L

Labetalol

Ability to drive, labetalol

Decreased ability to react

ACE inhibitors, labetalol

Possible enhancement of hypotensive effect of labetalol

Adrenaline, labetalol

The co-administration may cause bradycardia and hypertension

AIIRA, labetalol

Possible enhancement of hypotensive effect of labetalol

Alcohol, labetalol

The co-administration may increase the bioavailability of labetalol

Alfa-adrenergic receptor blockers, labetalol

Possible enhancement of hypotensive effect of labetalol

Alprostadil, labetalol

Possible enhancement of hypotensive effect of labetalol

Antihypertensives, labetalol

The co-administration may enhance the hypotensive effect

Anxiolytics, labetalol

Possible enhancement of hypotensive effect of labetalol

Benzothiazepines [1], labetalol ---> SmPC of [1] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Breast-feeding, labetalol

Labetalol passes into the mother milk. Mothers should discontinue breast-feeding

Cimetidine, labetalol

Cimetidine delays the elimination of betablocker and enhances or prolongs its effects and adverse effects (dose adjustment may be necessary)

Class I antiarrhythmic agents, labetalol [2] ---> SmPC of [2] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Digital glycosides [1], labetalol ---> SmPC of [1] of eMC

Digitalis glycosides in association with beta-blockers may increase auriculo-ventricular conduction time.

Diuretics, labetalol

Possible enhancement of hypotensive effect of labetalol

Ergot derivatives, labetalol

The co-administration may enhance the vasoconstrictor effect of ergot derivative. The concomitant use should be avoided

Estrogens [1], labetalol ---> SmPC of [1] of eMC

Concurrent use of oestrogens and betablockers may decrease the antihypertensive effect of betablockers because oestrogen-induced fluid retention may lead to increased blood pressure.

General anesthetics, labetalol [2] ---> SmPC of [2] of eMC

Use of beta-blockers with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.

Hydralazine, labetalol

The co-administration may increase the bioavailability of labetalol

Hypnotics, labetalol

Possible enhancement of hypotensive effect of labetalol

IMAOs, labetalol

Enhanced hypotensive effect of the beta-blocker but also the risk of hypertensive crisis. Concomitant use of labetalol and MAO inhibitors is contraindicated

Imipramine [1], labetalol ---> SmPC of [1] of eMC

Blood concentrations of imipramine may be increased by drugs such as labetalol.

Insulin [1], labetalol ---> SmPC of [1] of EMA

The beta-blocker may increase the hypoglycaemic effect of insulin. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Labetalol [1], phenylalkylamines ---> SmPC of [1] of eMC

Class I anti-arrhythmic drugs may increase atrial-conduction time and induce negative inotropic effect when administered concomitantly with beta-blockers.

Labetalol, lidocaine

Labetalol may decrease the hepatic metabolism of lidocaine and increase its toxicity

Labetalol, moxisylyte

Possible enhancement of hypotensive effect of labetalol

Labetalol, muscle relaxants (non-depolarizing)

The co-administration may enhance and/or prolong the neuromuscular block of non-depolarising blocker

Labetalol, nitroglycerine

The co-administration may potentiate the hypotensive effect of the nitroglycerin. Labetalol decreases the reflex tachycardia caused by nitroglycerin

Labetalol, NSAID

The NSAID can reduce the anti-hypertensive effect of beta-blocker

Labetalol, oral antidiabetics ---> SmPC of [brinzolamide/timolol] of EMA

The beta-blocker may increase the hypoglycaemic effect of antidiabetic agent. Blockade of beta-adrenoreceptors may mask the symptoms of hypoglycaemia

Labetalol, phenothiazines [2] ---> SmPC of [2] of eMC

Concomitant use may enhance the hypotensive effect of the beta-blockers (additive effect).

Labetalol, pregnancy

Labetalol crosses the placenta. Labetalol should be only used in the first trimester of pregnancy if unless the potential benefit outweighs the potential risk

Labetalol, prostaglandin synthesis inhibitors

NSAIDs (especially indometacin) may reduce the antihypertensive effects of beta-blockers possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.

Labetalol, tricyclic antidepressant

Mutual enhancement of effects. Increased incidence of tremor

Lacidipine

Ability to drive, lacidipine [2] ---> SmPC of [2] of eMC

Lacidipine may cause dizziness.

ACE inhibitors, lacidipine [2] ---> SmPC of [2] of eMC

Co-administration of lacidipine with other agents recognised to have a hypotensive effect may have an additive hypotensive effect.

Antihypertensives, lacidipine [2] ---> SmPC of [2] of eMC

Co-administration of lacidipine with other agents recognised to have a hypotensive effect may have an additive hypotensive effect.

Barbiturates, lacidipine

It has been shown that the plasma levels of other dihydropyridines are decreased with the co-administration of enzymatic inductors

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

Co-administration of lacidipine with other agents recognised to have a hypotensive effect may have an additive hypotensive effect.

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

Lacidipine should only be used during lactation when the potential benefits for the mother outweigh the possibility of adverse effects in the foetus or neonate.

Carbamazepine, lacidipine

It has been shown that the plasma levels of other dihydropyridines are decreased with the co-administration of enzymatic inductors

Cimetidine, lacidipine [2] ---> SmPC of [2] of eMC

The plasma level of lacidipine may be increased by simultaneous administration of cimetidine.

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

Concomitant use of lacidipine and corticoids or tetracosactide might decrease antihypertensive effect.

Cyclosporine, lacidipine [2] ---> SmPC of [2] of eMC

In clinical studies in patients with a renal transplant treated with cyclosporin, lacidipine reversed the decrease in renal plasma flow and glomerular filtration rate induced by cyclosporin.

Dihydropyridines, enzyme inductors

It has been shown that the plasma levels of dihydropyridines are decreased with the co-administration of enzymatic inductors

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

Co-administration of lacidipine with other agents recognised to have a hypotensive effect may have an additive hypotensive effect.

Enzyme inductors, lacidipine

It has been shown that the plasma levels of other dihydropyridines are decreased with the co-administration of enzymatic inductors

Enzyme inhibitors, lacidipine

The plasma level of lacidipine may be increased by simultaneous administration of enzyme inductors.

Grapefruit juice, lacidipine ---> SmPC of [lercanidipine] of eMC

Dihydropyridines are sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in their systemic availability and increased hypotensive effect. Dihydropyridines should not be taken with grapefruit juice.

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

Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.

Ivabradine [1], lacidipine ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the dihydropyridine calcium channel blockers on pharmacokinetics and pharmacodynamics of ivabradine

Lacidipine [1], pregnancy ---> SmPC of [1] of eMC

Lacidipine should only be used in pregnancy when the potential benefits for the mother outweigh the possibility of adverse effects in the foetus or neonate.

Lacidipine [1], rifampicin ---> SmPC of [1] of eMC

Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.

Lacidipine [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.

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

Lacidipine is known to be metabolised by cytochrome CYP3A4 and, therefore, significant inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lacidipine.

Lacidipine [1], tetracosactide ---> SmPC of [1] of eMC

Concomitant use of lacidipine and corticoids or tetracosactide might decrease antihypertensive effect.

Lacidipine, lomitapide [2] ---> SmPC of [2] of EMA

Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously. Separate the dose of the medications by 12 hours OR decrease the dose of Lojuxta by half.

Lacidipine, nebivolol [2] ---> SmPC of [2] of eMC

Concomitant use of dihydropyridines and nebivolol may increase the risk of hypotension, and cause an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure.

Lacidipine, phenytoin

It has been shown that the plasma levels of other dihydropyridines are decreased with the co-administration of enzymatic inductors

           CONTRAINDICATIONS of Lacidipine

           - MOTENS tablets are contraindicated in patients with known hypersensitivity to any ingredient of the preparation.

           - MOTENS should only be used with great care in patients with a previous allergic reaction to another dihydropyridine because there is a theoretical risk of cross-reactivity.

           - As with other calcium antagonists, MOTENS should be discontinued in patients who develop cardiogenic shock and unstable angina. In addition, dihydropyridines have been

           shown to reduce coronary arterial blood-flow in patients with aortic stenosis and in such patients MOTENS is contraindicated.

           - MOTENS should not be used during or within one month of a myocardial infarction.

           - In case of rare hereditary conditions that may be incompatible with an excipient of the product (please refer to section 4.4 Special Warnings and Precautions for Use) the use of the product is contraindicated.

           http://www.medicines.org.uk/emc/ CONTRAINDICATIONS of Lacidipine

           – MOTENS tablets are contraindicated in patients with known hypersensitivity to any ingredient of the preparation.

           – MOTENS should only be used with great care in patients with a previous allergic reaction to another dihydropyridine because there is a theoretical risk of cross–reactivity.

           – As with other calcium antagonists, MOTENS should be discontinued in patients who develop cardiogenic shock and unstable angina. In addition, dihydropyridines have been

           shown to reduce coronary arterial blood–flow in patients with aortic stenosis and in such patients MOTENS is contraindicated.

           – MOTENS should not be used during or within one month of a myocardial infarction.

           – In case of rare hereditary conditions that may be incompatible with an excipient of the product (please refer to section 4.4 Special Warnings and Precautions for Use) the use of the product is contraindicated.

           http://www.medicines.org.uk/emc/ CONTRAINDICATIONS of Lacidipine

           – MOTENS tablets are contraindicated in patients with known hypersensitivity to any ingredient of the preparation.

           – MOTENS should only be used with great care in patients with a previous allergic reaction to another dihydropyridine because there is a theoretical risk of cross–reactivity.

           – As with other calcium antagonists, MOTENS should be discontinued in patients who develop cardiogenic shock and unstable angina. In addition, dihydropyridines have been

           shown to reduce coronary arterial blood–flow in patients with aortic stenosis and in such patients MOTENS is contraindicated.

           – MOTENS should not be used during or within one month of a myocardial infarction.

           – In case of rare hereditary conditions that may be incompatible with an excipient of the product (please refer to section 4.4 Special Warnings and Precautions for Use) the use of the product is contraindicated.

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

Lacosamide (Vimpat)

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

It is unknown whether lacosamide is excreted in human breast milk. Animal studies have shown excretion of lacosamide in breast milk. For precautionary measures, breast-feeding should be discontinued during treatment with lacosamide.

Alcohol, lacosamide [2] ---> SmPC of [2] of EMA

Although no pharmacokinetic data on the interaction of lacosamide with alcohol are available, a pharmacodynamic effect cannot be excluded.

Antiepileptics, lacosamide [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analyses in different age groups estimated that co-treatment with other antiepileptic drugs known to be enzyme inducers decreased the overall systemic exposure of lacosamide by 25 % in adults and 17 % in paediatric patients.

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

Lacosamide is excreted in human breast milk. A risk to the newborns/infants cannot be excluded. It is recommended that breast-feeding should be discontinued during treatment with lacosamide.

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

The enzymatic induction may decrease the exposition to lacosamide. Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation

Cenobamate [1], lacosamide ---> SmPC of [1] of EMA

No dose adjustments are required.

Clarithromycin, lacosamide [2] ---> SmPC of [2] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

Class IA antiarrhythmic agents, lacosamide [2] ---> SmPC of [2] of EMA

Lacosamide should be used with caution in patients treated with class I antiarrhythmic drugs

Class IB antiarrhythmic agents, lacosamide [2] ---> SmPC of [2] of EMA

Lacosamide should be used with caution in patients treated with class I antiarrhythmic drugs

Class IC antiarrhythmic agents, lacosamide [2] ---> SmPC of [2] of EMA

Lacosamide should be used with caution in patients treated with class I antiarrhythmic drugs

Digoxin, lacosamide [2] ---> SmPC of [2] of EMA

Interaction studies showed that lacosamide had no effect on the pharmacokinetics of digoxin.

Drugs with high protein binding, lacosamide [2] ---> SmPC of [2] of EMA

Lacosamide has a low protein binding of less than 15 %. Therefore, clinically relevant interactions with other medicinal products through competition for protein binding sites are considered unlikely.

Enzyme inductors, lacosamide [2] ---> SmPC of [2] of EMA

The enzymatic induction may decrease plasma concentrations of lacosamide. Starting or ending treatment with enzyme inducers should be done with caution

Eslicarbazepine, lacosamide [2] ---> SmPC of [2] of EMA

Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation

Ethinyl estradiol, lacosamide [2] ---> SmPC of [2] of EMA

In an interaction trial there was no clinically relevant interaction between lacosamide and ethinylestradiol

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

No adverse reactions on male or female fertility or reproduction were observed in rats at doses producing plasma exposures (AUC) up to approximately 2 times the plasma AUC in humans at the maximum recommended human dose (MRHD).

Fluconazole, lacosamide [2] ---> SmPC of [2] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP2C9, which may lead to increased systemic exposure of lacosamide.

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

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

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

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

Lacosamide [1], lamotrigine ---> SmPC of [1] of EMA

Subgroup analysis did not identify an increased magnitude of PR prolongation in patients with concomitant administration of lamotrigine in clinical trials.

Lacosamide [1], levonorgestrel ---> SmPC of [1] of EMA

In an interaction trial there was no clinically relevant interaction between lacosamide and levonorgestrel.

Lacosamide [1], metformin ---> SmPC of [1] of EMA

There was no clinically relevant interaction between lacosamide and metformin.

Lacosamide [1], midazolam ---> SmPC of [1] of EMA

Lacosamide did not affect the AUC of midazolam (metabolised by CYP3A4, lacosamide given 200 mg twice a day), but Cmax of midazolam was slightly increased (30 %).

Lacosamide [1], moderate CYP2C9 inhibitors ---> SmPC of [1] of EMA

Thus, moderate inhibitors of CYP2C19 are unlikely to affect systemic lacosamide exposure to a clinically relevant extent.

Lacosamide [1], omeprazole ---> SmPC of [1] of EMA

The CYP2C19 inhibitor omeprazole (40 mg q.d.) did not give rise to a clinically significant change in lacosamide exposure. Thus moderate inhibitors of CYP2C19 are unlikely to affect systemic lacosamide exposure to a clinically relevant extent.

Lacosamide [1], oral contraceptives ---> SmPC of [1] of EMA

In an interaction study there was no clinically relevant interaction between lacosamide and the oral contraceptives ethinylestradiol and levonorgestrel.

Lacosamide [1], phenobarbital ---> SmPC of [1] of EMA

Population pharmacokinetic analyses in different age groups estimated that co-treatment with other antiepileptic drugs known to be enzyme inducers decreased the overall systemic exposure of lacosamide by 25 % in adults and 17 % in paediatric patients.

Lacosamide [1], phenytoin ---> SmPC of [1] of EMA

Population pharmacokinetic analyses in different age groups estimated that co-treatment with other antiepileptic drugs known to be enzyme inducers decreased the overall systemic exposure of lacosamide by 25 % in adults and 17 % in paediatric patients.

Lacosamide [1], PR interval prolonging drugs ---> SmPC of [1] of EMA

Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation

Lacosamide [1], pregabalin ---> SmPC of [1] of EMA

Lacosamide should be used with caution in patients treated with medicinal products known to be associated with PR prolongation

Lacosamide [1], pregnancy ---> SmPC of [1] of EMA

Lacosamide should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the foetus).

Lacosamide [1], progesterone ---> SmPC of [1] of EMA

Progesterone concentrations were not affected when the medicinal products were co-administered.

Lacosamide [1], rifampicin ---> 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

Lacosamide [1], ritonavir ---> SmPC of [1] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

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

Lacosamide [1], strong CYP2C9 inhibitors ---> SmPC of [1] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP2C9, which may lead to increased systemic exposure of lacosamide.

Lacosamide [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Caution is recommended in concomitant treatment of lacosamide with strong inhibitors of CYP3A4, which may lead to increased systemic exposure of lacosamide.

Lacosamide [1], warfarin ---> SmPC of [1] of EMA

Co-administration of warfarin with lacosamide does not result in a clinically relevant change in the pharmacokinetics and pharmacodynamics of warfarin.

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

Physicians should discuss family planning and contraception with women of childbearing potential taking lacosamide (see Pregnancy). If a woman decides to become pregnant, the use of lacosamide should be carefully re-evaluated.

            CONTRAINDICATIONS of Lacosamide (Vimpat)

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

            - Known second- or third-degree atrioventricular (AV) block.

            https://www.ema.europa.eu/en/documents/product-information/vimpat-epar-product-information_en.pdf 08/01/2024

Other trade names: Lacosamide Accord, Lacosamide Adroiq, Lacosamide UCB,

Lactitol

Amphotericin, lactitol

The co-administration of hypokaliemia-inducer drugs may enhance the potassium loss

Antacids, lactitol

Decrease of the stool acidifying effect of lactitol. The co-administration is not recommended

Breast-feeding, lactitol

It is unlikely a clinical relevance due to the absorption is minimal

Carbenoxolone, lactitol

The co-administration of hypokaliemia-inducer drugs may enhance the potassium loss

Cardiac glycosides, lactitol

The chronic use of laxatives may cause hypokaliemia, which enhances the effect of cardiac glycoside

Corticosteroids, lactitol

The co-administration of hypokaliemia-inducer drugs may enhance the potassium loss

Drugs inducing hypokaliemia, lactitol

The co-administration of hypokaliemia-inducer drugs may enhance the potassium loss

Glucocorticoids, lactitol

The co-administration of hypokaliemia-inducer drugs may enhance the potassium loss

Lactitol, mesalazine

Decreased mesalazine effect

Lactitol, neomycin

Decrease of the stool acidifying effect of lactitol. The co-administration is not recommended

Lactitol, pregnancy

Lactitol should not be used during the first trimester of pregnancy unless strictly necessary

Lactitol, thiazides

The co-administration of hypokaliemia-inducer drugs may enhance the potassium loss

Lactulose

Amphotericin B, lactulose

Lactulose may enhance other drug-induced hypokalemia

Amphotericin, lactulose

Lactulose may enhance other drug-induced hypokalemia

Antacids, lactulose

Weakening of the laxative effect

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

Lactulose can be used during breast-feeding.

Carbenoxolone, lactulose

Lactulose may enhance other drug-induced hypokalemia

Cardiac glycosides, lactulose

The co-administration may enhance the glycoside effect due to hypokalemia

Corticosteroids, lactulose

Lactulose may enhance other drug-induced hypokalemia

Lactulose, mesalazine

Possible decrease in mesalazine release due to pH reduction

Lactulose, non-potassium-sparing diuretics

Lactulose may enhance other drug-induced hypokalemia

Lactulose [1], pregnancy ---> SmPC of [1] of eMC

Lactulose can be used during pregnancy.

           CONTRAINDICATIONS of LACTULOSE

           - Hypersensitivity to the active substance or any of the ingredients.

           - Galactosaemia.

           - Gastro-intestinal obstruction, digestive perforation or risk of digestive perforation.

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

Lamivudine (Zeffix)

Abacavir/lamivudine [1], lamivudine ---> SmPC of [1] of EMA

Kivexa should not be taken with any other medicinal products containing lamivudine

Abacavir/lamivudine/zidovudine [1], lamivudine ---> SmPC of [1] of EMA

Abacavir/lamivudine/zidovudine should not be taken with any other medicinal products containing lamivudine

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

Patients should be informed that malaise and fatigue have been reported during treatment with lamivudine.

Adefovir dipivoxil [1], lamivudine ---> SmPC of [1] of EMA

Concomitant administration of 10 mg adefovir dipivoxil and 100 mg lamivudine did not alter the pharmacokinetic profile of either medicinal product.

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

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

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

Consideration should be given to discontinuing breastfeeding to reduce the risk of the emergence of lamivudine resistant mutants in the infant.

Cimetidine, lamivudine [2] ---> SmPC of [2] of EMA

Other medicinal products (e.g. ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine.

Cladribine, lamivudine [2] ---> SmPC of [2] of EMA

In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting.

Clarithromycin, lamivudine

Separate administration by at least 2 hours

Cotrimoxazole, lamivudine [2] ---> SmPC of [2] of EMA

Administration of trimethoprim/sulphamethoxazole 160 mg/800 mg increased lamivudine exposure by about 40 %. Lamivudine had no effect on the pharmacokinetics of trimethoprim or sulphamethoxazole.

Cyclosporine, lamivudine [2] ---> SmPC of [2] of EMA

There were no observed clinically significant adverse interactions in patients taking lamivudine concurrently with commonly used immunosuppressant medicinal products (e.g. cyclosporin A). However, formal interaction studies have not been performed.

Cytidine analogues, lamivudine [2] ---> SmPC of [2] of EMA

Due to similarities, lamivudine should not be administered concomitantly with other cytidine analogues, such as emtricitabine. Moreover, lamivudine should not be taken with any other medicinal products containing lamivudine

Daclatasvir [1], lamivudine ---> SmPC of [1] of EMA

No dose adjustment of Daklinza or the NRTI is required.

