N

Nabumetone (Relifex)

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

Undesirable effects such as dizziness, drowsiness, confusion, fatigue and visual disturbances are possible after taking NSAIDs.

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

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists (ARA) may present with decreased effect when concomitantly administered with NSAID

Acetylsalicylic acid, nabumetone [2] ---> SmPC of [2] of eMC

ASA doesn't affect nabumetone metabolism and bioavailability

AIIRA, nabumetone [2] ---> SmPC of [2] of eMC

Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists (ARA) may present with decreased effect when concomitantly administered with NSAID

Aluminium hydroxide, nabumetone [2] ---> SmPC of [2] of eMC

Aluminium hydroxide antacids don't affect nabumetone metabolism and bioavailability

Anticoagulants, nabumetone [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of anti-coagulants, such as warfarin; its concomitant administration with nabumetone should be undertaken with caution and overdose signals carefully monitored.

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

Diuretics and other antihypertensives drugs may present with decreased effect when concomitantly administered with NSAID

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

The use of nabumetone in nursing mothers is contraindicated

Cardiac glycosides, nabumetone ---> SmPC of [flurbiprofen] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

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

Cimetidine doesn't affect nabumetone metabolism and bioavailability

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

Increased risk of gastrointestinal ulceration or bleeding

Coxibs, nabumetone [2] ---> SmPC of [2] of eMC

The use of nabumetone with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors should be avoided

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

Increased risk of nephrotoxicity.

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

Diuretics and other antihypertensives drugs may present with decreased effect when concomitantly administered with NSAID

Drugs with high protein binding, nabumetone [2] ---> SmPC of [2] of eMC

Concomitant administration of nabumetone with other protein bound drugs should be undertaken with caution and overdose signals carefully monitored.

Hydantoins, nabumetone [2] ---> SmPC of [2] of eMC

Concomitant administration of nabumetone with other protein bound drugs should be undertaken with caution and overdose signals carefully monitored.

Hyperkalemia, nabumetone

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

Lithium, nabumetone [2] ---> SmPC of [2] of eMC

Decreased elimination of lithium.

Methotrexate, nabumetone [2] ---> SmPC of [2] of eMC

Decreased elimination of methotrexate.

Nabumetone [1], NSAID ---> SmPC of [1] of eMC

The use of nabumetone with concomitant NSAIDs, including cyclooxygenase-2 selective inhibitors should be avoided

Nabumetone [1], paracetamol ---> SmPC of [1] of eMC

Paracetamol doesn't affect nabumetone metabolism and bioavailability

Nabumetone [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Nabumetone [1], potassium-sparing diuretics ---> SmPC of [1] of eMC

Hyperkalaemia might develop, particularly with concomitant potassium-sparing diuretics administration.

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

NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the foetus. During the last trimester of pregnancy is contraindicated

Nabumetone [1], quinolones ---> SmPC of [1] of eMC

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Nabumetone [1], SSRI ---> SmPC of [1] of eMC

Increased risk of gastrointestinal bleeding

Nabumetone [1], sulfonylureas ---> SmPC of [1] of eMC

Concomitant administration of nabumetone with other protein bound drugs should be undertaken with caution and overdose signals carefully monitored.

Nabumetone [1], sulphonamides ---> SmPC of [1] of eMC

Concomitant administration of nabumetone with other protein bound drugs should be undertaken with caution and overdose signals carefully monitored.

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

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Nabumetone [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anti-coagulants, such as warfarin; its concomitant administration with nabumetone should be undertaken with caution and overdose signals carefully monitored.

Nabumetone [1], zidovudine ---> SmPC of [1] of eMC

Increased risk of haematological toxicity when NSAIDs are given with zidovudine.

Nabumetone, probenecide

Probenecid may delay the elimination of nabumetone

Nabumetone, sulfinpyrazone

Sulfinpyrazone may delay the elimination of nabumetone

CONTRAINDICATIONS of Nabumetone (Relifex)

- Use in patients with active, or a history of recurrent peptic ulcer/ GI haemorrhage, perforation or peptic disease (two or more distinct episodes).

- Use in patients hypersensitive to nabumetone or to any of the excipients

- Severe heart failure, hepatic failure and renal failure

- Use in patients who have shown previous hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs. Severe, rarely fatal, anaphylactic like reactions to NSAIDs have been reported in such patients.

- Use in patients with a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

- During the last trimester of pregnancy and in nursing mothers

- Patients with current cerebrovascular or other haemorrhage.

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Nadifloxacin

Breast-feeding, nadifloxacin

Contraindicated

Nadifloxacin, pregnancy

Caution should be exercised when prescribing to pregnant women

Nadolol

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

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur.

Adrenaline, nadolol [2] ---> SmPC of [2] of eMC

Beta-adrenoceptor stimulants such as isoprenaline and verapamil, or alpha-adrenoceptor stimulants such as noradrenaline and adrenaline, will reverse the hypotensive effects and increase vasoconstrictor activity.

Alfa-adrenergic agonists, nadolol [2] ---> SmPC of [2] of eMC

Amiodarone, nadolol

Alterations of contractility, automatism and conduction (suppression of sympathetic compensatory mechanisms). Concomitant use is not recommended

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

Nadolol with antihypertensives may cause an additive hypotensive effect.

Antimuscarinic agents, nadolol [2] ---> SmPC of [2] of eMC

Antimuscarinic agents may counteract the bradycardia caused by beta blockers.

Bepridil, nadolol

Bepridil can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and AV conduction disorders, and heart failure due to synergistic effects

Beta-adrenergic agonists, nadolol [2] ---> SmPC of [2] of eMC

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

Nadolol is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue therapy, taking into account the importance of nadolol to the mother.

Calcium antagonists, nadolol [2] ---> SmPC of [2] of eMC

Calcium channel blockers generally potentiate the pharmacologic effects of beta-blockers. Patients taking both agents should be carefully monitored for adverse cardiovascular events.

Cardiodepressants, nadolol [2] ---> SmPC of [2] of eMC

Myocardial depressants such as lidocaine and procainamide may subject the patient to protracted severe hypotension.

Catecholamine depleting drugs, nadolol [2] ---> SmPC of [2] of eMC

Catecholamine depleting drugs with nadolol may cause additive effects; monitor closely for evidence of hypotension and/or excessive bradycardia (e.g. vertigo, syncope, postural hypotension).

Chloroform, nadolol [2] ---> SmPC of [2] of eMC

General anaesthetics that cause myocardial depression should be avoided as the patient may be subject to protracted severe hypotension.

Class IA antiarrhythmic agents, nadolol [2] ---> SmPC of [2] of eMC

Additive or antagonistic effects may occur with nadolol and antiarrhythmic agents.

Clonidine, nadolol [2] ---> SmPC of [2] of eMC

If nadolol and clonidine are given concurrently, clonidine should not be discontinued until several days after nadolol withdrawal.

Corticosteroids, nadolol

Decreased antihypertensive effect due to water and sodium retention by corticosteroids

Cyclopropane, nadolol [2] ---> SmPC of [2] of eMC

General anaesthetics that cause myocardial depression should be avoided as the patient may be subject to protracted severe hypotension.

Digital glycosides, nadolol

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

Diltiazem, nadolol

Diltiazem can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and AV conduction disorders, and heart failure due to synergistic effects

Disopyramide, nadolol [2] ---> SmPC of [2] of eMC

Additive or antagonistic effects may occur with nadolol and antiarrhythmic agents.

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

Nadolol with antihypertensives may cause an additive hypotensive effect.

Ergot derivatives, nadolol [2] ---> SmPC of [2] of eMC

Effects of vasoconstrictor agents with nadolol can be additive (e.g. with ergot alkaloids).

Ether, nadolol [2] ---> SmPC of [2] of eMC

General anaesthetics that cause myocardial depression should be avoided as the patient may be subject to protracted severe hypotension.

Floctafenine, nadolol

Beta-adrenergic blocking agents may impede the compensatory cardiovascular reactions associated with hypotension or shock that may be induced by floctafenine.

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

General anaesthetics that cause myocardial depression should be avoided as the patient may be subject to protracted severe hypotension.

Hydralazine, nadolol

The co-administration may increase the hypotensive effect

Hydroquinidine, nadolol [2] ---> SmPC of [2] of eMC

Additive or antagonistic effects may occur with nadolol and antiarrhythmic agents.

Hypoglycemic drugs, nadolol [2] ---> SmPC of [2] of eMC

Beta-blockade may prevent the appearance of warning signs and symptoms (e.g. tachycardia and blood pressure changes) of acute hypoglycaemia and also reduce the release of insulin in response to hyperglycaemia. It may be necessary to adjust the dose

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

Isolated cases of bradycardia have occurred during concurrent use of beta blockers and MAOIs.

Insulin, nadolol [2] ---> SmPC of [2] of eMC

Iodinated contrast media, nadolol

In case of shock or hypotension after administering an iodinated contrast medium, the betablocker may cause reduction of cardiovascular compensatory mechanisms

Isoprenaline, nadolol [2] ---> SmPC of [2] of eMC

Ketoconazole [1], nadolol ---> SmPC of [1] of EMA

Increase in plasma concentrations of nadolol have been observed. Careful monitoring. Dose adjustment of nadolol may be required.

Lidocaine, nadolol [2] ---> SmPC of [2] of eMC

Significant reduction of IV lidocaine clearance can occur when a beta blocker is administered concurrently.

Mefloquine, nadolol

Addition of bradycardic effects and risk of bradycardia

Nadolol [1], noradrenaline ---> SmPC of [1] of eMC

Nadolol [1], NSAID ---> SmPC of [1] of eMC

The antihypertensive effects of beta blockers may be reduced during concurrent administration of indometacin and possibly other NSAIDs.

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

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

Nadolol [1], procainamide ---> SmPC of [1] of eMC

Myocardial depressants such as lidocaine and procainamide may subject the patient to protracted severe hypotension.

Nadolol [1], propafenone ---> SmPC of [1] of eMC

Additive or antagonistic effects may occur with nadolol and antiarrhythmic agents.

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

Additive or antagonistic effects may occur with nadolol and antiarrhythmic agents.

Nadolol [1], reserpine ---> SmPC of [1] of eMC

Catecholamine depleting drugs with nadolol may cause additive effects; monitor closely for evidence of hypotension and/or excessive bradycardia (e.g. vertigo, syncope, postural hypotension).

Nadolol [1], trichloroethylene ---> SmPC of [1] of eMC

General anaesthetics that cause myocardial depression should be avoided as the patient may be subject to protracted severe hypotension.

Nadolol [1], vasoconstrictors ---> SmPC of [1] of eMC

Effects of vasoconstrictor agents with nadolol can be additive

Nadolol [1], vasodilators ---> SmPC of [1] of eMC

Nadolol with antihypertensives may cause an additive hypotensive effect.

Nadolol [1], verapamil ---> SmPC of [1] of eMC

Nadolol, neuroleptics ---> SmPC of [nebivolol] of eMC

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

Nadolol, 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

Nadolol, sultopride

Changed automatism (excessive bradycardia) due to the bradycardic effects of both active ingredients may be additive. Concomitant use is contraindicated

Nadolol, tacrine

Excessive bradycardia due to the bradycardic effects of both active ingredients may be additive.

