

It is expected that concomitant administration of potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.

Riociguat [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant use of riociguat with strong CYP3A4 inducers may lead to decreased riociguat plasma concentration.

Ritonavir [1], St. John's wort ---> SmPC of [1] of EMA

Serum levels of ritonavir can be reduced by concomitant use of herbal preparations containing St John's wort (Hypericum perforatum). This is due to the induction of medicinal product metabolising enzymes by St John's wort.

Rivaroxaban [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 induction may decrease the plasma concentrations of rivaroxaban. Concomitant administration of strong CYP3A4 inducers should be avoided unless the patient is closely observed for signs and symptoms of thrombosis.

Rizatriptan [1], St. John's wort ---> SmPC of [1] of eMC

Undesirable effects may be more common during concomitant use of triptans (5-HT1B/1D agonists) and herbal preparations containing St John's wort (Hypericum perforatum)

Rolapitant [1], St. John's wort ---> SmPC of [1] of EMA

Due to its strong inducing effect, St John's wort is contraindicated with rolapitant

Rosiglitazone [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66 % decrease in rosiglitazone plasma concentrations. It cannot be excluded that other inducers may also affect rosiglitazone exposure.

Ruxolitinib [1], St. John's wort ---> SmPC of [1] of EMA

The strong CYP3A4 induction may reduce the AUC of ruxolitinib. It is possible that an increase of the ruxolitinib dose is needed with strong CYP3A4 inductors

Saquinavir [1], St. John's wort ---> SmPC of [1] of EMA

Serotonergic medicines, St. John's wort

The co-administration may increase the serotoninergic effects and the adverse reactions. St. John's Wort should be avoided

Serotonin agonists, St. John's wort

The co-administration may increase the serotoninergic effects and the adverse reactions. St. John's Wort should be avoided

Sertraline [1], St. John's wort ---> SmPC of [1] of EMA

Sevoflurane [1], St. John's wort ---> SmPC of [1] of eMC

Severe hypotension and delayed emergence from anaesthesia with halogenated inhalational anaesthetics have been reported in patients treated long-term with St John's Wort.

Simeprevir [1], St. John's wort ---> SmPC of [1] of EMA

The CYP3A4 enzyme induction by St John's wort may decrease the plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with products containing St John's wort

Simvastatine, St. John's wort

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of statine. St. John's Wort should be avoided

Sirolimus [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of CYP3A4 may increase the metabolism of sirolimus and decrease sirolimus blood levels

Sodium valproate, St. John's wort

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of valproate (with risk of seizures). St. John's Wort should be avoided

Sofosbuvir [1], St. John's wort ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir [1], St. John's wort ---> SmPC of [1] of EMA

Sofosbuvir/velpatasvir/voxilaprevir [1], St. John's wort ---> SmPC of [1] of EMA

Sonidegib [1], St. John's wort ---> SmPC of [1] of EMA

Sorafenib [1], St. John's wort ---> SmPC of [1] of EMA

Inducers of CYP3A4 activity and/or glucuronidation may increase metabolism of sorafenib and thus decrease sorafenib concentrations.

SSRI, St. John's wort

Dynamic interactions between SSRI and the herbal remedy St John's wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects

St. John's wort [1], sun ---> SmPC of [1] of eMC

While you are taking this product avoid excessive sunbathing or the use of sunbeds/solariums

St. John's wort [1], trazodone ---> SmPC of [1] of eMC

Undesirable effects may be more frequent when trazodone is administered together with preparations containing Hypericum perforatum (St John's wort).

St. John's wort [1], warfarin ---> SmPC of [1] of eMC

Herbal preparations containing St John's Wort (Hypericum perforatum) must not be used whilst taking warfarin due to a proven risk of decreased plasma concentrations and reduced clinical effects of warfarin.

St. John's wort, sumatriptan [2] ---> SmPC of [2] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's Wort (Hypericum perforatum)

St. John's wort, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

St. John's wort, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use of substances known to induce CYP3A4 may affect the metabolism of tacrolimus and thereby decrease tacrolimus blood levels.

St. John's wort, talinolol

Concomitant use of a P-gp inductor decreases the bioavailability of talinolol

St. John's wort, tapentadol [2] ---> SmPC of [2] of eMC

For patients on tapentadol treatment, caution should be exercised if concomitant drug administration of strong enzyme inducing drugs starts or stops, since this may lead to decreased efficacy or risk for adverse effects, respectively.

St. John's wort, telaprevir [2] ---> SmPC of [2] of EMA

Concomitant administration of telaprevir is contraindicated with active substances that strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of telaprevir

St. John's wort, telithromycin [2] ---> SmPC of [2] of EMA

Concomitant administration of CYP3A4 inducers is likely to result in subtherapeutic levels of telithromycin and loss of effect. Telithromycin should not be used during and 2 weeks after treatment with CYP3A4 inducers.

St. John's wort, telmisartan/amlodipine [2] ---> SmPC of [2] of EMA

The concomitant use of CYP3A4 inducers may lead to a lower plasma concentration of amlodipine.

St. John's wort, temsirolimus [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction may decrease exposure of the active moieties, temsirolimus and its metabolite, sirolimus. Concomitant treatment of temsirolimus with agents that have CYP3A4/5 induction potential should be avoided

St. John's wort, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

Co-administration of Vemlidy with inducers of P-glycoprotein (P-gp) may decrease tenofovir alafenamide plasma concentrations and is not recommended.

St. John's wort, teriflunomide [2] ---> SmPC of [2] of EMA

Rifampicin und andere bekannte starke CYP und Transporter-Induktoren, wie etwa Carbamazepin, Phenobarbital, Phenytoin und Johanniskraut, sollten während der Behandlung mit Teriflunomid mit Vorsicht angewendet werden.

St. John's wort, tezacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

Tezacaftor exposures can be expected to decrease significantly during co-administration with strong CYP3A inducers; therefore, co-administration with strong CYP3A inducers is not recommended.

St. John's wort, theophylline [2] ---> SmPC of [2] of eMC

The St John's Wort increases clearance of theophylline and it may be necessary to increase dosage to ensure a therapeutic effect. St. John's Wort should be avoided

St. John's wort, tibolone [2] ---> SmPC of [2] of eMC

St. John's wort may induce the metabolism of oestrogens and progestogens via CYP3A4. Clinically, an increased metabolism of oestrogens and progestogens may lead to decreased effect and changes in the uterine bleeding profile.

St. John's wort, tipranavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of tipranavir can be reduced by concomitant use of the herbal preparation St John's wort (Hypericum perforatum). This is due to induction of drug metabolising enzymes by St John's wort.

St. John's wort, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

St. John's wort must not be combined with tipranavir/ritonavir. Combination is expected to substantially decrease tipranavir and ritonavir levels and may result in suboptimal levels of tipranavir (loss of virologic response and possible resistance)

St. John's wort, tivozanib [2] ---> SmPC of [2] of EMA

Herbal preparations containing St. John's wort (Hypericum perforatum) are contraindicated. The inducing effect of St John's wort may persist for at least 2 weeks after cessation of treatment with St John's wort

St. John's wort, tolbutamide [2] ---> SmPC of [2] of eMC

Increased hypoglycaemic effects have occurred or might be expected

St. John's wort, topiramate [2] ---> SmPC of [2] of eMC

A risk of decreased plasma concentrations resulting in a loss of efficacy could be observed with coadministration of topiramate and St John's Wort.

St. John's wort, trabectedin [2] ---> SmPC of [2] of EMA

Concomitant use of a strong CYP3A4 inductor with trabectedin may decrease the plasma exposure of trabectedin. Therefore, the concomitant use of trabectedin with strong CYP3A4 inducers should be avoided if possible

St. John's wort, tramadol

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of tramadol. St. John's Wort should be avoided

St. John's wort, trandolapril/verapamil [2] ---> SmPC of [2] of eMC

Verapamil concentrations may be reduced by St. John's wort

St. John's wort, triptans ---> SmPC of [zolmitriptan] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's wort (Hypericum perforatum).

St. John's wort, trofosfamide

It has to be taken into account a prior or actual treatment with drugs that are enzyme inducers

St. John's wort, ulipristal [2] ---> SmPC of [2] of EMA

Administration of the potent CYP3A4 inducers markedly decreased Cmax and AUC of ulipristal acetate and its active metabolite. Concomitant use of ulipristal acetate and potent CYP3A4 inducers is not recommended

St. John's wort, valproic acid

St. John's wort, enzymatic inductor, may decrease the plasma concentrations of valproic acid (with risk of seizures). St. John's Wort should be avoided

St. John's wort, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St Johns' Wort, carbamazepine, phenobarbital) should be avoided

St. John's wort, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

St. John's wort, venetoclax [2] ---> SmPC of [2] of EMA

Preparations containing St. John's wort are contraindicated during treatment with venetoclax, as efficacy may be reduced

St. John's wort, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

St. John's wort, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil concentrations may be reduced by St. John's wort

St. John's wort, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inducers should be avoided since they may decrease vinflunine and DVFL concentrations

St. John's wort, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that induces this iso-enzyme can affect the concentration of vinorelbine

St. John's wort, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers, exposure to vismodegib may be decreased. St. John's wort is contraindicated

St. John's wort, voriconazole [2] ---> SmPC of [2] of EMA

St. John's wort, strong CYP3A4 inductor, may decrease the plasma concentrations of voriconazole. St. John's Wort should be avoided

St. John's wort, vortioxetine [2] ---> SmPC of [2] of EMA

Concomitant use of antidepressants with serotonergic effect and herbal remedies containing St. John's wort (Hypericum perforatum) may result in a higher incidence of adverse reactions including serotonin syndrome

St. John's wort, ziprasidone

The co-administration of ziprasidone with P glycoprotein inductors may decrease the plasma concentrations of ziprasidone

St. John's wort, zolmitriptan [2] ---> SmPC of [2] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's wort (Hypericum perforatum).

St. John's wort, zopiclone [2] ---> SmPC of [2] of eMC

Plasma levels of zopiclone may be decreased when co-administered with CYP3A4 inducers

CONTRAINDICATIONS of St. John's wort

DO NOT TAKE this product if:

- you are under 18 years of age

- you are pregnant or breast-feeding

- you are allergic to any of the ingredients

- your skin is exceptionally sensitive to sunlight (photosensitive)

- you are having light treatment (phototherapy) for any condition

- you are suffering from depression

http://www.medicines.org.uk/emc/

Stavudine

Abacavir [1], stavudine ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Abacavir/lamivudine/zidovudine [1], stavudine ---> SmPC of [1] of EMA

In vitro antagonism of anti-HIV activity between stavudine and zidovudine could result in decreased efficacy of both drugs. Combination not recommended.

Ability to drive, stavudine [2] ---> SmPC of [2] of EMA

Stavudine may cause dizziness and/or somnolence.

Breast-feeding, stavudine [2] ---> SmPC of [2] of EMA

It is recommended that HIV infected women should not breast-feed under any circumstances in order to avoid transmission of HIV. Mothers should be instructed to discontinue breast-feeding prior to receiving Zerit.

Daclatasvir [1], stavudine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

Darunavir/cobicistat [1], stavudine ---> SmPC of [1] of EMA

Based on the different elimination pathways, no interactions are expected with darunavir/cobicistat. The can be used without dose adjustment.

Darunavir/ritonavir, stavudine ---> SmPC of [darunavir] of EMA

Darunavir co-administered with low dose ritonavir can be used with stavudine without dose adjustment.

Didanosine, stavudine [2] ---> SmPC of [2] of EMA

The combination of stavudine with didanosine is contraindicated given that both drugs exhibits high risk of mitochondrial toxicity

Didanosine/nelfinavir, stavudine [2] ---> SmPC of [2] of EMA

Clinically significant interactions of stavudine or stavudine plus didanosine with nelfinavir have not been observed.

Doxorubicine, stavudine [2] ---> SmPC of [2] of EMA

In vitro studies indicate that the activation of stavudine is inhibited by doxorubicin and ribavirin therefore, coadministration of stavudine with either doxorubicin or ribavirin should be undertaken with caution.

Drugs with high protein binding, stavudine [2] ---> SmPC of [2] of EMA

Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of protein-bound medicines.