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

Symtuza should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate, phosphate or succinate), lamivudine, or adefovir dipivoxil used for the treatment of HBV infection.

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

Darunavir co-administered with low dose ritonavir can be used with lamivudine without dose adjustment.

Dolutegravir/abacavir/lamivudine [1], lamivudine ---> SmPC of [1] of EMA

Triumeq should not be taken with any other medicinal products containing dolutegravir, abacavir, lamivudine or emtricitabine.

Dolutegravir/lamivudine [1], lamivudine ---> SmPC of [1] of EMA

Dovato should not be taken with any other medicinal product containing dolutegravir or lamivudine, except where a dose adjustment of dolutegravir is indicated due to drug-drug interactions

Dolutegravir/rilpivirine [1], lamivudine ---> SmPC of [1] of EMA

No dose adjustment is required.

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

No dose adjustment is required.

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

Genvoya should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of HBV infection.

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

Stribild should not be administered concomitantly with other medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of hepatitis B virus infection

Emtricitabine, lamivudine

There is no clinical experience as yet on the co-administration of cytidine analogues. Consequently, the use of emtricitabine in combination with lamivudine for the treatment of HIV infection cannot be recommended at this time.

Emtricitabine, lamivudine [2] ---> SmPC of [2] of EMA

Due to similarities, lamivudine should not be administered concomitantly with other cytidine analogues, such as emtricitabine.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], lamivudine ---> SmPC of [1] of EMA

Odefsey should not be co-administered with other medicinal products containing tenofovir alafenamide, lamivudine, tenofovir disoproxil (as fumarate) or adefovir dipivoxil

Emtricitabine/rilpivirine/tenofovir disoproxil [1], lamivudine ---> SmPC of [1] of EMA

Truvada should not be administered concomitantly with other medicinal products containing emtricitabine, tenofovir disoproxil, tenofovir alafenamide or other cytidine analogues, such as lamivudine (see section 4.4).

Emtricitabine/tenofovir alafenamide [1], lamivudine ---> SmPC of [1] of EMA

Descovy should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), lamivudine or adefovir dipivoxil used for the treatment of HBV infection.

Emtricitabine/tenofovir disoproxil [1], lamivudine ---> SmPC of [1] of EMA

Truvada should not be administered concomitantly with other medicinal products containing emtricitabine, tenofovir disoproxil, tenofovir alafenamide or other cytidine analogues, such as lamivudine (see section 4.4).

Etravirine [1], lamivudine ---> SmPC of [1] of EMA

INTELENCE can be used with these NRTIs without dose adjustment.

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

Reproductive studies in animals have shown no effect on male or female fertility (see section 5.3).

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

No clinically significant interaction is observed. No dosage adjustment necessary.

Foscarnet, lamivudine

Co-administration intravenous is not recommended

Ganciclovir, lamivudine

Co-administration intravenous is not recommended

Hepatitis, lamivudine [2] ---> SmPC of [2] of EMA

For patients who are being treated with lamivudine and subsequently become pregnant consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine.

Immunosuppressives, lamivudine [2] ---> SmPC of [2] of EMA

There were no observed clinically significant adverse interactions in patients taking lamivudine concurrently with commonly used immunosuppressant medicinal products (e.g. cyclosporin A). However, formal interaction studies have not been performed.

Interferon alfa, lamivudine [2] ---> SmPC of [2] of EMA

Lamivudine has no pharmacokinetic interaction with alpha-interferon when the two medicinal products are concurrently administered.

Lamivudine [1], metabolic interactions ---> SmPC of [1] of EMA

The likelihood of metabolic interactions is low due to limited metabolism and plasma protein binding and almost complete renal elimination of unchanged substance.

Lamivudine [1], pregnancy ---> SmPC of [1] of EMA

Zeffix can be used during pregnancy if clinically needed.

Lamivudine [1], sorbitol ---> SmPC of [1] of EMA

When possible, avoid chronic co-administration of Zeffix with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

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

The possibility of interactions with other medicinal products administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system e.g. trimethoprim.

Lamivudine [1], trimethoprim/sulfamethoxazol ---> SmPC of [1] of EMA

Administration of trimethoprim/sulphamethoxazole 160 mg/800 mg increased lamivudine exposure by about 40 %. Lamivudine had no effect on the pharmacokinetics of trimethoprim or sulphamethoxazole.

Lamivudine [1], tubular secretion ---> SmPC of [1] of EMA

Lamivudine is predominantly eliminated by active organic cationic secretion. Should be considered the possibility of interactions with other medicinal products eliminated mainly by active renal secretion

Lamivudine [1], zidovudine ---> SmPC of [1] of EMA

A modest increase in Cmax (28 %) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) was not significantly altered. Zidovudine had no effect on the pharmacokinetics of lamivudine (see section 5.2).

Lamivudine, lamivudine [2] ---> SmPC of [2] of EMA

Lamivudine should not be taken with any other medicinal products containing lamivudine

Lamivudine, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Lamivudine, maraviroc [2] ---> SmPC of [2] of EMA

No significant interaction seen/expected. Maraviroc and NRTIs can be co-administered without dose adjustment.

Lamivudine, maribavir [2] ---> SmPC of [2] of EMA

No dose adjustment is required.

Lamivudine, nevirapine [2] ---> SmPC of [2] of EMA

Lamivudine and Viramune can be coadministered without dose adjustments.

Lamivudine, peginterferon alfa-2a [2] ---> SmPC of [2] of EMA

Results from pharmacokinetic substudies of pivotal phase III trials demonstrated no pharmacokinetic interaction of lamivudine on Pegasys in HBV patients or between Pegasys and ribavirin in HCV patients.

Lamivudine, rilpivirine [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interactions are expected. No dose adjustment is required.

Lamivudine, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment is required.

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, tafamidis [2] ---> SmPC of [2] of EMA

Tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters

Lamivudine, telbivudine [2] ---> SmPC of [2] of EMA

Telbivudine is not recommended to be used with lamivudine because in a phase II study, the treatment response observed with combination therapy of telbivudine and lamivudine was lower than with telbivudine alone.

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

No clinically significant interaction is observed. No dosage adjustment necessary.

Lamivudine, valganciclovir [2] ---> SmPC of [2] of eMC

Coadministration of valganciclovir with antiviral drugs that share the tubular secretion pathway may change the plasma concentrations of valganciclovir and/or the coadministered drug.

Lamivudine, zalcitabine

Lamivudine may inhibit the intracellular phosphorylation of zalcitabine. The combination is not recommended

Mitochondrial dysfunction, nucleoside analogues ---> SmPC of [lamivudine] of EMA

Nucleoside a. nucleotide analogues have been demonstrated in vitro a. in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in infants exposed in utero a./o. post-natally to nucleoside analogues.

Mitochondrial dysfunction, nucleotide analogues ---> SmPC of [lamivudine] of EMA

Nucleoside a. nucleotide analogues have been demonstrated in vitro a. in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in infants exposed in utero a./o. post-natally to nucleoside analogues.

            CONTRAINDICATIONS of Lamivudine (Zeffix)

            - 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/zeffix-epar-product-information_en.pdf 03/06/2025

Other trade names: Epivir, Lamivudine Teva, Lamivudine Teva Pharma B.V.,

Lamivudine/raltegravir (Dutrebis)

Ability to drive, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Dizziness has been reported in some patients during treatment with regimens containing raltegravir, which may influence some patients' ability to drive and use machines

Aluminium, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Taking an aluminium and magnesium antacid within 6 hours of raltegravir administration significantly decreased raltegravir plasma levels. Therefore, co-administration is not recommended.

Atazanavir, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of lamivudine/raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir.

Atazanavir/ritonavir, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

The inhibition of UGT1A1 may increase raltegravir exposition. No dosage adjustment necessary.

Breast-feeding, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Breastfeeding is not recommended while taking DUTREBIS. As a general rule, it is recommended that mothers infected by HIV do not breast-feed their babies in order to avoid transmission of HIV.

Calcium carbonate, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of raltegravir with a calcium carbonate antacid decreased raltegravir plasma levels; however, this interaction is not considered clinically meaningful.

Calcium carbonate, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

Co-administration of raltegravir with a calcium carbonate antacid decreased raltegravir plasma levels; however, this interaction is not considered clinically meaningful.

Cladribine, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical

Darunavir, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

In some studies, co-administration of raltegravir with darunavir resulted in a modest decrease in darunavir plasma concentrations

Divalent cations, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of lamivudine/raltegravir with antacids containing divalent metal cations may reduce raltegravir absorption by chelation, resulting in a decrease of raltegravir plasma levels.

Divalent cations, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

Co-administration of lamivudine/raltegravir with antacids containing divalent metal cations may reduce raltegravir absorption by chelation, resulting in a decrease of raltegravir plasma levels.

Drugs primarily metabolised by CYP3A4, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

The results indicate that raltegravir is not an inducer or inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the pharmacokinetics of medicinal products which are CYP3A4 substrates.

Drugs primarily metabolised by CYP3A4, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

The results indicate that raltegravir is not an inducer or inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the pharmacokinetics of medicinal products which are CYP3A4 substrates.

Efavirenz, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

The induction of UGT1A1 may decrease raltegravir exposition. No dosage adjustment necessary.

Emtricitabine, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Lamivudine/raltegravir is not recommended for use in combination with emtricitabine containing products, since both lamivudine and emtricitabine are cytidine analogues

Famotidine, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of lamivudine/raltegravir with other agents that increase gastric pH may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. No dose adjustment is required

Gastric pH increasing medication, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of lamivudine/raltegravir with other agents that increase gastric pH may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. No dose adjustment is required

H2 antagonists, lamivudine/raltegravir [2] ---> SmPC of [2] of EMA

Co-administration of lamivudine/raltegravir with other agents that increase gastric pH may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. No dose adjustment is required

Indinavir, lamivudine/raltegravir [2] ---> SmPC of [2] 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.

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

Taking an aluminium and magnesium antacid within 6 hours of raltegravir administration significantly decreased raltegravir plasma levels. Therefore, co-administration is not recommended.

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

The results indicate that raltegravir is not an inducer or inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the pharmacokinetics of medicinal products which are CYP3A4 substrates.

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

Co-administration of lamivudine/raltegravir with other agents that increase gastric pH may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. No dose adjustment is required

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

No dosage adjustment required for lamivudine/raltegravir or hormonal contraceptives (oestrogen-and/or progesterone-based).

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

DUTREBIS should not be used during pregnancy.

Lamivudine/raltegravir [1], proton pump inhibitors ---> SmPC of [1] of EMA

Co-administration of lamivudine/raltegravir with other agents that increase gastric pH may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. No dose adjustment is required

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

The induction of UGT1A1 may decrease raltegravir exposition. Concomitant use is 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.

Lamivudine/raltegravir [1], strong UGT1A1 inhibitors ---> SmPC of [1] of EMA

Co-administration of lamivudine/raltegravir with medicinal products that are known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir.

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

The induction of UGT1A1 may decrease raltegravir exposition. No dosage adjustment necessary.

Lamivudine/raltegravir [1], UGT1A1 inhibitors ---> 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.

Midazolam, raltegravir ---> SmPC of [lamivudine/raltegravir] of EMA

The results indicate that raltegravir is not an inducer or inhibitor of CYP3A4, and raltegravir is thus not anticipated to affect the pharmacokinetics of medicinal products which are CYP3A4 substrates.

            CONTRAINDICATIONS of Lamivudine/raltegravir (Dutrebis)

            - 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/dutrebis-epar-product-information_en.pdf 27/04/2017 (withdrawn)

Lamivudine/zidovudine (Combivir)

Amphotericin, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Anemia, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Consideration should be given to replacing zidovudine in a combination ART regimen if this is already established. This would be particularly important in patients with a known history of zidovudine induced anaemia.

Antiretrovirals, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Atazanavir [1], lamivudine/zidovudine ---> SmPC of [1] of EMA

No significant effect on lamivudine and zidovudine concentrations was observed.

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

No significant effect on lamivudine and zidovudine concentrations was observed when co-administered with atazanavir.

Atazanavir/ritonavir, lamivudine/zidovudine ---> SmPC of [atazanavir] of EMA

No significant effect on lamivudine and zidovudine concentrations was observed.

Atovaquone, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Increase in plasma zidovudine AUC. As only limited data available the clinical significance is unknown.

Breast-feeding, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

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

Cellular DNA replication, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

The active ingredients of Combivir may inhibit cellular DNA replication and zidovudine has been shown to be transplacental carcinogen in one animal study (see section 5.3). The clinical relevance of these findings is unknown.

Cimetidine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Cladribine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical. The concomitant use of lamivudine with cladribine is not recommended

Clarithromycin, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Clarithromycin reduces AUC of zidovudine. Separate administration by at least 2 hours

Cotrimoxazole, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

No Combivir dosage adjustment necessary, unless patient has renal impairment (See Section 4.2).

Cytochrome P450, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Lamivudine and zidovudine are not significantly metabolised by cytochrome P450 enzymes (such as CYP 3A4, CYP 2C9 or CYP 2D6) nor do they inhibit or induce this enzyme system.

Dapsone, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Didanosine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Doxorubicine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Fertility, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Neither zidovudine nor lamivudine have shown evidence of impairment of fertility in studies in male and female rats. There are no data on their effect on human female fertility.

Fluconazole, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

As only limited data are available the clinical significance is not known. Monitor for signs of zidovudine toxicity (see section 4.8).

Flucytosine, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Ganciclovir, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Glucuronidation inductors, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure.

Glucuronidation inhibitors, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure.

Hepatitis, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

For patients co-infected with hepatitis who are being treated with lamivudine containing medicines and subsequently become pregnant, consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine.

Interferon, lamivudine/zidovudine [2] ---> SmPC of [2] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], maltitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Combivir with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

Lamivudine/zidovudine [1], mannitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Combivir with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

Lamivudine/zidovudine [1], men ---> SmPC of [1] of EMA

In men zidovudine has not been shown to affect sperm count, morphology or motility.

Lamivudine/zidovudine [1], methadone ---> SmPC of [1] of EMA

Monitor for signs of zidovudine toxicity (see section 4.8). Methadone dosage adjustment unlikely in majority of patients; occasionally methadone re-titration may be required.

Lamivudine/zidovudine [1], mitochondrial dysfunction ---> SmPC of [1] of EMA

Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage.

Lamivudine/zidovudine [1], myelosuppressive agents ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], nephrotoxic substances ---> SmPC of [1] of EMA

Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated through organic cation transporters (OCTs); co-administration of lamivudine with nephrotoxic drugs may increase lamivudine exposure.

Lamivudine/zidovudine [1], OCT inhibitors ---> SmPC of [1] of EMA

Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated through organic cation transporters (OCTs); co-administration of lamivudine with OCT inhibitors may increase lamivudine exposure.

Lamivudine/zidovudine [1], pentamidine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], phenobarbital ---> SmPC of [1] of EMA

Potential to slightly decrease zidovudine plasma concentrations through UGT induction. Insufficient data to recommend dosage adjustment.

Lamivudine/zidovudine [1], phenytoin ---> SmPC of [1] of EMA

Monitor phenytoin concentrations

Lamivudine/zidovudine [1], pregnancy ---> SmPC of [1] of EMA

The malformative risk is unlikely in humans based on the large amount of data.

Lamivudine/zidovudine [1], probenecide ---> SmPC of [1] of EMA

As only limited data are available the clinical significance is not known. Monitor for signs of zidovudine toxicity (see section 4.8).

Lamivudine/zidovudine [1], pyrimethamine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], ranitidine ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Lamivudine/zidovudine [1], ribavirin ---> SmPC of [1] of EMA

The concomitant use of ribavirin with zidovudine is not recommended due to an increased risk of anaemia (see section 4.4).

Lamivudine/zidovudine [1], rifampicin ---> SmPC of [1] of EMA

The UGT induction may decrease AUC of zidovudine. Insufficient data to recommend dosage adjustment.

Lamivudine/zidovudine [1], sorbitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Combivir with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

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

Lamivudine/zidovudine [1], strong glucuronidation inductors ---> SmPC of [1] of EMA

Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure.

Lamivudine/zidovudine [1], trimethoprim/sulfamethoxazol ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], valproic acid ---> SmPC of [1] of EMA

As only limited data are available the clinical significance is not known. Monitor for signs of zidovudine toxicity (see section 4.8).

Lamivudine/zidovudine [1], vinblastine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], vincristine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lamivudine/zidovudine [1], xylitol ---> SmPC of [1] of EMA

When possible, avoid chronic coadministration of Combivir with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol).

Lamivudine/zidovudine, maraviroc [2] ---> SmPC of [2] of EMA

In addition, co-administration of maraviroc with lamivudine/zidovudine showed no effect of maraviroc on lamivudine (primarily renally cleared) or zidovudine (non-P450 metabolism and renal clearance) pharmacokinetics.

            CONTRAINDICATIONS of Lamivudine/zidovudine (Combivir)

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

            - Zidovudine is contraindicated in patients with abnormally low neutrophil counts (<0.75 x 109/l), or abnormally low haemoglobin levels (<7.5 g/dl or 4.65 mmol/l). Combivir is therefore contraindicated in these patients

            https://www.ema.europa.eu/en/documents/product-information/combivir-epar-product-information_en.pdf  29/08/2022

Other trade names: Lamivudine/zidovudine Teva (withdrawn),

Lamotrigine

Ability to drive, lamotrigine [2] ---> SmPC of [2] of eMC

Patients should see how lamotrigine therapy affects them before driving or operating machinery.

Aripiprazole [1], lamotrigine ---> SmPC of [1] of EMA

When aripiprazole was administered concomitantly with lamotrigine there was no clinically important change in concentrations of lamotrigine. Thus, no dosage adjustment is required

Atazanavir/ritonavir, lamotrigine ---> SmPC of [atazanavir] of EMA

Co-administration of lamotrigine and atazanavir/ritonavir may decrease lamotrigine plasma concentrations due to UGT1A4 induction.

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

The potential benefits of breast-feeding should be weighed against the potential risk of adverse effects occurring in the infant.

Bupropion, lamotrigine [2] ---> SmPC of [2] of eMC

Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of lamotrigine in 12 subjects and had only a slight increase in the AUC of lamotrigine glucuronide.

Carbamazepine, lamotrigine [2] ---> SmPC of [2] of eMC

Carbamazepine may lower the plasma level of lamotrigine

Drugs primarily metabolised by CYP2D6, lamotrigine [2] ---> SmPC of [2] of eMC

A study of bufuralol metabolism using human liver microsome preparations suggested that lamotrigine would not reduce the clearance of medicinal products metabolised predominantly by CYP2D6.

Eslicarbazepine [1], lamotrigine ---> SmPC of [1] of EMA

Minor decrease in lamotrigine exposure. Due to interindividual variability, the effect may be clinically relevant in some individuals

Ethinylestradiol/desogestrel [1], lamotrigine ---> SmPC of [1] of eMC

Oral contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may be decreased (e.g., lamotrigine)

Ethinylestradiol/drospirenone [1], lamotrigine ---> SmPC of [1] of eMC

Oral contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations may decrease (e.g. lamotrigine)

Ethinylestradiol/etonogestrel [1], lamotrigine ---> SmPC of [1] of eMC

Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).

Ethinylestradiol/norgestimate [1], lamotrigine ---> SmPC of [1] of eMC

Combination hormonal contraceptives with lamotrigine may decrease plasma (due to induction of glucuronidation) of lamotrigine

Etonogestrel [1], lamotrigine ---> SmPC of [1] of eMC

Oral contraceptives may affect the metabolism of certain other active substances. Accordingly, plasma and tissue concentrations of lamotrigine may decrease

Felbamate, lamotrigine [2] ---> SmPC of [2] of eMC

In a study of healthy volunteers, coadministration of felbamate (1200 mg twice daily) with lamotrigine (100 mg twice daily for 10 days)appeared to have no clinically relevant effects on the pharmacokinetics of lamotrigine.

Fosphenytoin [1], lamotrigine ---> SmPC of [1] of eMC

Blood levels and/or effects of lamotrigine may be altered by phenytoin

Gabapentin, lamotrigine [2] ---> SmPC of [2] of eMC

Co-administration of lamotrigine (OCT2 inhibitor) with renally excreted medicinal products which are substrates of OCT2 may result in increased plasma levels of these drugs.

Hormonal contraceptives, lamotrigine ---> SmPC of [ethinylestradiol/desogestrel] of eMC

Oral contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may be decreased (e.g., lamotrigine)

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

Ritonavir induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsant.