Nadolol, tetracosactide

Decreased antihypertensive effect due to water and sodium retention by corticosteroids

Nadolol, tricyclic antidepressant ---> SmPC of [nebivolol] of eMC

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

CONTRAINDICATIONS of Nadolol

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

- Bronchial asthma or a history of asthma

- Sinus bradycardia

- Greater than first degree atrioventricular conduction block

- Cardiogenic shock

- Right ventricular failure secondary to pulmonary hypertension

- Overt cardiac failure

- Previously demonstrated hypersensitivity to nadolol

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Nadroparin

ACE inhibitors, nadroparin

The use of heparin may inhibit the adrenal secretion of aldosterone giving rise to hypercaliemia, in particular if patients are taking drugs that may cause hypercaliemia

Acetylsalicylic acid, nadroparin

The co-administration may increase the nadroparin effect

Antihistamines, nadroparin

The co-administration may weaken the nadroparin effect

Ascorbic acid, nadroparin

The co-administration may weaken the nadroparin effect

Benzodiazepines, nadroparin

Displacement of nadroparin from its plasma protein binding

Breast-feeding, nadroparin

Not recommended during the breast-feeding

Dextran, nadroparin

Nadroparin should be used with caution by patients treated with dextran

Digital glycosides, nadroparin

The co-administration may weaken the nadroparin effect

Dipyridamole, nadroparin

The co-administration may increase the nadroparin effect

Doxorubicine, nadroparin

The co-administration may weaken the nadroparin effect

Ethacrynic acid, nadroparin

The co-administration of nadroparin and intravenous etacrynic acid may increase the nadroparin effect

Glucocorticoids, nadroparin

Nadroparin should be used with caution by patients treated with systemic glucocorticoids

Hyperkalemia, nadroparin

The use of heparin may inhibit the adrenal secretion of aldosterone giving rise to hypercaliemia, in particular if patients are taking drugs that may cause hypercaliemia

Indometacin, nadroparin

The co-administration may increase the nadroparin effect

Nadroparin, nicotine

The co-administration may weaken the nadroparin effect

Nadroparin, nonsteroidal antiinflammatory drugs

The co-administration may increase the nadroparin effect

Nadroparin, oral anticoagulants

Nadroparin should be used with caution by patients treated with oral anticoagulants

Nadroparin, penicillins

The co-administration of nadroparin and intravenous penicillin may increase the nadroparin effect

Nadroparin, phenylbutazone

The co-administration may increase the nadroparin effect

Nadroparin, phenytoin

Displacement of nadroparin from its plasma protein binding

Nadroparin, platelet aggregation inhibitors

Increased risk of bleeding (inhibition of platelet function)

Nadroparin, pregnancy

Should not be used during pregnancy unless clearly necessary

Nadroparin, probenecide

The co-administration may increase the nadroparin effect

Nadroparin, propranolol

Displacement of nadroparin from its plasma protein binding

Nadroparin, quinidine

Displacement of nadroparin from its plasma protein binding

Nadroparin, quinine

Nadroparin may bind the basic drug and decrease its effect

Nadroparin, salicylates

The co-administration may increase the nadroparin effect

Nadroparin, sulfinpyrazone

The co-administration may increase the nadroparin effect

Nadroparin, tetracyclines

The co-administration may weaken the nadroparin effect

Nadroparin, tricyclic antidepressants

Nadroparin may bind the basic drug and decrease its effect

Nafareline

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

Nafarelin should not be used by breast-feeding women.

Nafareline [1], nasal decongestants ---> SmPC of [1] of eMC

The use of the decongestant oxymetazoline 30 minutes prior to nafarelin acetate administration significantly reduced the extent of nasal absorption of nafarelin. The concomitant use of decongestants should be discouraged

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

Nafarelin should not therefore be used during pregnancy or suspected pregnancy.

CONTRAINDICATIONS of Nafareline

A small loss of trabecula bone mineral content occurs during 6 months treatment with nafarelin. Although this is mostly reversible within 6 months of stopping treatment, there are no data on the effects of repeat courses on bone loss. Retreatment with Synarel or use for longer than 6 months is, therefore, not recommended. (See Special warnings and precautions for use section on 'Changes in bone density').

Synarel should not be administered to patients who:

1. are hypersensitive to GnRH, GnRH agonist analogues or any of the excipients in Synarel;

2. have undiagnosed vaginal bleeding;

3. are pregnant or may become pregnant whilst taking Synarel

4. are breast]feeding.

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Nalbuphine

Ability to drive, nalbuphine

The injection solution has a great influence on ability to react

Alcohol, nalbuphine

Alcohol enhances the sedative effect of morphinic analgesics. Alcoholic drinks or medications containing alcohol should be avoided

Antihypertensives, nalbuphine

The co-administration may cause symptoms of an orthostatic hypotension

Antitussives, nalbuphine

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Anxiolytics, nalbuphine

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Barbiturates, nalbuphine

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Benzodiazepines, nalbuphine

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Breast-feeding, nalbuphine

Nalbuphine passes into breast milk. Breastfeeding should be discontinued for 24 hours after treatment

Clonidine, nalbuphine

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

CNS depressants, nalbuphine

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Dextromoramide, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Dextropropoxyphene, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Dihydrocodeine, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Drugs with a narrow therapeutic window, nalbuphine

Caution is recommended when coadministering nalbuphine with drugs with small therapeutic index

Enzyme inhibitors, nalbuphine

Caution is recommended when coadministering nalbuphine with strong enzym inhibitors

Fentanyl [1], nalbuphine ---> SmPC of [1] of EMA

The concomitant use of partial opioid agonists/antagonists is not recommended. They have high affinity to opioid receptors and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependant patients

Hydromorphone, nalbuphine

The co-administration may decrease the analgetic effect by competitive blocking of receptors and increase the risk of abstinence syndrome. Combination contraindicated

Levacetylmethadol, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Methadone, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Morphine, nalbuphine

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Nalbuphine, neuroleptics

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Nalbuphine, penicillins

The co-administration may potentiate the fatigue and vomiting

Nalbuphine, pethidine

The use of pethidine with opioid agonist/antagonists may decrease the analgetic efect of pethidine and cause a withdrawal syndrome

Nalbuphine, phenothiazines

The co-administration may potentiate the fatigue and vomiting

Nalbuphine, pregnancy

Nalbuphine should not be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus.

Nalbuphine, pure morphine agonists

Pure µ agonists decrease the analgetic effect due to competitive blockade of receptors. Concomitant use is contraindicated.

Nalbuphine, sedating antihistamines

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Nalbuphine, sedative antidepressants

Other central nervous system depressant drugs may increase the risk of respiratory depression, which can be life-threatening in the case of an overdose

Nalbuphine, sufentanil

Decreased analgetic effects due to competitive blockade of receptors. Concomitant use is contraindicated.

Nalbuphine, tapentadol [2] ---> SmPC of [2] of eMC

Care should be taken when combining tapentadol with mixed mu-opioid agonist/antagonists or partial mu-opioid agonists

Nalbuphine, tramadol [2] ---> SmPC of [2] of eMC

Co-administration of tramadol with mixed agonist/antagonist drugs may reduce the analgesic effect of tramadol which is a pure agonist. A withdrawal syndrome may occur.

Naldemedine (Rizmoic)

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

A risk to the suckling child cannot be excluded. Naldemedine should not be used during breast-feeding.

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

Concomitant use of strong CYP3A inducers such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended.

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

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

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

Concomitant use of P-gp inhibitors such as cyclosporine may increase plasma concentrations of naldemedine. If naldemedine is used with strong P-gp inhibitors, monitor for adverse reactions.

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

There is no risk of interaction with concomitant use of mild CYP3A inhibitors.

Efavirenz, naldemedine [2] ---> SmPC of [2] of EMA

Concomitant use of naldemedine with moderate inducers (e.g. efavirenz) has not been established, and patients should be monitored (see section 4.4).

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

No human data on the effect of naldemedine on fertility are available. Naldemedine was found to have no clinically relevant adverse effects on fertility or reproductive performance in male and female rats (see section 5.3).

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

Concomitant use of moderate CYP3A inhibitors such as fluconazole, may increase the plasma concentration of naldemedine. If used with moderate CYP3A inhibitors, monitor for adverse reactions.

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

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

Indinavir, naldemedine [2] ---> SmPC of [2] of EMA

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

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

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

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

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

Moderate CYP3A4 inductors, naldemedine [2] ---> SmPC of [2] of EMA

Concomitant use of naldemedine with moderate inducers (e.g. efavirenz) has not been established, and patients should be monitored (see section 4.4).

Moderate CYP3A4 inhibitors, naldemedine [2] ---> SmPC of [2] of EMA

Concomitant use of moderate CYP3A inhibitors such as fluconazole, may increase the plasma concentration of naldemedine. If used with moderate CYP3A inhibitors, monitor for adverse reactions.

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

Concomitant use of strong CYP3A inducers such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended.

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

Concomitant use of strong CYP3A inducers such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended.

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

Naldemedine should not be used during pregnancy unless the clinical condition of the woman requires treatment with naldemedine.

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

Concomitant use of strong CYP3A inducers such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended.

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

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

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

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

Naldemedine [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A inducers such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended.

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

Concomitant use of strong CYP3A inducers such as St. John's wort (Hypericum perforatum), rifampicin, carbamazepine, phenobarbital and phenytoin is not recommended.

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

Concomitant use of naldemedine with strong CYP3A inhibitors leads to an increase in naldemedine exposure and may increase the risk of adverse reactions. Concomitant use with strong CYP3A inhibitors should be avoided.

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

Concomitant use of P-gp inhibitors such as cyclosporine may increase plasma concentrations of naldemedine. If naldemedine is used with strong P-gp inhibitors, monitor for adverse reactions.

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

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

CONTRAINDICATIONS of Naldemedine (Rizmoic)

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

- Patients with known or suspected gastrointestinal obstruction or perforation or patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation

https://www.ema.europa.eu/en/documents/product-information/rizmoic-epar-product-information_en.pdf 10/12/2025

Nalmefene (Selincro)

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

Adverse reactions such as disturbance in attention, visual impairment, feeling abnormal, nausea, dizziness, somnolence, insomnia, and headache may occur following administration of nalmefene (see section 4.8).

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

Simultaneous intake of alcohol and Selincro does not prevent the intoxicating effects of alcohol.

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

There is no clinically relevant pharmacokinetic drug-drug interaction between nalmefene and alcohol. There seems to be a small impairment in cognitive and psychomotor performance after administration of nalmefene.

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

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Selincro therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.

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

Es ist Vorsicht geboten bei der Anwendung von Buprenorphin zusammen mit Naltrexon und Nalmefen: Hierbei handelt es sich um Opioid-Antagonisten, die die pharmakologischen Wirkungen von Buprenorphin blockieren können.

Buprenorphine/naloxone [1], nalmefene ---> SmPC of [1] of EMA

Naltrexone and nalmefene are opioid antagonists that can block the pharmacological effects of buprenorphine. Co-administration during buprenorphine/naloxone treatment is contraindicated due to the potentially dangerous interaction

Cytochrome P450, nalmefene [2] ---> SmPC of [2] of EMA

Based on in vitro studies, no clinically relevant interactions between nalmefene, or its metabolites, and concomitantly administered medicinal products metabolised by the most common CYP450 and UGT enzymes or membrane transporters are anticipated.