Elvitegravir [1], stavudine ---> SmPC of [1] of EMA

No dose adjustment is required when elvitegravir is co-administered with stavudine.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], stavudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Emtricitabine [1], stavudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine

Emtricitabine/rilpivirine/tenofovir disoproxil [1], stavudine ---> SmPC of [1] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Emtricitabine/tenofovir disoproxil [1], stavudine ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Foods, stavudine [2] ---> SmPC of [2] of EMA

Should be taken on an empty stomach, and preferably at least 1 hour before a meal

Ganciclovir, stavudine ---> SmPC of [valganciclovir] of eMC

No clinically significant interactions were observed when stavudine and oral ganciclovir were given in combination.

Indinavir [1], stavudine ---> SmPC of [1] of EMA

Indinavir and NRTIs can be co-administered without dose adjustment.

Lamivudine, stavudine [2] ---> SmPC of [2] of EMA

No clinically relevant pharmacokinetic interaction has been seen with lamivudine. Peripheral neuropathy was seen in combination studies of Zerit with lamivudine plus efavirenz

Lamivudine/zidovudine [1], stavudine ---> SmPC of [1] of EMA

In vitro antagonism of anti-HIV activity between stavudine and zidovudine could result in decreased efficacy of both drugs. Combination not recommended

Lopinavir/ritonavir [1], stavudine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Methadone [1], stavudine ---> SmPC of [1] of eMC

Methadone treatment has been found to decrease the rate of absorption and decrease the bioavailability of the nucleoside reverse transcriptase inhibitors didanosine stavudine.

Mitochondrial dysfunction, nucleoside analogues ---> SmPC of [stavudine] of EMA

Nucleoside and nucleotide analogues have been demonstrated to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues

Mitochondrial dysfunction, nucleotide analogues ---> SmPC of [stavudine] of EMA

Mitochondrial function, stavudine ---> SmPC of [abacavir/lamivudine/zidovudine] of EMA

Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Nevirapine [1], stavudine ---> SmPC of [1] of EMA

Stavudine and Viramune can be coadministered without dose adjustments.

Pancreatitis, stavudine [2] ---> SmPC of [2] of EMA

Pancreatitis (fatal and nonfatal) and peripheral neuropathy (severe in some cases) have been reported in HIV infected patients receiving stavudine in association with hydroxyurea and didanosine

Pharmacokinetics, stavudine [2] ---> SmPC of [2] of EMA

Stavudine does not inhibit the major cytochrome P450 isoforms CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4; therefore, it is unlikely that clinically significant drug interactions will occur with medicines metabolised through these pathways.

Pregnancy, stavudine [2] ---> SmPC of [2] of EMA

Zerit should not be used during pregnancy unless clearly necessary.

Ribavirin, stavudine [2] ---> SmPC of [2] of EMA

Rilpivirine [1], stavudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Simeprevir [1], stavudine ---> SmPC of [1] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

Stavudine [1], trimethoprim ---> SmPC of [1] of EMA

Since stavudine is actively secreted y he renal tubules, interactions with other actively secreted medicinal products are possible, e.g. with trimethoprim.

Stavudine [1], tubular secretion ---> SmPC of [1] of EMA

Since stavudine is actively secreted y he renal tubules, interactions with other actively secreted medicinal products are possible, e.g. with trimethoprim.

Stavudine, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

Stavudine, tipranavir [2] ---> SmPC of [2] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Stavudine, tipranavir/ritonavir ---> SmPC of [tipranavir] of EMA

No clinically significant interaction is observed. No dosage adjustment necessary.

Stavudine, valganciclovir [2] ---> SmPC of [2] of eMC

No clinically significant interactions were observed when stavudine and oral ganciclovir were given in combination.

Stavudine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

In vitro antagonism of anti-HIV activity between stavudine and zidovudine could result in decreased efficacy of both drugs. Combination not recommended

CONTRAINDICATIONS of Stavudine

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Co-administration with didanosine due to the potential for serious and/or life-threatening events notably lactic acidosis, liver function abnormalities, pancreatitis and peripheral neuropathy

http://www.ema.europa.eu/

Sterculia

Digoxin, sterculia

Agents causing hypokalaemia may cause increased sensitivity to digoxin

Glycyrrhiza, sterculia

The co-administration may cause electrolyte imbalance

Hypokalemia, sterculia

The co-administration may cause electrolyte imbalance

Loperamide, sterculia

The co-administration may cause intestinal obstruction

Sterculia, thiazides

The co-administration may cause electrolyte imbalance

CONTRAINDICATIONS of Sterculia

- Intestinal obstruction,

- faecal impaction, and

- total atony of the colon.

Known hypersensitivity to any of the ingredients

http://www.medicines.org.uk/emc/

Stiripentol (Diacomit)

Ability to drive, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol has major influence on the ability to drive and use machines because it may cause dizziness and ataxia.

Alprazolam, stiripentol [2] ---> SmPC of [2] of EMA

Increased plasma benzodiazepine levels may occur via decreased hepatic metabolism leading to excessive sedation. Caution should be exercised

Antiepileptics, stiripentol [2] ---> SmPC of [2] of EMA

Clinical monitoring of plasma levels of other anticonvulsants when combined with stiripentol with possible dose adjustments is recommended.

Astemizole, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances due to the increased risk of adverse reactions

Atorvastatin, stiripentol [2] ---> SmPC of [2] of EMA

Decreased hepatic metabolism of statine and increased risk of dose-dependent adverse reactions such as rhabdomyolysis. Undesirable combination (to be avoided unless strictly necessary)

Azole antifungals, stiripentol [2] ---> SmPC of [2] of EMA

The impact of macrolides and azole antifungal medicinal products on stiripentol metabolism, that are known to be inhibitors of CYP3A4 and substrates of the same enzyme, is not known. Likewise, the effect of stiripentol on their metabolism is not known.

Bepridil, stiripentol [2] ---> SmPC of [2] of EMA

Increased risk of cardiac arrhythmias and torsades de pointes/wave burst arrhythmia in particular. To be avoided unless strictly necessary

Breast-feeding, stiripentol [2] ---> SmPC of [2] of EMA

In case stiripentol therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects.

Breast-feeding, stiripentol [2] ---> SmPC of [2] of EMA

In the absence of human studies on excretion in breast milk, and given that stiripentol passes freely from plasma into milk in the goat, breast-feeding is not recommended during treatment.

Caffeine, stiripentol [2] ---> SmPC of [2] of EMA

Data on the potential for inhibition of CYP1A2 are limited. Interactions with theophylline and caffeine cannot be excluded because of the increased plasma levels of theophylline and caffeine may potentially lead to toxicity.

Calcium antagonists, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol is an inhibitor of the enzymes CYP3A4 and may markedly increase the plasma concentrations of substances metabolised by these enzymes and increase the risk of adverse reactions

Cannabidiol [1], stiripentol ---> SmPC of [1] of EMA

When cannabidiol was combined with stiripentol in a healthy volunteer trial there was an increase in stiripentol levels of 28% for maximum measured plasma concentration (Cmax) and 55% for AUC.

Carbamazepine, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Carvedilol, stiripentol [2] ---> SmPC of [2] of EMA

As stiripentol inhibited CYP2D6 in vitro at concentrations that are achieved clinically in plasma, substances that are metabolized by this isoenzyme may be subject to metabolic interactions with stiripentol

Chlorpheniramine, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances due to the increased risk of adverse reactions

Chlorpromazine, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol enhances the central depressant effect of chlorpromazine.

Chocolate, stiripentol [2] ---> SmPC of [2] of EMA

Patient should not drink cola drinks, which contain significant quantities of caffeine or chocolate, which contains trace amounts of theophylline (see section 4.2).

Cisapride, stiripentol [2] ---> SmPC of [2] of EMA

Increased risk of cardiac arrhythmias and torsades de pointes/wave burst arrhythmia in particular. To be avoided unless strictly necessary

Citalopram, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) due to the increased risk of adverse reactions

Clobazam, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Clomipramine, stiripentol [2] ---> SmPC of [2] of EMA

Codeine, stiripentol [2] ---> SmPC of [2] of EMA

Coffee, stiripentol [2] ---> SmPC of [2] of EMA

This warning is not only restricted to medicinal products but also to a considerable number of foods (for example: cola, chocolate, coffee, tea, and energy drinks)

Cola drinks, stiripentol [2] ---> SmPC of [2] of EMA

Patient should not drink cola drinks, which contain significant quantities of caffeine or chocolate, which contains trace amounts of theophylline (see section 4.2).

Cyclosporine, stiripentol [2] ---> SmPC of [2] of EMA

Raised blood levels of immunosuppressant (decreased hepatic metabolism). The combination is to be avoided unless strictly necessary

Dextromethorphan, stiripentol [2] ---> SmPC of [2] of EMA

Diazepam, stiripentol [2] ---> SmPC of [2] of EMA

The CYP3A4 and CYP2C19 inhibition may increase the plasma levels of diazepam with potential risk of overdose.

Dihydroergocristine, stiripentol [2] ---> SmPC of [2] of EMA

Ergotism with possibility of necrosis of the extremities (inhibition of hepatic elimination of rye ergot). Undesirable combination (to be avoided unless strictly necessary)

Dihydroergotamine, stiripentol [2] ---> SmPC of [2] of EMA

Ergotism with possibility of necrosis of the extremities (inhibition of hepatic elimination of rye ergot). Undesirable combination (to be avoided unless strictly necessary)

Drugs primarily metabolised by CYP1A2, stiripentol [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP2C19, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) due to the increased risk of adverse reactions

Drugs primarily metabolised by CYP2D6, stiripentol [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, stiripentol [2] ---> SmPC of [2] of EMA

Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse reactions.

Drugs primarily metabolised by CYP3A4, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances due to the increased risk of adverse reactions

Energy drinks, stiripentol [2] ---> SmPC of [2] of EMA

This warning is not only restricted to medicinal products but also to a considerable number of foods (for example: cola, chocolate, coffee, tea, and energy drinks)

Ergot derivatives, stiripentol [2] ---> SmPC of [2] of EMA

Ergotism with possibility of necrosis of the extremities (inhibition of hepatic elimination of rye ergot). Undesirable combination (to be avoided unless strictly necessary)

Ergotamine, stiripentol [2] ---> SmPC of [2] of EMA

Ergotism with possibility of necrosis of the extremities (inhibition of hepatic elimination of rye ergot). Undesirable combination (to be avoided unless strictly necessary)

Ethosuximide, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Ezetimibe/atorvastatin [1], stiripentol ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Coadministration of potent CYP3A4 inhibitors should be avoided if possible.

Fenfluramine [1], stiripentol ---> SmPC of [1] of EMA

Co-administration of a single 0.7 mg/kg dose of fenfluramine, with a single dose of a stiripentol, clobazam, and valproic acid combination, did not affect the pharmacokinetics

Fertility, stiripentol [2] ---> SmPC of [2] of EMA

No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, potential risk for human is unknown.

Fluoxetine, stiripentol [2] ---> SmPC of [2] of EMA

Foods, stiripentol [2] ---> SmPC of [2] of EMA

Stiripentol should not be taken with milk or dairy products (yoghurt, soft cream cheese, etc.), carbonated drinks, fruit juice or food and drinks that contain caffeine or theophylline.

Foods, stiripentol [2] ---> SmPC of [2] of EMA

The capsule should be swallowed whole with a glass of water during a meal. Stiripentol must always be taken with food as it degrades rapidly in an acidic environment (e.g. exposure to gastric acid in an empty stomach).

Halofantrine, stiripentol [2] ---> SmPC of [2] of EMA

Increased risk of cardiac arrhythmias and torsades de pointes/wave burst arrhythmia in particular. To be avoided unless strictly necessary

Haloperidol, stiripentol [2] ---> SmPC of [2] of EMA

Imipramine, stiripentol [2] ---> SmPC of [2] of EMA

Levetiracetam, stiripentol [2] ---> SmPC of [2] of EMA

Levetiracetam does not undergo hepatic metabolism to a major extent. As a result, no pharmacokinetic metabolic drug interaction between stiripentol and levetiracetam is anticipated.