Lacosamide [1], lamotrigine ---> SmPC of [1] of EMA

Subgroup analysis did not identify an increased magnitude of PR prolongation in patients with concomitant administration of lamotrigine in clinical trials.

Lamotrigine [1], lithium ---> SmPC of [1] of eMC

The pharmacokinetics of lithium after 2 g of anhydrous lithium gluconate given twice daily for six days to 20 healthy subjects were not altered by co-administration of 100 mg/day lamotrigine.

Lamotrigine [1], metformin ---> SmPC of [1] of eMC

Co-administration of lamotrigine (OCT2 inhibitor) with renally excreted medicinal products which are substrates of OCT2 may result in increased plasma levels of these drugs.

Lamotrigine [1], olanzapine ---> SmPC of [1] of eMC

In a study in healthy adult volunteers, 15 mg olanzapine reduced the AUC and Cmax of lamotrigine by an average of 24% and 20%, respectively.

Lamotrigine [1], phenobarbital ---> SmPC of [1] of eMC

Phenobarbital induces hepatic drug-metabolising enzymes and the glucuronidation of lamotrigine and enhances the metabolism of lamotrigine

Lamotrigine [1], phenytoin ---> SmPC of [1] of eMC

Phenytoin induces hepatic drug-metabolising enzymes and the glucuronidation of lamotrigine and enhances the metabolism of lamotrigine

Lamotrigine [1], pregabalin ---> SmPC of [1] of eMC

Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin (200 mg, 3 times daily) administration. There are no pharmacokinetic interactions between lamotrigine and pregabalin.

Lamotrigine [1], pregnancy ---> SmPC of [1] of eMC

If therapy with lamotrigine is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended.

Lamotrigine [1], primidone ---> SmPC of [1] of eMC

Primidone induces hepatic drug-metabolising enzymes and the glucuronidation of lamotrigine and enhances the metabolism of lamotrigine

Lamotrigine [1], rifampicin ---> SmPC of [1] of eMC

Rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation.

Lamotrigine [1], risperidone ---> SmPC of [1] of eMC

Multiple oral doses of lamotrigine 400 mg daily had no clinically significant effect on the single dose pharmacokinetics of 2 mg risperidone in 14 healthy adult volunteers.

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.

Lamotrigine [1], substrates of OCT2 renally excreted ---> SmPC of [1] of eMC

Co-administration of lamotrigine (OCT2 inhibitor) with renally excreted medicinal products which are substrates of OCT2 may result in increased plasma levels of these drugs.

Lamotrigine [1], topiramate ---> SmPC of [1] of eMC

Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of lamotrigine resulted in a 15% increase in topiramate concentrations.

Lamotrigine [1], varenicline ---> SmPC of [1] of eMC

Co-administration of lamotrigine (OCT2 inhibitor) with renally excreted medicinal products which are substrates of OCT2 may result in increased plasma levels of these drugs.

Lamotrigine, levetiracetam [2] ---> SmPC of [2] of EMA

Pre-marketing data from clinical studies conducted indicate that levetiracetam did not influence the serum levels of existing antiepileptic medicinal products and that these antiepileptics did not influence the pharmacokinetics of levetiracetam

Lamotrigine, levonorgestrel/ethinylestradiol [2] ---> SmPC of [2] of eMC

Oral contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may be decreased (e.g. lamotrigine)

Lamotrigine, lopinavir/ritonavir [2] ---> SmPC of [2] of EMA

The glucuronidation induction decreases the exposition of lamotrigine

Lamotrigine, mesuximide

Mesuximide may decrease the plasma levels of lamotrigine

Lamotrigine, norelgestromin/ethinylestradiol [2] ---> SmPC of [2] of EMA

Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when coadministered likely due to induction of lamotrigine glucuronidation.

Lamotrigine, oral contraceptives ---> SmPC of [ethinylestradiol/desogestrel] of eMC

Oral contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may be decreased (e.g. lamotrigine)

Lamotrigine, oral contraceptives ---> SmPC of [nomegestrol/estradiol] of EMA

Oral contraceptives may affect the metabolism of other medicinal products. Special attention should be paid to the interaction with lamotrigine.

Lamotrigine, orlistat [2] ---> SmPC of [2] of EMA

Orlistat may unbalance anticonvulsivant treatment by decreasing the absorption of antiepileptic drugs, leading to convulsions

Lamotrigine, paracetamol

Paracetamol may decrease the bioavailability and effect of lamotrigine

Lamotrigine, retigabine [2] ---> SmPC of [2] of EMA

Based on these pooled data, retigabine did not cause clinically significant effects on the plasma trough concentrations of this antiepileptic medicinal product. The antiepileptic had no clinically significant effects on retigabine pharmacokinetics

Lamotrigine, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir, inductor of CYP2C9 and glucuronidation, may decrease the plasma concentrations of lamotrigine

Lamotrigine, rufinamide [2] ---> SmPC of [2] of EMA

Rufinamide appears not to have clinically relevant effect on lamotrigine steady state concentrations

Lamotrigine, sultiame

The co-administration may increase the plasma levels of lamotrigine

Lamotrigine, valproic acid [2] ---> SmPC of [2] of eMC

Valproic acid reduces the metabolism of lamotrigine and increases the lamotrigine mean half-life by nearly two fold.

Lamotrigine, zonisamide [2] ---> SmPC of [2] of EMA

The strong CYP3A4 induction decreases the zonisamide exposition. This effect is unlikely to be of clinical significance when zonisamide is added to existing therapy

           CONTRAINDICATIONS of Lamotrigine

           - Hypersensitivity to the active substance or to any of the excipients

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

Lanadelumab (Takhzyro)

Breast-feeding, lanadelumab [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 afterwards

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

Lanadelumab's effect on fertility has not been evaluated in humans. Lanadelumab had no effect on male or female fertility in cynomolgus monkeys (see section 5.3).

Lanadelumab [1], pharmacokinetics ---> SmPC of [1] of EMA

Based on the characteristics of lanadelumab, no pharmacokinetic interactions with co-administered medicinal products is expected.

Lanadelumab [1], pregnancy ---> SmPC of [1] of EMA

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

Lanadelumab [1], rescue medication  ---> SmPC of [1] of EMA

As expected, concomitant use of the rescue medication C1 esterase inhibitor results in an additive effect on lanadelumab-cHMWK response based on the mechanism of action of lanadelumab and C1 esterase inhibitor (see section 5.1).  

            CONTRAINDICATIONS of Lanadelumab (Takhzyro)         

            - 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/takhzyro-epar-product-information_en.pdf  02/06/2025 

Lanreotide

Ability to drive, lanreotide [2] ---> SmPC of [2] of eMC

Dizziness has been reported

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

Concomitant administration of bradycardia-inducing drugs (e.g. beta blockers) may have an additive effect on the slight reduction of heart rate associated with lanreotide.

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

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when lanreotide is administered during lactation.

Bromocriptine, lanreotide [2] ---> SmPC of [2] of eMC

Limited published data indicate that concomitant administration of somatostatin analogues and bromocriptine may increase the availability of bromocriptine.

Bromocriptine, somatostatin analogues ---> SmPC of [lanreotide] of eMC

Limited published data indicate that concomitant administration of somatostatin analogues and bromocriptine may increase the availability of bromocriptine.

Cyclosporine, lanreotide [2] ---> SmPC of [2] of eMC

Concomitant administration of ciclosporin with lanreotide may decrease the relative bioavailability of ciclosporin and therefore may necessitate the adjustment of ciclosporin dose to maintain therapeutic levels.

Drugs inducing bradycardia, lanreotide [2] ---> SmPC of [2] of eMC

Concomitant administration of bradycardia-inducing drugs (e.g. beta blockers) may have an additive effect on the slight reduction of heart rate associated with lanreotide.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, lanreotide [2] ---> SmPC of [2] of eMC

Lanreotide (may decrease the metabolic clearance of other drugs) should be used with caution with other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index

Insulin aspart [1], lanreotide ---> SmPC of [1] of EMA

Lanreotide may either increase or decrease the insulin requirement.

Insulin degludec/insulin aspart [1], lanreotide ---> SmPC of [1] of EMA

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Insulin, lanreotide ---> SmPC of [insulin glargin] of EMA

Lanreotide may both decrease and increase insulin requirement

Lanreotide [1], pregnancy ---> SmPC of [1] of eMC

Lanreotide should be administered to pregnant women only if clearly needed.

Lanreotide [1], quinidine ---> SmPC of [1] of eMC

Lanreotide (may decrease the metabolic clearance of other drugs) should be used with caution with other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index

Lanreotide [1], somatostatin analogues ---> SmPC of [1] of eMC

The limited published data available indicate that somatostatin analogues may decrease the metabolic clearance of compounds known to be metabolised by Cytochrome P450 enzymes, which may be due to the suppression of growth hormone.

Lanreotide [1], terfenadine ---> SmPC of [1] of eMC

Lanreotide (may decrease the metabolic clearance of other drugs) should be used with caution with other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index

Lanreotide, nateglinide [2] ---> SmPC of [2] of EMA

Somatostatin analogues may reduce the hypoglycaemic effect of nateglinide

           CONTRAINDICATIONS of Lanreotide

           - Hypersensitivity to lanreotide or related peptides or any of the excipients.

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

Lansoprazole

Ability to drive, lansoprazole [2] ---> SmPC of [2] of eMC

Adverse drug reactions such as dizziness, vertigo, visual disturbances and somnolence may occur. Under these conditions the ability to react may be decreased.

Almasilate, lansoprazole

There are studies which describe an absorption reduction of the active principle co-administered with almasilate

Antacids, lansoprazole [2] ---> SmPC of [2] of eMC

Antacids may decrease the bioavailability of lansoprazole. Lansoprazole should be given at least 1 hour after taking the antacid

Atazanavir, lansoprazole [2] ---> SmPC of [2] of eMC

A study has shown that co-administration of lansoprazole with atazanavir to healthy volunteers resulted in a substantial reduction in atazanavir exposure. Lansoprazole should not be co-administered with atazanavir

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

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with lansoprazole should be made taking into account the benefit of breast-feeding and the benefit of lansoprazole therapy to the woman.

Brivaracetam [1], lansoprazole ---> SmPC of [1] of EMA

Brivaracetam may increase plasma concentrations of medicinal products metabolised by CYP2C19 (e.g. lansoprazole, omeprazole, diazepam).

Citalopram [1], lansoprazole ---> SmPC of [1] of eMC

The strong CYP2C19 inhibition may increase the plasma concentrations of citalopram. Caution should be exercised when used concomitantly with CYP2C19 inhibitors

CYP3A4 and CYP2C19 inductors, lansoprazole [2] ---> SmPC of [2] of eMC

Enzyme inducers affecting CYP2C19 and CYP3A4 can markedly reduce the plasma concentrations of lansoprazole.

Cyproterone/ethinylestradiol [1], lansoprazole ---> 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.

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

Based on theoretical considerations, no mechanistic interaction is expected. REZOLSTA can be co-administered with proton pump inhibitors without dose adjustments.

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

Based on theoretical considerations, no mechanistic interaction is expected. Symtuza can be co-administered with proton pump inhibitors without dose adjustments.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, lansoprazole ---> SmPC of [dasabuvir] of EMA

Co-administration of dasabuvir with ombitasvir/paritaprevir/ritonavir can decrease exposures of medicinal products that are metabolized by CYP2C19, which may require dose adjustment/clinical monitoring.

Digoxin, lansoprazole [2] ---> SmPC of [2] of eMC

Co-administration of Lansoprazole and digoxin may lead to increased digoxin plasma levels.

Digoxin, proton pump inhibitors ---> SmPC of [lansoprazole] of eMC

For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia, health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment

Diuretics, proton pump inhibitors ---> SmPC of [lansoprazole] of eMC

For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia, health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment

Dolutegravir/rilpivirine [1], lansoprazole ---> SmPC of [1] of EMA

Co-administration may significantly decrease rilpivirine plasma concentration. This may result in loss of therapeutic effect of Juluca. Co-administration of Juluca with proton pump inhibitors is contraindicated

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, lansoprazole [2] ---> SmPC of [2] of eMC

Lansoprazole may increase plasma concentrations of drugs that are metabolised by CYP3A4. Caution is advised when combining lansoprazole with drugs which are metabolised by this enzyme and have a narrow therapeutic window.

Drugs primarily metabolised by CYP3A4, lansoprazole [2] ---> SmPC of [2] of eMC

Lansoprazole may increase plasma concentrations of drugs that are metabolised by CYP3A4. Caution is advised when combining lansoprazole with drugs which are metabolised by this enzyme and have a narrow therapeutic window.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], lansoprazole ---> SmPC of [1] of EMA

Significant decreases in rilpivirine plasma concentrations are expected (reduced absorption, increase in gastric pH). Co-administration is contraindicated.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], lansoprazole ---> SmPC of [1] of EMA

Co-administration of proton pump inhibitors has been observed to decrease the plasma concentrations of rilpivirine (due to an increase in gastric pH) which could potentially lead to loss of therapeutic effect. Concomitant use contraindicated

Enoxacin, lansoprazole

Lansoprazole may decrease the absorption of enoxacine.

Escitalopram [1], lansoprazole ---> SmPC of [1] of eMC

Caution should be exercised when used escitalopram concomitantly with CYP2C19 inhibitors. A reduction in the dose of escitalopram may be necessary based on monitoring of side-effects during concomitant treatment.

Fluvoxamine, lansoprazole [2] ---> SmPC of [2] of eMC

A dose reduction may be considered when combining Lansoprazole with the CYP2C19 inhibitor fluvoxamine. The plasma concentrations of Lansoprazole increase up to 4-fold.

Hypomagnesemia, lansoprazole [2] ---> SmPC of [2] of eMC

Severe hypomagnesaemia has been reported in patients treated with PPIs like lansoprazole for at least three months, and in most cases for a year.

Hypomagnesemia, proton pump inhibitors ---> SmPC of [lansoprazole] of eMC

Severe hypomagnesaemia has been reported in patients treated with PPIs for at least three months, and in most cases for a year.

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

Administration of lansoprazole may result in subtherapeutic concentrations of itraconazole and the combination should be avoided.

Ivabradine [1], lansoprazole ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the proton pump inhibitors on pharmacokinetics and pharmacodynamics of ivabradine

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

Administration of lansoprazole may result in subtherapeutic concentrations of ketoconazole and the combination should be avoided.

Lansoprazole [1], pregnancy ---> SmPC of [1] of eMC

The use of lansoprazole during pregnancy is not recommended.

Lansoprazole [1], rifampicin ---> SmPC of [1] of eMC

Enzyme inducers affecting CYP2C19 and CYP3A4 can markedly reduce the plasma concentrations of lansoprazole.

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.

Lansoprazole [1], strong P-gp inhibitors ---> SmPC of [1] of eMC

Lansoprazole has been observed to inhibit the transport protein, P-glycoprotein (P-gp)in vitro .The clinical relevance of this is unknown.

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.

Lansoprazole [1], tacrolimus ---> SmPC of [1] of eMC

Co-administration of Lansoprazole increases the plasma concentrations of tacrolimus (a CYP3A and P-gp substrate). Lansoprazole exposure increased the mean exposure of tacrolimus by up to 81%.

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

Lansoprazole reduces the plasma concentration of theophylline, which may decrease the expected clinical effect at the dose. Caution is advised when combining the two medicinal products.

Lansoprazole, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Lansoprazole, letermovir [2] ---> SmPC of [2] of EMA

Letermovir has the potential to decrease the exposure of CYP2C9 and/or CYP2C19 substrates potentially resulting in subtherapeutic levels.

Lansoprazole, lumacaftor/ivacaftor [2] ---> SmPC of [2] of EMA

A higher dose of this proton pump inhibitors may be required to obtain the desired clinical effect. Lumacaftor/ivacaftor may decrease this exposure of the proton pump inhibitor, which may reduce its efficacy.

Lansoprazole, mycophenolate mofetil [2] ---> SmPC of [2] of EMA

Decreased mycophenolic acid (MPA) exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with mycophenolate mofetil.

Lansoprazole, mycophenolate [2] ---> SmPC of [2] of EMA

Decreased mycophenolic acid (MPA) exposure has been observed when antacids, such as magnesium and aluminium hydroxides, and PPIs, including lansoprazole and pantoprazole, were administered with mycophenolate mofetil.

Lansoprazole, nelfinavir [2] ---> SmPC of [2] of EMA

Co-administration of nelfinavir with inhibitors of CYP2C19 may be expected to reduce the conversion of nelfinavir to its major active metabolite M8 (tert-butyl hydroxy nelfinavir) with a concomitant increase in plasma nelfinavir levels

Lansoprazole, ombitasvir/paritaprevir/ritonavir [2] ---> SmPC of [2] of EMA

Co-administration of Viekirax with or without dasabuvir can decrease exposures of medicinal products that are metabolized by CYP2C19 (e.g. lansoprazole, esomeprazole, s-mephenytoin), which may require dose adjustment/clinical monitoring.

Lansoprazole, prasugrel [2] ---> SmPC of [2] of EMA

Daily co-administration of ranitidine (an H2 blocker) or lansoprazole (a proton pump inhibitor) did not change the prasugrel active metabolite's AUC and Tmax, but decreased the Cmax by 14% and 29%, respectively.

Lansoprazole, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine. Rilpivirine must not be used with proton pump inhibitors

Lansoprazole, simeprevir [2] ---> SmPC of [2] of EMA

No clinically relevant drug-drug interaction is expected. No dose adjustment 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.

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.

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

The plasma concentrations of lansoprazole are difficult to predict due to inhibition of CYP3A4 and induction of CYP2C19. The combined use of tipranavir/ritonavir with proton pump inhibitors is not recommended

           CONTRAINDICATIONS of Lansoprazole

           - Hypersensitivity to lansoprazole or to any of the excipients.

           - Lansoprazole should not be administered with atazanavir

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

Lanthanum carbonate

Ability to drive, lanthanum carbonate [2] ---> SmPC of [2] of eMC

Lanthanum carbonate may induce dizziness and vertigo, which may impair the ability to drive and use machinery.

Ampicillin, lanthanum carbonate

Decreased absorption of ampicillin. Separate administration by at least 2 hours

Breast-feeding, lanthanum carbonate [2] ---> SmPC of [2] of eMC

Caution should be used in taking a decision whether to continue/discontinue breast feeding or to continue/discontinue therapy with lanthanum carbonate

Cefuroxime, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of cefuroxime. Separate administration by at least 2 hours

Chloroquine, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The lanthanum carbonate decreases the absorption of chloroquine. Separate administration by at least 2 hours

Ciprofloxacin, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The co-administration decreases the bioavailability of quinolone. Separate administration by at least 2 hours

Doxycycline, lanthanum carbonate [2] ---> SmPC of [2] of eMC

Interactions with tetracycline and doxycycline are theoretically possible and if these compounds are to be co-administered, it is recommended that they are not to be taken within 2 hours of dosing with lanthanum carbonate

Fosamprenavir, lanthanum carbonate

Decreased absorption of fosamprenavir. Separate administration by at least 2 hours

Fosamprenavir/ritonavir, lanthanum carbonate [2] ---> SmPC of [2] of EMA

Decreased absorption of fosamprenavir. Separate administration by at least 2 hours

Gefitinib, lanthanum carbonate

Substances that cause significant sustained elevation in gastric pH may reduce gefitinib plasma concentrations and thereby reduce the efficacy of gefitinib.

Hydroxychloroquine, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The lanthanum carbonate decreases the absorption of hydroxychloroquine. Separate administration by at least 2 hours

Iron, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The lanthanum carbonate decreases absorption of iron salt. Separate administration by at least 2 hours

Ketoconazole, lanthanum carbonate [2] ---> SmPC of [2] of eMC

The lanthanum carbonate decreases absorption of ketoconazole. Separate administration by at least 2 hours

Lanthanum carbonate [1], levothyroxine ---> SmPC of [1] of eMC

Phosphate binders have been shown to reduce the absorption of levothyroxine. Consequently, thyroid hormone replacement therapy should not be taken within 2 hours of dosing with phosphate binder

Lanthanum carbonate [1], pregnancy ---> SmPC of [1] of eMC

Lanthanum carbonate is not recommended for use during pregnancy.

Lanthanum carbonate [1], quinolones ---> SmPC of [1] of eMC

The co-administration decreases the bioavailability of quinolone. Separate administration by at least 2 hours

Lanthanum carbonate [1], tetracyclines ---> SmPC of [1] of eMC

Interactions with tetracycline and doxycycline are theoretically possible and if these compounds are to be co-administered, it is recommended that they are not to be taken within 2 hours of dosing with lanthanum carbonate

Lanthanum carbonate, lapatinib [2] ---> SmPC of [2] of EMA

Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease

Lanthanum carbonate, rilpivirine [2] ---> SmPC of [2] of EMA

The increase of the gastric pH decreases the absorption, plasma level and therapeutic effect of rilpivirine.