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

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

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

Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme may significantly increase the exposure to nalmefene.

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

In fertility studies in rats, no effects were observed for nalmefene on fertility, mating, pregnancy, or sperm parameters.

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

Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme may significantly increase the exposure to nalmefene.

Glucuronidation inductors, nalmefene [2] ---> SmPC of [2] of EMA

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

Meclofenamic acid, nalmefene [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme may significantly increase the exposure to nalmefene.

Medroxyprogesterone acetate, nalmefene [2] ---> SmPC of [2] of EMA

Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme may significantly increase the exposure to nalmefene.

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

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

Nalmefene [1], opiate agonists ---> SmPC of [1] of EMA

If Selincro is taken concomitantly with opioid agonists (for example, certain types of cough and cold medicinal products, certain antidiarrhoeal medicinal products, and opioid analgesics), the patient may not benefit from the opioid agonist.

Nalmefene [1], opioid analgesics ---> SmPC of [1] of EMA

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

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

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

Animal studies have shown reproductive toxicity (see section 5.3). Selincro is not recommended during pregnancy.

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

Concomitant administration with a UGT inducer may potentially lead to subtherapeutic nalmefene plasma concentrations.

Nalmefene [1], strong UGT2B7 inhibitors ---> SmPC of [1] of EMA

Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme may significantly increase the exposure to nalmefene.

CONTRAINDICATIONS of Nalmefene (Selincro)

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

- Patients taking opioid agonists (such as opioid analgesics, opioids for substitution therapy with opioid agonists (e.g. methadone) or partial agonists (e.g. buprenorphine)) (see section 4.4).

- Patients with current or recent opioid addiction.

- Patients with acute symptoms of opioid withdrawal.

- Patients for whom recent use of opioids is suspected.

- Patients with severe hepatic impairment (Child-Pugh classification).

- Patients with severe renal impairment (eGFR <30 ml/min per 1.73 m²).

- Patients with a recent history of acute alcohol withdrawal syndrome (including hallucinations, seizures, and delirium tremens).

https://www.ema.europa.eu/en/documents/product-information/selincro-epar-product-information_en.pdf 13/01/2025

Naloxegol (Moventig)

Alprazolam, naloxegol [2] ---> SmPC of [2] of EMA

No dose adjustment is required for patients taking weak CYP3A4 inhibitors (e.g. alprazolam, atorvastatin)

Atorvastatin, naloxegol [2] ---> SmPC of [2] of EMA

No dose adjustment is required for patients taking weak CYP3A4 inhibitors (e.g. alprazolam, atorvastatin)

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

Use in breast-feeding mothers is not recommended.

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

Naloxegol is not recommended in patients who are taking strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John's Wort)

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

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

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

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. No dosage adjustment is required for patients taking weak CYP3A4 inhibitors.

Diltiazem, naloxegol [2] ---> SmPC of [2] of EMA

The starting dose for patients taking moderate CYP3A4 inhibitors (e.g. diltiazem, verapamil) is 12.5 mg once daily. The dose can be increased to 25 mg if 12.5 mg is well tolerated by the patient (see section 4.5).

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

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

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

Naloxegol was found to have no effect on fertility of male and female rats at oral doses up to 1,000 mg/kg per day (greater than 1,000 times the human therapeutic exposure (AUC) at the recommended human dose of 25 mg/day).

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

Moventig should be taken on an empty stomach at least 30 minutes prior to the first meal of the day or 2 hours after the first meal of the day.

Gastrointestinal perforation, naloxegol [2] ---> SmPC of [2] of EMA

Naloxegol is contraindicated in patients with known or suspected gastrointestinal (GI) obstruction or in patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation

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

Concomitant consumption of grapefruit juice while taking naloxegol should generally be avoided and considered only in consultation with a healthcare provider

Indinavir, naloxegol [2] ---> SmPC of [2] of EMA

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

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

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

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

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

Moderate CYP3A4 inhibitors, naloxegol [2] ---> SmPC of [2] of EMA

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

Use of naloxegol with another opioid antagonist (e.g. naltrexone, naloxone) should be avoided due to the potential for an additive effect of opioid receptor antagonism and an increased risk of opioid withdrawal.

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

Naloxegol [1], opiate antagonists ---> SmPC of [1] of EMA

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

The effects of P-gp inhibitors on the PK of naloxegol were small relative to the effects CYP3A4 inhibitors

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

Naloxegol use is not recommended during pregnancy.

Naloxegol [1], protease inhibitors ---> SmPC of [1] of EMA

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

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

The effects of P-gp inhibitors on the PK of naloxegol were small relative to the effects CYP3A4 inhibitors

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

Concomitant use of naloxegol with CYP3A4 inductors decreases naloxegol exposition. Naloxegol is not recommended in patients who are taking strong CYP3A4 inducers

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

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

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

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

Naloxegol [1], St. John's wort ---> SmPC of [1] of EMA

Naloxegol is not recommended in patients who are taking strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John's Wort)

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

Moventig is not recommended in patients who are taking strong CYP3A4 inducers (see section 4.4).

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

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

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

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

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

Naloxegol, selpercatinib [2] ---> SmPC of [2] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Naloxegol, tucatinib [2] ---> SmPC of [2] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

Naloxegol, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to significantly increase the plasma concentrations of naloxegol. The co-administration is Contraindicated.

CONTRAINDICATIONS of Naloxegol (Moventig)

Hypersensitivity

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

Gastrointestinal obstruction

- Patients with known or suspected gastrointestinal (GI) obstruction or in patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation

Conditions in patients with cancer pain

- Patients with underlying cancer who are at heightened risk of GI perforation, such as those with:

- underlying malignancies of gastrointestinal tract or peritoneum

- recurrent or advanced ovarian cancer

- vascular endothelial growth factor (VEGF) inhibitor treatment.

Strong CYP3A4 inhibitors

- Concomitant use with strong CYP3A4 inhibitors (e.g. clarithromycin, ketoconazole, itraconazole or telithromycin; protease inhibitors such as ritonavir, indinavir or saquinavir; grapefruit juice when consumed in large quantities)

https://www.ema.europa.eu/en/documents/product-information/moventig-epar-product-information_en.pdf. 13/11/2023

Naloxone (Nyxoid)

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

Patients who have received naloxone to reverse the effects of opioids should be warned not to drive, to operate machinery or to engage in other activities demanding physical or mental exertion for at least 24 hours

Barbiturates, naloxone

With the usual dose of naloxone there is no interaction with barbiturates

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

Breast-fed babies from mothers who have been treated with Nyxoid should be monitored to check for sedation or irritability.

Buprenorphine, naloxone [2] ---> SmPC of [2] of EMA

When administering naloxone to patients who have received buprenorphine as an analgesic, complete analgesia may be restored However, reversal of respiratory depression caused by buprenorphine is limited.

Clonidine, naloxone

Severe hypertension has been reported on administration of naloxone in cases of coma due to a clonidine overdose.

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

Crizotinib, weak UGT2B7 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by UGT2B7

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

Based on drug-drug interaction studies conducted with the components of Odefsey, no clinically significant interactions are expected when Odefsey is combined with naloxone

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

No clinical data on effects of naloxone on fertility are available, however data from rat studies (see section 5.3) indicate no effects.

Methadone [1], naloxone ---> SmPC of [1] of eMC

Naloxone will precipitate an acute withdrawal syndrome in methadone-dependent individuals.

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

Naloxone [1], opiates ---> SmPC of [1] of EMA

Administration of Nyxoid may decrease the analgesic effects of opioids used primarily to provide pain relief, due to its antagonist properties (see section 4.4).

Naloxone [1], opioid dependence ---> SmPC of [1] of EMA

When administered to opioid dependent subjects, naloxone can cause acute withdrawal symptoms in some individuals. Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have been described

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

Studies in animals have shown reproductive toxicity only at maternally toxic doses. The potential risk for humans is unknown. Nyxoid should not be used during pregnancy unless the clinical condition of the woman requires treatment with naloxone.

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

In pregnant women who have been treated with Nyxoid, the fetus should be monitored for signs of distress.

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

In opioid dependent pregnant women, naloxone administration can cause withdrawal symptoms in newborn infants (see section 4.4).

Naloxone, pentazocine [2] ---> SmPC of [2] of eMC

Naloxone reverses the analgesic effects of opioid analgesics (e.g. nalbupine, pentazocine) and opioid agonist analgesics (e.g. alfentanil, fentanyl, remifentanil)

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

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

Naloxone, succinylcholine

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Naloxone, suxamethonium

The co-administration may enhance or prolong the neuromuscular blocking effects of suxamethonium

Naloxone, tranquilizers

With the usual dose of naloxone there is no interaction with tranquilizer

CONTRAINDICATIONS of Naloxone (Nyxoid)

- 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/nyxoid-epar-product-information_en.pdf 12/06/2025

Other trade names: Naloxona B. Braun, Naloxona Kern Pharma, Nexodal,

Naltrexone

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

Naltrexone may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery.

Acamprosate, naltrexone [2] ---> SmPC of [2] of eMC

Co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level.

Alcohol, naltrexone [2] ---> SmPC of [2] of eMC

There are no known interactions between naltrexone and alcohol.

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

Breast feeding is not recommended during naltrexone treatment.

Buprenorphine, naltrexone ---> SmPC of [buprenorphine/naloxone] of EMA

Naltrexone is an opioid antagonist that can block the pharmacological effects of buprenorphine.

Buprenorphine/naloxone [1], naltrexone ---> SmPC of [1] of EMA

Naltrexone is an opioid antagonist that can block the pharmacological effects of buprenorphine.

Codeine [1], naltrexone ---> SmPC of [1] of eMC

Opioid antagonists eg buprenorphine, naltrexone, naloxone - may precipitate withdrawal symptoms

Enzyme inhibitors, naltrexone [2] ---> SmPC of [2] of eMC

It is unlikely that the pharmacokinetics of naltrexone is affected by cytochrome P450 enzyme inhibiting drugs.

Methadone [1], naltrexone ---> SmPC of [1] of eMC

Naltrexone will precipitate an acute withdrawal syndrome in methadone-dependent individuals.

Naltrexone [1], opiate agonists ---> SmPC of [1] of eMC

Concomitant administration of naltrexone with an opioid-containing medication should be avoided.

Naltrexone [1], opioid agonist/antagonists ---> SmPC of [1] of eMC

Concomitant administration of naltrexone with an opioid-containing medication should be avoided.

Naltrexone [1], opioid analgesics ---> SmPC of [1] of eMC

Concomitant administration of naltrexone with an opioid-containing medication should be avoided.

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

Naltrexone should only be given to pregnant women when, in the judgment of the attending physician the potential benefits outweigh and the possible risk.

Naltrexone [1], thioridazine ---> SmPC of [1] of eMC

There have been reports of cases of lethargy and somnolence following concomitant administration of naltrexone and thioridazine.