Macrolide antibiotics, stiripentol [2] ---> SmPC of [2] of EMA

Midazolam, stiripentol [2] ---> SmPC of [2] of EMA

Increased plasma benzodiazepine levels may occur via decreased hepatic metabolism leading to excessive sedation. Caution should be exercised

Omeprazole, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances metabolised by CYP2C19 (e.g. citalopram, omeprazole) due to the increased risk of adverse reactions

Oral contraceptives, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances due to the increased risk of adverse reactions

Paroxetine, stiripentol [2] ---> SmPC of [2] of EMA

Phenobarbital, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Phenytoin, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Pimozide, stiripentol [2] ---> SmPC of [2] of EMA

Increased risk of cardiac arrhythmias and torsades de pointes/wave burst arrhythmia in particular. To be avoided unless strictly necessary

Pregnancy, stiripentol [2] ---> SmPC of [2] of EMA

Caution should be exercised when prescribing to pregnant women and use of efficient methods of contraception is advisable.

Pregnancy, stiripentol [2] ---> SmPC of [2] of EMA

The clinical decision for use of stiripentol in pregnancy needs to be made on an individual basis taking into consideration the potential clinical benefits and risks

Primidone, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Propranolol, stiripentol [2] ---> SmPC of [2] of EMA

Protease inhibitors, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances due to the increased risk of adverse reactions

Quinidine, stiripentol [2] ---> SmPC of [2] of EMA

Increased risk of cardiac arrhythmias and torsades de pointes/wave burst arrhythmia in particular. To be avoided unless strictly necessary

Sertraline, stiripentol [2] ---> SmPC of [2] of EMA

Simvastatine, stiripentol [2] ---> SmPC of [2] of EMA

Decreased hepatic metabolism of statine and increased risk of dose-dependent adverse reactions such as rhabdomyolysis. Undesirable combination (to be avoided unless strictly necessary)

Sirolimus, stiripentol [2] ---> SmPC of [2] of EMA

Raised blood levels of immunosuppressant (decreased hepatic metabolism). The combination is to be avoided unless strictly necessary

Sodium valproate, stiripentol [2] ---> SmPC of [2] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Statins, stiripentol [2] ---> SmPC of [2] of EMA

Caution must be exercised if clinical circumstances require combining stiripentol with substances due to the increased risk of adverse reactions

Stiripentol [1], strong CYP1A2 inductors ---> SmPC of [1] of EMA

In vitro studies suggested that stiripentol phase 1 metabolism is catalyzed by CYP1A2, CYP2C19 and CYP3A4. Caution is advised when combining stiripentol with other substances that induce one or more of these enzymes.

Stiripentol [1], strong CYP1A2 inhibitors ---> SmPC of [1] of EMA

Stiripentol [1], strong CYP2C19 inductors ---> SmPC of [1] of EMA

Stiripentol [1], strong CYP2C19 inhibitors ---> SmPC of [1] of EMA

Stiripentol [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Stiripentol [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Stiripentol [1], tacrolimus ---> SmPC of [1] of EMA

Raised blood levels of immunosuppressant (decreased hepatic metabolism). The combination is to be avoided unless strictly necessary

Stiripentol [1], tea ---> SmPC of [1] of EMA

This warning is not only restricted to medicinal products but also to a considerable number of foods (for example: cola, chocolate, coffee, tea, and energy drinks)

Stiripentol [1], theophylline ---> SmPC of [1] of EMA

Stiripentol [1], tiagabine ---> SmPC of [1] of EMA

Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions. The consequences are increased plasma levels of the anticonvulsant with potential risk of overdose.

Stiripentol [1], timolol ---> SmPC of [1] of EMA

Stiripentol [1], topiramate ---> SmPC of [1] of EMA

With regard to topiramate, it is considered that potential competition of inhibition on CYP2C19 should not occur because it probably requires plasma concentrations 5-15 times higher than plasma concentrations obtained

Stiripentol [1], tramadol ---> SmPC of [1] of EMA

Stiripentol [1], triazolam ---> SmPC of [1] of EMA

Increased plasma benzodiazepine levels may occur via decreased hepatic metabolism leading to excessive sedation. Caution should be exercised

CONTRAINDICATIONS of Stiripentol (Diacomit)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- A past history of psychoses in the form of episodes of delirium

https://www.ema.europa.eu/en/documents/product-information/diacomit-epar-product-information_en.pdf 20/10/2025

Streptokinase

Acetylsalicylic acid, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Aminocaproic acid, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Anticoagulants, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Antifibrinolytics, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Antihemorrhagics, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Aprotinin, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Breast-feeding, streptokinase [2] ---> SmPC of [2] of eMC

It is not known whether streptokinase is excreted in breast milk. Breast milk should be discarded during the first 24 hours following thrombolytic therapy.

Dextran, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Eptifibatide [1], streptokinase ---> SmPC of [1] of EMA

Eptifibatide appeared to increase the risk of bleeding when administered with streptokinase in an acute myocardial infarction study.

Heparin, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Indometacin, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Lepirudin [1], streptokinase ---> SmPC of [1] of EMA

Concomitant treatment of lepirudin with thrombolytics (e.g. rt-PA or streptokinase) may increase the risk of bleeding complications and considerably enhance the effect of lepirudin on aPTT prolongation.

NSAID, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Oral anticoagulants, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Phenylbutazone, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Platelet aggregation inhibitors, streptokinase [2] ---> SmPC of [2] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Pregnancy, streptokinase [2] ---> SmPC of [2] of eMC

Bleeding and anaphylactic reactions might cause abortion and foetal death, especially when streptokinase is given within the first 18 weeks of pregnancy. Use only when there is no safer alternative.

Streptokinase [1], sulfinpyrazone ---> SmPC of [1] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Streptokinase [1], tranexamic acid ---> SmPC of [1] of eMC

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

CONTRAINDICATIONS of Streptokinase

Streptase must not be used in case of severe allergic reactions to the product.

Because of the increased risk of haemorrhage under thrombolytic therapy Streptase must not be given in the following situations:

- existing or recent internal haemorrhages

- all forms of reduced blood coagulability, in particular spontaneous fibrinolysis and extensive clotting disorders

- recent cerebrovascular insults, intracranial or intraspinal surgery

- intracranial neoplasm

- recent head trauma

- arteriovenous malformation or aneurysm

- known neoplasm with risk of haemorrhage

- acute pancreatitis

- uncontrollable hypertension with systolic values above 200 mm Hg and/or diastolic values above 100 mm Hg or hypertensive retinal changes grades III/IV

- recent implantation of a vessel prosthesis

- simultaneous treatment with oral anticoagulants (INR >1.3)

- severe liver or kidney damage

- endocarditis or pericarditis. Isolated cases of pericarditis, misdiagnosed as acute myocardial infarction and treated with Streptase, have resulted

in pericardial effusions including tamponade

- known haemorrhagic diathesis

- recent major operations (6th to 10th postoperative day, depending on the severity of surgical intervention)

- invasive operations, e.g. recent organ biopsy, long-term (traumatic) closed-chest cardiac massage

http://www.medicines.org.uk/emc/

Streptokinase/streptodornase

Acetylsalicylic acid, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Aminocaproic acid, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Anticoagulants, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Antifibrinolytics, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Aprotinin, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Breast-feeding, streptokinase/streptodornase

Breast-feeding should be avoided during treatment

Dextran, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Indometacin, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

NSAID, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Oral anticoagulants, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Phenylbutazone, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Platelet aggregation inhibitors, streptokinase/streptodornase

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Pregnancy, streptokinase/streptodornase

It should not be used during pregnancy

Streptokinase/streptodornase, sulfinpyrazone

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Streptokinase/streptodornase, tranexamic acid

There is an increased risk of haemorrhage in patients who are receiving or who have recently been treated with anticoagulants or drugs which inhibit platelet formation or function

Strimvelis (Strimvelis)

Breast-feeding, Strimvelis [2] ---> SmPC of [2] of EMA

As Strimvelis is not intended for use in adults, human data on use during pregnancy or lactation and animal reproduction studies are not available.

Cryopreservation, Strimvelis [2] ---> SmPC of [2] of EMA

It should be noted that the treating physician should inform the patient's parents/carers about options for cryopreservation of spermatogonial stem cells or ovarian tissue.

Cytochrome P450, Strimvelis [2] ---> SmPC of [2] of EMA

No interaction studies have been performed. Strimvelis is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters.

Donation, Strimvelis [2] ---> SmPC of [2] of EMA

Patients treated with Strimvelis should not donate blood, organs, tissues and cells for transplantation, at any time in the future. This information is provided in the Patient Alert Card.

Fertility, Strimvelis [2] ---> SmPC of [2] of EMA

With regard to fertility, consult the SmPC of the conditioning medicinal product.

Pregnancy, Strimvelis [2] ---> SmPC of [2] of EMA

As Strimvelis is not intended for use in adults, human data on use during pregnancy or lactation and animal reproduction studies are not available.

Strimvelis [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Vaccination with live virus vaccines is not recommended during the 6 weeks preceding the start of non-myeloablative conditioning, and until haematological and immunological recovery following treatment with Strimvelis.

CONTRAINDICATIONS of Strimvelis (Strimvelis)

- Hypersensitivity to the product or to any of the excipients listed in section 6.1.

- Current or previous history of leukaemia or myelodysplasia.

- Positive test for human immunodeficiency virus (HIV) or presence of any other transmissible infectious agent listed in the current EU Cell and Tissue Directive prior to bone marrow harvest.

- History of previous gene therapy.

https://www.ema.europa.eu/en/documents/product-information/strimvelis-epar-product-information_en.pdf 27/03/2025

Strontium ranelate (Protelos)

ACE inhibitors, strontium ranelate [2] ---> SmPC of [2] of EMA

No evidence of clinical interactions or relevant increase of blood strontium levels with medicinal products expected to be commonly prescribed concomitantly with PROTELOS in the target population were found during clinical trials.

Acetylsalicylic acid, strontium ranelate [2] ---> SmPC of [2] of EMA

AIIRA, strontium ranelate [2] ---> SmPC of [2] of EMA

Anilide, strontium ranelate [2] ---> SmPC of [2] of EMA

Antacids, strontium ranelate [2] ---> SmPC of [2] of EMA

It is preferable to take antacids at least 2 hours after strontium ranelate

Antiplatelet therapy, strontium ranelate [2] ---> SmPC of [2] of EMA

Benzodiazepines, strontium ranelate [2] ---> SmPC of [2] of EMA

Beta-adrenergic receptor blockers, strontium ranelate [2] ---> SmPC of [2] of EMA

Betablockers, strontium ranelate [2] ---> SmPC of [2] of EMA

Breast-feeding, strontium ranelate [2] ---> SmPC of [2] of EMA

PROTELOS should not be used during breast-feeding

Calcium antagonists, strontium ranelate [2] ---> SmPC of [2] of EMA

Calcium carbonate/cholecalciferol, strontium ranelate

Calcium salts may reduce the absorption of strontium ranelate. It is advisable to allow a minimum period of 2 hours before taking the calcium.

Calcium, strontium ranelate [2] ---> SmPC of [2] of EMA

Food, milk and derivative products, and medicinal products containing calcium may reduce the bioavailability of strontium ranelate by approximately 60-70%. Therefore, administration of ranelate and such products should be separated by at least 2 hours

Cheese, strontium ranelate [2] ---> SmPC of [2] of EMA

Chlortetracycline, divalent cations ---> SmPC of [strontium ranelate] of EMA

As divalent cations can form complexes with oral tetracycline at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Ciprofloxacin, strontium ranelate [2] ---> SmPC of [2] of EMA

As divalent cations can form complexes with oral quinolone antibiotics at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Dairy products, strontium ranelate [2] ---> SmPC of [2] of EMA

Digital glycosides, strontium ranelate [2] ---> SmPC of [2] of EMA

Digoxin, strontium ranelate [2] ---> SmPC of [2] of EMA

Diuretics, strontium ranelate [2] ---> SmPC of [2] of EMA

Divalent cations, quinolones ---> SmPC of [strontium ranelate] of EMA

As divalent cations can form complexes with oral quinolone antibiotics at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Doxycycline, strontium ranelate [2] ---> SmPC of [2] of EMA

As divalent cations can form complexes with oral tetracycline at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Fertility, strontium ranelate [2] ---> SmPC of [2] of EMA

No effects were observed on males and females fertility in animal studies.