Levothyroxine, phosphate binders ---> SmPC of [lanthanum carbonate] of eMC

Phosphate binders have been shown to reduce the absorption of levothyroxine. Consequently, thyroid hormone replacement therapy should not be taken within 2 hours of dosing with phosphate binder

           CONTRAINDICATIONS of Lanthanum carbonate

           - Hypersensitivity to the active substance or to any of the excipients

           - Hypophosphataemia.

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

Lapatinib (Tyverb)

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

The clinical status of the patient and the adverse event profile of lapatinib should be borne in mind when considering the patient's ability to perform tasks that require judgement, motor or cognitive skills.

Alectinib [1], lapatinib ---> 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.

Alpelisib [1], lapatinib ---> SmPC of [1] of EMA

Caution and monitoring for toxicity are advised during concomitant treatment with inhibitors of BCRP (e.g. eltrombopag, lapatinib, pantoprazole).

Antacids, lapatinib [2] ---> SmPC of [2] of EMA

The solubility of lapatinib is pH-dependent. Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease.

Apalutamide [1], lapatinib ---> SmPC of [1] of EMA

When substrates of P-gp, BCRP or OATP1B1 are co-administered with Erleada, evaluation for loss of efficacy of the substrate should be performed and dose adjustment of the substrate may be required to maintain optimal plasma concentrations.

BCRP inductors, lapatinib [2] ---> SmPC of [2] of EMA

Lapatinib is a substrate for the transport proteins Pgp and BCRP. Inducers of these proteins may alter the exposure and/or distribution of lapatinib

BCRP inhibitors, lapatinib [2] ---> SmPC of [2] of EMA

Lapatinib is a substrate for the transport proteins Pgp and BCRP. Inhibitors of these proteins may alter the exposure and/or distribution of lapatinib

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

Inhibitors (ketoconazole, itraconazole, quinidine, verapamil, cyclosporine, and erythromycin) and inducers (rifampicin and St John's Wort) of these proteins may alter the exposure and/or distribution of lapatinib (see section 5.2).

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

In rats, growth retardation was observed in pups which were exposed to lapatinib via breast milk. Breast-feeding must be discontinued in women who are receiving therapy with Tyverb and for at least 5 days after the last dose.

Capecitabine, lapatinib [2] ---> SmPC of [2] of EMA

Concomitant administration of Tyverb with capecitabine, letrozole or trastuzumab did not meaningfully alter the pharmacokinetics of these medicinal products (or the metabolites of capecitabine) or lapatinib.

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

Chemotherapy, lapatinib [2] ---> SmPC of [2] of EMA

Data have shown that lapatinib combined with chemotherapy is less effective than trastuzumab when combined with chemotherapy. Lapatinib is not indicated in the adjuvant setting.

Cisapride, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of Tyverb with orally administered medicinal products with narrow therapeutic windows that are substrates of CYP3A4 (e.g. cisapride, pimozide and quinidine) should be avoided (see sections 4.4 and 5.2).

Cyclosporine, lapatinib [2] ---> SmPC of [2] of EMA

The CYP3A4 and P-glycoprotein inhibition may increase the systemic exposure of lapatinib. Concomitant use should be avoided

CYP2C8 substrates with narrow therapeutic index, lapatinib [2] ---> SmPC of [2] of EMA

Lapatinib inhibits CYP2C8 in vitro at clinically relevant concentrations. Co-administration of lapatinib with medicinal products with narrow therapeutic windows that are substrates of CYP2C8 should be avoided

CYP3A4 and P-glycoprotein inductors, lapatinib

The CYP3A4 and P-glycoprotein induction may decrease the exposure of lapatinib

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

Digoxin, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of lapatinib with orally administered digoxin resulted in an approximate 80% increase in the AUC of digoxin.

Docetaxel, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of lapatinib with intravenously administered docetaxel did not significantly affect the AUC or Cmax of either active substance. However, the occurrence of docetaxel-induced neutropenia was increased.

Drugs primarily metabolised by CYP2C8, lapatinib

Lapatinib, CYP2C8 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by CYP2C8

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of Tyverb with orally administered medicinal products with narrow therapeutic windows that are substrates of CYP3A4 (e.g. cisapride, pimozide and quinidine) should be avoided (see sections 4.4 and 5.2).

Drugs primarily metabolised by CYP3A4, lapatinib

Lapatinib, CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by CYP3A4

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

Caution is advised when sensitive oral BCRP substrates (e.g. methotrexate, mitoxantrone, topotecan, lapatinib) are co-administered with entrectinib, due to the risk of increased absorption.

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

The CYP3A4 and P-glycoprotein inhibition may increase the systemic exposure of lapatinib. Concomitant use should be avoided

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

Furthermore, depending on type of food the bioavailability is approximately 2-3 times higher when lapatinib is taken 1 hour after food compared with 1 hour before the first meal of the day (see sections 4.2 and 5.2).

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

The bioavailability of lapatinib is increased up to about 4 times by food, depending on e.g. the fat content in the meal.

Gastric pH increasing medication, lapatinib [2] ---> SmPC of [2] of EMA

The solubility of lapatinib is pH-dependent. Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease.

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

Grapefruit juice may inhibit CYP3A4 in the gut wall and increase the bioavailability of lapatinib and should therefore be avoided during treatment with Tyverb.

Grapefruit, lapatinib

The induction of the P-glycoprotein transporter may decrease the exposure and/or distribution of lapatinib.

H2 antagonists, lapatinib [2] ---> SmPC of [2] of EMA

The solubility of lapatinib is pH-dependent. Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease.

Hypokalemia, lapatinib [2] ---> SmPC of [2] of EMA

Caution should be taken if lapatinib is administered to patients with conditions that could result in prolongation of QTc

Hypomagnesemia, lapatinib [2] ---> SmPC of [2] of EMA

Caution should be taken if lapatinib is administered to patients with conditions that could result in prolongation of QTc

Irinotecan, lapatinib [2] ---> SmPC of [2] of EMA

Co-administration of lapatinib with irinotecan (when administered as part of the FOLFIRI regimen) resulted in an approximate 40% increase in the AUC of SN-38, the active metabolite of irinotecan.

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

No CRESEMBA dose adjustment necessary. Daunorubicin, doxorubicin, imatinib, irinotecan, lapatinib, mitoxantrone or topotecan: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Itraconazol, lapatinib [2] ---> SmPC of [2] 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.

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

In healthy volunteers receiving ketoconazole, a strong CYP3A4 inhibitor, at 200 mg twice daily for 7 days, systemic exposure to lapatinib (100 mg daily) was increased approximately 3.6-fold, and half-life increased 1.7-fold.

Lanthanum carbonate, lapatinib [2] ---> SmPC of [2] of EMA

Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease

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

Concomitant administration of Tyverb with capecitabine, letrozole or trastuzumab did not meaningfully alter the pharmacokinetics of these medicinal products (or the metabolites of capecitabine) or lapatinib.

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

Co-administration of Tyverb with orally administered midazolam resulted in an approximate 45% increase in the AUC of midazolam. There was no clinically meaningful increase in AUC when midazolam was dosed intravenously.

Lapatinib [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

Lapatinib is predominantly metabolised by CYP3A. Co-administration of lapatinib with moderate inhibitors of CYP3A4 should proceed with caution and clinical adverse reactions should be carefully monitored.

Lapatinib [1], nefazodone ---> 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.

Lapatinib [1], OATP1B1 substrates ---> SmPC of [1] of EMA

La inhibition of OATP1B1 may increase the plasma levels of OATP1B1 substrates. The co-administration should be undertaken with caution

Lapatinib [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Inhibitors (ketoconazole, itraconazole, quinidine, verapamil, cyclosporine, and erythromycin) and inducers (rifampicin and St John's Wort) of these proteins may alter the exposure and/or distribution of lapatinib (see section 5.2).

Lapatinib [1], P-glycoprotein substrates with small therapeutic index ---> SmPC of [1] of EMA

Caution should be exercised when dosing lapatinib concurrently with medicinal products with narrow therapeutic windows that are substrates of Pgp, and a reduction in the dose of the Pgp substrate should be considered.

Lapatinib [1], P-gp inductors ---> SmPC of [1] of EMA

Lapatinib is a substrate for the transport proteins Pgp and BCRP. Inducers of these proteins may alter the exposure and/or distribution of lapatinib

Lapatinib [1], P-gp inhibitors ---> SmPC of [1] of EMA

Lapatinib is a substrate for the transport proteins Pgp and BCRP. Inhibitors of these proteins may alter the exposure and/or distribution of lapatinib

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

Co-administration of lapatinib with intravenous paclitaxel increased the exposure of paclitaxel by 23%, due to lapatinib inhibition of CYP2C8 and/or Pgp. Caution is advised if lapatinib is co-administered with paclitaxel.

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

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

Co-administration of Tyverb with orally administered medicinal products with narrow therapeutic windows that are substrates of CYP3A4 (e.g. cisapride, pimozide and quinidine) should be avoided (see sections 4.4 and 5.2).

Lapatinib [1], posaconazole ---> 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.

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

There are no adequate data from the use of Tyverb in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is not known. Tyverb should not be used during pregnancy unless clearly necessary.

Lapatinib [1], proton pump inhibitors ---> SmPC of [1] of EMA

The solubility of lapatinib is pH-dependent. Concomitant treatment with substances that increase gastric pH should be avoided, as lapatinib solubility and absorption may decrease.

Lapatinib [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Caution should be taken if lapatinib is administered with other medicines known to cause QT prolongation

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

Co-administration of Tyverb with orally administered medicinal products with narrow therapeutic windows that are substrates of CYP3A4 (e.g. cisapride, pimozide and quinidine) should be avoided (see sections 4.4 and 5.2).

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

Lapatinib inhibits CYP2C8 in vitro at clinically relevant concentrations. Co-administration of lapatinib with medicinal products with narrow therapeutic windows that are substrates of CYP2C8 should be avoided

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

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

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

Lapatinib [1], ritonavir ---> 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.

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.

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

Lapatinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Lapatinib is predominantly metabolised by CYP3A. The CYP3A4 induction decreases the exposition to lapatinib. Co-administration of lapatinib with known inducers of CYP3A4 should be avoided.

Lapatinib [1], strong CYP3A4 inhibitors ---> 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.

Lapatinib [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Lapatinib is a substrate for the transport proteins Pgp and BCRP. Inhibitors of these proteins may alter the exposure and/or distribution of lapatinib

Lapatinib [1], telithromycin ---> 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.

Lapatinib [1], tipranavir ---> 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.

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

It cannot be excluded that lapatinib will affect the pharmacokinetics of substrates of BCRP (e.g. topotecan) and OATP1B1 (e.g. rosuvastatin) (see section 5.2).

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

Concomitant administration of Tyverb with capecitabine, letrozole or trastuzumab did not meaningfully alter the pharmacokinetics of these medicinal products (or the metabolites of capecitabine) or lapatinib.

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

The CYP3A4 and P-glycoprotein inhibition may increase the systemic exposure of lapatinib. Concomitant use should be avoided

Lapatinib [1], voriconazole ---> 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.

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

Women of childbearing potential should be advised to use adequate contraception and avoid becoming pregnant while receiving treatment with Tyverb and for at least 5 days after the last dose.

Lapatinib, lomitapide [2] ---> SmPC of [2] of EMA

Weak CYP3A4 inhibitors are expected to increase the exposure of lomitapide when taken simultaneously. Separate the dose of the medications by 12 hours OR decrease the dose of Lojuxta by half.

Lapatinib, miconazole

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Lapatinib, pazopanib [2] ---> SmPC of [2] of EMA

Co-administration of pazopanib with a CYP3A4, P-gp, and BCRP inhibitor, such as lapatinib, will result in an increase in plasma pazopanib concentrations.

Lapatinib, primidone

The induction of the P-glycoprotein transporter may decrease the exposure and/or distribution of lapatinib.

Lapatinib, rosuvastatin [2] ---> SmPC of [2] of EMA

It cannot be excluded that lapatinib will affect the pharmacokinetics of substrates of BCRP (e.g. topotecan) and OATP1B1 (e.g. rosuvastatin) (see section 5.2).

Lapatinib, sotorasib [2] ---> SmPC of [2] of EMA

When LUMYKRAS is co-administered with a BCRP substrate, monitor for adverse reactions of the BCRP substrate and reduce the BCRP substrate dose in accordance with its current summary of product characteristics.

Lapatinib, talazoparib [2] ---> SmPC of [2] of EMA

Concomitant use of strong P-gp inhibitors should be avoided. If co-administration with a strong P-gp inhibitor is unavoidable, the Talzenna dose should be reduced (see section 4.2).

Lapatinib, 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.

Lapatinib, tolbutamide

Coadministration of lapatinib with orally administered medicines with narrow therapeutic windows that are substrates of CYP2C8 should be avoided

Lapatinib, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Lapatinib, trazodone

The CYP3A4 inhibition may increase the exposition to trazodone

Lapatinib, tretinoin

The CYP2C8 inhibition may increase the exposition to oral tretinoin

Lapatinib, 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.

             CONTRAINDICATIONS of Lapatinib (Tyverb)               

             - 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/tyverb-epar-product-information_en.pdf 17/12/2024      

Laronidase (Aldurazyme)

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

No studies on the effects on the ability to drive and use machines have been performed.

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

Laronidase may be excreted in milk. Because there are no data available in neonates exposed to laronidase via breast milk, it is recommended to stop breast-feeding during Aldurazyme treatment.

Chloroquine, laronidase [2] ---> SmPC of [2] of EMA

Laronidase should not be administered simultaneously with chloroquine due to a potential risk of interference with the intracellular uptake of laronidase

Cytochrome P450, laronidase [2] ---> SmPC of [2] of EMA

No interaction studies have been performed. Based on its metabolism, laronidase is an unlikely candidate for Cytochrome P450 mediated interactions.

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

There are no clinical data on the effects of laronidase on fertility. Preclinical data did not reveal any significant adverse finding (see section 5.3).

Laronidase [1], pregnancy ---> SmPC of [1] of EMA

The potential risk for humans is unknown. Therefore Aldurazyme should not be used during pregnancy unless clearly necessary.

Laronidase [1], procaine ---> SmPC of [1] of EMA

Laronidase should not be administered simultaneously with procaine due to a potential risk of interference with the intracellular uptake of laronidase

             CONTRAINDICATIONS of Laronidase (Aldurazyme)

             - Severe hypersensitivity (e.g. anaphylactic reaction) to the active substance or to any of the excipients listed in section 6          

             https://www.ema.europa.eu/en/documents/product-information/aldurazyme-epar-product-information_en.pdf 28/02/2024      

Laropiprant/nicotinic acid

Ability to drive, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Dizziness has been reported

Acetylsalicylic acid, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

In a clinical study, concomitant administration of laropiprant with acetylsalicylic acid did not have an effect on collagen-induced platelet aggregation or on bleeding time compared to treatment with acetylsalicylic acid alone

Alcohol, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Drinking alcohol or hot drinks or eating spicy foods can enhance the effects of flushing and should therefore be avoided around the time of ingestion of Pelzont.

Antihypertensives, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive medicinal products such as nitrates, calcium channel blockers, and adrenergic receptor blocking agents, resulting in postural hypotension.

Bile-acid sequestrants, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Because co-administration of bile acid sequestrants may reduce the bioavailability of acidic medicinal products, it is recommended that Pelzont be administered > 1 hour before or > 4 hours after administration of a bile acid sequestrant.

Breast-feeding, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy

Calcium antagonists, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive medicinal products such as nitrates, calcium channel blockers, and adrenergic receptor blocking agents, resulting in postural hypotension.

Clarithromycin, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Clarithromycin (a potent inhibitor of CYP3A4 and P-gp) did not have a clinically meaningful effect on the pharmacokinetics of laropiprant. Laropiprant is not a substrate of human P-gp

Clopidogrel, laropiprant/nicotinic acid

In a clinical study in dyslipidaemic patients receiving both acetylsalicylic acid and clopidogrel, laropiprant induced transient (4 hours post-dose) inhibition of platelet function in vivo (as evaluated by bleeding time and platelet aggregation studies)

Clopidogrel, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

In a clinical study, there was no meaningful effect of laropiprant on the inhibition of ADP-induced platelet aggregation by clopidogrel, but there was a modest increase in the inhibition of collagen-induced platelet aggregation by clopidogrel.

Drugs primarily metabolised by UGT2B7, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

Laropiprant is a mild to moderate inhibitor of UGT2B4/UGT2B7. Caution should be used when Pelzont is co-administered with medicinal products metabolised predominantly by UGT2B4 or UGT2B7, for instance zidovudine.

Foods, laropiprant/nicotinic acid [2] ---> SmPC of [2] of EMA

The tablets should be taken whole, with food, in the evening or at bedtime.

Laropiprant/nicotinic acid [1], midazolam ---> SmPC of [1] of EMA

Multiple doses of laropiprant 40 mg did not affect the pharmacokinetics of midazolam, a sensitive CYP3A4 substrate. Therefore, laropiprant is not an inducer or inhibitor of CYP3A4.

Laropiprant/nicotinic acid [1], midazolam ---> SmPC of [1] of EMA

The plasma concentration of a metabolite of midazolam, 1'-hydroxymidazolam, was increased approximately 2-fold with multiple doses of laropiprant.

Laropiprant/nicotinic acid [1], organic nitrates ---> SmPC of [1] of EMA

Nicotinic acid may potentiate the effects of ganglionic blocking agents and vasoactive medicinal products such as nitrates, calcium channel blockers, and adrenergic receptor blocking agents, resulting in postural hypotension.

Laropiprant/nicotinic acid [1], pharmacokinetics ---> SmPC of [1] of EMA

In interaction studies, laropiprant did not have clinically significant effects on the pharmacokinetics of the following medicinal products: simvastatin, warfarin, oral contraceptives, rosiglitazone and digoxin.

Laropiprant/nicotinic acid [1], pregnancy ---> SmPC of [1] of EMA

Pelzont should not be used during pregnancy unless clearly necessary.

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.

Laropiprant/nicotinic acid [1], zidovudine ---> SmPC of [1] of EMA

Laropiprant is a mild to moderate inhibitor of UGT2B4/UGT2B7. Caution should be used when Pelzont is co-administered with medicinal products metabolised predominantly by UGT2B4 or UGT2B7, for instance zidovudine.

           CONTRAINDICATIONS of Laropiprant/nicotinic acid

           - Hypersensitivity to the active substances or to any of the excipients

           - Significant or unexplained hepatic dysfunction.

           - Active peptic ulcer disease.

           - Arterial bleeding.

           http://www.ema.europa.eu/

Larotrectinib (Vitrakvi)

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

Dizziness and fatigue have been reported in patients receiving larotrectinib, mostly Grade 1 and 2 during the first 3 months of treatment. This may influence the ability to drive and use machines during this time period.

Alfentanyl, larotrectinib [2] ---> SmPC of [2] 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.

Atazanavir, larotrectinib [2] ---> SmPC of [2] 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).

BCRP inhibitors, larotrectinib [2] ---> SmPC of [2] 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).

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

Breast-feeding should be discontinued during treatment with VITRAKVI and for 3 days following the final dose.

Bupropion, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib induces CYP2B6. Co-administration of larotrectinib with CYP2B6 substrates (e.g. bupropion, efavirenz) may decrease their exposure.

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

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

Clarithromycin, larotrectinib [2] ---> SmPC of [2] 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).

Cyclosporine, larotrectinib [2] ---> SmPC of [2] 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.

Dihydroergotamine, larotrectinib [2] ---> SmPC of [2] 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.

Drugs primarily metabolised by CYP2B6, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib induces CYP2B6. Co-administration of larotrectinib with CYP2B6 substrates (e.g. bupropion, efavirenz) may decrease their exposure.

Drugs primarily metabolised by CYP2C19, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Drugs primarily metabolised by CYP2C8, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Drugs primarily metabolised by CYP2C9, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, larotrectinib [2] ---> SmPC of [2] 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.

Efavirenz, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib induces CYP2B6. Co-administration of larotrectinib with CYP2B6 substrates (e.g. bupropion, efavirenz) may decrease their exposure.

Ergotamine, larotrectinib [2] ---> SmPC of [2] 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.

Fentanyl, larotrectinib [2] ---> SmPC of [2] 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.

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

There are no clinical data on the effect of larotrectinib on fertility. No relevant effects on fertility were observed in repeat-dose toxicity studies (see section 5.3).