Naltrexone, tramadol

The use of tramadol mit naltrexone may decrease the analgetic effect

CONTRAINDICATIONS of Naltrexone

Nalorex is contraindicated:

- in patients with acute hepatitis or liver failure.

- in patients currently dependent on opioids since an acute withdrawal syndrome may ensue.

- in any patient who has a positive screen for opioids or who has failed the naloxone challenge test.

- in combination with methadone

- in conjunction with an opioid containing medication

- in patients who have demonstrated hypersensitivity to naltrexone hydrochloride or any of the excipients

- severe renal failure

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

Naltrexone/bupropion (Mysimba)

Ability to drive, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Patients who experience dizziness, somnolence, loss of consciousness or seizure should be advised to avoid driving or operating machines until these adverse effects have resolved.

Alcohol, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

The consumption of alcohol during naltrexone / bupropion treatment should be minimised or avoided.

Amantadine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Administration of naltrexone / bupropion to patients receiving either levodopa or amantadine concurrently should be undertaken with caution. Limited clinical data suggest a higher incidence of adverse reactions

Antidepressants, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Antidiarrheals, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Due to the antagonistic effect of naltrexone at the opioid receptor, patients taking naltrexone/bupropion may not fully benefit from treatment with opioid-containing medicinal products

Antidiarrhoeals, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Due to the antagonistic effect of naltrexone at the opioid receptor, patients taking naltrexone/bupropion may not fully benefit from treatment with opioid-containing medicinal products

Antimalarial agents, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Antitussives, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Due to the antagonistic effect of naltrexone at the opioid receptor, patients taking naltrexone/bupropion may not fully benefit from treatment with opioid-containing medicinal products

Benzodiazepines, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Naltrexone/bupropion is contraindicated in patients receiving concomitant treatment with MAOI, bupropion or naltrexone, patients undergoing acute alcohol or benzodiazepine withdrawal, patients currently dependent on chronic opioids, or opiate agonists

Breast-feeding, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Naltrexone and bupropion and their metabolites are excreted in human milk. Naltrexone / bupropion should not be used during breast-feeding.

Carbamazepine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Since bupropion is extensively metabolised, caution is advised when naltrexone/bupropion is co-administered with medicinal products known to induce CYP2B6 as these may affect the clinical efficacy of naltrexone/bupropion.

Cimetidine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Bupropion and its metabolites competitively inhibit the OCT2 in the basolateral membrane of the renal tubule responsible for creatinine secretion, in a manner similar to the OCT2 substrate cimetidine.

Clonidine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Naltrexone/bupropion has not been studied in conjunction with alpha-adrenergic blockers or clonidine.

Clopidogrel, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products that may inhibit the metabolism of bupropion via CYP2B6 isoenzyme may result in increased bupropion plasma levels and lower levels of active metabolite hydroxybupropion.

Corticosteroids, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Cyclophosphamide, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

CYP2B6 inhibitors, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

CYP2B8 inductors, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Desipramine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Co-administration of bupropion with drugs that are metabolised by CYP2D6 isozyme should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medicinal product.

Digoxin, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Coadministration of naltrexone/bupropion with digoxin may decrease plasma digoxin levels. Monitor plasma digoxin levels in patients treated concomitantly with naltrexone/bupropion and digoxin.

Drugs primarily metabolised by CYP2B6, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Bupropion is metabolised to its major active metabolite hydroxybupropion primarily by the cytochrome P450 CYP2B6; thus, the potential exists for interaction when administered with medicinal products that induce or inhibit CYP2B6.

Drugs primarily metabolised by CYP2D6 with narrow therapeutic index, naltrexone/bupropion [2] ---> SmPC of [2] of

If naltrexone / bupropion is added to the therapy with a drug metabolised by CYP2D6, the need to decrease the dose of the original drug should be considered, particularly for those concomitant medicinal products with a narrow therapeutic index.

Drugs primarily metabolised by CYP2D6, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Efavirenz, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Enzyme inhibitors, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Since bupropion is extensively metabolised, caution is advised when naltrexone / bupropion is co-administered with medicinal products known to inhibit metabolism (e.g. valproate), as these may affect its clinical efficacy and safety.

Flecainide, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Foods, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Clinical experience included varying prandial conditions and supports the use of naltrexone / bupropion tablets with food.

Haloperidol, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Hypertensive drugs, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Naltrexone/bupropion should be given with caution to those patients with controlled hypertension and must not be given to patients with uncontrolled hypertension

Ifosfamide, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

IMAOs, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Since monoamine oxidase A and B inhibitors also enhance the catecholaminergic pathways, by a different mechanism from bupropion, naltrexone / bupropion must not be used with MAOI

Imipramine, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Insulin, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

As treatment with naltrexone/bupropion may result in lowered glucose in patients with diabetes, the dose of insulin and/or oral diabetic medicines should be assessed to minimise the risk of hypoglycaemia, which could predispose patients to seizure

Intermittent opiate treatment, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

In patients requiring intermittent opiate treatment, naltrexone/bupropion therapy should be temporarily discontinued and opiate dose should not be increased above the standard dose (see section 4.4).

Levodopa, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Lopinavir/ritonavir, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Metformin, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Use of naltrexone / bupropion with other OCT2 substrates (e.g., metformin) in clinical trials did not indicate the need for dose adjustment or other precautions.

Methadone, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Naltrexone/bupropion is contraindicated in patients currently dependent on chronic opioid or opiate agonist therapy (e.g., methadone), or patients in acute opiate withdrawal

Metoprolol, naltrexone/bupropion [2] ---> SmPC of [2] of EMA

Naltrexone/bupropion [1], neuroleptics ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Naltrexone/bupropion [1], OCT2 substrates ---> SmPC of [1] of EMA

Use of naltrexone / bupropion with other OCT2 substrates (e.g., metformin) in clinical trials did not indicate the need for dose adjustment or other precautions.

Naltrexone/bupropion [1], opiate agonists ---> SmPC of [1] of EMA

Naltrexone/bupropion is contraindicated in patients currently dependent on chronic opioid or opiate agonist therapy (e.g., methadone), or patients in acute opiate withdrawal

Naltrexone/bupropion [1], opiate treatment ---> SmPC of [1] of EMA

If chronic opiate therapy is required, naltrexone/bupropion treatment must be stopped. Naltrexone/bupropion may be used with caution after chronic opioid use has been stopped for 7 to 10 days in order to prevent precipitation of withdrawal.

Naltrexone/bupropion [1], opiates ---> SmPC of [1] of EMA

Naltrexone / bupropion must not be administered to patients receiving chronic opiate therapy. If chronic opiate therapy is required, naltrexone / bupropion treatment must be stopped.

Naltrexone/bupropion [1], opioid analgesics ---> SmPC of [1] of EMA

Naltrexone/bupropion is contraindicated in patients currently dependent on chronic opioid or opiate agonist therapy (e.g., methadone), or patients in acute opiate withdrawal

Naltrexone/bupropion [1], oral antidiabetics ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], orphenadrine ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], paroxetine ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], phenytoin ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], pregnancy ---> SmPC of [1] of EMA

Naltrexone / bupropion should not be used during pregnancy or in women currently attempting to become pregnant.

Naltrexone/bupropion [1], propafenone ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], quinolones ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Naltrexone/bupropion [1], risperidone ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], ritonavir ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], sedating antihistamines ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Naltrexone/bupropion [1], seizure-threshold lowering drugs ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Naltrexone/bupropion [1], tamoxifen ---> SmPC of [1] of EMA

Drugs which require metabolic activation by CYP2D6 in order to be effective (e.g., tamoxifen), may have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion.

Naltrexone/bupropion [1], theophylline ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Naltrexone/bupropion [1], thioridazine ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], ticlopidine ---> SmPC of [1] of EMA

Naltrexone/bupropion [1], tramadol ---> SmPC of [1] of EMA

Caution should be used when prescribing naltrexone/bupropion to patients with predisposing factors that may increase the risk of seizure

Naltrexone/bupropion [1], UGT1A2 inductors ---> SmPC of [1] of EMA

Administration of naltrexone / bupropion with inhibitors or inducers of UGT 1A2 and 2B7 should be undertaken with caution as these may alter the exposure of naltrexone.

Naltrexone/bupropion [1], UGT1A2 inhibitors ---> SmPC of [1] of EMA

Administration of naltrexone / bupropion with inhibitors or inducers of UGT 1A2 and 2B7 should be undertaken with caution as these may alter the exposure of naltrexone.

Naltrexone/bupropion [1], UGT2B7 inductors ---> SmPC of [1] of EMA

Administration of naltrexone / bupropion with inhibitors or inducers of UGT 1A2 and 2B7 should be undertaken with caution as these may alter the exposure of naltrexone.

Naltrexone/bupropion [1], UGT2B7 inhibitors ---> SmPC of [1] of EMA

Administration of naltrexone / bupropion with inhibitors or inducers of UGT 1A2 and 2B7 should be undertaken with caution as these may alter the exposure of naltrexone.

Naltrexone/bupropion [1], valproate ---> SmPC of [1] of EMA

Since bupropion is extensively metabolised, caution is advised when naltrexone/bupropion is co-administered with medicinal products known to inhibit metabolism (e.g. valproate), as these may affect its clinical efficacy and safety.

CONTRAINDICATIONS of Naltrexone/bupropion (Mysimba)

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

- Patients with uncontrolled hypertension (see section 4.4)

- Patients with a current seizure disorder or a history of seizures (see section 4.4)

- Patients with a known central nervous system tumour

- Patients undergoing acute alcohol or benzodiazepine withdrawal

- Patients with a history of bipolar disorder

- Patients receiving any concomitant treatment containing bupropion or naltrexone

- Patients with a current or previous diagnosis of bulimia or anorexia nervosa

- Patients currently dependent on chronic opioids (see sections 4.4 and 4.5) or opiate agonists (e.g., methadone), or patients in acute opiate withdrawal

- Patients receiving concomitant administration of monoamine oxidase inhibitors (MAOI). At least 14 days should elapse between discontinuation of MAOI and initiation of treatment with naltrexone / bupropion (see section 4.5)

- Patients with severe hepatic impairment (see sections 4.2 and 5.2)

- Patients with endstage renal failure (sections 4.2 and 5.2)

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

Naproxen

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

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs.

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

Concomitant administration of naproxen may reduce the antihypertensive effect and may increase the risk of renal impairment associated with the use of ACE inhibitors

Acenocoumarol, naproxen [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of anti-coagulants

AIIRA, naproxen [2] ---> SmPC of [2] of eMC

Concomitant administration of naproxen may reduce the antihypertensive effect and may increase the risk of renal impairment associated with the use of angiotensin II receptor antagonists.

Alcohol, naproxen

Enhancement of the adverse effects of the NSAID, especially those of the gastrointestinal tract and CNS

Aluminium hydroxide, naproxen

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Aluminium, naproxen

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 2 hours

Antacids, naproxen

Antacid decreases the absorption of NSAID. Separate administration by at least 2 hours

Apixaban [1], naproxen ---> SmPC of [1] of EMA

Active substances which are not considered strong inhibitors of both CYP3A4 and P-gp are expected to increase apixaban plasma concentration to a lesser extent. No dose adjustment for apixaban is required

Aurothiomalate, naproxen

Naproxen may enhance the immunosuppressive toxic effects

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

Concomitant administration of naproxen with beta blockers may reduce their antihypertensive effect

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

NSAIDs should, if possible, be avoided when breastfeeding.