Fibrates, strontium ranelate [2] ---> SmPC of [2] of EMA

Foods, strontium ranelate [2] ---> SmPC of [2] of EMA

H2 antagonists, strontium ranelate [2] ---> SmPC of [2] of EMA

Milk, strontium ranelate [2] ---> SmPC of [2] of EMA

Nitrates, strontium ranelate [2] ---> SmPC of [2] of EMA

NSAID, strontium ranelate [2] ---> SmPC of [2] of EMA

Oral anticoagulants, strontium ranelate [2] ---> SmPC of [2] of EMA

Paracetamol, strontium ranelate [2] ---> SmPC of [2] of EMA

Pregnancy, strontium ranelate [2] ---> SmPC of [2] of EMA

If PROTELOS is used inadvertently during pregnancy, treatment must be stopped

Proton pump inhibitors, strontium ranelate [2] ---> SmPC of [2] of EMA

Quinolones, strontium ranelate [2] ---> SmPC of [2] of EMA

As divalent cations can form complexes with oral quinolone antibiotics at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Statins, strontium ranelate [2] ---> SmPC of [2] of EMA

Strontium ranelate [1], tetracyclines ---> SmPC of [1] of EMA

As divalent cations can form complexes with oral tetracycline at the gastro-intestinal level and thereby reduce their absorption, simultaneous administration is not recommended.

Strontium ranelate [1], vitamin D ---> SmPC of [1] of EMA

No interaction was observed with oral supplementation of vitamin D.

CONTRAINDICATIONS of Strontium ranelate (Protelos)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Current or previous venous thromboembolic events (VTE), including deep vein thrombosis and pulmonary embolism

- Temporary or permanent immobilisation due to e.g. post-surgical recovery or prolonged bed rest

- Established, current or past history of ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease

- Uncontrolled hypertension

https://www.ema.europa.eu/en/documents/product-information/protelos-epar-product-information_en.pdf 07/12/2018 (withdrawn)

Other trade names: Osseor (withdrawn),

Sucralfate

Alfacalcidol, sucralfate

Decreased absorption of alfacalcidol

Algeldrate/magnesium hydroxide, sucralfate

The co-administration may decrease the effect of sucralfate. It is recommended to administer the two substances at least 2-4 hours apart.

Aluminium oxide/magnesium hydroxide, sucralfate

The co-administration may decrease the effect of sucralfate. It is recommended to administer the two substances at least 2-4 hours apart.

Amisulpride, sucralfate

Concomitant use of amisulpride with sucralfate may decrease plasma concentration of amisulpride

Amitriptyline, sucralfate

Concomitant administration of sucralfate may reduce the bioavailability of amitriptyline. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Amphotericin, sucralfate

The co-administration may decrease the absorption of amphotericin. It is recommended to administer the two substances at least 2 hours apart.

Antacids, sucralfate ---> SmPC of [algeldrate/magnesium hydroxide] of

The co-administration may decrease the effect of sucralfate. It is recommended to administer the two substances at least 2-4 hours apart.

Bictegravir/emtricitabine/tenofovir alafenamide [1], sucralfate ---> SmPC of [1] of EMA

Co-administration is not recommended.

Biphosphonates, sucralfate

Decreased absorption of bisphosphonate. Administer on empty stomach at least 1 hour before or 1-2 hours after food.

Breast-feeding, sucralfate [2] ---> SmPC of [2] of eMC

It is not known whether this drug is excreted in human milk. Caution should be exercised when sucralfate is administered to breast-feeding women.

Chenodeoxycholic acid, sucralfate

Concomitant administration of sucralfate may reduce the bioavailability of chenodeoxycholic acid. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Cimetidine, sucralfate

Concomitant administration of sucralfate may reduce the bioavailability of cimetidine. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Ciprofloxacin [1], sucralfate ---> SmPC of [1] of eMC

The co-administration may decrease the absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of sucralfate.

Citrate, sucralfate [2] ---> SmPC of [2] of eMC

Sucralfate should not be co-administered with citrate preparations. Co-administration may increase the blood concentrations of aluminium. The mechanism may be due to chelation of aluminium, which is assumed to increase its absorption.

Colistin, sucralfate [2] ---> SmPC of [2] of eMC

An in vitro study with colistin found that it became markedly and irreversibly bound to sucralfate at the pH values found in the gut. This suggests that efficacy for gut decontamination or gastrointestinal infections might be decreased.

Digoxin, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of digoxin. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Doxycycline [1], sucralfate ---> SmPC of [1] of eMC

Absorption of doxycycline may be impaired by concurrently administered with drugs containing aluminium, calcium, magnesium or other these cations; oral zinc, iron salts or bismuth preparations. Dosages should be maximally separated.

Famotidine, sucralfate

Sucralfate decreases the absorption of famotidine. Separate administration by at least 2 hours

Fosphenytoin [1], sucralfate ---> SmPC of [1] of eMC

Sucralfate may decrease phenytoin serum levels

Furosemide [1], sucralfate ---> SmPC of [1] of eMC

Sucralfate decreases the absorption of furosemide. Must not be taken within 2 hours of each other

H2 antagonists, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of H2 antagonists. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Ketoconazole, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of ketoconazole. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Lansoprazole [1], sucralfate ---> SmPC of [1] of eMC

Sucralfate may decrease the bioavailability of lansoprazole. Therefore Lansoprazole should be taken at least 1 hour after taking these drugs.

Levofloxacin, sucralfate [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of sucralfate.

Levothyroxine, sucralfate

Concomitant administration of sucralfate may reduce the bioavailability of levothyroxine. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Magnesium hydroxide, sucralfate

The co-administration may decrease the effect of sucralfate. It is recommended to administer the two substances at least 2-4 hours apart.

Minocycline [1], sucralfate ---> SmPC of [1] of eMC

Absorption of minocycline is impaired by the concomitant administration. Dosages should be maximally separated.

Moxifloxacin [1], sucralfate ---> SmPC of [1] of eMC

An interval of about 6 hours should be left between administration of agents containing bivalent or trivalent cations and administration of moxifloxacin.

Norfloxacin, sucralfate [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of sucralfate.

Ofloxacin [1], sucralfate ---> SmPC of [1] of eMC

The co-administration may decrease the absorption of ofloxacin. Separate administration by at least 2 hours

Oral anticoagulants, sucralfate

Decreased absorption of orale anticoagulants cannot be precluded

Phenytoin, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of phenytoin. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Pregnancy, sucralfate [2] ---> SmPC of [2] of eMC

Safety in pregnant women has not been established and sucralfate should be used during pregnancy only if clearly needed.

Proton pump inhibitors, sucralfate

The co-administration may decrease the effect of sucralfate. It is recommended to administer the two substances at least 2-4 hours apart.

Quinidine, sucralfate [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of quinidine. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Quinolones, sucralfate [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of sucralfate.

Ranitidine, sucralfate

Concomitant administration of sucralfate may reduce the bioavailability of ranitidine. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Sucralfate [1], tetracyclines ---> SmPC of [1] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of tetracyclines. The bioavailability of tetracyclines may be restored by separating the administration from sucralfate by 2 hours.

Sucralfate [1], theophylline ---> SmPC of [1] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of theophylline. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Sucralfate, sulpiride [2] ---> SmPC of [2] of eMC

The absorption of sulpiride is decreased after co-administration with sucralfate. Therefore, sulpiride should be administered 2 hours before sucralfate

Sucralfate, ursodeoxycholic acid

Concomitant administration of sucralfate may reduce the bioavailability of ursodeoxycholic acid. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Sucralfate, warfarin [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of warfarin. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

CONTRAINDICATIONS of Sucralfate

- Hypersensitivity to the active substance or to any of the excipients

http://www.medicines.org.uk/emc/

Sucroferric oxyhydroxide (Velphoro)

Acetylsalicylic acid, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Alendronate, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

When administering any medicinal product that is already known to interact with iron (like alendronate and doxycycline), the medicinal product should be administered at least one hour before or two hours after Velphoro.

Atorvastatin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Data from clinical studies have shown that Velphoro does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin).

Breast-feeding, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

A decision on whether to continue breast-feeding or to continue therapy with Velphoro should be made taking into account the benefit of breast-feeding to the child and the benefit of Velphoro therapy to the mother.

Cephalexin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Cinacalcet, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Ciprofloxacin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Clopidogrel, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Digoxin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Co-administration of Velphoro did not affect the bioavailability of these products as measured by the area under the curve (AUC).

Doxycycline, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Drugs with a narrow therapeutic window, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

The clinical effect and adverse events should be monitored, on initiation or dose adjustment of either Velphoro or the concomitant medicinal product, or the physician should consider measuring blood levels.

Enalapril, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Foods, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Velphoro is a chewable tablet that must be taken with meals.

Furosemide, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Co-administration of Velphoro did not affect the bioavailability of these products as measured by the area under the curve (AUC).

HMG-CoA reductase inhibitors, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Data from clinical studies have shown that Velphoro does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin).

Hydrochlorothiazide, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Iron, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Levothyroxine, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

When administering any medicinal product that has the potential to interact with Velphoro based only on in vitro studies like levothyroxine, the medicinal product should be administered at least one hour before or two hours after Velphoro.

Losartan, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Co-administration of Velphoro did not affect the bioavailability of these products as measured by the area under the curve (AUC).

Metformin, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Metoprolol, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Nifedipine, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Omeprazole, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Co-administration of Velphoro did not affect the bioavailability of these products as measured by the area under the curve (AUC).

Pioglitazone, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Pregnancy, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Velphoro should only be used by pregnant women if clearly needed following careful assessment of benefit/risk.

Quinidine, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Simvastatine, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

Data from clinical studies have shown that Velphoro does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin).

Sucroferric oxyhydroxide [1], vitamin D and analogues ---> SmPC of [1] of EMA

Post-hoc analyses from clinical studies demonstrated no impact of Velphoro on iPTH lowering effect of oral Vitamin D analogues. Vitamin D and 1,25-dihydroxy Vitamin D levels remained unchanged.

Sucroferric oxyhydroxide [1], warfarin ---> SmPC of [1] of EMA

Co-administration of Velphoro did not affect the bioavailability of these products as measured by the area under the curve (AUC).

CONTRAINDICATIONS of Sucroferric oxyhydroxide (Velphoro)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

- Haemochromatosis and any other iron accumulation disorders.

https://www.ema.europa.eu/en/documents/product-information/velphoro-epar-product-information_en.pdf. 08/12/2022

Sufentanil (Zalviso)

Ability to drive, sufentanil [2] ---> SmPC of [2] of EMA

Patients should only drive and use machines if sufficient time has elapsed after the last administration of Zalviso.

Alcohol, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of CNS depressants, including barbiturates, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.

Anxiolytics, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

Barbiturates, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of CNS depressants, including barbiturates, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.

Benzodiazepines, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of opioids with sedating medicinal products such as benzodiazepines or related substances increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect.

Breast-feeding, sufentanil [2] ---> SmPC of [2] of EMA

Breastfeeding is not recommended when sufentanil is administered, due to the risk of opioid effects or toxicity in the breastfed newborns/infants

Buprenorphine, sufentanil

Decreased analgetic effects due to competitive blockade of receptors. Concomitant use is contraindicated.

CNS depressants, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of CNS depressants, including barbiturates, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.

Etomidate, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

Fertility, sufentanil [2] ---> SmPC of [2] of EMA

There are no data on the effects of sufentanil on fertility in women or men.

General anesthetics, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

Halogenated anaesthetics, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of CNS depressants, including barbiturates, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.

Hypnotics, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

IMAOs, sufentanil [2] ---> SmPC of [2] of EMA

Discontinuation of MAO inhibitors is generally recommended 2 weeks before treatment with Zalviso, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

IMAOs, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant administration of sufentanyl with a serotonergic agent may increase the risk of serotonergic syndrome, a potential, life-threatening condition, increase

Itraconazol, sufentanil [2] ---> SmPC of [2] of EMA

Sufentanil is primarily metabolised by the CYP3A4. Ketoconazole, a potent CYP3A4 inhibitor, can significantly increase the systemic exposure to sublingual sufentanil. Similar effects with other potent CYP3A4 inhibitors cannot be excluded.

Ketoconazole, sufentanil [2] ---> SmPC of [2] of EMA

Nalbuphine, sufentanil

Decreased analgetic effects due to competitive blockade of receptors. Concomitant use is contraindicated.