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

The capsules can be taken with or without food but should not be taken with grapefruit or grapefruit juice.

Grapefruit, larotrectinib [2] ---> SmPC of [2] 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).

Hormonal contraceptives, larotrectinib [2] ---> SmPC of [2] of EMA

It is currently unknown whether larotrectinib may reduce the effectiveness of systemically acting hormonal contraceptives. Therefore, women using systemically acting hormonal contraceptives should be advised to add a barrier method.

Indinavir, larotrectinib [2] ---> SmPC of [2] 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).

Induce PXR regulated enzymes, larotrectinib [2] ---> SmPC of [2] of EMA

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Itraconazol, larotrectinib [2] ---> SmPC of [2] 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).

Ketoconazole, larotrectinib [2] ---> SmPC of [2] 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).

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

Males of reproductive potential with a non-pregnant woman partner of childbearing potential should be advised to use highly effective contraception during treatment with VITRAKVI and for at least one month after the final dose.

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

The co-administration of VITRAKVI (100 mg twice daily for 10 days) increased the Cmax and AUC of oral midazolam 1.7-fold compared to midazolam alone, suggesting that larotrectinib is a weak inhibitor of CYP3A.

Larotrectinib [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

No clinical data is available on the effect of a moderate inducer, but a decrease in larotrectinib exposure is expected.

Larotrectinib [1], moderate CYP3A4 inhibitors ---> 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).

Larotrectinib [1], moderate P-gp inductors ---> SmPC of [1] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

Larotrectinib [1], nefazodone ---> 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).

Larotrectinib [1], nelfinavir ---> 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).

Larotrectinib [1], OATP1B1 substrates ---> SmPC of [1] of EMA

In vitro studies indicate that larotrectinib is an inhibitor of OATP1B1. Therefore, it cannot be excluded whether co-administration of larotrectinib with OATP1B1 substrates (e.g. valsartan, statins) may increase their exposure.

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

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Larotrectinib [1], P-gp inhibitors ---> 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).

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

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

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

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

Larotrectinib [1], pimozide ---> 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.

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

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

Larotrectinib [1], quinidine ---> 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.

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

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

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

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

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

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

Larotrectinib [1], ritonavir ---> 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).

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).

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.

Larotrectinib [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

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

In vitro studies indicate that larotrectinib is an inhibitor of OATP1B1. Therefore, it cannot be excluded whether co-administration of larotrectinib with OATP1B1 substrates (e.g. valsartan, statins) may increase their exposure.

Larotrectinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

Larotrectinib [1], strong CYP3A4 inhibitors ---> 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).

Larotrectinib [1], strong P-gp inductors ---> SmPC of [1] of EMA

Co-administration of VITRAKVI with strong or moderate CYP3A and P-gp inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's Wort) may decrease larotrectinib plasma concentrations and should be avoided

Larotrectinib [1], tacrolimus ---> 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.

Larotrectinib [1], telithromycin ---> 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).

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

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

Larotrectinib [1], troleandomycin ---> 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).

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

In vitro studies indicate that larotrectinib is an inhibitor of OATP1B1. Therefore, it cannot be excluded whether co-administration of larotrectinib with OATP1B1 substrates (e.g. valsartan, statins) may increase their exposure.

Larotrectinib [1], voriconazole ---> 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).

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

In vitro studies indicate that larotrectinib may induce PXR regulated enzymes (e.g. CYP2C family and UGT). Co-administration of larotrectinib with CYP2C8, CYP2C9 or CYP2C19 substrates may decrease their exposure.

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

Women of reproductive potential should be advised to use highly effective contraception during treatment with VITRAKVI and for at least one month after the final dose.

             CONTRAINDICATIONS of Larotrectinib (Vitrakvi)          

             - 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/vitrakvi-epar-product-information_en.pdf  04/08/2025 

Lasmiditan (Rayvow)

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

Administration of single 50 mg, 100 mg, or 200 mg doses of lasmiditan significantly impaired subjects' ability to drive 90 minutes after dosing.

Alcohol, lasmiditan [2] ---> SmPC of [2] of EMA

Because of the potential of lasmiditan to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, lasmiditan should be used with caution if used in combination with alcohol or other CNS depressants.

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

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from RAYVOW therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

CNS depressants, lasmiditan [2] ---> SmPC of [2] of EMA

Because of the potential of lasmiditan to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, lasmiditan should be used with caution if used in combination with alcohol or other CNS depressants.

Cytochrome P450, lasmiditan [2] ---> SmPC of [2] of EMA

Based on its metabolism clearance pathways, CYP inhibitors or inducers are unlikely to affect lasmiditan exposure

Dabigatran, lasmiditan [2] ---> SmPC of [2] of EMA

In a drug interaction study, lasmiditan increased the systemic exposure of coadministered dabigatran (P-gp substrate) by approximately 25%.

Digoxin, lasmiditan [2] ---> SmPC of [2] of EMA

Therefore, when RAYVOW is administered with P-gp substrates that have a narrow therapeutic index (such as digoxin), increases in the systemic exposure of the coadministered medication may be clinically meaningful (see section 5.2).

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

It is unknown whether lasmiditan affects human reproductive potential. Animal studies do not indicate any effect on fertility (see section 5.3).

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

Concomitant administration of lasmiditan and medicinal products (e.g., SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome.

Lasmiditan [1], midazolam ---> SmPC of [1] of EMA

Daily dosing of lasmiditan did not alter the PK of midazolam, caffeine, or tolbutamide, which are substrates of CYP3A, CYP1A2, and CYP2C9, respectively.

Lasmiditan [1], P-glycoprotein substrates with small therapeutic index ---> SmPC of [1] of EMA

Therefore, when RAYVOW is administered with P-gp substrates that have a narrow therapeutic index (such as digoxin), increases in the systemic exposure of the coadministered medication may be clinically meaningful (see section 5.2).

Lasmiditan [1], pregnancy ---> SmPC of [1] of EMA

The effects of lasmiditan on human foetal development are not known. RAYVOW is not recommended during pregnancy.

Lasmiditan [1], propranolol ---> SmPC of [1] of EMA

Propranolol and lasmiditan together decreased HR by a mean maximum of 19.3 beats per minute (bpm), i.e., an additional lowering of 5.1 bpm compared to propranolol alone.

Lasmiditan [1], rosuvastatin ---> SmPC of [1] of EMA

In the same study, no significant change in rosuvastatin (BCRP substrate) PK was observed when it was coadministered with lasmiditan.

Lasmiditan [1], serotonergic medicines ---> SmPC of [1] of EMA

Concomitant administration of lasmiditan and medicinal products (e.g., SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome.

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

Concomitant administration of lasmiditan and medicinal products (e.g., SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome.

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

Concomitant administration of lasmiditan and medicinal products (e.g., SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome.

Lasmiditan [1], sumatriptan ---> SmPC of [1] of EMA

Coadministration of lasmiditan with sumatriptan (MAO-A and OCT1 substrate) or propranolol (CYP2D6 substrate) resulted in no clinically meaningful changes in exposure of these medicinal products.

Lasmiditan [1], topiramate ---> SmPC of [1] of EMA

No change in lasmiditan PK was observed when coadministered with topiramate (CYP3A4 inducer and CYP2C19 inhibitor).

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

Concomitant administration of lasmiditan and medicinal products (e.g., SSRIs, SNRIs, TCAs) that increase serotonin may increase the risk of serotonin syndrome.

Lasmiditan [1], triptans ---> SmPC of [1] of EMA

Clinical experience for the use of lasmiditan and triptans in temporal proximity is limited.

             CONTRAINDICATIONS of Lasmiditan (Rayvow)                          

             - 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/rayvow-epar-product-information_en.pdf 21/10/2025 

 Latanoprost (Catiolanze)

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

In common with other eye preparations, instillation of Catiolanze may cause transient blurring of vision. Until this has resolved, patients should not drive or use machines.

Acetazolamide, latanoprost [2] ---> SmPC of [2] of EMA

The effect of latanoprost is additive in combination with adrenergic agonists studies (dipivalyl epinephrine), oral carbonic anhydrase inhibitors (acetazolamide) and at least partly c additive with cholinergic agonists (pilocarpine).

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

Latanoprost and its metabolites may pass into breast milk. Catiolanze should therefore not be used breast-feeding women or breast feeding should be stopped.

Carbonic anhydrase inhibitors, latanoprost [2] ---> SmPC of [2] of EMA

The effect of latanoprost is additive in combination with adrenergic agonists studies (dipivalyl epinephrine), oral carbonic anhydrase inhibitors (acetazolamide) and at least partly c additive with cholinergic agonists (pilocarpine).

Dipivefrine, latanoprost [2] ---> SmPC of [2] of EMA

The effect of latanoprost is additive in combination with adrenergic agonists studies (dipivalyl epinephrine), oral carbonic anhydrase inhibitors (acetazolamide) and at least partly c additive with cholinergic agonists (pilocarpine).

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

Latanoprost has not been found to have any effect on male or female f fertility in animal studies (see fertility section 5.3).

Latanoprost [1], pilocarpine ---> SmPC of [1] of EMA

The effect of latanoprost is additive in combination with adrenergic agonists studies (dipivalyl epinephrine), oral carbonic anhydrase inhibitors (acetazolamide) and at least partly c additive with cholinergic agonists (pilocarpine).

Latanoprost [1], pregnancy ---> SmPC of [1] of EMA

It has potential hazardous pharmacological effects with respect to the course of pregnancy, to the unborn or the neonate. Therefore, Catiolanze should not be used during pregnancy.

Latanoprost [1], prostaglandin analogues ---> SmPC of [1] of EMA

There have been reports of paradoxical elevations in intraocular pressure following the concomitant ophthalmic administration of two prostaglandin analogues. Therefore, the concomitant use is not recommended.

Latanoprost [1], prostaglandins ---> SmPC of [1] of EMA

There have been reports of paradoxical elevations in intraocular pressure following the concomitant ophthalmic administration of two prostaglandin analogues. Therefore, the concomitant use is not recommended.

Latanoprost [1], timolol ---> SmPC of [1] of EMA

Latanoprost is effective in combination with beta-adrenergic antagonists (timolol).

Latanoprost, parasympathomimetics

Enhancement of hypotensive effect of latanoprost on intraocular pressure

             CONTRAINDICATIONS of Latanoprost (Catiolanze)      

             - Hypersensitivity to the Latanoprost or to any of the excipients

             https://www.ema.europa.eu/en/documents/product-information/catiolanze-epar-product-information_en.pdf 13/02/2024

Other trade names: Arulatan, Latanoprost Aurovitas, Latanoprost (Actavis), Monoprost, Tonlit, Xalatan,

Latanoprost/netarsudil (Roclanda)

Ability to drive, latanoprost/netarsudil [2] ---> SmPC of [2] of EMA

If transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machines.

Breast-feeding, latanoprost/netarsudil [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Roclanda therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Latanoprost/netarsudil [1], pregnancy ---> SmPC of [1] of EMA

Latanoprost has potentially harmful pharmacological effects during pregnancy and/or on the fetus/newborn child (see section 5.3). Therefore, latanoprost + netarsudil should not be used during pregnancy.

Latanoprost/netarsudil [1], prostaglandin analogues ---> SmPC of [1] of EMA

There have been reports of paradoxical elevations in IOP following the ophthalmic coadministration of 2 prostaglandin analogues. Therefore, the use of two or more prostaglandins, prostaglandin analogues or prostaglandin derivatives is not recommended.

Latanoprost/netarsudil [1], thimerosal ---> SmPC of [1] of EMA

In vitro interaction studies have shown that precipitation can occur when eye drops containing thimerosal are mixed with latanoprost + netarsudil. Administer other eye drops at least five minutes apart

           CONTRAINDICATIONS of Latanoprost/netarsudil (Roclanda)

           - 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/roclanda-epar-product-information_en.pdf 22/05/2024

Latanoprost/timolol

Ability to drive, latanoprost/timolol [2] ---> SmPC of [2] of eMC

Instillation of eye drops may cause transient blurring of vision.

Amiodarone, latanoprost/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with antiarrhythmics (including amiodarone)

Antiadrenergics, latanoprost/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with beta-blocking agents

Antiarrhythmics, latanoprost/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with antiarrhythmics (including amiodarone)

Antidiabetics, betablockers ---> SmPC of [latanoprost/timolol] of eMC

Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents. Beta-blockers can mask the signs and symptoms of hypoglycaemia

Antidiabetics, latanoprost/timolol [2] ---> SmPC of [2] of eMC

Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents. Beta-blockers can mask the signs and symptoms of hypoglycaemia

Betablockers, latanoprost/timolol [2] ---> SmPC of [2] of eMC

The effect on intraocular pressure or the known effects of systemic beta-blockade may be potentiated when latanoprost/timolol is given to patients already receiving an oral beta-blocking agent

Breast-feeding, latanoprost/timolol [2] ---> SmPC of [2] of eMC

Latanoprost/Timolol should not be used in women who are breast-feeding.

Calcium antagonists, latanoprost/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium channel blockers

Clonidine, latanoprost/timolol [2] ---> SmPC of [2] of eMC

The hypertensive reaction to sudden withdrawal of clonidine can be potentiated when taking beta-blockers.

Digital glycosides, latanoprost/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with digitalis glycosides

Epinephrine, latanoprost/timolol [2] ---> SmPC of [2] of eMC

Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally.

Fluoxetine, latanoprost/timolol [2] ---> SmPC of [2] of eMC

Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.

Guanethidine, latanoprost/timolol [2] ---> SmPC of [2] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with guanethidine

Latanoprost/timolol [1], parasympathomimetics ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with parasympathomimetics

Latanoprost/timolol [1], paroxetine ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.

Latanoprost/timolol [1], pregnancy ---> SmPC of [1] of eMC

Latanoprost/Timolol should not be used during pregnancy

Latanoprost/timolol [1], prostaglandin analogues ---> SmPC of [1] of eMC

There have been reports of paradoxical elevations in intraocular pressure following ophthalmic coadministration of 2 prostaglandin analogues. The use of 2 or more prostaglandins, prostaglandin analogues, or prostaglandin derivatives is not recommended.

Latanoprost/timolol [1], prostaglandins ---> SmPC of [1] of eMC

There have been reports of paradoxical elevations in intraocular pressure following ophthalmic coadministration of 2 prostaglandin analogues. The use of 2 or more prostaglandins, prostaglandin analogues, or prostaglandin derivatives is not recommended.

Latanoprost/timolol [1], quinidine ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.

Latanoprost/timolol [1], strong CYP2D6 inhibitors ---> SmPC of [1] of eMC

Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, fluoxetine, paroxetine) and timolol.

           CONTRAINDICATIONS of Latanoprost/timolol

           Latanoprost/Timolol is contraindicated in patients with:

           - Reactive airway disease including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease.

           - Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker, overt cardiac failure, cardiogenic shock.

           - Hypersensitivity to the active substances or to any of the excipients

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

Lazertinib (Lazcluze)

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

If patients experience treatment-related symptoms (such as fatigue) affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.

BCRP substrates with narrow therapeutic range, lazertinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are BCRP substrates (e.g., sunitinib) should be used with caution, as lazertinib may increase the plasma concentrations of these medicinal products.

Bosentan, lazertinib [2] ---> SmPC of [2] of EMA

The co-administration of Lazcluze with moderate CYP3A4 inducers may also decrease lazertinib plasma concentrations and hence moderate CYP3A4 inducers (e.g. bosentan, efavirenz, modafinil) should be used with caution.

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

Because the risk to the breast-feeding child cannot be excluded, female patients should be advised not to breast-feed during treatment and for 3 weeks after the last dose of lazertinib.

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

The co-administration of Lazcluze with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided.

Cyclosporine, lazertinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

CYP1A2 substrates, lazertinib [2] ---> SmPC of [2] of EMA

Induction of CYP1A2 cannot be excluded. Therefore, caution is advised when co-administering with substrates of CYP1A2 (e.g., tizanidine).

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

No initial dose adjustment is required when Lazcluze is co-administered with CYP3A4 inhibitors.

CYP3A4 substrates with narrow therapeutic index, lazertinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

Efavirenz, lazertinib [2] ---> SmPC of [2] of EMA

The co-administration of Lazcluze with moderate CYP3A4 inducers may also decrease lazertinib plasma concentrations and hence moderate CYP3A4 inducers (e.g. bosentan, efavirenz, modafinil) should be used with caution.

Everolimus, lazertinib [2] ---> SmPC of [2] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

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

Studies in animals have shown that lazertinib has effects on reproductive organs in females (decreased numbers of oestrus cycles and corpora lutea) and males (degenerative changes in the testis) and may impair female and male fertility

Gastric pH increasing medication, lazertinib [2] ---> SmPC of [2] of EMA

No dose adjustments are required when Lazcluze is used with gastric acid reducing agents.

H2 antagonists, lazertinib [2] ---> SmPC of [2] of EMA

No clinically relevant differences in lazertinib pharmacokinetics were observed when co-administered with gastric acid reducing agents (proton pump inhibitors and H2-receptor antagonists).

Itraconazol [1], lazertinib ---> SmPC of [1] of EMA

The co-administration of multiple doses of itraconazole (strong CYP3A4 inhibitor) increased lazertinib Cmax by 1.19-fold and AUC by 1.46-fold in healthy subjects.

Lazertinib [1], men ---> SmPC of [1] of EMA

Male patients with female partners of reproductive potential should be advised to use effective contraception (e.g., condom) and not donate or store semen during treatment and for 3 weeks after the last dose of lazertinib.

Lazertinib [1], midazolam ---> SmPC of [1] of EMA

The co-administration of multiple doses of 160 mg Lazcluze once daily increased midazolam (CYP3A4 substrate) Cmax by 1.39-fold and AUC by 1.47-fold.

Lazertinib [1], modafinil ---> SmPC of [1] of EMA

The co-administration of Lazcluze with moderate CYP3A4 inducers may also decrease lazertinib plasma concentrations and hence moderate CYP3A4 inducers (e.g. bosentan, efavirenz, modafinil) should be used with caution.

Lazertinib [1], moderate CYP3A4 inhibitors ---> SmPC of [1] of EMA

The co-administration of Lazcluze with moderate CYP3A4 inducers may also decrease lazertinib plasma concentrations and hence moderate CYP3A4 inducers (e.g. bosentan, efavirenz, modafinil) should be used with caution.

Lazertinib [1], phenytoin ---> SmPC of [1] of EMA

The co-administration of Lazcluze with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided.

Lazertinib [1], pimozide ---> SmPC of [1] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

Lazertinib [1], pregnancy ---> SmPC of [1] of EMA

Lazertinib should not be used during pregnancy unless the benefit of treatment of the woman is considered to outweigh potential risks to the foetus.

Lazertinib [1], pregnancy ---> SmPC of [1] of EMA

If the patient becomes pregnant while taking this medicinal product the patient should be informed of the potential risk to the foetus.

Lazertinib [1], proton pump inhibitors ---> SmPC of [1] of EMA

No clinically relevant differences in lazertinib pharmacokinetics were observed when co-administered with gastric acid reducing agents (proton pump inhibitors and H2-receptor antagonists).

Lazertinib [1], quinidine ---> SmPC of [1] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

Lazertinib [1], rifampicin ---> SmPC of [1] of EMA

The co-administration of Lazcluze with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided.

Lazertinib [1], rosuvastatin ---> SmPC of [1] of EMA

The co-administration of multiple doses of 160 mg Lazcluze once daily increased rosuvastatin (BCRP substrate) Cmax by 2.24-fold and AUC by 2.02-fold.

Lazertinib [1], sirolimus ---> SmPC of [1] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

Lazertinib [1], St. John's wort ---> SmPC of [1] of EMA

The co-administration of Lazcluze with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided.

Lazertinib [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

The co-administration of Lazcluze with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) should be avoided.

Lazertinib [1], sunitinib ---> SmPC of [1] of EMA

Narrow therapeutic index medicinal products that are BCRP substrates (e.g., sunitinib) should be used with caution, as lazertinib may increase the plasma concentrations of these medicinal products.

Lazertinib [1], tacrolimus ---> SmPC of [1] of EMA

Narrow therapeutic index medicinal products that are CYP3A4 substrates (e.g., cyclosporine, everolimus, pimozide, quinidine, sirolimus, tacrolimus) should be used with caution, as lazertinib may increase the plasma levels of these medicinal products.

Lazertinib [1], tizanidine ---> SmPC of [1] of EMA

Induction of CYP1A2 cannot be excluded. Therefore, caution is advised when co-administering with substrates of CYP1A2 (e.g., tizanidine).

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

Women of childbearing potential should be advised to use effective contraception during treatment and up to 3 weeks after treatment.