Carbaldrate, naproxen

The aluminium salt decreases the absorption of the co-administered active principle. Separate administration by at least 2 hours

Cardiac glycosides, naproxen [2] ---> SmPC of [2] of eMC

NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels when co-administered with cardiac glycosides.

Cholestyramine, naproxen ---> SmPC of [naproxen/esomeprazole] of eMC

As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of naproxen.

Clopidogrel [1], naproxen ---> SmPC of [1] of EMA

In a clinical study conducted in healthy volunteers, the concomitant administration of clopidogrel and naproxen increased occult gastrointestinal blood loss.

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

As with all NSAIDs, caution should be taken when co-administering naproxen with corticosteroids because of the increased risk of gastrointestinal ulceration or bleeding

Coumarin anticoagulants, naproxen [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of anti-coagulants

Cyclosporine [1], naproxen ---> SmPC of [1] of eMC

Care should be taken when using ciclosporin together with other active substances that exhibit nephrotoxic synergy

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

NSAIDs may reduce the effect of diuretics and antihypertensive medicinal products.

Drugs with high albumin binding, naproxen

Naproxen may interact with other albumin binding agents. Adjustment of the dose may be required

Drugs with high protein binding, naproxen

Naproxen may interact with other protein binding agents. Adjustment of the dose may be required

Febuxostat [1], naproxen ---> SmPC of [1] of EMA

Febuxostat can be co-administered with naproxen with no dose adjustment of febuxostat or naproxen being necessary.

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

Fluconazole has the potential to increase the systemic exposure of NSAIDs that are metabolized by CYP2C9. Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dose of NSAIDs may be needed.

Furosemide, naproxen

NSAID may reduce the diuretic effects of furosemide.

Gadofosveset [1], naproxen ---> SmPC of [1] of EMA

Gadofosveset demonstrated no adverse interaction at clinically relevant concentrations.

Hydantoins, naproxen ---> SmPC of [naproxen/esomeprazole] of eMC

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs

Hyperkalemia, naproxen

The combination may lead to hyperkalemia, particularly in renal failure. Co-administration is not recommended

Lesinurad [1], naproxen ---> SmPC of [1] 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.

Lithium, naproxen [2] ---> SmPC of [2] of eMC

NSAIDs, including naproxen, have been reported to increase steady state plasma lithium levels by inhibition of renal lithium clearance. Decreased elimination of lithium.

Methotrexate, naproxen [2] ---> SmPC of [2] of eMC

Caution is advised when methotrexate is administered with naproxen, due to the possible enhancement of its toxicity as naproxen, like other NSAIDs, has been reported to reduce tubular secretion of methotrexate in an animal model.

Naproxen [1], NSAID ---> SmPC of [1] of eMC

Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects

Naproxen [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

Anti-platelet agents may increase the risk of gastrointestinal bleeding

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

During the first and second trimester of pregnancy, naproxen should not be given unless clearly necessary. Naproxen is contraindicated during the last trimester of pregnancy.

Naproxen [1], SSRI ---> SmPC of [1] of eMC

Selective serotonin reuptake inhibitors (SSRls) may increase the risk of gastrointestinal bleeding

Naproxen [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anti-coagulants

Naproxen, pantoprazole [2] ---> SmPC of [2] of EMA

No clinically significant interactions were observed

Naproxen, phenytoin ---> SmPC of [naproxen/esomeprazole] of eMC

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs

Naproxen, probenecide ---> SmPC of [naproxen/esomeprazole] of eMC

Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.

Naproxen, quinolones ---> SmPC of [ibuprofen] of eMC

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking quinolones may have an increased risk of developing convulsions.

Naproxen, rivaroxaban [2] ---> SmPC of [2] of EMA

No clinically relevant prolongation of bleeding time was observed after concomitant administration of rivaroxaban and naproxen. Nevertheless, there may be individuals with a more pronounced pharmacodynamic response.

Naproxen, sulfinpyrazone

Sulfinpyrazone delays the elimination of NSAID

Naproxen, sulfonylureas

Naproxen may interact with other albumin binding agents. Adjustment of the dose may be required

Naproxen, sultiame

The co-administration may increase the plasma levels of naproxen. Adjustment of the dose may be required

Naproxen, tapentadol

The co-administration may increase the systemic exposition of tapentadol

CONTRAINDICATIONS of Naproxen

- Patients with active gastrointestinal bleeding or peptic ulceration, known hypersensitivity to naproxen, naproxen sodium or any other ingredient in the formulation.

- Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

- NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.

- Severe heart failure, hepatic failure and renal failure

- During the last trimester of pregnancy

- History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

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

Naproxen/esomeprazole

Ability to drive, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Based on that some of the adverse effects (e.g. dizziness) reported following the use naproxen/omeprazole may reduce the ability to react.

ACE inhibitors, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. NSAIDs may also increase the risk of renal impairment associated with the use of ACE-inhibitors

AIIRA, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may diminish the antihypertensive effect of angiotensin II receptor antagonists. NSAIDs may also increase the risk of renal impairment associated with the use of angiotensin II receptor antagonists.

Atazanavir, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Naproxen/esomeprazole must not be used concomitantly with atazanavir

Betablockers, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Naproxen and other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers.

Breast-feeding, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

It should not be used during breastfeeding.

Cardiac glycosides, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may increase plasma cardiac glycoside levels when co-administered with cardiac glycosides such as digoxin.

Cholestyramine, naproxen ---> SmPC of [naproxen/esomeprazole] of eMC

As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of naproxen.

Cholestyramine, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of naproxen.

Clopidogrel, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

As a precaution, concomitant use should be discouraged

Corticosteroids, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

There is an increased risk of gastrointestinal bleeding when corticosteroids are combined with NSAIDs including COX-2 selective inhibitors.

Coumarin anticoagulants, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Coumarin anticoagulants, NSAID ---> SmPC of [naproxen/esomeprazole] of eMC

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Coumarin anticoagulants, tenoxicam ---> SmPC of [naproxen/esomeprazole] of eMC

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Coxibs, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Concomitant use of two or more NSAIDs should be avoided as this may increase the risk of adverse effects, especially gastrointestinal ulcers and bleeding.

Cyclosporine, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

As with all NSAIDs, caution is advised when ciclosporin is co-administered because of the increased risk of nephrotoxicity.

CYP3A4 and CYP2C19 inductors, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Drugs known to induce CYP2C19 and CYP3A4 may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

CYP3A4 and CYP2C19 inhibitors, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4 may result in more than doubling of the esomeprazole exposure. Dose adjustment of esomeprazole is not required

Digoxin, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may increase plasma cardiac glycoside levels when co-administered with cardiac glycosides such as digoxin.

Erlotinib, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of erlotinib can decrease

Furosemide, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Clinical studies, as well as postmarketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis

Gastric pH increasing medication, posaconazole ---> SmPC of [naproxen/esomeprazole] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of posaconazole can decrease

Heparin, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of heparins

Hydantoins, naproxen ---> SmPC of [naproxen/esomeprazole] of eMC

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs

Hydantoins, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs

Itraconazol, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of itraconazole can decrease

Ketoconazole, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of ketoconazole can decrease

Lithium, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID.

Methotrexate, naproxen/esomeprazole [2] ---> SmPC of [2] of eMC

When given together with proton pump inhibitors, methotrexate levels have been reported to increase in some patients. NSAIDs have been reported to reduce the tubular secretion of methotrexate in an animal model.

Naproxen, phenytoin ---> SmPC of [naproxen/esomeprazole] of eMC

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs

Naproxen, probenecide ---> SmPC of [naproxen/esomeprazole] of eMC

Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.

Naproxen/esomeprazole [1], nelfinavir ---> SmPC of [1] of eMC

Naproxen/esomeprazole must not be used concomitantly with nelfinavir

Naproxen/esomeprazole [1], NSAID ---> SmPC of [1] of eMC

Concomitant use of two or more NSAIDs should be avoided as this may increase the risk of adverse effects, especially gastrointestinal ulcers and bleeding.

Naproxen/esomeprazole [1], oral anticoagulants ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Naproxen/esomeprazole [1], platelet aggregation inhibitors ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of thrombocyte aggregation inhibitors

Naproxen/esomeprazole [1], posaconazole ---> SmPC of [1] of eMC

Like with other drugs that decrease the intragastric acidity, the absorption of posaconazole can decrease

Naproxen/esomeprazole [1], pregnancy ---> SmPC of [1] of eMC

During the first and second trimester of pregnancy, it should not be given unless the potential benefit to the patient outweighs the potential risk to the foetus. It is contraindicated during the third trimester of pregnancy

Naproxen/esomeprazole [1], probenecide ---> SmPC of [1] of eMC

Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.

Naproxen/esomeprazole [1], propranolol ---> SmPC of [1] of eMC

Naproxen and other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers.

Naproxen/esomeprazole [1], quinolones ---> SmPC of [1] of eMC

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking quinolones may have an increased risk of developing convulsions.

Naproxen/esomeprazole [1], rifampicin ---> SmPC of [1] of eMC

Drugs known to induce CYP2C19 and CYP3A4 may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Naproxen/esomeprazole [1], SSRI ---> SmPC of [1] of eMC

Concomitant use of NSAIDs, including COX-2 selective inhibitors, and SSRIs increases the risk of gastrointestinal bleeding

Naproxen/esomeprazole [1], St. John's wort ---> SmPC of [1] of eMC

Drugs known to induce CYP2C19 and CYP3A4 may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.

Naproxen/esomeprazole [1], sulfonylureas ---> SmPC of [1] of eMC

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs

Naproxen/esomeprazole [1], tacrolimus ---> SmPC of [1] of eMC

As with all NSAIDs, there is a possible risk of nephrotoxicity when naproxen is co-administered with tacrolimus. Concomitant administration of esomeprazole has been reported to increase the serum levels of tacrolimus.

Naproxen/esomeprazole [1], thiazides ---> SmPC of [1] of eMC

Naproxen/esomeprazole [1], voriconazole ---> SmPC of [1] of eMC

Naproxen/esomeprazole, strong CYP2C19 inhibitors ---> SmPC of [esomeprazole] of EMA

Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concomitant administration of esomeprazole and a CYP3A4 inhibitor resulted in an increased exposure (AUC) to esomeprazole. A dose adjustment of esomeprazole is not regularly required

CONTRAINDICATIONS of Naproxen/esomeprazole

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

- History of asthma, urticaria or allergic-type reactions induced by administration of acetylsalicylic acid or other NSAIDs

- Third trimester of pregnancy

- Severe hepatic impairment (e.g. Childs-Pugh C)

- Severe heart failure

- Severe renal impairment

- Active peptic ulceration

- Gastrointestinal bleeding, cerebrovascular bleeding or other bleeding disorders

- VIMOVO must not be used concomitantly with atazanavir and nelfinavir

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

Naratriptan

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

Caution is recommended in patients performing skilled tasks (e.g. driving or operating machinery) as drowsiness may occur as a result of migraine.