Neuroleptics, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of CNS depressants, including barbiturates, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.

Nitrous oxide, sufentanil

The co-administration may decrease the blood pressure, heart frequency, and cardiac output

Opiates, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

Opiates, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant use of CNS depressants, including barbiturates, neuroleptics or other opioids, halogen gases or other non-selective CNS depressants (e.g. alcohol) may enhance respiratory depression.

Pentazocine, sufentanil

Decreased analgetic effects due to competitive blockade of receptors. Concomitant use is contraindicated.

Pregnancy, sufentanil [2] ---> SmPC of [2] of EMA

Sufentanil crosses the placenta. Zalviso is not recommended during pregnancy and in women of childbearing potential not using contraception.

Ritonavir, sufentanil [2] ---> SmPC of [2] of EMA

Sedating antihistamines, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

Sedative antidepressants, sufentanil

The co-administration may enhance the respiratory depressor effect of sufentanil

Sedatives, sufentanil [2] ---> SmPC of [2] of EMA

Serotonergic medicines, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant administration of sufentanyl with a serotonergic agent may increase the risk of serotonergic syndrome, a potential, life-threatening condition, increase

Sevoflurane [1], sufentanil ---> SmPC of [1] of eMC

Opioids are expected to decrease the MAC of sevoflurane. Opioids, when combined with sevoflurane, may lead to a synergistic fall in heart rate, blood pressure and respiratory rate.

SNRIs, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant administration of sufentanyl with a serotonergic agent may increase the risk of serotonergic syndrome, a potential, life-threatening condition, increase

SSRI, sufentanil [2] ---> SmPC of [2] of EMA

The concomitant administration of sufentanyl with a serotonergic agent may increase the risk of serotonergic syndrome, a potential, life-threatening condition, increase

Strong CYP3A4 inhibitors, sufentanil [2] ---> SmPC of [2] of EMA

Succinylcholine, sufentanil

The co-administration may cause bradycardia

Sufentanil, suxamethonium

The co-administration may cause bradycardia

Sufentanil, terlipressin [2] ---> SmPC of [2] of eMC

Concomitant treatment of terlipressin with medicinal products with a known bradycardic effect may lower the heart rate and cardiac output.

Sufentanil, vecuronium

The co-administration may cause bradycardia

Sufentanil, voriconazole [2] ---> SmPC of [2] of EMA

Dose reduction of short-acting opiates similar in structure to alfentanil and metabolised by CYP3A4 should be considered. Extended and frequent monitoring for respiratory depression and other opiate-associated adverse reactions is recommended.

CONTRAINDICATIONS of Sufentanil (Zalviso)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Significant respiratory depression.

https://www.ema.europa.eu/en/documents/product-information/zalviso-epar-product-information_en.pdf 27/09/2022 (withdrawn)

Other trade names: SUFENTANILO G.E.S., Dzuveo,

Sugammadex (Bridion)

Breast-feeding, sugammadex [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sugammadex therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Dabigatran, sugammadex [2] ---> SmPC of [2] of EMA

In in vitro experiments a pharmacodynamic interaction (aPTT and PT prolongation) was noted with vitamin K antagonists, unfractionated heparin, low molecular weight heparinoids, rivaroxaban and dabigatran (see section 4.4).

Estrogens, sugammadex [2] ---> SmPC of [2] of EMA

The administration of a bolus dose of sugammadex is considered to be equivalent to one missed daily dose of oral contraceptive steroids (either combined or progestogen only).

Fertility, sugammadex [2] ---> SmPC of [2] of EMA

The effects with sugammadex on human fertility have not been investigated. Animal studies to evaluate fertility do not reveal harmful effects.

Fusidic acid, sugammadex [2] ---> SmPC of [2] of EMA

The use of fusidic acid in the pre-operative phase may give some delay in the recovery of the T4/T1 ratio to 0.9. No recurrence of neuromuscular blockade is expected in the post-operative phase

Gestagens, sugammadex [2] ---> SmPC of [2] of EMA

The administration of a bolus dose of sugammadex is considered to be equivalent to one missed daily dose of oral contraceptive steroids (either combined or progestogen only).

Hormonal contraceptives, sugammadex [2] ---> SmPC of [2] of EMA

For hormonal contraceptives a clinically relevant capturing interaction could not be excluded (no displacement interactions are expected).

Low molecular weight heparinoids, sugammadex [2] ---> SmPC of [2] of EMA

Pregnancy, sugammadex [2] ---> SmPC of [2] of EMA

Caution should be exercised when administering sugammadex to pregnant women.

Progesterone, sugammadex [2] ---> SmPC of [2] of EMA

In general sugammadex does not interfere with laboratory tests, with the possible exception of the serum progesterone assay.

Rivaroxaban, sugammadex [2] ---> SmPC of [2] of EMA

Rocuronium, sugammadex [2] ---> SmPC of [2] of EMA

Due to the administration of certain medicinal products after sugammadex, theoretically rocuronium or vecuronium could be displaced from sugammadex. As a result recurrence of neuromuscular blockade might be observed.

Sugammadex [1], toremifene ---> SmPC of [1] of EMA

Clinicians should be aware that the recovery of the T4/T1 ratio to 0.9 could therefore be delayed in patients who have received toremifene on the same day of the operation.

Sugammadex [1], unfractionated heparins ---> SmPC of [1] of EMA

Sugammadex [1], vecuronium ---> SmPC of [1] of EMA

Sugammadex [1], vitamin K antagonists ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Sugammadex (Bridion)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/bridion-epar-product-information_en.pdf 06/11/2025

Other trade names: Sugammadex Adroiq, Sugammadex Amomed, Sugammadex Mylan,

Sugemalimab (Cejemly)

Ability to drive, sugemalimab [2] ---> SmPC of [2] of EMA

Sugemalimab has minor influence on the ability to drive and use machines. In some patients, fatigue has been reported following administration of sugemalimab (see section 4.8).

Breast-feeding, sugemalimab [2] ---> SmPC of [2] of EMA

A decision should be made whether to discontinue breast-feeding or to discontinue sugemalimab treatment, taking into account the benefit of breast-feeding for the child and the benefit of sugemalimab therapy for the woman.

Corticosteroids, sugemalimab [2] ---> SmPC of [2] of EMA

The use of systemic corticosteroids or immunosuppressants before starting sugemalimab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of sugemalimab.

Fertility, sugemalimab [2] ---> SmPC of [2] of EMA

No clinical data are available on the possible effects of sugemalimab on fertility. Animal data did not show notable effects on the male and female reproductive organs (see section 5.3).

Immunosuppressives, sugemalimab [2] ---> SmPC of [2] of EMA

However, systemic corticosteroids or other immunosuppressants can be used after starting sugemalimab to treat immune -related adverse reactions (see section 4.4).

Medicinal products, sugemalimab [2] ---> SmPC of [2] of EMA

Since sugemalimab is cleared from the circulation through catabolism, no metabolic interactions with other medicinal products are expected.

Pregnancy, sugemalimab [2] ---> SmPC of [2] of EMA

Sugemalimab is not recommended during pregnancy and in women of childbearing potential not using contraception.

Sugemalimab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must be advised to avoid pregnancy during treatment with sugemalimab.

Sugemalimab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential receiving sugemalimab should use reliable contraception methods during treatment and for at least 4 months after the last dose of sugemalimab (see below and section 5.3).

CONTRAINDICATIONS of Sugemalimab (Cejemly)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/cejemly-epar-product-information_en.pdf 05/11/2024

Sulesomab (LeukoScan)

Breast-feeding, sulesomab [2] ---> SmPC of [2] of EMA

Before administering a radioactive medicinal product to a mother who is breast feeding, consideration should be given as to whether the investigation could be delayed

Pregnancy, sulesomab [2] ---> SmPC of [2] of EMA

Sulesomab is contraindicated in pregnancy

Sulesomab [1], women of childbearing potential ---> SmPC of [1] of EMA

When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy.

CONTRAINDICATIONS of Sulesomab (LeukoScan)

- Patients with known allergies or hypersensitivity to mouse proteins.

- Pregnancy.

https://www.ema.europa.eu/en/documents/product-information/leukoscan-epar-product-information_en.pdf 09/02/2018 (withdrawn)

Sulfasalazine

Afatinib [1], sulfasalazine ---> SmPC of [1] of EMA

In vitro studies indicated that afatinib is a substrate and an inhibitor of the transporter BCRP. Afatinib may increase the bioavailability of orally administered BCRP substrates (including but not limited to rosuvastatin and sulfasalazine).

Ampicillin, sulfasalazine

The combination with antibiotics may decrease the sulfasalazine effect due to partial inhibition of bacterial metabolism because of reduction of gastrointestinal flora

Antibiotics, sulfasalazine

The combination with antibiotics may decrease the sulfasalazine effect due to partial inhibition of bacterial metabolism because of reduction of gastrointestinal flora

Azathioprine [1], sulfasalazine ---> SmPC of [1] of eMC

There is in vitro and in vivo evidence that aminosalicylate derivatives inhibit the TPMT enzyme. Therefore, lower doses of azathioprine may need to be considered when administered concomitantly with aminosalicylate derivatives.

Bile-acid sequestrants, sulfasalazine

Anion exchange resins bind sulfasalazine and its metabolites in the intestine

Breast-feeding, sulfasalazine [2] ---> SmPC of [2] of eMC

Sulfasalazine and sulfapyridine are found in low levels in breast milk. Patients should avoid breastfeeding while taking this medicine.

Brigatinib [1], sulfasalazine ---> SmPC of [1] of EMA

Coadministration of brigatinib with substrates of P-gp, BCRP may increase their plasma concentrations. Patients should be closely monitored when Alunbrig is coadministered with substrates of these transporters with a narrow therapeutic index

Calcium gluconate, sulfasalazine

Calcium gluconate delays the absorption of sulfasalazine

Ceritinib [1], sulfasalazine ---> SmPC of [1] of EMA

Based on in vitro data, ceritinib is predicted to inhibit intestinal BCRP. Therefore, ceritinib may have the potential to increase plasma concentrations of co-administered medicinal products transported by BCRP.

Cholestyramine, sulfasalazine

Anion exchange resins bind sulfasalazine and its metabolites in the intestine

Colestipol, sulfasalazine

Anion exchange resins bind sulfasalazine and its metabolites in the intestine

Cyclosporine, sulfasalazine

The co-administration may decrease the plasma levels of cyclosporine

Dasabuvir with ombitasvir/paritaprevir/ritonavir, sulfasalazine ---> SmPC of [ombitasvir/paritaprevir/ritonavir] o

BCRP inhibition by paritaprevir, ritonavir and dasabuvir. Caution should be used when sulfasalazine is coadministered with Viekirax with or without dasabuvir.

Dicoumarol, sulfasalazine

The co-administration may enhance the anticoagulant effect and increase the bleeding risk. Special caution is recommended

Digoxin, sulfasalazine [2] ---> SmPC of [2] of eMC

Reduced absorption of digoxin, resulting in non-therapeutic serum levels, has been reported when used concomitantly with oral sulfasalazine.

Drugs with high protein binding, sulfasalazine

Sulfasalazine may displace other principle actives from its plasma protein binding and increase their effects

Etanercept [1], sulfasalazine ---> SmPC of [1] of EMA

Statistically significant decrease in mean white blood cell counts

Ethambutol, sulfasalazine

The combination with antibiotics may decrease the sulfasalazine effect due to partial inhibition of bacterial metabolism because of reduction of gastrointestinal flora

Folic acid, sulfasalazine [2] ---> SmPC of [2] of eMC

Oral sulfasalazine inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency

Hepatotoxic drugs, sulfasalazine

The co-administration of hepatotoxic medicinal products increase the probability of hepatotoxic effects

Iron, sulfasalazine

The co-administration forms chelates, which inhibit the absorption of sulfasalazine, but not the absorption of sulfapyridine

Leflunomide [1], sulfasalazine ---> SmPC of [1] of EMA

For substrates of BCRP, concomitant administration with leflunomide should be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products

Medicinal products metabolized by TPMT, sulfasalazine

Sulfasalazine, thiopurine methyl transferase (TPMT) inhibitor, may increase the plasma levels of medicinal products metabolized by TPMT. Caution is recommended

Medicines with myelotoxic effects, sulfasalazine

Leucopenia, anemia and/or thrombocytopenia may occur more frequent and intensive

Mercaptopurine [1], sulfasalazine ---> SmPC of [1] of EMA

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, which metabolises 6 -mercaptopurine, they should be administered with caution to patients receiving concurrent mercaptopurine therapy

Methenamine, sulfasalazine

Increased risk of crystalluria. The co-administration is contraindicated

Methotrexate [1], sulfasalazine ---> SmPC of [1] of EMA

Patients taking potentially hepatotoxic and haematoxic medicinal products during methotrexate therapy should be closely monitored for possibly increased hepatotoxicity.