            CONTRAINDICATIONS of Lazertinib (Lazcluze)   

            - 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/lazcluze-epar-product-information_en.pdf 31/10/2025 

Lebrikizumab (Ebglyss)

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

A decision must be made whether to discontinue breast-feeding or to discontinue from lebrikizumab therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

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

Animal studies showed no impairment of fertility (see section 5.3).

Inactivated vaccines, lebrikizumab [2] ---> SmPC of [2] of EMA

Patients receiving lebrikizumab may receive concurrent inactivated or non-live vaccinations.

Lebrikizumab [1], pharmacokinetics ---> SmPC of [1] of EMA

Given that lebrikizumab is a monoclonal antibody, no pharmacokinetic interactions are expected.

Lebrikizumab [1], pregnancy ---> SmPC of [1] of EMA

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

Lebrikizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

The safety and efficacy of concurrent use of lebrikizumab with live and live attenuated vaccines has not been studied. Live and live attenuated vaccines should not be given concurrently with lebrikizumab.

             CONTRAINDICATIONS of Lebrikizumab (Ebglyss)          

             - 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/ebglyss-epar-product-information_en.pdf  10/04/2025 

Lecanemab (Leqembi)

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

Patients should be advised to use caution when driving or operating machinery in case they experience dizziness or confusion during treatment with lecanemab.

Bleeding risk, lecanemab [2] ---> SmPC of [2] of EMA

The risk of intracerebral haemorrhage with lecanemab treatment may be increased in patients receiving anticoagulant therapy or thrombolytic agents (see sections 4.3 and 4.4).

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

Therefore, a decision should be made whether to discontinue breastfeeding or to discontinue lecanemab, taking into account the benefit of breast-feeding for the child and the benefit of lecanemab therapy for the woman.

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

There are no data on the effects of lecanemab on human fertility.

Lecanemab [1], pharmacokinetics ---> SmPC of [1] of EMA

Therefore, it is not expected that lecanemab will cause or be susceptible to pharmacokinetic (PK) drug interactions with concomitantly administered agents.

Lecanemab [1], pregnancy ---> SmPC of [1] of EMA

The effects of lecanemab on the developing foetus are unknown. Lecanemab is not recommended during pregnancy.

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

Pregnancy status of females of child-bearing potential should be verified prior to initiating treatment with lecanemab.

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

Women of childbearing potential should use effective contraception during treatment and for 2 months after the last dose of lecanemab.

            CONTRAINDICATIONS of Lecanemab (Leqembi)  

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

            - Patients with bleeding disorders that are not under adequate control.     

            - Pre-treatment MRI findings of prior intracerebral haemorrhage, more than 4 microhaemorrhages, superficial siderosis or vasogenic oedema, or other findings, which are suggestive of cerebral amyloid angiopathy (CAA) (see section 4.4).          

            - Treatment with lecanemab should not be initiated in patients receiving ongoing anticoagulant therapy (see section 4.4).  

            https://www.ema.europa.eu/en/documents/product-information/leqembi-epar-product-information_en.pdf 05/05/2025

Ledipasvir/sofosbuvir (Harvoni)

Abacavir/lamivudine, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment is required

Ability to drive, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Patients should be advised that fatigue was more common in patients treated with ledipasvir/sofosbuvir compared to placebo.

Aluminium hydroxide, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Ledipasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir. It is recommended to separate the administration by 4 hours.

Amiodarone, ledipasvir/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.

Antacids, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Ledipasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir. It is recommended to separate the administration by 4 hours.

Atazanavir/ritonavir + emtricitabine/tenofovir, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

When given with tenofovir disoproxil fumarate used in conjunction with atazanavir/ritonavir, Harvoni increased the concentration of tenofovir.

Atazanavir/ritonavir, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Harvoni or atazanavir (ritonavir boosted) is required.

BCRP inhibitors, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that inhibit P-gp and/or BCRP may increase ledipasvir and sofosbuvir plasma concentrations without increasing GS-331007 plasma concentration; Harvoni may be co-administered with P-gp and/or BCRP inhibitors

BCRP substrates, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Ledipasvir is an in vitro inhibitor of breast cancer resistance protein (BCRP) and may increase intestinal absorption of co-administered substrates for these transporters.

Bictegravir/emtricitabine/tenofovir alafenamide [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required upon co-administration.

Breast-feeding, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Therefore, Harvoni should not be used during breast-feeding.

Calcium carbonate, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Ledipasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir. It is recommended to separate the administration by 4 hours.

Carbamazepine, ledipasvir/sofosbuvir [2] ---> SmPC of [2] 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

Cimetidine, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

H2-receptor antagonists may be administered simultaneously with or staggered from ledipasvir/sofosbuvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily

Contraceptives, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of oral contraceptives is required.

Cyclosporine, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Harvoni or ciclosporin is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of ciclosporin may be required.

CYP450 substrates, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Clinically significant medicinal product interactions with ledipasvir/sofosbuvir mediated by CYP450s or UGT1A1 enzymes are not expected.

Dabigatran etexilate, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Clinical monitoring, looking for signs of bleeding and anaemia is recommended when dabigatran etexilate is co-administered with ledipasvir/sofosbuvir (inhibition of P-glycoprotein)

Darunavir/ritonavir + emtricitabine/tenofovir, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

When given with darunavir/ritonavir used in conjunction with tenofovir disoproxil fumarate, Harvoni increased the concentration of tenofovir.

Darunavir/ritonavir, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dose adjustment of Harvoni or darunavir (ritonavir boosted) is required.

Digoxin, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Co-administration of ledipasvir/sofosbuvir (inhibition of P-gp) with digoxin may increase the concentration of digoxin.

Dolutegravir, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Dolutegravir/lamivudine [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is necessary.

Dolutegravir/rilpivirine [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

Patients receiving doravirine/lamivudine/tenofovir disoproxil concomitantly with ledipasvir/sofosbuvir should be monitored for adverse reactions associated with tenofovir disoproxil.

Drugs metabolised by UGT1A1, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

In vitro data indicate that ledipasvir may be a weak inducer of UGT1A1. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with ledipasvir/sofosbuvir.

Drugs primarily metabolised by CYP2C19, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

In vitro data indicate that ledipasvir may be a weak inducer of CYP2C. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with ledipasvir/sofosbuvir.

Drugs primarily metabolised by CYP2C9, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

In vitro data indicate that ledipasvir may be a weak inducer of CYP2C. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with ledipasvir/sofosbuvir.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of

In vitro ledipasvir inhibits intestinal CYP3A4 and UGT1A1. Medicinal products that have a narrow therapeutic range and which are metabolised by these isoenzymes should be used with caution and carefully monitored.

Drugs primarily metabolised by CYP3A4, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

In vitro data indicate that ledipasvir may be a weak inducer of CYP3A4. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with ledipasvir/sofosbuvir.

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

No dose adjustment of ledipasvir/sofosbuvir and Genvoya is warranted upon co-administration.

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

When given with elvitegravir/ cobicistat/ emtricitabine/ tenofovir disoproxil fumarate, Harvoni is expected to increase the concentration of tenofovir.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment is recommended. The increased exposure of tenofovir could potentiate adverse reactions associated with tenofovir disoproxil fumarate, including renal disorders. Renal function should be closely monitored

Emtricitabine/tenofovir alafenamide [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

No dose adjustment of ledipasvir or sofosbuvir is required. Dose Descovy according to the concomitant antiretroviral

Emtricitabine/tenofovir disoproxil [1], ledipasvir/sofosbuvir ---> SmPC of [1] of EMA

Co-administration of tenofovir disoproxil fumarate with ledipasvir/sofosbuvir has been shown to increase plasma concentrations of tenofovir

Esomeprazole, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Ethinylestradiol/norgestimate, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No dosage adjustment necessary.

Famotidine, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

H2-receptor antagonists may be administered simultaneously with or staggered from ledipasvir/sofosbuvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily

Fertility, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

No human data on the effect of Harvoni on fertility are available. Animal studies do not indicate harmful effects of ledipasvir or sofosbuvir on fertility.

Gastric pH increasing medication, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Ledipasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir.

H2 antagonists, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

H2-receptor antagonists may be administered simultaneously with or staggered from ledipasvir/sofosbuvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily

Hepatic metabolism, ledipasvir/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.

Lansoprazole, ledipasvir/sofosbuvir [2] ---> SmPC of [2] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Ledipasvir/sofosbuvir [1], lopinavir/ritonavir + emtricitabine/tenofovir ---> SmPC of [1] of EMA

When given with lopinavir/ritonavir used in conjunction with tenofovir disoproxil fumarate, Harvoni is expected to increase the concentration of tenofovir.

Ledipasvir/sofosbuvir [1], magnesium hydroxide ---> SmPC of [1] of EMA

Ledipasvir solubility decreases as pH increases. Medicinal products that increase gastric pH are expected to decrease concentration of ledipasvir. It is recommended to separate the administration by 4 hours.

Ledipasvir/sofosbuvir [1], methadone ---> SmPC of [1] of EMA

No dose adjustment of Harvoni or methadone is required.

Ledipasvir/sofosbuvir [1], midazolam ---> SmPC of [1] of EMA

No dose adjustment of Harvoni or midazolam is required.

Ledipasvir/sofosbuvir [1], moderate P-gp inductors ---> SmPC of [1] of EMA

Medicinal products that are moderate P-gp inducers in the intestine may decrease ledipasvir/sofosbuvir plasma concentrations leading to reduced therapeutic effect of Harvoni. Co-administration with such medicinal products is not recommended with Harvoni

Ledipasvir/sofosbuvir [1], nizatidine ---> SmPC of [1] of EMA

H2-receptor antagonists may be administered simultaneously with or staggered from ledipasvir/sofosbuvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily

Ledipasvir/sofosbuvir [1], omeprazole ---> SmPC of [1] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Ledipasvir/sofosbuvir [1], oxcarbazepine ---> SmPC of [1] of EMA

Medicinal products that are moderate P-gp inducers in the intestine may decrease ledipasvir/sofosbuvir plasma concentrations leading to reduced therapeutic effect of Harvoni. Co-administration with such medicinal products is not recommended with Harvoni

Ledipasvir/sofosbuvir [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Ledipasvir is an in vitro inhibitor of drug transporter P-gp and may increase intestinal absorption of co-administered substrates for these transporters.

Ledipasvir/sofosbuvir [1], pantoprazole ---> SmPC of [1] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Ledipasvir/sofosbuvir [1], phenobarbital ---> 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

Ledipasvir/sofosbuvir [1], phenytoin ---> 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

Ledipasvir/sofosbuvir [1], pravastatine ---> SmPC of [1] of EMA

Co-administration may significantly increase the concentration of pravastatine which is associated with increased risk of myopathy. Clinical and biochemical control is recommended

Ledipasvir/sofosbuvir [1], pregnancy ---> SmPC of [1] of EMA

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

Ledipasvir/sofosbuvir [1], proton pump inhibitors ---> SmPC of [1] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Ledipasvir/sofosbuvir [1], rabeprazole ---> SmPC of [1] of EMA

Proton pump inhibitor doses comparable to omeprazole 20 mg can be administered simultaneously with ledipasvir/sofosbuvir. Proton pump inhibitors should not be taken before ledipasvir/sofosbuvir.

Ledipasvir/sofosbuvir [1], raltegravir ---> SmPC of [1] of EMA

No dose adjustment of Harvoni or raltegravir is required.

Ledipasvir/sofosbuvir [1], ranitidine ---> SmPC of [1] of EMA

H2-receptor antagonists may be administered simultaneously with or staggered from ledipasvir/sofosbuvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily

Ledipasvir/sofosbuvir [1], rifabutin ---> 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

Ledipasvir/sofosbuvir [1], rifampicin ---> 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

Ledipasvir/sofosbuvir [1], rifapentine ---> SmPC of [1] of EMA

Co-administration of ledipasvir/sofosbuvir with rifapentine (P-gp induction) is expected to decrease the concentration of ledipasvir and sofosbuvir, leading to reduced therapeutic effect. Co-administration is not recommended.

Ledipasvir/sofosbuvir [1], rosuvastatin ---> SmPC of [1] of EMA

Co-administration of Harvoni with rosuvastatin may significantly increase the concentration of rosuvastatin which is associated with increased risk of myopathy, including rhabdomyolysis. Co-administration of Harvoni with rosuvastatin is contraindicated

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.

Ledipasvir/sofosbuvir [1], sofosbuvir ---> SmPC of [1] of EMA

Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir.

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

Ledipasvir/sofosbuvir [1], statins ---> SmPC of [1] of EMA

Interactions cannot be excluded with other HMG-CoA reductase inhibitors. When co-administered with Harvoni, a reduced dose of statins should be considered and careful monitoring for statin adverse reactions should be undertaken (see section 4.4).

Ledipasvir/sofosbuvir [1], strong P-gp inductors ---> 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

Ledipasvir/sofosbuvir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Co-administration with medicinal products that inhibit P-gp and/or BCRP may increase ledipasvir and sofosbuvir plasma concentrations without increasing GS-331007 plasma concentration; Harvoni may be co-administered with P-gp and/or BCRP inhibitors

Ledipasvir/sofosbuvir [1], tacrolimus ---> SmPC of [1] of EMA

No dose adjustment of Harvoni or tacrolimus is required at initiation of co-administration. Afterwards, close monitoring and potential dose adjustment of tacrolimus may be required.

Ledipasvir/sofosbuvir [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

Co-administration of Harvoni with tipranavir (ritonavir boosted) is expected to decrease the concentration of ledipasvir, leading to reduced therapeutic effect of Harvoni. Co-administration is not recommended.

Ledipasvir/sofosbuvir [1], UGT1A1 substrates ---> SmPC of [1] of EMA

Clinically significant medicinal product interactions with ledipasvir/sofosbuvir mediated by CYP450s or UGT1A1 enzymes are not expected.

Ledipasvir/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 Harvoni.

Ledipasvir/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.

Ledipasvir/sofosbuvir, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or ledipasvir/sofosbuvir is required.

Ledipasvir/sofosbuvir, tenofovir disoproxil [2] ---> SmPC of [2] of EMA

Co-administration of tenofovir disoproxil fumarate with ledipasvir/sofosbuvir has been shown to increase plasma concentrations of tenofovir, especially when used together with an HIV

             CONTRAINDICATIONS of Ledipasvir/sofosbuvir (Harvoni)        

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

             - Co-administration with rosuvastatin

             Use with potent P-gp inducers

             - Medicinal products that are strong P-glycoprotein (P-gp) inducers in the intestine (carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin and St. John's wort). Co-administration will significantly decrease ledipasvir and sofosbuvir plasma concentrations and could result in loss of efficacy of Harvoni (see section 4.5).

             https://www.ema.europa.eu/en/documents/product-information/harvoni-epar-product-information_en.pdf. 27/09/2023

Lefamulin (Xenleta)

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

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Alprazolam, lefamulin [2] ---> SmPC of [2] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Atorvastatin, lefamulin [2] ---> SmPC of [2] of EMA

Inhibition of CYP3A, BCRP, OATP1. Use with caution.

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

Caution is recommended when co-administering lefamulin with sensitive substrates of the transporters OATP1B1, OATP1B3, BCRP, OCT1 and MATE1, especially for those substrates with a narrow therapeutic window.

Bosentan, lefamulin [2] ---> SmPC of [2] of EMA

Medicinal products that are moderate/strong CYP3A inducers could significantly decrease lefamulin plasma concentration and may lead to reduced therapeutic effect of lefamulin. Co-administration of such medicinal products with lefamulin is contraindicated

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

A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Xenleta.

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

Medicinal products that are moderate/strong CYP3A inducers could significantly decrease lefamulin plasma concentration and may lead to reduced therapeutic effect of lefamulin. Co-administration of such medicinal products with lefamulin is contraindicated

Clarithromycin, lefamulin [2] ---> SmPC of [2] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Darunavir, lefamulin [2] ---> SmPC of [2] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Digoxin, lefamulin [2] ---> SmPC of [2] of EMA

In a clinical drug-drug interaction study, no clinically relevant interaction was observed when lefamulin was co-administered with the P-gp substrate digoxin.

Diltiazem, lefamulin [2] ---> SmPC of [2] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Drugs primarily metabolised by CYP2C8, lefamulin [2] ---> SmPC of [2] of EMA

Co-administration of lefamulin with agents metabolised by CYP2C8 (e.g. repaglinide) may result in increased plasma concentrations of these medicinal products. Co-administration with sensitive substrates of CYP2C8 is contraindicated

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

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Efavirenz, lefamulin [2] ---> SmPC of [2] of EMA

Moderate induction of CYP3A4. Co-administration of moderate CYP3A inducers may result in reduced therapeutic effect of lefamulin and is contraindicated

Ethinyl estradiol, lefamulin [2] ---> SmPC of [2] of EMA

Inhibition of CYP3A4. Use with caution.

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

The effects of lefamulin on fertility in humans have not been studied. Lefamulin caused no impairment of fertility or reproductive performance in rats (see section 5.3).

Fluconazole, lefamulin [2] ---> SmPC of [2] of EMA

Moderate inhibition of CYP3A. Co-administration of medicinal products known to prolong QT interval is contraindicated

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

Mild inhibition of CYP3A. No dose adjustment required.

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

Xenleta should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal. This is because food and some drinks can affect the way medicines work.

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

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Grapefruit, lefamulin [2] ---> SmPC of [2] of EMA

You must not eat grapefruit or drink grapefruit juice while on treatment with Xenleta as it might interact with Xenleta and increase side effects.

Ibrutinib, lefamulin [2] ---> SmPC of [2] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

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

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

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

Strong inhibition of CYP3A4. Co-administration with strong CYP3A inhibitors like ketoconazole may lead to increased exposures of lefamulin and is contraindicated

Lefamulin [1], lovastatine ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lefamulin [1], lovastatine ---> SmPC of [1] of EMA

Inhibition of CYP3A, BCRP, OATP1. Use with caution.

Lefamulin [1], metformin ---> SmPC of [1] of EMA

Inhibition of MATE, OCT1, OCT2. Caution is recommended. Co- administration with lefamulin may lead to higher exposures of metformin.

Lefamulin [1], midazolam ---> SmPC of [1] of EMA

Inhibition of CYP3A4. Caution is recommended. When co-administered with oral lefamulin. Consider dosage adjustment of midazolam.

Lefamulin [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Medicinal products that are moderate/strong CYP3A inducers could significantly decrease lefamulin plasma concentration and may lead to reduced therapeutic effect of lefamulin. Co-administration of such medicinal products with lefamulin is contraindicated

Lefamulin [1], nefazodone ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lefamulin [1], omeprazole ---> SmPC of [1] of EMA

No dose adjustment required.

Lefamulin [1], phenytoin ---> SmPC of [1] of EMA

Medicinal products that are moderate/strong CYP3A inducers could significantly decrease lefamulin plasma concentration and may lead to reduced therapeutic effect of lefamulin. Co-administration of such medicinal products with lefamulin is contraindicated

Lefamulin [1], posaconazole ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lefamulin [1], pravastatine ---> SmPC of [1] of EMA

Inhibition of CYP3A, BCRP, OATP1. Use with caution.

Lefamulin [1], pregnancy ---> SmPC of [1] of EMA

Xenleta is not recommended during pregnancy.

Lefamulin [1], primidone ---> SmPC of [1] of EMA

Medicinal products that are moderate/strong CYP3A inducers could significantly decrease lefamulin plasma concentration and may lead to reduced therapeutic effect of lefamulin. Co-administration of such medicinal products with lefamulin is contraindicated

Lefamulin [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Co-administration of lefamulin with other medicinal products known to prolong the QT interval is contraindicated

Lefamulin [1], repaglinide ---> SmPC of [1] of EMA

Inhibition of CYP3A4, CYP2C8. Co-administration with lefamulin may lead to higher exposures of repaglinide and is contraindicated

Lefamulin [1], rifampicin ---> SmPC of [1] of EMA

Strong induction of CYP3A. Co-administration of strong CYP3A inducers may result in reduced therapeutic effect of lefamulin and is contraindicated

Lefamulin [1], ritonavir ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lefamulin [1], rosuvastatin ---> SmPC of [1] of EMA

Inhibition of CYP3A, BCRP, OATP1. Use with caution.