Alcohol, naratriptan [2] ---> SmPC of [2] of eMC

There is no evidence of a pharmacokinetic interaction with alcohol or food.

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

There is no evidence of a pharmacokinetic interaction of naratriptan with betablockers

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

It is recommended that infant exposure be minimized by avoiding breast-feeding for 24 hours after treatment.

Dihydroergotamine, naratriptan [2] ---> SmPC of [2] of eMC

The co-administration (contraindicated) increases the risk of coronary vasospasms. At least 24 hours should elapse between the use of each one

Ergotamine, naratriptan [2] ---> SmPC of [2] of eMC

The co-administration (contraindicated) increases the risk of coronary vasospasms. At least 24 hours should elapse between the use of each one

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

Naratriptan does not inhibit monoamine oxidase enzymes; therefore interactions with monoamine oxidase inhibitors are not anticipated.

Lithium, naratriptan

Potential risk of a serotoninergic syndrome. The concomitant use should be done with caution

Methysergide, naratriptan [2] ---> SmPC of [2] of eMC

The concomitant administration of ergotamine, derivatives or ergotamine (including methysergide) with naratriptan is contraindicated

Naratriptan [1], nicotine ---> SmPC of [1] of eMC

Nicotine increases the total clearance of naratriptan. But no dosing adjustments are required.

Naratriptan [1], oral contraceptives ---> SmPC of [1] of eMC

The oral contraceptive decreases the total clearance of naratriptan. But no dosing adjustments are required.

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

Should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus

Naratriptan [1], serotonin agonists ---> SmPC of [1] of eMC

The co-administration (contraindicated) increases the risk of coronary vasospasms. At least 24 hours should elapse between the use of each one

Naratriptan [1], SNRIs ---> SmPC of [1] of eMC

Serotonin syndrome has been reported following concomitant treatment with triptans and SSRIs/SNRIs

Naratriptan [1], SSRI ---> SmPC of [1] of eMC

Serotonin syndrome has been reported following concomitant treatment with triptans and SSRIs/SNRIs

Naratriptan [1], St. John's wort ---> SmPC of [1] of eMC

Undesirable effects may be more common during concomitant use of triptans and herbal preparations containing St John's Wort (Hypericum perforatum)

Naratriptan [1], tricyclic antidepressant ---> SmPC of [1] of eMC

There is no evidence of a pharmacokinetic interaction of naratriptan with tricyclic antidepressants

Naratriptan [1], triptans ---> SmPC of [1] of eMC

The co-administration (contraindicated) increases the risk of coronary vasospasms. At least 24 hours should elapse between the use of each one

Naratriptan [1], tubular secretion ---> SmPC of [1] of eMC

Due to the safety profile of naratriptan, inhibition of naratriptan secretion is probably of minor importance, while the possibility of naratriptan to inhibit other drugs actively secreted should be considered

Naratriptan, rizatriptan [2] ---> SmPC of [2] of eMC

Due to an additive effect, the concomitant use increases the risk of coronary artery vasoconstriction and hypertensive effects. This combination is contraindicated

Naratriptan, serotonergic medicines

Potential risk of a serotoninergic syndrome. The concomitant use should be done with caution

Naratriptan, tryptophan

The co-administration can cause serotoninergic syndrome. The combination is contraindicated

Naratriptan, zolmitriptan [2] ---> SmPC of [2] of eMC

Increased risk of coronary vasospasm is a theoretical possibility. Concomitant use is contraindicated.

CONTRAINDICATIONS of Naratriptan

- Hypersensitivity to naratriptan or to any of the excipients

- As with other 5-hydroxytryptamine1 (5-HT1) receptor agonists naratriptan should not be used in patients who have had a myocardial infarction or have ischaemic heart disease, or Prinzmetal's angina/coronary vasospasm, peripheral vascular disease or patients who have symptoms or signs consistent with ischaemic heart disease.

- Naratriptan should not be administered to patients with a history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA).

- The use of naratriptan in patients with moderate or severe hypertension, and mild uncontrolled hypertension is contraindicated.

- The concomitant administration of ergotamine, derivatives or ergotamine (including methysergide) or/and any triptan/5-hydroxytryptamine1 (5-HT1) receptor agonist with naratriptan is contraindicated

- Naratriptan is contraindicated in patients with severely impaired renal (creatinine clearance < 15 ml/min) or hepatic function (Child-Pugh grade C).

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

Narcotine

Ability to drive, narcotine

Noscapine can impair alertness and reactivity

Analgesics, narcotine

Noscapine with other CNS depressant drugs may increase the sedation and somnolence of the CNS depressants

Anxiolytics, narcotine

Noscapine with other CNS depressant drugs may increase the sedation and somnolence of the CNS depressants

Breast-feeding, narcotine

Noscapine enters the mother's milk, but in small quantities. A risk for the child is unlikely

CNS depressants, narcotine

Noscapine with other CNS depressant drugs may increase the sedation and somnolence of the CNS depressants

Hypnotics, narcotine

Noscapine with other CNS depressant drugs may increase the sedation and somnolence of the CNS depressants

Narcotine, neuroleptics

Noscapine with other CNS depressant drugs may increase the sedation and somnolence of the CNS depressants

Narcotine, oral anticoagulants

Noscapine may enhance the effect of oral anticoagulants of the type coumarine

Narcotine, pregnancy

Contraindicated in the first trimester. Strict indication in the second and third trimester

Natalizumab (Tysabri)

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

Tysabri has a minor influence on the ability to drive and use machines. Dizziness may occur following administration of this medicinal product (see section 4.8).

Antineoplastics, natalizumab [2] ---> SmPC of [2] of EMA

Combination with other immunosuppressive and antineoplastic therapies. Concurrent use of these agents with TYSABRI may increase the risk of infections, including opportunistic infections, and is contraindicated

Azathioprine, natalizumab [2] ---> SmPC of [2] of EMA

Some patients may have been exposed to immunosuppressive medicinal products (e.g. mitoxantrone, cyclophosphamide, azathioprine). These medicinal products have the potential to cause prolonged immunosuppression, even after dosing is discontinued.

Beta interferon, natalizumab [2] ---> SmPC of [2] of EMA

Natalizumab is contraindicated in combination with beta-interferons

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

Natalizumab is excreted in human milk. The effect of natalizumab on newborn/infants is unknown. Breast-feeding should be discontinued during treatment with natalizumab.

Corticosteroids, natalizumab [2] ---> SmPC of [2] of EMA

In Phase 3 MS clinical trials, concomitant treatment of relapses with a short course of corticosteroids was not associated with an increased rate of infection. Short courses of corticosteroids can be used in combination with TYSABRI.

Cyclophosphamide, natalizumab [2] ---> SmPC of [2] of EMA

Disease modifying therapy, natalizumab [2] ---> SmPC of [2] of EMA

Natalizumab is contraindicated in combination with other DMTs (see section 4.3).

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

Reductions in female guinea pig fertility were observed in one study at doses in excess of the human dose; natalizumab did not affect male fertility.

Fingolimod [1], natalizumab ---> SmPC of [1] of EMA

Caution is indicated when switching from long-acting therapies with immune effects

Glatiramer, natalizumab [2] ---> SmPC of [2] of EMA

Natalizumab is contraindicated in combination with glatiramer acetate

Hydroxychloroquine, natalizumab

Hydroxychloroquine may increase the toxicity of natalizumab, especially the risk of infection

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

Patients with a treatment history of immunosuppressant medicinal products are at increased risk for PML. Care should be taken with patients who have previously received immunosuppressants to allow sufficient time for immune function recovery to occur.

Mitoxantrone, natalizumab [2] ---> SmPC of [2] of EMA

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

This drug should be used during pregnancy only if clearly needed.

Natalizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Live vaccines have not been studied.

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

If a woman becomes pregnant while taking this medicinal product, discontinuation should be considered.

Natalizumab, thiotepa

Thiotepa may increase the adverse effects of natalizumab

Natalizumab, vedolizumab [2] ---> SmPC of [2] of EMA

No vedolizumab clinical trial data are available for patients previously treated with natalizumab or rituximab. Caution should be exercised when considering the use of Entyvio in these patients.

CONTRAINDICATIONS of Natalizumab (Tysabri)

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

- Progressive multifocal leukoencephalopathy (PML).

- Patients with increased risk for opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies) (see sections 4.4 and 4.8).

- Combination with other DMTs.

- Known active malignancies, except for patients with cutaneous basal cell carcinoma.

https://www.ema.europa.eu/en/documents/product-information/tysabri-epar-product-information_en.pdf 09/01/2026

Other trade names: Tyruko,

Nateglinide (Starlix)

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

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.

ACE inhibitors, nateglinide [2] ---> SmPC of [2] of EMA

Angiotensin-converting enzyme inhibitors (ACEI) may enhance the hypoglycaemic effect of nateglinide

Anabolic steroids, nateglinide [2] ---> SmPC of [2] of EMA

Anabolic hormones may enhance the hypoglycaemic effect of nateglinide

Beta2-adrenergic agonists, nateglinide [2] ---> SmPC of [2] of EMA

Beta2 agonists may reduce the hypoglycaemic effect of nateglinide

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

The potential for hypoglycaemia in breast-fed infants may exist and therefore nateglinide should not be used in lactating women.

Bulevirtide [1], nateglinide ---> SmPC of [1] of EMA

In vitro an inhibition of OATP1B1/3 transporters by bulevirtide was observed, albeit only at a concentration ≥ 0.5 然. As a precautionary measure, close clinical monitoring is warranted when OATP1B1/3 substrates are co-administered.

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

Corticosteroids may reduce the hypoglycaemic effect of nateglinide

CYP2C9 inhibitors, nateglinide [2] ---> SmPC of [2] of EMA

A more prolonged effect and possibly a risk of hypoglycaemia cannot be excluded in patients when nateglinide is co-administered with CYP2C9 inhibitors.

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

The pharmacokinetics (PK) of warfarin (a substrate for CYP3A4 and CYP2C9), diclofenac (a substrate for CYP2C9), and digoxin were unaffected by coadministration with nateglinide. Conversely, these medicinal products had no effect on the PK of nateglinide.

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

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

Diuretics may reduce the hypoglycaemic effect of nateglinide

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

Nateglinide did not impair fertility in male or female rats (see section 5.3).

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

Particular caution is recommended when nateglinide is co-administered with potent inhibitors of CYP2C9, or in patients known to be poor metabolisers for CYP2C9.

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

It is recommended to administer prior to meals

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

Particular caution is recommended when nateglinide is co-administered with potent inhibitors of CYP2C9, or in patients known to be poor metabolisers for CYP2C9.

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

Similarly, there was no clinically significant pharmacokinetic interaction of Starlix with other oral antidiabetic agents such as metformin or glibenclamide.

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

Monoamine oxidase inhibitors may enhance the hypoglycaemic effect of nateglinide

Ivacaftor/tezacaftor/elexacaftor [1], nateglinide ---> SmPC of [1] of EMA

Coadministration may increase exposures of substrates of these transporters, such as statins, glyburide, nateglinide and repaglinide. When used concomitantly with substrates of OATP1B1 or OATP1B3, caution and appropriate monitoring should be used.