Metildigoxin, sulfasalazine

Decreased plasma levels of metildigoxin

Myelosuppressive agents, sulfasalazine

Leucopenia, anemia and/or thrombocytopenia may occur more frequent and intensive

Neomycin, sulfasalazine

The combination with antibiotics may decrease the sulfasalazine effect due to partial inhibition of bacterial metabolism because of reduction of gastrointestinal flora

Neratinib [1], sulfasalazine ---> SmPC of [1] of EMA

Patients who are treated with BCRP inhibitors (e.g., rosuvastatin and sulfasalazine) should be monitored carefully.

Ombitasvir/paritaprevir/ritonavir [1], sulfasalazine ---> SmPC of [1] of EMA

BCRP inhibition by paritaprevir, ritonavir and dasabuvir. Caution should be used when sulfasalazine is coadministered with Viekirax with or without dasabuvir.

Oral anticoagulants, sulfasalazine

The co-administration may enhance the anticoagulant effect and increase the bleeding risk. Special caution is recommended

Palbociclib [1], sulfasalazine ---> SmPC of [1] of EMA

Administration of palbociclib with medicinal products that are substrates of BCRP (e.g., rosuvastatin, sulfasalazine) may increase their therapeutic effect and adverse reactions.

Phenprocoumon, sulfasalazine

The co-administration may enhance the anticoagulant effect and increase the bleeding risk. Special caution is recommended

Phenylbutazone, sulfasalazine

Sulfasalazine may displace other principle actives from its plasma protein binding

Ponatinib [1], sulfasalazine ---> SmPC of [1] of EMA

In vitro, ponatinib is an inhibitor of BCRP. Therefore, ponatinib may have the potential to increase plasma concentrations of co-administered substrates of BCRP and may increase their therapeutic effect and adverse reactions.

Pregnancy, sulfasalazine [2] ---> SmPC of [2] of eMC

Because the possibility of harm cannot be completely ruled out, sulfasalazine should be used during pregnancy only if clearly needed.

Pyritinol, sulfasalazine

Pyritinol enhances the adverse effects of sulfasalazine

Rifamicyn, sulfasalazine

The combination with antibiotics may decrease the sulfasalazine effect due to partial inhibition of bacterial metabolism because of reduction of gastrointestinal flora

Rolapitant [1], sulfasalazine ---> SmPC of [1] of EMA

Rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP). Increased plasma concentrations of BCRP substrates may result in potential adverse reactions.

Sulfasalazine, sulfinpyrazone

Sulfasalazine may displace other principle actives from its plasma protein binding

Sulfasalazine, sulfonylureas

Sulfasalazine may enhance the hypoglycemic effect of the sulfonylurea

Sulfasalazine, tedizolid [2] ---> SmPC of [2] of EMA

Orally administered Sivextro can result in inhibition of BCRP at the intestinal level. If possible, an interruption of the co-administered BCRP substrate medicinal product should be considered during the six days of treatment with oral Sivextro.

Sulfasalazine, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, BCRP inhibitor, may increase the AUC of BCRP substrate. The co-administration should be undertaken with caution

Sulfasalazine, thioguanine [2] ---> SmPC of [2] of eMC

As there is in vitro evidence that aminosalicylate derivatives inhibit the TPMT enzyme, they should be administered with caution to patients receiving concurrent tioguanine therapy

Sulfasalazine, typhoid-fever vaccine

Possible decrease of the immune reaction. At least 24 hours should elapse between the administration of both.

Sulfasalazine, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib, BCRP inhibitor, may increase exposure of medicinal products transported by this protein. The co-administration should be undertaken with caution

CONTRAINDICATIONS of Sulfasalazine

Sulfasalazine is contraindicated in:

- Patients with a known hypersensitivity to sulfasalazine, its metabolites or any of the excipients as well as sulfonamides or salicylates.

- Patients with porphyria.

http://www.medicines.org.uk/emc/

Sulphur hexafluoride (SonoVue)

Breast-feeding, sulphur hexafluoride [2] ---> SmPC of [2] of EMA

It is not known if sulphur hexafluoride is excreted in human milk. However, based on its rapid elimination from the body via the expired air, it is considered that the breastfeeding can be resumed two to three hours after administration of SonoVue.

Pregnancy, sulphur hexafluoride [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of SonoVue during pregnancy.

CONTRAINDICATIONS of Sulphur hexafluoride (SonoVue)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

- SonoVue is contraindicated in patients known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure >90 mmHg), uncontrolled systemic hypertension, and in patients with adult respiratory distress syndrome.

- Sonovue should not be used in combination with dobutamine in patients with conditions suggesting cardiovascular instability where dobutamine is contraindicated.

https://www.ema.europa.eu/en/documents/product-information/sonovue-epar-product-information_en.pdf 05/06/2023

Sulpiride

Ability to drive, sulpiride [2] ---> SmPC of [2] of eMC

Even used as recommended, sulpiride may cause sedation so that the ability to drive vehicles or operate machinery can be impaired.

Alcohol, sulpiride [2] ---> SmPC of [2] of eMC

Alcohol enhances the sedative effect of neuroleptics. Association not recommended

Amiodarone [1], sulpiride ---> SmPC of [1] of eMC

Combined therapy of amiodarone with drugs which prolong the QT interval is contra-indicated due to the increased risk of torsades de pointes

Amphotericin, sulpiride [2] ---> SmPC of [2] of eMC

The co-administration of sulpiride and amphotericin IV may induce torsades de pointes or prolong the QT interval. The combination is not recommended

Antacids, sulpiride [2] ---> SmPC of [2] of eMC

The absorption of sulpiride is decreased after co-administration with antacids. Therefore, sulpiride should be administered 2 hours before antacid

Antihypertensives, sulpiride [2] ---> SmPC of [2] of eMC

Antihypertensive effect and possibility of enhanced postural hypotension (additive effect).

Anxiolytics, sulpiride

Sulpiride enhances the sedative effect of anxiolytic agent

Barbiturates, sulpiride

Sulpiride enhances the sedative effect of barbiturate

Benzodiazepines, sulpiride

Sulpiride enhances the sedative effect of benzodiazepine

Bepridil, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Betablockers, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Breast-feeding, sulpiride [2] ---> SmPC of [2] of eMC

Sulpiride has been found in the breast milk of treated women. Therefore breast-feeding is not recommended during treatment.

Carteolol, sulpiride

The co-administration increases the risk of heart rhythm disorders, particularly torsades de pointes

Cisapride, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Class IA antiarrhythmic agents, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with class Ia antiarrhythmic agents is not recommended

Class III antiarrhythmic agents, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with class III antiarrhythmic agents is not recommended

Clonidine, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

CNS depressants, sulpiride

Sulpiride enhances the sedative effect of CNS depressant

Digital glycosides, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Diltiazem, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Disopyramide, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with class Ia antiarrhythmic agents is not recommended

Dopamine agonists, sulpiride

Sulpiride antagonizes specifically the D2 and D3 dopamine receptors

Droperidol [1], sulpiride ---> SmPC of [1] of eMC

Medicinal products known to prolong the QTc interval should not be concomitantly administered with droperidol.

Drugs inducing bradycardia, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Erythromycin, sulpiride [2] ---> SmPC of [2] of eMC

The co-administration of sulpiride and erythromycin IV may induce torsades de pointes or prolong the QT interval. The combination is not recommended

Glucocorticoids, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with hypokaliemia-inducing medications is not recommended

Grapefruit juice, sulpiride

The intake of grapefruit juice is contraindicated during the treatment

Guanfacin, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Halofantrine, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Haloperidol, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Hydrochlorothiazide, sulpiride ---> SmPC of [losartan/hydrochlorothiazide] of

Periodic monitoring of serum potassium and ECG is recommended, when hydrochlorothiazide is administered with drugs which may induce torsades de pointes

Hydroquinidine, sulpiride

Concomitant use is not recommended due to increased risk of heart rhythm disorders (torsades de pointes)

Hypnotics, sulpiride

Sulpiride enhances the sedative effect of hypnotic agent

Hypokalemia, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with hypokaliemia-inducing medications is not recommended

Ibutilide, sulpiride

Possible increase of proarrhythmic risk if ibutilide is used with drugs that prolong the QT interval. Contraindicated within 4 hours after completing infusion

Indapamide [1], sulpiride ---> SmPC of [1] of eMC

The co-administration may increase the risk of ventricular arrhythmias, particularly torsades de pointes (hypokalemia is a risk factor)

Levodopa, sulpiride [2] ---> SmPC of [2] of eMC

Reciprocal antagonism of effects between levodopa and neuroleptics. Association contra-indicated

Lisuride, sulpiride

Dopamine antagonists may decrease the effect of lisuride. Co-administration is not recommended

Lithium, sulpiride [2] ---> SmPC of [2] of eMC

Lithium increases the risk of extrapyramidal side effects.

Losartan/hydrochlorothiazide [1], sulpiride ---> SmPC of [1] of eMC

Periodic monitoring of serum potassium and ECG is recommended when losartan/hydrochlorothiazide is administered with torsades de pointes-inducing medicinal products

Methadone, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Narcotics, sulpiride

Sulpiride enhances the sedative effect of narcotic agent

Non-potassium-sparing diuretics, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with hypokaliemia-inducing medications is not recommended

Pentamidine, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Pimozide, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Pregnancy, sulpiride [2] ---> SmPC of [2] of eMC

The use of sulpiride is not recommended during pregnancy because of the limited experience.

Protirelin, sulpiride

Enhancement of TSH-increase

QT interval prolonging drugs, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Quinidine, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with class Ia antiarrhythmic agents is not recommended

Rivastigmine [1], sulpiride ---> SmPC of [1] of EMA

Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination of rivastigmine with torsades de pointes-inducing medicinal products should be observed with caution and clinical monitoring (ECG) may also be required.

Ropinirole [1], sulpiride ---> SmPC of [1] of eMC

Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and therefore, concomitant use of these medicinal products should be avoided.

Sedating antihistamines, sulpiride

Sulpiride enhances the sedative effect of sedating antihistamine

Sotalol, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sparfloxacin, sulpiride [2] ---> SmPC of [2] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Stimulant laxatives, sulpiride [2] ---> SmPC of [2] of eMC

The combination of sulpiride with hypokaliemia-inducing medications is not recommended

Sucralfate, sulpiride [2] ---> SmPC of [2] of eMC

The absorption of sulpiride is decreased after co-administration with sucralfate. Therefore, sulpiride should be administered 2 hours before sucralfate

Sulpiride [1], sultopride ---> SmPC of [1] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sulpiride [1], tetracosactide ---> SmPC of [1] of eMC

The combination of sulpiride with hypokaliemia-inducing medications is not recommended

Sulpiride [1], thioridazine ---> SmPC of [1] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sulpiride [1], torsades de pointes inducing drugs ---> SmPC of [1] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sulpiride [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sulpiride [1], verapamil ---> SmPC of [1] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Sulpiride [1], vincamine ---> SmPC of [1] of eMC

The co-administration of sulpiride and vincamine IV may induce torsades de pointes or prolong the QT interval. The combination is not recommended

Sulpiride, telmisartan/hydrochlorothiazide [2] ---> SmPC of [2] of EMA

Sulpiride, tiapride

Tiapride should not be combined with drugs that prolong the QT interval. These drugs (with the exception of anti-infectious) should be discontinued, if possible, if they induce torsades de pointes

Sulpiride, vandetanib [2] ---> SmPC of [2] of EMA

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sulpiride, xipamide [2] ---> SmPC of [2] of eMC

The combination increases the risk of ventricular arrhythmias, particularly torsades de pointes (favored by hypokaliemia). It is recommended a special caution

CONTRAINDICATIONS of Sulpiride

- Phaeochromocytoma and acute porphyria.