Lefamulin [1], simvastatine ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lefamulin [1], St. John's wort ---> SmPC of [1] of EMA

Strong induction of CYP3A4. Co-administration of strong CYP3A inducers may result in reduced therapeutic effect of lefamulin and is contraindicated

Lefamulin [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Medicinal products that are moderate/strong CYP3A inducers could significantly decrease lefamulin plasma concentration and may lead to reduced therapeutic effect of lefamulin. Co-administration of such medicinal products with lefamulin is contraindicated

Lefamulin [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lefamulin [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lefamulin [1], tipranavir ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lefamulin [1], triazolam ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lefamulin [1], vardenafil ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lefamulin [1], verapamil ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lefamulin [1], voriconazole ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

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

Women of childbearing potential should use effective contraception during treatment with Xenleta. Women taking oral contraceptives should use an additional barrier method of contraception.

Lefamulin [1], zolpidem ---> SmPC of [1] of EMA

Inhibition of CYP3A4. Monitor for adverse reactions during coadministration with lefamulin. Consider dosage adjustment of zolpidem.

            CONTRAINDICATIONS of Lefamulin (Xenleta)    

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

            - Hypersensitivity to any other members of the pleuromutilin class.         

            - Coadministration with moderate or strong inducers of CYP3A (e.g. efavirenz, phenytoin, rifampicin) or with strong inhibitors of CYP3A (e.g. clarithromycin, itraconazole, ritonavir) (see section 4.5).    

            - Coadministration with CYP3A substrates (e.g. antipsychotics, erythromycin, tricyclic antidepressants) that prolong the QT interval (see section 4.5).     

            - Coadministration with medicinal products that prolong the QT interval such as Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medicinal products (see section 4.5).    

            - Known QT prolongation.         

            - Electrolyte disturbances, particularly uncorrected hypokalemia.            

            - Clinically relevant bradycardia, unstable congestive heart failure, or history of symptomatic ventricular arrhythmias.             

            - Coadministration with sensitive CYP2C8 substrates (e.g. repaglinide) (see section 4.5).

            https://www.ema.europa.eu/en/documents/product-information/xenleta-epar-product-information_en.pdf 29/04/2025 

Leflunomide (Arava)

Abatacept [1], leflunomide ---> SmPC of [1] of EMA

No major safety issues were identified with use of abatacept in combination with sulfasalazine, hydroxychloroquine, or leflunomide.

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

In the case of side effects such as dizziness the patient's ability to concentrate and to react properly may be impaired. In such cases patients should refrain from driving cars and using machines.

Activated charcoal, leflunomide [2] ---> SmPC of [2] of EMA

It is recommended that patients receiving leflunomide are not treated with colestyramine or activated powdered charcoal because this leads to a rapid and significant decrease in plasma A771726 (the active metabolite of leflunomide)

Activated powdered charcoal, leflunomide [2] ---> SmPC of [2] of EMA

It is recommended that patients receiving leflunomide are not treated with colestyramine or activated powdered charcoal because this leads to a rapid and significant decrease in plasma A771726 (the active metabolite of leflunomide)

Alcohol, leflunomide [2] ---> SmPC of [2] of EMA

Due to a potential for additive hepatotoxic effects, it is recommended that alcohol consumption be avoided during treatment with leflunomide.

Alosetron, leflunomide [2] ---> SmPC of [2] of EMA

Medicinal products metabolised by CYP1A2 (such as duloxetine, alosetron, theophylline and tizanidine) should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

Atorvastatin, leflunomide [2] ---> SmPC of [2] 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

BCRP substrates, leflunomide [2] ---> SmPC of [2] 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

Benzylpenicillin, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

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

Animal studies indicate that leflunomide or its metabolites pass into breast milk. Breast-feeding women must, therefore, not receive leflunomide.

Caffeine, leflunomide [2] ---> SmPC of [2] of EMA

Effect on caffeine (CYP1A2 substrate) Repeated doses of A771726 decreased mean Cmax and AUC of caffeine (CYP1A2 substrate) by 18% and 55%, respectively, suggesting that A771726 may be a weak inducer of CYP1A2 in vivo.

Cefaclor, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Cholestyramine, leflunomide [2] ---> SmPC of [2] of EMA

It is recommended that patients receiving leflunomide are not treated with colestyramine or activated powdered charcoal because this leads to a rapid and significant decrease in plasma A771726 (the active metabolite of leflunomide)

Cimetidine, leflunomide [2] ---> SmPC of [2] of EMA

An in vivo interaction study with leflunomide and cimetidine (non-specific weak cytochrome P450 (CYP) inhibitor) has demonstrated a lack of a significant impact on A771726 exposure.

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

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Corticosteroids, leflunomide [2] ---> SmPC of [2] of EMA

If the patient is already receiving nonsteroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, these may be continued after starting leflunomide.

Coumarin anticoagulants, leflunomide [2] ---> SmPC of [2] of EMA

There have been case reports of increased prothrombin time, when leflunomide and warfarin were co-administered. Therefore, when warfarin or another coumarin anticoagulant is co-administered, close INR follow-up and monitoring is recommended.

Daunorubicin, leflunomide [2] ---> SmPC of [2] 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

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

A771726 displaced diclofenac from its plasma protein binding, but the unbound fraction is only increased by 10% to 50%. There is no indication that these effects are of clinical relevance.

Disease modifying anti-rheumatic drug, leflunomide [2] ---> SmPC of [2] of EMA

Since such therapy can lead to additive or even synergistic toxicity (e.g. hepato- or haematotoxicity), combination with another DMARD (e.g. methotrexate) is not advisable.

Doxorubicine, leflunomide [2] ---> SmPC of [2] 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

Drugs primarily metabolised by CYP1A2, leflunomide [2] ---> SmPC of [2] of EMA

Medicinal products metabolised by CYP1A2 (such as duloxetine, alosetron, theophylline and tizanidine) should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

Drugs primarily metabolised by CYP2C8, leflunomide [2] ---> SmPC of [2] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Drugs with high protein binding, leflunomide [2] ---> SmPC of [2] of EMA

The active metabolite (A771726) of leflunomide may displace other principle actives from its plasma protein binding

Duloxetine, leflunomide [2] ---> SmPC of [2] of EMA

Medicinal products metabolised by CYP1A2 (such as duloxetine, alosetron, theophylline and tizanidine) should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

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

Results of animal fertility studies have shown no effect on male and female fertility, but adverse effects on male reproductive organs were observed in repeated dose toxicity studies (see section 5.3).

Furosemide, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Hematotoxic drugs, leflunomide [2] ---> SmPC of [2] of EMA

Increased side effects may occur in case of recent or concomitant use of hepatotoxic or haematotoxic drugs or when leflunomide treatment is followed by such drugs without a washout period

Hepatotoxic drugs, leflunomide [2] ---> SmPC of [2] of EMA

Increased side effects may occur in case of recent or concomitant use of hepatotoxic or haematotoxic drugs or when leflunomide treatment is followed by such drugs without a washout period

Ibuprofen, leflunomide [2] ---> SmPC of [2] of EMA

A771726 displaced ibuprofen from its plasma protein binding, but the unbound fraction is only increased by 10% to 50%. There is no indication that these effects are of clinical relevance.

Indometacin, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Ketoprofen, leflunomide [2] ---> SmPC of [2] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Leflunomide [1], methotrexate ---> SmPC of [1] of EMA

In patients with rheumatoid arthritis, no pharmacokinetic interaction between the leflunomide (10 to 20 mg per day) and methotrexate (10 to 25 mg per week) was demonstrated.

Leflunomide [1], nateglinide ---> 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

Leflunomide [1], NSAID ---> SmPC of [1] of EMA

If the patient is already receiving nonsteroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, these may be continued after starting leflunomide.

Leflunomide [1], OAT3 substrates ---> SmPC of [1] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Leflunomide [1], OATP substrates ---> 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

Leflunomide [1], oral contraceptives ---> SmPC of [1] of EMA

As similar drug-drug interactions cannot be excluded for leflunomide at recommended doses, the following study results and recommendations should be considered in patients treated with leflunomide:

Leflunomide [1], paclitaxel ---> SmPC of [1] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Leflunomide [1], peripheral neuropathy ---> SmPC of [1] of EMA

Cases of peripheral neuropathy have been reported in patients receiving leflunomide. Most patients improved after discontinuation of leflunomide.

Leflunomide [1], pioglitazone ---> SmPC of [1] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Leflunomide [1], pravastatine ---> 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

Leflunomide [1], pregnancy ---> SmPC of [1] of EMA

The active metabolite of leflunomide, A771726 is suspected to cause serious birth defects when administered during pregnancy. Leflunomide Zentiva is contraindicated in pregnancy

Leflunomide [1], repaglinide ---> SmPC of [1] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Leflunomide [1], rifampicin ---> SmPC of [1] of EMA

A771726 peak levels were increased by approximately 40%, whereas the AUC was not significantly changed. The mechanism of this effect is unclear.

Leflunomide [1], rosiglitazone ---> SmPC of [1] of EMA

Monitoring patients with concomitant use of medicinal products metabolised by CYP2C8, such as repaglinide, paclitaxel, pioglitazone or rosiglitazone, is recommended as they may have higher exposure.

Leflunomide [1], rosuvastatin ---> SmPC of [1] of EMA

There was an increase in mean rosuvastatin Cmax and AUC (2.65-and 2.51-fold, respectively), following repeated doses of A771726. If used together, the dose of rosuvastatin should not exceed 10 mg once daily.

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

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

Leflunomide [1], theophylline ---> SmPC of [1] of EMA

Medicinal products metabolised by CYP1A2 (such as duloxetine, alosetron, theophylline and tizanidine) should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

Leflunomide [1], tizanidine ---> SmPC of [1] of EMA

Medicinal products metabolised by CYP1A2 (such as duloxetine, alosetron, theophylline and tizanidine) should be used with caution during treatment, as it could lead to the reduction of the efficacy of these products.

Leflunomide [1], tolbutamide ---> SmPC of [1] of EMA

A771726 displaced tolbutamide from its plasma protein binding, but the unbound fraction is only increased by 10% to 50%. There is no indication that these effects are of clinical relevance.

Leflunomide [1], topotecan ---> 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

Leflunomide [1], vaccinations ---> SmPC of [1] of EMA

No clinical data are available on the efficacy and safety of vaccinations under leflunomide treatment.

Leflunomide [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Vaccination with live attenuated vaccines is, however, not recommended. The long half-life of leflunomide should be considered when contemplating administration of a live attenuated vaccine after stopping Leflunomide Zentiva.

Leflunomide [1], waiting period ---> SmPC of [1] of EMA

A771726 plasma levels can be expected to be above 0.02 mg/L for a prolonged period. The concentration may be expected to decrease below 0.02 mg/L about 2 years after stopping the treatment with leflunomide.

Leflunomide [1], warfarin ---> SmPC of [1] of EMA

There have been case reports of increased prothrombin time, when leflunomide and warfarin were co-administered. Therefore, when warfarin or another coumarin anticoagulant is co-administered, close INR follow-up and monitoring is recommended.

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

Women of childbearing potential have to use effective contraception during and up to 2 years after treatment (see "waiting period" below) or up to 11 days after treatment (see abbreviated "washout period" below).

Leflunomide [1], zidovudine ---> SmPC of [1] of EMA

A771726 is an inhibitor of OAT3 in vivo .Therefore, when co-administered leflunomide with substrates of OAT3 caution is recommended.

Leflunomide, methotrexate [2] ---> SmPC of [2] of EMA

In patients with rheumatoid arthritis, no pharmacokinetic interaction between the leflunomide (10 to 20 mg per day) and methotrexate (10 to 25 mg per week) was demonstrated.

Leflunomide, teriflunomide [2] ---> SmPC of [2] of EMA

As leflunomide is the parent compound of teriflunomide, co-administration of teriflunomide with leflunomide is not recommended.

             CONTRAINDICATIONS of Leflunomide (Arava)

             - Hypersensitivity (especially previous Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) to the active substance, to the principal active metabolite teriflunomide or to any of the excipients listed in section 6.1.

             - Patients with impairment of liver function.

             - Patients with severe immunodeficiency states, e.g. AIDS.

             - Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia due to causes other than rheumatoid or psoriatic arthritis.

             - Patients with serious infections

             - Patients with moderate to severe renal insufficiency, because insufficient clinical experience is available in this patient group.

             - Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.

             - Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with leflunomide and thereafter as long as the plasma levels of the active metabolite are above 0.02 mg/l. Pregnancy must be excluded before start of treatment with leflunomide.

             - Breast-feeding women

             https://www.ema.europa.eu/en/documents/product-information/arava-epar-product-information_en.pdf 17/10/2025    

Other trade names: Afludol, Lefluartil, Leflunomide medac, Leflunomide ratiopharm, Leflunomide Teva, Leflunomide Zentiva (previously Leflunomide Winthrop), Nilocur, Repso,

Lenacapavir (Sunlenca)

Antiandrogens, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. No dose adjustment of these gender affirming hormones is required.

Antiepileptics, lenacapavir [2] ---> SmPC of [2] of EMA

Alternative anticonvulsants others than carbamazepine, oxcarbazepine, phenobarbital, or phenytoin should be considered

Atazanavir/cobicistat, lenacapavir [2] ---> SmPC of [2] of EMA

Strong inhibitors of CYP3A, P-gp and UGT1A1 together (i.e., all 3 pathways), such as atazanavir/cobicistat, may significantly increase plasma concentrations of lenacapavir, therefore co-administration is not recommended

Atorvastatin, lenacapavir [2] ---> SmPC of [2] of EMA

No dose adjustment of atorvastatin is required.

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

In order to avoid transmission of HIV to the infant it is recommended that HIV-infected women do not breast-feed their infants.

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

Co-administration of carbamazepine or phenytoin with lenacapavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is contraindicated

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

Strong inhibitors of CYP3A4 and P-gp together (e.g. cobicistat) do not result in a clinically meaningful increase in lenacapavir exposures.

Corticosteroids primarily metabolised by CYP3A, lenacapavir [2] ---> SmPC of [2] of EMA

Co-administration of Sunlenca with corticosteroids whose exposures are significantly increased by CYP3A inhibitors can increase the risk for Cushing's syndrome and adrenal suppression.

Corticosteroids, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of corticosteroids may be increased when co-administered with lenacapavir.

Cortisone, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of corticosteroids may be increased when co-administered with lenacapavir.

CYP3A4 substrates with narrow therapeutic index, lenacapavir [2] ---> SmPC of [2] of EMA

Lenacapavir is a moderate inhibitor of CYP3A. Caution is advised if Sunlenca is co-administered with a sensitive CYP3A substrate with a narrow therapeutic index

Dabigatran, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentration of DOAC may be increased when co-administered with lenacapavir. Due to potential bleeding risk, dose adjustment of DOAC may be required.

Darunavir/cobicistat, lenacapavir [2] ---> SmPC of [2] of EMA

No dose adjustment of lenacapavir is required.

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

Plasma concentrations of corticosteroids may be increased when co-administered with lenacapavir.

Digoxin, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentration of digoxin may be increased when co-administered with lenacapavir. Caution is warranted and therapeutic concentration monitoring of digoxin is recommended.

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

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. Caution is warranted when dihydroergotamine or ergotamine, is co-administered with Sunlenca.

Direct thrombin inhibitors, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentration of DOAC may be increased when co-administered with lenacapavir. Due to potential bleeding risk, dose adjustment of DOAC may be required.

Edoxaban [1], lenacapavir ---> SmPC of [1] of EMA

Plasma concentration of DOAC may be increased when co-administered with lenacapavir. Due to potential bleeding risk, dose adjustment of DOAC may be required.

Efavirenz, lenacapavir [2] ---> SmPC of [2] of EMA

Moderate inducers of CYP3A and P-gp, such as efavirenz, may also significantly decrease plasma concentrations of lenacapavir, therefore co-administration is not recommended

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

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. Caution is warranted when dihydroergotamine or ergotamine, is co-administered with Sunlenca.

Estradiol, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. No dose adjustment of these gender affirming hormones is required.

Ethinyl estradiol, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of ethinylestradiol and progestins may be increased when co-administered with lenacapavir. No dose adjustment of ethinylestradiol and progestins is required.

Etravirine, lenacapavir [2] ---> SmPC of [2] of EMA

Co-administration of etravirine, nevirapine, or tipranavir/ritonavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is not recommended

Famotidine, lenacapavir [2] ---> SmPC of [2] of EMA

No dose adjustment of famotidine is required.

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

Animal studies indicate no effects on lenacapavir on male or female fertility

HMG-CoA reductase inhibitors, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir.

Hydrocortisone, lenacapavir [2] ---> SmPC of [2] of EMA

Plasma concentrations of corticosteroids may be increased when co-administered with lenacapavir.

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

Plasma concentration of lenacapavir may be increased when co-administered with itraconazole or ketoconazole.

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

Plasma concentration of lenacapavir may be increased when co-administered with itraconazole or ketoconazole.

Lenacapavir [1], lovastatine ---> SmPC of [1] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. Initiate lovastatin and simvastatin with the lowest starting dose and titrate carefully while monitoring for safety (e.g. myopathy).

Lenacapavir [1], midazolam ---> SmPC of [1] of EMA

Caution is warranted when midazolam or triazolam, is co-administered with Sunlenca.

Lenacapavir [1], moderate CYP3A4 inductors ---> SmPC of [1] of EMA

Moderate inducers of CYP3A and P-gp, such as efavirenz, may also significantly decrease plasma concentrations of lenacapavir, therefore co-administration is not recommended

Lenacapavir [1], moderate P-gp inductors ---> SmPC of [1] of EMA

Moderate inducers of CYP3A and P-gp, such as efavirenz, may also significantly decrease plasma concentrations of lenacapavir, therefore co-administration is not recommended

Lenacapavir [1], nevirapine ---> SmPC of [1] of EMA

Co-administration of etravirine, nevirapine, or tipranavir/ritonavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is not recommended

Lenacapavir [1], oxcarbazepine ---> SmPC of [1] of EMA

Co-administration of oxcarbazepine or phenobarbital with lenacapavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is not recommended

Lenacapavir [1], PDE5 inhibitors ---> SmPC of [1] of EMA

Plasma concentration of PDE-5 inhibitors may be increased when co-administered with lenacapavir.

Lenacapavir [1], phenobarbital ---> SmPC of [1] of EMA

Co-administration of oxcarbazepine or phenobarbital with lenacapavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is not recommended

Lenacapavir [1], phenytoin ---> SmPC of [1] of EMA

Co-administration of carbamazepine or phenytoin with lenacapavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is contraindicated

Lenacapavir [1], pitavastatin ---> SmPC of [1] of EMA

No dose adjustment of pitavastatin is required.

Lenacapavir [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of Sunlenca during pregnancy unless the clinical condition of the women requires treatment with Sunlenca.

Lenacapavir [1], progestagens ---> SmPC of [1] of EMA

Plasma concentrations of ethinylestradiol and progestins may be increased when co-administered with lenacapavir. No dose adjustment of ethinylestradiol and progestins is required.

Lenacapavir [1], progestagens ---> SmPC of [1] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. No dose adjustment of these gender affirming hormones is required.

Lenacapavir [1], rifabutin ---> SmPC of [1] of EMA

Co-administration of rifabutin may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is not recommended

Lenacapavir [1], rifampicin ---> SmPC of [1] of EMA

Strong inducers of CYP3A, P-gp, and UGT1A1, such as rifampicin, may significantly decrease plasma concentrations of lenacapavir resulting in loss of therapeutic effect and development of resistance, therefore co-administration is contraindicated

Lenacapavir [1], ritonavir ---> SmPC of [1] of EMA

No dose adjustment of lenacapavir is required.

Lenacapavir [1], rivaroxaban ---> SmPC of [1] of EMA

Plasma concentration of DOAC may be increased when co-administered with lenacapavir. Due to potential bleeding risk, dose adjustment of DOAC may be required.

Lenacapavir [1], rosuvastatin ---> SmPC of [1] of EMA

No dose adjustment of rosuvastatin is required.

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.

Lenacapavir [1], simvastatine ---> SmPC of [1] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. Initiate lovastatin and simvastatin with the lowest starting dose and titrate carefully while monitoring for safety (e.g. myopathy).

Lenacapavir [1], St. John's wort ---> SmPC of [1] of EMA

Co-administration of St. John's wort may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is contraindicated

Lenacapavir [1], strong CYP3A4 and P-glycoprotein-inhibitors ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 and P-gp together (e.g. cobicistat) do not result in a clinically meaningful increase in lenacapavir exposures.

Lenacapavir [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Strong inducers of CYP3A, P-gp, and UGT1A1, such as rifampicin, may significantly decrease plasma concentrations of lenacapavir resulting in loss of therapeutic effect and development of resistance, therefore co-administration is contraindicated

Lenacapavir [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Strong CYP3A4 inhibitors alone (e.g. voriconazole) or strong inhibitors of CYP3A4 and P-gp together (e.g. cobicistat) do not result in a clinically meaningful increase in lenacapavir exposures.