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

Somatostatin analogues may reduce the hypoglycaemic effect of nateglinide

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

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

Similarly, there was no clinically significant pharmacokinetic interaction of Starlix with other oral antidiabetic agents such as metformin or glibenclamide.

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

Anabolic hormones may enhance the hypoglycaemic effect of nateglinide

Nateglinide [1], non-selective betablockers ---> SmPC of [1] of EMA

Non-selective beta-adrenergic-blocking agents may enhance the hypoglycaemic effect of nateglinide

Nateglinide [1], NSAID ---> SmPC of [1] of EMA

Non-steroidal anti-inflammatory agents may enhance the hypoglycaemic effect of nateglinide

Nateglinide [1], octreotide ---> SmPC of [1] of EMA

Somatostatin analogues may reduce the hypoglycaemic effect of nateglinide

Nateglinide [1], oral antidiabetics ---> SmPC of [1] of EMA

Similarly, there was no clinically significant pharmacokinetic interaction of Starlix with other oral antidiabetic agents such as metformin or glibenclamide.

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

Phenytoin may reduce the hypoglycaemic effect of nateglinide

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

Starlix, like other oral antidiabetic agents, must not be used in pregnancy.

Nateglinide [1], protein displacement ---> SmPC of [1] of EMA

Nateglinide has shown a low potential for protein displacement in in vitro studies.

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

Rifampin may reduce the hypoglycaemic effect of nateglinide

Nateglinide [1], salicylates ---> SmPC of [1] of EMA

Salicylates may enhance the hypoglycaemic effect of nateglinide

Nateglinide [1], somatostatin analogues ---> SmPC of [1] of EMA

Somatostatin analogues may reduce the hypoglycaemic effect of nateglinide

Nateglinide [1], somatotropin ---> SmPC of [1] of EMA

Somatropin may reduce the hypoglycaemic effect of nateglinide

Nateglinide [1], St. John's wort ---> SmPC of [1] of EMA

St John's wort may reduce the hypoglycaemic effect of nateglinide

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

Particular caution is recommended when nateglinide is co-administered with potent inhibitors of CYP2C9, or in patients known to be poor metabolisers for CYP2C9.

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

Interaction studies with a 3A4 inhibitor have not been carried out in vivo.

Nateglinide [1], sulfinpyrazone ---> SmPC of [1] of EMA

Particular caution is recommended when nateglinide is co-administered with potent inhibitors of CYP2C9, or in patients known to be poor metabolisers for CYP2C9.

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

Nateglinide, pasireotide [2] ---> SmPC of [2] of EMA

Dose adjustments (decrease or increase) of insulin and antidiabetic medicinal products may be required when administered concomitantly with pasireotide

Nateglinide, teriflunomide [2] ---> SmPC of [2] of EMA

Teriflunomide, OATP inhibitor, may increase the AUC of OATP substrate. The co-administration should be undertaken with caution

CONTRAINDICATIONS of Nateglinide (Starlix)

Starlix is contraindicated in patients with:

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

- Type 1 diabetes (C-peptide negative)

- Diabetic ketoacidosis, with or without coma

- Pregnancy and breast-feeding

- Severe hepatic impairment

https://www.ema.europa.eu/en/documents/product-information/starlix-epar-product-information_en.pdf 28/06/2022 (withdrawn)

Nebivolol

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

When driving vehicles or operating machines it should be taken into account that dizziness and fatigue may occasionally occur.

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

Co-administration of alcohol did not affect the pharmacokinetics of nebivolol.

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

Concomitant use of amifostine with antihypertensives is likely to increase the fall in blood pressure, therefore the dosage of the antihypertensive medication should be adjusted accordingly.

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

The concomitant use should be done with caution as the effect on atrioventricular conduction time may be potentiated

Amlodipine, 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.

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

Concomitant use of baclofen with antihypertensives is likely to increase the fall in blood pressure, therefore the dosage of the antihypertensive medication should be adjusted accordingly.

Barbiturates, betablockers ---> SmPC of [nebivolol] of eMC

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

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

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

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

Negative influence on contractility and atrio-ventricular conduction. Concomitant treatment is not recommended

Betablockers, phenothiazines ---> SmPC of [nebivolol] of eMC

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

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

Breast feeding in not recommended during administration of nebivolol.

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

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Centrally-acting antihypertensives, nebivolol [2] ---> SmPC of [2] of eMC

Concomitant use of nebivolol with centrally acting antihypertensive drugs may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation)

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

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

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

Co-administration of cimetidine increased the plasma levels of nebivolol, without changing the clinical effect.

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Class IA antiarrhythmic agents, nebivolol [2] ---> SmPC of [2] of eMC

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Class IB antiarrhythmic agents, nebivolol [2] ---> SmPC of [2] of eMC

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Class IC antiarrhythmic agents, nebivolol [2] ---> SmPC of [2] of eMC

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Class III antiarrhythmic agents, nebivolol [2] ---> SmPC of [2] of eMC

The concomitant use should be done with caution as the effect on atrioventricular conduction time may be potentiated

Clobazam [1], nebivolol ---> SmPC of [1] of eMC

Clobazam is a weak CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 may be necessary.

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

Digital glycosides, nebivolol [2] ---> SmPC of [2] of eMC

Digitalis glycosides in association with beta-blockers may increase auriculo-ventricular conduction time although clinical trials with nebivolol have not shown any clinical evidence of an interaction

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

Nebivolol does not influence the kinetics of digoxin

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

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

Negative influence on contractility and atrio-ventricular conduction. Concomitant treatment is not recommended

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

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

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Floctafenine, nebivolol

Nebivolol may impede the compensatory cardiovascular reactions associated with hypotension or shock that may be induced by floctafenine. The combination is contraindicated

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

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

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

Co-administration of furosemide did not affect the pharmacokinetics of nebivolol.

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

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

Concomitant use of beta-adrenergic antagonists and anaesthetics may attenuate reflex tachycardia and increase the risk of hypotension. Sudden withdrawal of beta-blocker treatment should be avoided if possible.

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

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

Co-administration of hydrochlorothiazide did not affect the pharmacokinetics of nebivolol.

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

Although nebivolol does not affect glucose levels, concomitant use may mask symptoms of hypoglycaemia (palpitations, tachycardia).

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

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

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Lidocaine, nebivolol ---> SmPC of [lidocaine/prilocaine] of EMA

Medicinal products that reduce the clearance of lidocaine may cause potentially toxic plasma concentrations when lidocaine is given intravenously in repeated high doses over a long time period (30 hours).

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

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

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

Nadolol, neuroleptics ---> SmPC of [nebivolol] of eMC

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

Nadolol, tricyclic antidepressant ---> SmPC of [nebivolol] of eMC

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

Nebivolol [1], neuroleptics ---> SmPC of [1] of eMC

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

Nebivolol [1], nicardipine ---> SmPC of [1] of eMC

Nebivolol [1], nifedipine ---> SmPC of [1] of eMC

Nebivolol [1], nimodipine ---> SmPC of [1] of eMC

Nebivolol [1], nitrendipine ---> SmPC of [1] of eMC

Nebivolol [1], NSAID ---> SmPC of [1] of eMC

Non-steroidal anti-inflammatory drugs (NSAID) are thought to have no effect on the blood pressure lowering effect of nebivolol.

Nebivolol [1], oral antidiabetics ---> SmPC of [1] of eMC

Although nebivolol does not affect glucose levels, concomitant use may mask symptoms of hypoglycaemia (palpitations, tachycardia).

Nebivolol [1], paroxetine ---> SmPC of [1] of eMC

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Nebivolol [1], phenothiazines ---> SmPC of [1] of eMC

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

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

Negative influence on contractility and atrio-ventricular conduction. Concomitant treatment is not recommended

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

Nebivolol should not be used during pregnancy unless clearly necessary.

Nebivolol [1], propafenone ---> SmPC of [1] of eMC

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

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

Combination not recommended as the effect on atrio-ventricular conduction time may be potentiated and the negative inotropic effect increased

Nebivolol [1], ranitidine ---> SmPC of [1] of eMC

Co-administration of ranitidine did not affect the pharmacokinetics of nebivolol.

Nebivolol [1], rilmenidine ---> SmPC of [1] of eMC

Nebivolol [1], strong CYP2D6 inhibitors ---> SmPC of [1] of eMC

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Nebivolol [1], sympathomimetics ---> SmPC of [1] of eMC

Concomitant use may counteract betablocker effect. Betablocker may lead to unopposed alfa-adrenergic activity of sympathomimetic with alfa- a. beta-adrenergic effect causing increased risk of hypertension, severe bradycardia a. heart block

Nebivolol [1], terbinafine ---> SmPC of [1] of eMC

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Nebivolol [1], thioridazine ---> SmPC of [1] of eMC

The CYP2D6 inhibition may lead to increased plasma levels of nebivolol (metabolized by CYP2D6) that is associated with an increased risk of excessive bradycardia and adverse events.

Nebivolol [1], tricyclic antidepressant ---> SmPC of [1] of eMC

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

Nebivolol [1], verapamil ---> SmPC of [1] of eMC

Negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients with ß-blocker treatment may lead to profound hypotension and atrio-ventricular block

Nebivolol [1], warfarin ---> SmPC of [1] of eMC

Nebivolol does not affect the pharmacokinetics and pharmacodynamics of warfarin.

Nebivolol, panobinostat [2] ---> SmPC of [2] of EMA

Panobinostat increased the Cmax and the AUC of dextromethorphan (a substrate of CYP2D6) by 1.8- and 1.6-fold, respectively, and it cannot be excluded that the effect may be larger on a more sensitive CYP2D6 substrate.

Nebivolol, sultopride

There is a risk of ventricular arrhythmias, particularly torsades de pointes tachycardias. The combination is contraindicated

Nebivolol, tiapride

Tiapride with betablockers given in heart failure increases the risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and electrocardiographic monitoring is necessary

CONTRAINDICATIONS of Nebivolol

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

- Liver insufficiency or liver function impairment.

- Acute heart failure, cardiogenic shock or episodes of heart failure decompensation requiring I.V. inotropic therapy.

In addition, as with other beta-blocking agents, nebivolol is contra-indicated in:

- Sick sinus syndrome, including sino-atrial block.

- Second and third degree heart block (without a pacemaker).

- History of bronchospasm and bronchial asthma.

- Untreated phaeochromocytoma

- Metabolic acidosis.

- Bradycardia (heart rate < 60 bpm prior to start of therapy)

- Hypotension (systolic blood pressure < 90 mmHg)

- Severe peripheral circulatory disturbances.

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

Necitumumab (Portrazza)

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

If patients experience treatment-related symptoms affecting their ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.

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

A risk to newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Portrazza and for at least 4 months after the last dose.

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

There are no data on the effect of necitumumab on human fertility. Animal studies to assess fertility directly have not been conducted (see section 5.3).

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

Portrazza should not be used during pregnancy or in women not using effective contraception, unless the potential benefit justifies the potential risk to the foetus.

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

Women of childbearing potential have to use effective contraception during necitumumab treatment and up to 3 months after last administration of necitumumab treatment. Contraceptive measures or abstinence are recommended.