- Hypersensitivity to sulpiride or to any of the excipients.

- Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas and breast cancer

- Association with levodopa

http://www.medicines.org.uk/emc/

Sumatriptan

Ability to drive, sumatriptan [2] ---> SmPC of [2] of eMC

Drowsiness may occur as a result of migraine or its treatment with sumatriptan.

Alcohol, sumatriptan [2] ---> SmPC of [2] of eMC

Studies in healthy subjects show that sumatriptan does not interact with alcohol

Breast-feeding, sumatriptan [2] ---> SmPC of [2] of eMC

It has been demonstrated that following subcutaneous administration, sumatriptan is excreted into breast milk. Infant exposure can be minimised by avoiding breast feeding for 12 hours after treatment

Citalopram [1], sumatriptan ---> SmPC of [1] of eMC

Co-administration with serotonergic medicinal products may lead to enhancement of 5-HT associated effects. The combination is not recommended

Ergot derivatives, sumatriptan [2] ---> SmPC of [2] of eMC

The increased risk of coronary vasospasm is a theoretical possibility and concomitant administration is contraindicated. At least 24 hours should elapse between the use of each one

Ergotamine, sumatriptan [2] ---> SmPC of [2] of eMC

The increased risk of coronary vasospasm is a theoretical possibility and concomitant administration is contraindicated. At least 24 hours should elapse between the use of each one

Escitalopram [1], sumatriptan ---> SmPC of [1] of eMC

Co-administration of escitalopram with serotonergic medicinal products may lead to serotonin syndrome.

Flunarizine, sumatriptan [2] ---> SmPC of [2] of eMC

Studies in healthy subjects show that sumatriptan does not interact with flunarizine

IMAOs, sumatriptan [2] ---> SmPC of [2] of eMC

An interaction may occur between sumatriptan and monoamine oxidase inhibitors (MAOIs) and concomitant administration is contraindicated

Lithium, sumatriptan

Potential risk of a serotoninergic syndrome. The concomitant use should be done with caution

Methysergide, sumatriptan [2] ---> SmPC of [2] of eMC

The increased risk of coronary vasospasm is a theoretical possibility and concomitant administration is contraindicated. At least 24 hours should elapse between the use of each one

Milnacipran, sumatriptan

Risk of hypertension and coronary arterial vasoconstriction due to additive serotoninergic effect. The co-administration is contraindicated

Pizotifen, sumatriptan [2] ---> SmPC of [2] of eMC

Studies in healthy subjects show that sumatriptan does not interact with pizotifen

Pregnancy, sumatriptan [2] ---> SmPC of [2] of eMC

Administration of sumatriptan should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Propranolol, sumatriptan [2] ---> SmPC of [2] of eMC

Studies in healthy subjects show that sumatriptan does not interact with propranolol

Rizatriptan [1], sumatriptan ---> SmPC of [1] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Serotonergic medicines, sumatriptan

Potential risk of a serotoninergic syndrome. The concomitant use should be done with caution

Sibutramine [1], sumatriptan ---> SmPC of [1] of eMC

As sibutramine inhibits serotonin reuptake (among other effects), sibutramine should not be used concomitantly with other drugs which also raise serotonin levels in the brain (serotonin syndrome)

SNRIs, sumatriptan [2] ---> SmPC of [2] of eMC

Serotonin syndrome has been reported following concomitant treatment with triptans and SNRIs

SSNRI, sumatriptan

Serotonin syndrome has been reported following concomitant treatment with triptans and SNRIs

SSRI, sumatriptan [2] ---> SmPC of [2] of eMC

There have been rare post-marketing reports describing patients with serotonin syndrome following the use of SSRIs and sumatriptan.

St. John's wort, sumatriptan [2] ---> SmPC of [2] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's Wort (Hypericum perforatum)

Sumatriptan [1], triptans ---> SmPC of [1] of eMC

The increased risk of coronary vasospasm is a theoretical possibility and concomitant administration is contraindicated. At least 24 hours should elapse between the use of each one

Sumatriptan, tricyclic antidepressant

Potential risk of a serotoninergic syndrome. The concomitant use should be done with caution

Sumatriptan, tryptophan

The co-administration can cause serotoninergic syndrome. The combination is contraindicated

Sumatriptan, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect may lead to serotonin syndrome

Sumatriptan, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

CONTRAINDICATIONS of Sumatriptan

- Hypersensitivity to sumatriptan or to any of the excipients

- Sumatriptan should not be given to patients who have had myocardial infarction or have ischaemic heart disease, coronary vasospasm (Prinzmetal's angina), peripheral vascular disease or patients who have symptoms or signs consistent with ischaemic heart disease.

- Sumatriptan should not be administered to patients with a history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

- Sumatriptan should not be administered to patients with severe hepatic impairment.

- The use of sumatriptan in patients with moderate and severe hypertension and mild uncontrolled hypertension is contraindicated.

- The concomitant administration of ergotamine or derivatives of ergotamine (including methysergide) or any triptan/5-hydroxytryptamine1 (5-HT1) receptor agonist with sumatriptan is contraindicated.

- Concurrent administration of monoamine oxidase inhibitors and sumatriptan is contraindicated.

- This medicinal product must not be used within two weeks of discontinuation of therapy with monoamine oxidase inhibitors.

http://www.medicines.org.uk/emc/

Sunitinib (Sutent)

Ability to drive, sunitinib [2] ---> SmPC of [2] of EMA

Sutent has minor influence on the ability to drive and use machines. Patients should be advised that they may experience dizziness during treatment with sunitinib.

Acenocoumarol, sunitinib [2] ---> SmPC of [2] of EMA

Patients receiving concomitant treatment with anticoagulants (e.g., warfarin, acenocoumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/INR), and physical examination.

Antiarrhythmics, sunitinib [2] ---> SmPC of [2] of EMA

Sunitinib should be used with caution in patients with a known history of QT interval prolongation, patients who are taking antiarrhythmics, or patients with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances.

Anticoagulants, sunitinib [2] ---> SmPC of [2] of EMA

BCRP inhibitors, sunitinib [2] ---> SmPC of [2] of EMA

Limited clinical data are available on the interaction between sunitinib and BCRP inhibitors and the possibility of an interaction between sunitinib and other BCRP inhibitors cannot be excluded (see section 5.2).

Bevacizumab [1], sunitinib ---> SmPC of [1] of EMA

In two clinical trials of metastatic renal cell carcinoma, microangiopathic haemolytic anaemia (MAHA) was reported in 7 of 19 patients treated with bevacizumab and sunitinib malate combination.

Breast-feeding, sunitinib [2] ---> SmPC of [2] of EMA

Because active substances are commonly excreted in human milk and because of the potential for serious adverse reactions in breast-feeding infants, women should not breast-feed while taking Sutent.

Carbamazepine, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Clarithromycin, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

CYP3A4 inductors, sunitinib [2] ---> SmPC of [2] of EMA

Combination with CYP3A4 inductors should be avoided, or the selection of an alternate concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered.

CYP3A4 inhibitors, sunitinib [2] ---> SmPC of [2] of EMA

Combination with CYP3A4 inhibitors should therefore be avoided, or the selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered.

Dexamethasone, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Drugs inducing bradycardia, sunitinib [2] ---> SmPC of [2] of EMA

Elbasvir/grazoprevir [1], sunitinib ---> SmPC of [1] of EMA

Co-administration of ZEPATIER with sunitinib may increase sunitinib concentrations leading to an increased risk of sunitinib-associated adverse events.

Electrolyte imbalance, sunitinib [2] ---> SmPC of [2] of EMA

Erythromycin, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Fertility, sunitinib [2] ---> SmPC of [2] of EMA

Based on nonclinical findings, male and female fertility may be compromised by treatment with sunitinib (see section 5.3).

Grapefruit juice, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Itraconazol, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Ketoconazole [1], sunitinib

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

Ketoconazole, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Levothyroxine, sunitinib

The tyrosine kinase inhibitor may decrease the effect of levothyroxine

Miconazole, sunitinib

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Mitotane [1], sunitinib ---> SmPC of [1] of EMA

Mitotane has been shown to have an inductive effect on cytochrome 3A4. Therefore, the plasma concentrations of the substances metabolised via cytochrome 3A4 may be modified.

P-glycoprotein substrates, sunitinib

Sunitinib, P-glycoprotein inhibitor, may increase the plasma concentrations of substrates of P-glycoprotein

Phenobarbital, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Phenytoin, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Pregnancy, sunitinib [2] ---> SmPC of [2] of EMA

If Sutent is used during pregnancy or if the patient becomes pregnant while on treatment with Sutent, the patient should be apprised of the potential hazard to the foetus.

Pregnancy, sunitinib [2] ---> SmPC of [2] of EMA

SUTENT should not be used during pregnancy or in women not using effective contraception, unless the potential benefit justifies the potential risk to the foetus.

QT interval prolonging drugs, sunitinib [2] ---> SmPC of [2] of EMA

Rifampicin, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Ritonavir, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

St. John's wort, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Strong CYP3A4 inductors, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inducers may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided

Strong CYP3A4 inhibitors, sunitinib [2] ---> SmPC of [2] of EMA

Administration of sunitinib with potent CYP3A4 inhibitors may increase sunitinib concentrations. Combination with CYP3A4 inhibitors should therefore be avoided

Sunitinib [1], warfarin ---> SmPC of [1] of EMA

Sunitinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should be advised to use effective contraception and avoid becoming pregnant while receiving treatment with Sutent.

Sunitinib, tacrolimus

The additive QT-prolonging may increase the risk of severe ventricular arrhythmias. The co-administration should be avoided

Sunitinib, telotristat ethyl [2] ---> SmPC of [2] of EMA

Sunitinib, temsirolimus [2] ---> SmPC of [2] of EMA

The combination of temsirolimus and sunitinib resulted in dose-limiting toxicity.

Sunitinib, thiothixene

The additive QT-prolonging may increase the risk of ventricular arrhythmias. The co-administration should be avoided

Sunitinib, topotecan

Sunitinib, P-glycoprotein inhibitor, may increase the plasma concentrations of topotecan. Concomitant use should be avoided

Sunitinib, trimipramine

The additive QT-prolonging may increase the risk of severe ventricular arrhythmias. The co-administration should be avoided

Sunitinib, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole may increase plasma concentrations of tyrosine kinase inhibitors metabolised by CYP3A4. If concomitant use cannot be avoided, dose reduction of the tyrosine kinase inhibitor is recommended (see section 4.4).

CONTRAINDICATIONS of Sunitinib (Sutent)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/sutent-epar-product-information_en.pdf 02/04/2024

Other trade names: Sunitinib Accord,

Susoctocog alfa (Obizur)

Breast-feeding, susoctocog alfa [2] ---> SmPC of [2] of EMA

Experience regarding the use of OBIZUR during pregnancy and breast-feeding is not available. Therefore, OBIZUR should be used during pregnancy and lactation only if clearly indicated.

Pregnancy, susoctocog alfa [2] ---> SmPC of [2] of EMA

Experience regarding the use of OBIZUR during pregnancy and breast-feeding is not available. Therefore, OBIZUR should be used during pregnancy and lactation only if clearly indicated.

CONTRAINDICATIONS of Susoctocog alfa (Obizur)

- Known anaphylactic reactions to the active substance, hamster protein, or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/obizur-epar-product-information_en.pdf 21/11/2025

Sutimlimab (Enjaymo)

Breast-feeding, sutimlimab [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from sutimlimab therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Carbamazepine, sutimlimab [2] ---> SmPC of [2] of EMA

Caution should be exercised when starting or discontinuing sutimlimab treatment in patients also receiving substrates of CYP450 3A4, 1A2, 2C9 or 2C19, particularly those with a narrow therapeutic index, and doses adjusted if needed.

CYP450, sutimlimab [2] ---> SmPC of [2] of EMA

Fertility, sutimlimab [2] ---> SmPC of [2] of EMA

In repeat-dose studies with sutimlimab with exposures at up to approximately 4 times the recommended human dose, no effects on reproductive organs were observed in cynomolgus monkeys.