Lenacapavir [1], strong CYP3A4, P-glycoprotein, and UGT1A1-inhibitors ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A, P-gp and UGT1A1 together (i.e., all 3 pathways), such as atazanavir/cobicistat, may significantly increase plasma concentrations of lenacapavir, therefore co-administration is not recommended

Lenacapavir [1], strong P-gp inductors ---> SmPC of [1] of EMA

Strong inducers of CYP3A, P-gp, and UGT1A1, such as rifampicin, may significantly decrease plasma concentrations of lenacapavir resulting in loss of therapeutic effect and development of resistance, therefore co-administration is contraindicated

Lenacapavir [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

Strong CYP3A4 inhibitors alone (e.g. voriconazole) or strong inhibitors of CYP3A4 and P-gp together (e.g. cobicistat) do not result in a clinically meaningful increase in lenacapavir exposures.

Lenacapavir [1], strong UGT1A1 inductors ---> SmPC of [1] of EMA

Strong inducers of CYP3A, P-gp, and UGT1A1, such as rifampicin, may significantly decrease plasma concentrations of lenacapavir resulting in loss of therapeutic effect and development of resistance, therefore co-administration is contraindicated

Lenacapavir [1], strong UGT1A1 inhibitors ---> SmPC of [1] of EMA

Strong CYP3A4 inhibitors alone (e.g. voriconazole) or strong inhibitors of CYP3A4 and P-gp together (e.g. cobicistat) do not result in a clinically meaningful increase in lenacapavir exposures.

Lenacapavir [1], tadalafil ---> SmPC of [1] of EMA

Use of PDE-5 inhibitors for pulmonary arterial hypertension: Co-administration with tadalafil is not recommended. Erectile dysfunction: For use as needed: no more than 10 mg every 72 hours. For once daily use: dose not to exceed 2.5 mg

Lenacapavir [1], tenofovir alafenamide ---> SmPC of [1] of EMA

No dose adjustment of tenofovir alafenamide is required.

Lenacapavir [1], testosterone ---> SmPC of [1] of EMA

Plasma concentrations of these medicinal products may be increased when co-administered with lenacapavir. No dose adjustment of these gender affirming hormones is required.

Lenacapavir [1], tipranavir/ritonavir ---> SmPC of [1] of EMA

Co-administration of etravirine, nevirapine, or tipranavir/ritonavir may decrease lenacapavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance. Co-administration is not recommended

Lenacapavir [1], triazolam ---> SmPC of [1] of EMA

Plasma concentration of triazolam may be increased when co-administered with lenacapavir.

Lenacapavir [1], vardenafil ---> SmPC of [1] of EMA

Use of PDE-5 inhibitors for erectile dysfunction: Vardenafil: No more than 5 mg in a 24-hour period.

Lenacapavir [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment of lenacapavir is required.

             CONTRAINDICATIONS of Lenacapavir (Sunlenca)

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

             - Co-administration with strong inducers of CYP3A, P-gp, and UGT1A1, such as:

               antimycobacterials: rifampicin

               anticonvulsants: carbamazepine, phenytoin

               herbal products: St. John's wort (Hypericum perforatum) (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/sunlenca-epar-product-information_en.pdf  26/02/2026 

Lenalidomide (Revlimid)

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

Fatigue, dizziness, somnolence, vertigo and blurred vision have been reported with the use of lenalidomide. Therefore, caution is recommended when driving or operating machines.

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

It is not known whether lenalidomide is excreted in human milk. Therefore breast-feeding should be discontinued during therapy with lenalidomide.

Coumarin anticoagulants, lenalidomide

A treatment with coumarins is not recommended due to the hight risk of thrombocytopenia

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

Co-administration of single or multiple doses of dexamethasone (40 mg once daily) has no clinically relevant effect on the multiple dose pharmacokinetics of lenalidomide (25 mg once daily).

Digoxin, lenalidomide [2] ---> SmPC of [2] of EMA

The monitoring of the digoxin concentration is advised

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

A fertility study in rats with lenalidomide doses up to 500 mg/kg (approximately 200 to 500 times the human doses of 25 mg and 10 mg, respectively, based on body surface area) produced no adverse effects on fertility and no parental toxicity.

Hormone replacement therapy, lenalidomide [2] ---> SmPC of [2] of EMA

Erythropoietic agents, or other agents that may increase the risk of thrombosis, such as hormone replacement therapy, should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone

Lenalidomide [1], men ---> SmPC of [1] of EMA

If pregnancy occurs in a partner of a male patient taking lenalidomide, it is recommended to refer the female partner to a physician specialised or experienced in teratology for evaluation and advice.

Lenalidomide [1], men ---> SmPC of [1] of EMA

As a precaution and taking into account special populations with prolonged elimination time such as renal impairment, all male patients taking lenalidomide should use condoms throughout treatment duration, during dose interruption and for 1 week after

Lenalidomide [1], oral contraceptives ---> SmPC of [1] of EMA

It may not be excluded that the efficacy of oral contraceptives may be reduced during treatment. Effective measures to avoid pregnancy must be taken

Lenalidomide [1], pregnancy ---> SmPC of [1] of EMA

Lenalidomide induced malformation in monkeys similar to those described with thalidomide (see section 5.3). Therefore, a teratogenic effect of lenalidomide is expected and lenalidomide is contraindicated during pregnancy (see section 4.3).

Lenalidomide [1], quinidine ---> SmPC of [1] of EMA

In vitro, lenalidomide is a substrate of P-gp. Co-administration of multiple doses of the strong P-gp inhibitor quinidine or the moderate P-gp inhibitor/substrate temsirolimus has no clinically relevant effect on the pharmacokinetics of lenalidomide

Lenalidomide [1], statins ---> SmPC of [1] of EMA

There is an increased risk of rhabdomyolysis when statins are administered with lenalidomide, which may be simply additive. Enhanced clinical and laboratory monitoring is warranted notably during the first weeks of treatment.

Lenalidomide [1], strong P-gp inhibitors ---> SmPC of [1] of EMA

In vitro, lenalidomide is a substrate of P-gp. Co-administration of multiple doses of the strong P-gp inhibitor quinidine or the moderate P-gp inhibitor/substrate temsirolimus has no clinically relevant effect on the pharmacokinetics of lenalidomide

Lenalidomide [1], warfarin ---> SmPC of [1] of EMA

Close monitoring of warfarin concentration is advised during the treatment.

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

Women of childbearing potential should use effective method of contraception. If pregnancy occurs in a woman treated with lenalidomide, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology

Lenalidomide, temsirolimus [2] ---> SmPC of [2] of EMA

When temsirolimus is co-administered with medicinal products which are P-gp substrates close monitoring for adverse events related to the co-administered medicinal products should be observed.

            CONTRAINDICATIONS of Lenalidomide (Revlimid)          

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

            - Women who are pregnant.

            - Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met

            https://www.ema.europa.eu/en/documents/product-information/revlimid-epar-product-information_en.pdf  09/09/2025 

Other trade names: Lenalidomide Accord, Lenalidomide Mylan, Lenalidomide Krka (previously Lenalidomide Krka d.d. Novo),

Lenograstim

Antineoplastics, lenograstim [2] ---> SmPC of [2] of eMC

In view of the sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, the use of lenograstim is not recommended from 24 hours before until 24 hours after chemotherapy ends

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

Breast-feeding should be discontinued during therapy

Cytotoxic agents, lenograstim [2] ---> SmPC of [2] of eMC

Lenograstim should not be administered concurrently with cytotoxic chemotherapy.

Lenograstim [1], pregnancy ---> SmPC of [1] of eMC

Lenograstim should not be used during pregnancy unless clearly necessary.

           CONTRAINDICATIONS of Lenograstim

           - GRANOCYTE should not be administered to patients with known hypersensitivity to lenograstim or to any of the excipients

           - GRANOCYTE should not be used to increase the dose intensity of cytotoxic chemotherapy beyond established doses and dosage regimens since the drug could reduce myelo-toxicity but not overall toxicity of cytotoxic drugs.

           - It should not be administered concurrently with cytotoxic chemotherapy.

           - It should not be administered to patients

           - with myeloid malignancy other than de novo acute myeloid leukaemia,

           - with de novo acute myeloid leukaemia aged below 55 years, and/or

           - with de novo acute myeloid leukaemia with good cytogenetics, i.e. t(8 ;21), t(15 ;17) and inv (16).

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

Lenvatinib (Lenvima)

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

Lenvatinib has a minor influence on the ability to drive and use machines, due to undesirable effects such as fatigue and dizziness. Patients who experience these symptoms should use caution when driving or operating machines.

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

A risk to newborns or infants cannot be excluded and, therefore, lenvatinib is contraindicated during breast-feeding

Chemotherapy, lenvatinib [2] ---> SmPC of [2] of EMA

Concomitant administration of lenvatinib, carboplatin, and paclitaxel has no significant impact on the pharmacokinetics of any of these 3 substances.

Class IA antiarrhythmic agents, lenvatinib [2] ---> SmPC of [2] of EMA

Electrocardiograms should be monitored in patients taking medicinal products known to prolong the QT interval

Class III antiarrhythmic agents, lenvatinib [2] ---> SmPC of [2] of EMA

Electrocardiograms should be monitored in patients taking medicinal products known to prolong the QT interval

CYP3A4 substrates, lenvatinib [2] ---> SmPC of [2] of EMA

No significant drug-drug interaction is therefore expected between lenvatinib and other CYP3A4/Pgp substrates.

Electrolyte imbalance, lenvatinib [2] ---> SmPC of [2] of EMA

Electrolyte disturbances such as hypokalaemia, hypocalcaemia, or hypomagnesaemia increase the risk of QT prolongation, therefore electrolyte abnormalities should be monitored and corrected in all patients before starting treatment.

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

Effects in humans are unknown. However, testicular and ovarian toxicity has been observed in rats, dogs, and monkeys (see section 5.3).

Hormonal contraceptives, lenvatinib [2] ---> SmPC of [2] of EMA

It is currently unknown whether lenvatinib may reduce the effectiveness of hormonal contraceptives, and therefore women using oral hormonal contraceptives should add a barrier method.

Lenvatinib [1], midazolam ---> SmPC of [1] of EMA

A clinical drug-drug interaction (DDI) study in cancer patients showed that plasma concentrations of midazolam (a sensitive CYP3A and Pgp substrate) were not altered in the presence of lenvatinib.

Lenvatinib [1], pregnancy ---> SmPC of [1] of EMA

Lenvatinib should not be used during pregnancy unless clearly necessary and after a careful consideration of the needs of the mother and the risk to the foetus.

Lenvatinib [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Electrocardiograms should be monitored in patients taking medicinal products known to prolong the QT interval

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

Women of childbearing potential should avoid becoming pregnant and use highly effective contraception while on treatment with lenvatinib and for at least one month after finishing treatment.

             CONTRAINDICATIONS of Lenvatinib (Lenvima)

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

             - Breast-feeding

             https://www.ema.europa.eu/en/documents/product-information/lenvima-epar-product-information_en.pdf 18/04/2024

Other trade names: Kisplyx,

Lepirudin (Refludan)

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

Should not be used during lactation

Coumarin anticoagulants, lepirudin [2] ---> SmPC of [2] of EMA

Concomitant treatment of lepirudin with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding.

Lepirudin [1], platelet aggregation inhibitors ---> SmPC of [1] of EMA

Concomitant treatment of lepirudin with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding.

Lepirudin [1], pregnancy ---> SmPC of [1] of EMA

Should not be used during pregnancy

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.

Lepirudin [1], thrombolytics ---> 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.

Lepirudin [1], vitamin K antagonists ---> SmPC of [1] of EMA

Concomitant treatment of lepirudin with coumarin derivatives (vitamin K antagonists) and drugs that affect platelet function may also increase the risk of bleeding.

            CONTRAINDICATIONS of Lepirudin (Refludan)   

            - Known hypersensitivity to lepirudin, to hirudins or to any of the excipients

            - Pregnancy and lactation

            Where there is active bleeding or bleeding tendency it is generally not advisable to administer lepirudin. The physician should carefully weigh the risk of lepirudin administration versus its anticipated benefit, taking into account possible measures to control bleeding.

            This particularly includes the following situations with increased bleeding risk:

            - Recent puncture of large vessels or organ biopsy

            - Anomaly of vessels or organs

            - Recent cerebrovascular accident, stroke, or intracerebral surgery

            - Severe uncontrolled hypertension

            - Bacterial endocarditis

            - Advanced renal impairment

            - Haemorrhagic diathesis

            - Recent major surgery

            - Recent bleeding (e.g. intracranial, gastrointestinal, intraocular, pulmonary)

            - Overt signs of bleeding

            - Recent active peptic ulcer

            - Age > 65 years.

            https://www.ema.europa.eu/en/documents/product-information/refludan-epar-product-information_en.pdf 27/07/2012 (withdrawn)

Lercanidipine

Ability to drive, lercanidipine [2] ---> SmPC of [2] of eMC

Caution should be exercised because dizziness, asthenia, fatigue and rarely somnolence may occur.

ACE inhibitors, lercanidipine [2] ---> SmPC of [2] of eMC

Lercanidipine has been safely administered with diuretics and ACE inhibitors.

Alcohol, antihypertensives ---> SmPC of [lercanidipine] of eMC

Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs.

Alcohol, lercanidipine [2] ---> SmPC of [2] of eMC

Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs.

Amiodarone, lercanidipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when lercanidipine is co-prescribed with other substrates of CYP3A4

Astemizole, lercanidipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when lercanidipine is co-prescribed with other substrates of CYP3A4

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

Decreased bioavailability of lercanidipine. Lercanidipine may be safely administered with beta-adrenoceptor blocking drugs, but dose adjustment may be required.

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

Because of high lipophilicity of lercanidipine, distribution in milk may be expected. Therefore, it should not be administered to nursing mothers.

Carbamazepine, lercanidipine [2] ---> SmPC of [2] of eMC

Co-administration of lercanidipine with CYP3A4 inducers should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

Cimetidine, lercanidipine [2] ---> SmPC of [2] of eMC

At high doses of cimetidine caution is required since the bioavailability and the hypotensive effect of lercanidipine may be increased.

Class III antiarrhythmic agents, lercanidipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when lercanidipine is co-prescribed with other substrates of CYP3A4

Cyclosporine [1], lercanidipine ---> SmPC of [1] of eMC

The co-administration of lercanidipine with ciclosporin has caused a 3-fold increase of the plasma levels of lercanidipine and a 21% increase of the ciclosporin AUC. Ciclosporin and lercanidipine should not be administered together.

CYP3A4 inductors, lercanidipine [2] ---> SmPC of [2] of eMC

Co-administration of lercanidipine with CYP3A4 inducers should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

CYP3A4 inhibitors, lercanidipine [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Digoxin, lercanidipine [2] ---> SmPC of [2] of eMC

Patients on concomitant digoxin treatment should be closely monitored clinically for signs of digoxin toxicity.

Dihydropyridines, grapefruit juice ---> SmPC of [lercanidipine] of eMC

Dihydropyridines are sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in their systemic availability and increased hypotensive effect. Dihydropyridines should not be taken with grapefruit juice.

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

Lercanidipine has been safely administered with diuretics and ACE inhibitors.

Drugs primarily metabolised by CYP3A4, lercanidipine [2] ---> SmPC of [2] of eMC

Caution should be exercised when lercanidipine is co-prescribed with other substrates of CYP3A4

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

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Fluoxetine, lercanidipine [2] ---> SmPC of [2] of eMC

An interaction study with fluoxetine (an inhibitor of CYP2D6 and CYP3A4) has shown no clinically relevant modification of the pharmacokinetics of lercanidipine.

Grapefruit juice, lacidipine ---> SmPC of [lercanidipine] of eMC

Dihydropyridines are sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in their systemic availability and increased hypotensive effect. Dihydropyridines should not be taken with grapefruit juice.

Grapefruit juice, lercanidipine [2] ---> SmPC of [2] of eMC

Lercanidipine is sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in its systemic availability and increased hypotensive effect. Lercanidipine should not be taken with grapefruit juice.

Grapefruit juice, nitrendipine ---> SmPC of [lercanidipine] of eMC

Dihydropyridines are sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in their systemic availability and increased hypotensive effect. Dihydropyridines should not be taken with grapefruit juice.

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

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

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

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Lercanidipine [1], metoprolol ---> SmPC of [1] of eMC

Decreased bioavailability of lercanidipine. Lercanidipine may be safely administered with beta-adrenoceptor blocking drugs, but dose adjustment may be required.

Lercanidipine [1], midazolam ---> SmPC of [1] of eMC

Midazolam concentrations were not modified.

Lercanidipine [1], phenytoin ---> SmPC of [1] of eMC

Co-administration of lercanidipine with CYP3A4 inducers should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

Lercanidipine [1], pregnancy ---> SmPC of [1] of eMC

Lercanidipine should not be administered during pregnancy or to women with child-bearing potential unless effective contraception is used.

Lercanidipine [1], quinidine ---> SmPC of [1] of eMC

Caution should be exercised when lercanidipine is co-prescribed with other substrates of CYP3A4

Lercanidipine [1], rifampicin ---> SmPC of [1] of eMC

Co-administration of lercanidipine with CYP3A4 inducers should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

Lercanidipine [1], ritonavir ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

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.

Lercanidipine [1], strong CYP3A4 inductors ---> SmPC of [1] of eMC

Co-administration of lercanidipine with CYP3A4 inducers should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

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

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Lercanidipine [1], terfenadine ---> SmPC of [1] of eMC

Caution should be exercised when lercanidipine is co-prescribed with other substrates of CYP3A4

Lercanidipine [1], troleandomycin ---> SmPC of [1] of eMC

The strong CYP3A4 inhibition increases plasma concentrations of lercanidipine. Co-administration of lercanidipine with inhibitors of CYP3A4 should be avoided

Lercanidipine [1], warfarin ---> SmPC of [1] of eMC

The co-administration of 20 mg lercanidipine to healthy volunteers given fasted did not alter the pharmacokinetics of warfarin.

Lercanidipine, posaconazole

Posaconazole, strong CYP3A4 inhibitor, may increase the plasma concentrations of lercanidipine

           CONTRAINDICATIONS of Lercanidipine

           - Hypersensitivity to the active substance, to any dihydropyridine or to any of the excipients.

           - Pregnancy and lactation

           - Women of child-bearing potential unless effective contraception is used.

           - Left ventricular outflow tract obstruction.

           - Untreated congestive cardiac failure.

           - Unstable angina pectoris.

           - Severe renal or hepatic impairment.

           - Within 1 month of a myocardial infarction.

           - Co-administration with:

             - strong inhibitors of CYP3A4,

             - ciclosporin,

             - grapefruit juice

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

Lesinurad (Zurampic)

Acetylsalicylic acid, lesinurad [2] ---> SmPC of [2] of EMA

Consistent serum uric acid lowering was observed in patients who were receiving low dose acetylsalicylic acid in the placebo-controlled clinical studies in combination with allopurinol or febuxostat.

Allopurinol, lesinurad [2] ---> SmPC of [2] of EMA

Based on interaction studies in healthy subjects or gout patients, Zurampic does not have clinically significant interactions with NSAIDs (naproxen and indomethacin), colchicine, repaglinide, tolbutamide, febuxostat or allopurinol.

Amiodarone, lesinurad [2] ---> SmPC of [2] of EMA

Lesinurad exposure is increased when it is co-administered with inhibitors of CYP2C9. It is recommended that Zurampic should be used with caution in patients taking moderate inhibitors of CYP2C9.

Amlodipine, lesinurad [2] ---> SmPC of [2] of EMA

In interaction studies conducted in healthy subjects with Zurampic and CYP3A substrates, lesinurad reduced the plasma concentrations of sildenafil and amlodipine.

Antihypertensive medicines that were CYP3A substrates, lesinurad [2] ---> SmPC of [2] of EMA

The possibility of reduced efficacy of concomitant medicinal products that are CYP3A substrates should be considered and their efficacy (e.g. blood pressure and cholesterol levels) should be monitored

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

A risk to the newborns/infants cannot be excluded. Zurampic should not be used during breast-feeding.

Bupropion, lesinurad [2] ---> SmPC of [2] of EMA

Lesinurad may be a mild inducer of CYP2B6. Therefore, it is recommended that patients are monitored for reduced efficacy of CYP2B6 substrates (e.g. bupropion, efavirenz) when co-administered with Zurampic.

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

Lesinurad exposure is expected to decrease when it is co-administered with inducers of CYP2C9 (e.g. carbamazepine, a moderate CYP2C9 inducer). Monitor for decreased efficacy when Zurampic is co-administered with a CYP2C9 inducer.