Phenytoin, sutimlimab [2] ---> SmPC of [2] of EMA

Pregnancy, sutimlimab [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of sutimlimab during pregnancy. Sutimlimab should be given during pregnancy only if clearly indicated.

Sutimlimab [1], theophylline ---> SmPC of [1] of EMA

Sutimlimab [1], vaccinations ---> SmPC of [1] of EMA

Patients should be vaccinated against encapsulated bacteria before treatment with Enjaymo is started, please see "Vaccinations" below.

Sutimlimab [1], warfarin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Sutimlimab (Enjaymo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/enjaymo-epar-product-information_en.pdf 01/08/2025

Suxamethonium (succinylcholine)

Ability to drive, suxamethonium [2] ---> SmPC of [2] of eMC

Suxamethonium will always be used in combination with a general anaesthetic and therefore the usual precautions relating to performance of tasks following general anaesthesia apply.

Ajmaline, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Amifampridine [1], suxamethonium ---> SmPC of [1] of EMA

The concomitant use of amifampridine and medicinal products with depolarising muscle relaxant effects may lead to a decreased effect of both products and should be taken into consideration.

Aminoglycoside antibiotics, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Aminoglycoside antibiotics, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Amphotericin, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Anticholinesterase, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Aprotinin, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Atenolol, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Atenolol/nifedipine, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Atracurium [1], suxamethonium ---> SmPC of [1] of eMC

A depolarising muscle relaxant should not be administered to prolong the neuromuscular blocking effects of non-depolarising blocking agents, as this may result in a prolonged and complex block

Atropine, suxamethonium

The co-administration may enhance the effect and increase the blood pressure

Azathioprine [1], suxamethonium ---> SmPC of [1] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Bambuterol [1], suxamethonium ---> SmPC of [1] of eMC

Bambuterol prolongs the muscle-relaxing effect of suxamethonium (succinylcholine). This is due to the fact that plasma cholinesterase, which inactivates suxamethonium, is partly inhibited by bambuterol.

Betablockers, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Betablockers, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Betaxolol, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects

Blood, suxamethonium

The concomitant infusion with blood decreases the effect of suxamethonium

Breast-feeding, suxamethonium [2] ---> SmPC of [2] of eMC

It is not known whether suxamethonium or its metabolites are excreted in human milk.

Calcium antagonists, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Celiprolol, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Chloroquine, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Chlorpromazine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Clindamycin, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Clindamycin, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Cyclophosphamide, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Desflurane, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Desflurane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Diazepam, suxamethonium

Possible pharmacodynamic antagonism. Modified intensity of neuromuscular blockage. Special caution is recommended.

Diethyl ether, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Digital glycosides, succinylcholine ---> SmPC of [suxamethonium] of

Patients receiving digitalis-like drugs are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.

Digital glycosides, suxamethonium [2] ---> SmPC of [2] of eMC

Patients receiving digitalis-like drugs are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.

Digitoxin, suxamethonium

The co-administration may increase the digitoxin effect and promote heart rhythm disorders

Digoxin [1], suxamethonium ---> SmPC of [1] of eMC

Patients receiving digoxin are more susceptible to the effects of suxamethonium-exacerbated hyperkalaemia.

Diphenhydramine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Distigmine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Donepezil [1], suxamethonium ---> SmPC of [1] of eMC

There is the potential for synergistic activity of donepezil with concomitant treatment involving medications such as succinylcholine

Ecothiopate, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Edrophonium, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Enflurane, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Enflurane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Eserine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Esketamine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Esmolol [1], suxamethonium ---> SmPC of [1] of eMC

The onset of neuromuscular blockade by suxamethonium chloride was unaffected by esmolol, but the duration of neuromuscular blockade was prolonged from 5 minutes to 8 minutes.

Estriol [1], suxamethonium ---> SmPC of [1] of eMC

Estriol may possibly increase the pharmacological effects of succinylcholine

Estrogens, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Galantamine [1], suxamethonium ---> SmPC of [1] of eMC

Galantamine, as a cholinomimetic, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia, especially in cases of pseudocholinesterase deficiency.

Halogenated anaesthetics, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Halogenated anaesthetics, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Halothane, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Halothane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Ifosfamide, suxamethonium

The co-administration may prolong the neuromuscular blocking effects of suxamethonium and cause a long-lasting apnea

Irinotecan, suxamethonium [2] ---> SmPC of [2] of eMC

Since irinotecan has anticholinesterase activity, drugs with anticholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Isoflurane, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Isoflurane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Lignocaine, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Lignocaine, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Lithium carbonate [1], suxamethonium ---> SmPC of [1] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Magnesium sulfate, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Magnesium sulfate, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Mechloroethamine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Medroxyprogesterone, suxamethonium

The co-administration may cause a prolongation of neuromuscular block

Methoxyflurane, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Methoxyflurane, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Metildigoxin, suxamethonium

Enhanced digitalis effect. The concomitant use should be done with caution, in order to avoid the risk of arrythmias

Metoclopramide, succinylcholine ---> SmPC of [suxamethonium] of

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Metoclopramide, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Metrifonate, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Mivacurium [1], suxamethonium ---> SmPC of [1] of eMC

Mivacurium has been safely administered following succinylcholine facilitated intubation. Evidence of spontaneous recovery from succinylcholine should be observed prior to administration of mivacurium.

Morphine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Muscle relaxants (non-depolarizing), suxamethonium ---> SmPC of [atracurium] of

A depolarising muscle relaxant should not be administered to prolong the neuromuscular blocking effects of non-depolarising blocking agents, as this may result in a prolonged and complex block

Nalorphine, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Naloxone, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Neostigmine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Opiate antagonists, suxamethonium

The co-administration may increase or prolong the neuromuscular blocking action of suxamethonium

Oral contraceptives, succinylcholine ---> SmPC of [suxamethonium] of

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Oral contraceptives, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Organophosphorous insecticides, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Oxprenolol, suxamethonium

The neuromuscular blockade by peripheral muscle relaxants may be potentiate by betablockers

Oxytocin, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Pancuronium, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Parasympathomimetics, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Paroxetine, suxamethonium

Selective serotonin reuptake inhibitors may reduce the activity of plasma cholinesterase, what may cause prolongation of neuromuscular blocking action of mivacurium and suxamethonium

Perphenazine, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Pethidine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Phenelzine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Phenothiazines, suxamethonium

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Physostigmine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Plasma cholinesterase inhibitors, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Polymyxin, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Polymyxin, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Polypeptide antibiotics, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Polypeptide antibiotics, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Potassium chloride, suxamethonium

The co-administration of potassium and suxamethonium may cause hypercaliemia with negative effects on the heart rhythm

Potassium, suxamethonium

The co-administration of potassium and suxamethonium may cause hypercaliemia with negative effects on the heart rhythm

Pregnancy, suxamethonium [2] ---> SmPC of [2] of eMC

The benefits of the use of suxamethonium as part of a rapid sequence induction for general anaesthesia normally outweigh the possible risk to the foetus.

Procainamide, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Procainamide, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Procaine, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Procaine, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Promazine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Promethazine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Propanidid, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Propofol, suxamethonium

After treatment with suxamethonium may occur bradycardia and cardiac arrest

Propranolol, suxamethonium

Enhancement of neuromuscular blockade

Proxymetacaine, suxamethonium

Enhanced neuromuscular block by suxamethonium

Pyridostigmine, suxamethonium [2] ---> SmPC of [2] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Quinidine, succinylcholine ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Quinidine, suxamethonium [2] ---> SmPC of [2] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Quinine, suxamethonium [2] ---> SmPC of [2] of eMC

Quinine enhances the neuromuscular effects of suxamethonium.

Remifentanil, suxamethonium

Remifentanil may prolong the neuromuscular blocking effects of suxamethonium

Rocuronium [1], suxamethonium ---> SmPC of [1] of eMC

Suxamethonium given after the administration of rocuronium may produce potentiation or attenuation of the neuromuscular blocking effect of rocuronium.

Sevoflurane [1], suxamethonium ---> SmPC of [1] of eMC

The effect of sevoflurane on succinylcholine and the duration of depolarising neuromuscular blockade has not been studied.

Succinylcholine, verapamil ---> SmPC of [suxamethonium] of

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Sufentanil, suxamethonium

The co-administration may cause bradycardia

Suxamethonium [1], tacrine ---> SmPC of [1] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Suxamethonium [1], terbutaline ---> SmPC of [1] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Suxamethonium [1], trimetaphan ---> SmPC of [1] of eMC

The decrease in the normal plasma cholinesterase activity may prolong the neuromuscular blocking effects of suxamethonium

Suxamethonium [1], verapamil ---> SmPC of [1] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Suxamethonium, terizidone

Possible prolongation of suxamethonium effect

Suxamethonium, tetracyclines

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Suxamethonium, thiopental

The co-administration may enhance the neuromuscular blocking action of suxamethonium

Suxamethonium, thiotepa [2] ---> SmPC of [2] of EMA

Alkylating chemotherapeutic agents, including thiotepa, inhibit plasma pseudocholinesterase by 35% to 70%. The action of succinyl-choline can be prolonged by 5 to 15 minutes.

Suxamethonium, trofosfamide

The plasma cholinesterase activity inhibition may increase or prolong the neuromuscular blocking action of suxamethonium, what may cause a long-lasting apnea

Suxamethonium, vecuronium [2] ---> SmPC of [2] of eMC

Suxamethonium given after the administration of vecuronium may produce potentiation or attenuation of the neuromuscular blocking effect of vecuronium.

CONTRAINDICATIONS of Suxamethonium

- Anectine has no effect on the level of consciousness and should not be administered to a patient who is not fully anaesthetised.

- Hypersensitivity to suxamethonium may exist in rare instances, and Anectine should not be administered to patients known to be hypersensitive to the drug.

- As suxamethonium can act as a trigger of sustained myofibrillar contraction in susceptible individuals, Anectine is contraindicated in patients with a personal or family history of malignant hyperthermia. If this condition occurs unexpectedly, all anaesthetic agents known to be associated with its development (including Anectine) must be immediately discontinued, and full supportive measures must be immediately instituted. Intravenous dantrolene sodium is the primary specific therapeutic drug and is recommended as soon as possible after the diagnosis is made. - Anectine is contra-indicated in patients known to have an inherited atypical plasma cholinesterase activity.

- An acute transient rise in serum potassium often occurs following the administration of Anectine in normal individuals; the magnitude of this rise is of the order of 0.5 mmol/litre. In certain pathological states or conditions this increase in serum potassium following Anectine administration may be excessive and cause serious cardiac arrhythmias and cardiac arrest. For this reason the use of Anectine is contra-indicated in: - In patients recovering from major trauma or severe burns; the period of greatest risk of hyperkalaemia is from about 5 to 70 days after the injury and may be further prolonged if there is delayed healing due to persistent infection.

- Patients with neurological deficits involving acute major muscle wasting (upper and/or lower motor neurone lesions); the potential for potassium release occurs within the first 6 months after the acute onset of the neurological deficit and correlates with the degree and extent of muscle paralysis. Patients who have been immobilised for prolonged periods of time may be at similar risk. - Patients with pre-existing hyperkalaemia. In the absence of hyperkalaemia and neuropathy, renal failure is not a contra-indication to the administration of a normal single dose of Anectine Injection, but multiple or large doses may cause clinically significant rises in serum potassium and should not be used. - Suxamethonium causes a significant transient rise in intra-ocular pressure, and should therefore not be used in the presence of open eye injuries or where an increase in intra-ocular pressure is undesirable unless the potential benefit of its use outweighs the potential risk to the eye. - Anectine should be avoided in patients with a personal or family history of congenital myotonic diseases such as myotonia congenita and dystrophia myotonica since its administration may on occasion be associated with severe myotonic spasms and rigidity. - Anectine should not be used in patients with skeletal muscle myopathies e.g. Duchenne muscular dystrophy since its administration may be associated with malignant hyperthermia, ventricular dysrhythmias and cardiac arrest secondary to acute rhabdomyolysis with hyperkalaemia.

http://www.medicines.org.uk/emc/

Suxibuzone

Breast-feeding, suxibuzone

The lactation is not recommended

Pregnancy, suxibuzone

Strict indication in the first and second trimester. Contraindicated in the third trimester

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