CONTRAINDICATIONS of Necitumumab (Portrazza)

- Patients with a history of severe or life-threatening 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/portrazza-epar-product-information_en.pdf 27/07/2021 (withdrawn)

Nedocromil

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

There is no information to suggest that the use of nedocromil sodium by nursing mothers has any undesirable effects upon the baby.

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

As with all medications caution should be exercised during pregnancy (especially during the first trimester)

CONTRAINDICATIONS of Nedocromil

- It is contraindicated in patients with known hypersensitivity to nedocromil sodium, benzalkonium chloride or other constituents of the formulation.

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

Nelarabine (Atriance)

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

Patients treated with nelarabine are potentially at risk of suffering from somnolence during and for several days after treatment.

Adenosine deaminase inhibitors, nelarabine [2] ---> SmPC of [2] of EMA

Coadministration of nelarabine in combination with adenosine deaminase inhibitors such as pentostatin is not recommended. Coadministration may reduce the efficacy of nelarabine and/or change the adverse event profile of either active substance.

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

It is unknown whether nelarabine or its metabolites are excreted in human breast milk. A risk to the newborn/infant cannot be excluded. Breast-feeding should be discontinued during treatment with Atriance.

Cytochrome P450, nelarabine [2] ---> SmPC of [2] of EMA

Nelarabine and ara-G did not significantly inhibit the activities of the major hepatic cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in vitro.

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

The effect of nelarabine on fertility in humans is unknown. Based on the pharmacological action of the compound, undesirable effects on fertility are possible. Family planning should be discussed with patients as appropriate.

Men, nelarabine [2] ---> SmPC of [2] of EMA

Men with partners who are pregnant or could become pregnant should use condoms during treatment with nelarabine and for at least three months following cessation of treatment.

Nelarabine [1], pentostatine ---> SmPC of [1] of EMA

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

Nelarabine should not be used during pregnancy unless clearly necessary. If a patient becomes pregnant during treatment with nelarabine, they should be informed of the possible risk to the foetus.

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

Both sexually active men and women should use effective methods of contraception during treatment with nelarabine.

CONTRAINDICATIONS of Nelarabine (Atriance)

- 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/atriance-epar-product-information_en.pdf 26/07/2024

Nelfinavir

Acenocoumarol [1], nelfinavir ---> SmPC of [1] of eMC

The co-administration may decrease the anticoagulant effect

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

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

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

Amitriptyline, 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

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

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

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Increased AUC of atorvastatin. Atorvastatin is less dependent on CYP3A4 for metabolism. When used with nelfinavir, the lowest possible dose of atorvastatin should be administered.

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

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

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

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

Azithromycin, nelfinavir

Increased plasma concentrations of azithromycin

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

Concomitant use of bosentan and nelfinavir may increase plasma levels of bosentan. When administered concomitantly with nelfinavir, the patient's tolerability of bosentan should be monitored.

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

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

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

Mothers must be instructed to discontinue breast-feeding if they are receiving nelfinavir.

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

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

Buprenorphine [1], nelfinavir ---> SmPC of [1] of eMC

Concomitant administration of buprenorphine and potent CYP3A4 inhibitors can lead to markedly increased plasma concentrations of buprenorphine and norbuprenorphine. The combination should be avoided or monitored closely

Buprenorphine/naloxone [1], nelfinavir ---> SmPC of [1] of EMA

Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.

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

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

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

Potent inducers of CYP3A4 (e.g., rifampicin, phenobarbital and carbamazepine) may reduce nelfinavir plasma concentrations and their coadministration is contraindicated

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

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

Ciclesonide [1], nelfinavir ---> SmPC of [1] of eMC

The concomitant administration of ciclesonide with potent inhibitors of CYP 3A4 should be avoided unless the benefit outweighs the increased risk of systemic side effects of corticosteroids.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

Clarithromycin, nelfinavir

Clarithromycin, CYP3A4 inhibitor, may increase the plasma concentrations of nelfinavir (small therapeutic range). Clarithromycin should be used with caution

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

Concomitant use of colchicine and nelfinavir may increase plasma levels of colchicine. Patients with renal or hepatic impairment should not be given colchicine with nelfinavir

Conjugated oestrogens/bazedoxifene [1], nelfinavir ---> SmPC of [1] of EMA

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

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

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

Cyclophosphamide, nelfinavir

The CYP2B6 and CYP3A4 inhibition may decrease the efficacy of cyclophosphamide (prodrug)

CYP2C19 inhibitors, nelfinavir [2] ---> SmPC of [2] of EMA

CYP2D6 inhibitors, nelfinavir

The CYP2D6 inhibition may increase plasma concentrations of nelfinavir, which has a narrow therapeutic index

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

Potent inducers of CYP3A4 may reduce nelfinavir plasma concentrations and their coadministration is contraindicated. Caution should be used when co-administering other agents that induce CYP3A4

CYP3A4 substrates with narrow therapeutic index, nelfinavir

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

CYP3A4 substrates with narrow therapeutic index, nelfinavir [2] ---> SmPC of [2] of EMA

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

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

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

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

Decreased/increased plasma concentrations of delavirdine/nelfinavir. Safety of combination not established; combination not recommended

Desogestrel [1], nelfinavir ---> SmPC of [1] of eMC

Interactions can occur with medicinal products that induce microsomal enzymes, which can result in increased clearance of sex hormones

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

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

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

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

Nelfinavir should be administered (with food) 1 hour after or more than 2 hours before didanosine.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

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

Dolutegravir [1], nelfinavir ---> SmPC of [1] of EMA

No dosage adjustment necessary.

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

No dosage adjustment necessary.

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

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

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

Nelfinavir, CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP3A4. A dose reduction or consideration of an alternative may be required

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Nelfinavir, CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP3A4. A dose reduction or consideration of an alternative may be required

Dydrogesterone/estradiol [1], nelfinavir ---> SmPC of [1] of eMC

Nelfinavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

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

No dose adjustment is necessary for either medicinal product.

Eletriptan [1], nelfinavir ---> SmPC of [1] of eMC

In clinical studies with potent inhibitors of CYP3A4 significant increases in eletriptan Cmax and AUC were observed. Eletriptan should not be used together with potent CYP3A4 inhibitors

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

Strong CYP3A4 inhibitors may increase the AUC of eplerenone. The concomitant use of eplerenone with strong CYP3A4 inhibitors is contra-indicated

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

For nelfinavir, decreased serum levels have been reported when given together with omeprazole. Concomitant administration with esomeprazole and nelfinavir is contraindicated

Estradiol valerate/norgestrel [1], nelfinavir ---> SmPC of [1] of eMC

Nelfinavir, although known as strong inhibitor, by contrast exhibits inducing properties when used concomitantly with steroid hormones

Estradiol [1], nelfinavir ---> SmPC of [1] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estradiol/norethisterone [1], nelfinavir ---> SmPC of [1] of eMC

Nelfinavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estriol [1], nelfinavir ---> SmPC of [1] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Estrogens, nelfinavir ---> SmPC of [estradiol] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

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

Decreased AUC of ethinyl estradiol. Contraceptives with ethinyl estradiol should not be coadministered with nelfinavir. Alternative contraceptive measures should be considered.

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

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

Ethinylestradiol/gestodene [1], nelfinavir ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

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

Drugs or herbal products that induce enzymes, especially CYP3A4, may decrease the plasma concentrations of contraceptive hormones, and may decrease their effectiveness and/or increase breakthrough bleeding.

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

Interactions can occur with medicinal products that induce microsomal enzymes, specifically cytochrome P450 enzymes, which can result in increased clearance of sex hormones

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

Etravirine is expected to increase nelfinavir plasma concentrations. It is not recommended to co-administer etravirine with nelfinavir.

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

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

Fenofibrate/simvastatin [1], nelfinavir ---> SmPC of [1] of EMA

Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy. Concomitant use is contraindicated

Fentanyl [1], nelfinavir ---> SmPC of [1] of EMA

The concomitant use of fentanyl with strong CYP3A4 inhibitors may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression.

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

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

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

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

Fluticasone propionate, nelfinavir [2] ---> SmPC of [2] of EMA

Coadministration of nelfinavir with fluticasone propionate may increase plasma concentrations of fluticasone propionate. Consider alternatives that are not metabolised by CYP3A4 such as beclomethasone.

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

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

VIRACEPT is administered orally and should always be ingested with food

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

No dose recommendations can be given.

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

Nelfinavir may decrease phenytoin serum levels

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

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Concomitant use of ibrutinib and medicinal products that strongly inhibit CYP3A4 can increase ibrutinib exposure and should be avoided.

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

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

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

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

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

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

Interferon, nelfinavir

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

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

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

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

No CRESEMBA dose adjustment necessary. Protease inhibitors: careful monitoring for any occurrence of drug toxicity and /or lack of antiviral efficacy, and dose adjustment if required.

Isradipine [1], nelfinavir ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

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

The concomitant use of ivabradine and potent CYP3A4 inhibitors increases plasma concentrations of ivabradine (may be associated with the risk of excessive bradycardia). The concomitant use of ivabradine with these medicinal products is contraindicated

Ixabepilone, nelfinavir

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

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

Coadministration of nelfinavir and a strong inhibitor of CYP3A, ketoconazole, resulted in a 35 % increase in nelfinavir plasma AUC. The changes in nelfinavir concentrations are not considered clinically significant and no dose adjustment is needed

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

Levomethadone, nelfinavir

The enzymatic induction may decrease the plasma levels of levomethadone and abstinence syndrome may occur

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

Decreased plasma concentrations of lopinavir. The appropriate doses for this combination, with respect to efficacy and safety, have not been established.

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

Coadministration of nelfinavir with lovastatin may result in significant increases in lovastatin plasma concentrations and is contraindicated product

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

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

Maraviroc [1], nelfinavir ---> SmPC of [1] of EMA

Nelfinavir is a potent CYP3A4 inhibitor and would be expected to increase maraviroc concentrations.

Medroxyprogesterone, nelfinavir ---> SmPC of [estradiol/norethisterone] of eMC

Nelfinavir, although known as strong inhibitor, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

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

Methadone AUC may be decreased when co-administered with nelfinavir; therefore upward adjustment of methadone dose may be required during concomitant use with nelfinavir.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

Methysergide [1], nelfinavir ---> SmPC of [1] of eMC

The concomitant use of cytochrome P450 3A (CYP3A) inhibitors, since this can result in an elevated exposure to methysergide and ergot toxicity (vasospasm and ischemia of the extremities and other tissues).

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated. Nelfinavir is contraindicated with oral midazolam

Mometasone [1], nelfinavir ---> SmPC of [1] of eMC

There may be a potential for increased systemic exposure to mometasone furoate when strong CYP3A4 inhibitors are co-administered

Naproxen/esomeprazole [1], nelfinavir ---> SmPC of [1] of eMC

Naproxen/esomeprazole must not be used concomitantly with nelfinavir

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

Nelfinavir and nevirapine can be co-administered without dose adjustments.

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

Decreased AUC of norethindrone. Contraceptives with norethindrone should not be coadministered with nelfinavir. Alternative contraceptive measures should be considered.

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

Nelfinavir should not be co-administered with omeprazole due to a reduction in exposure to nelfinavir and its active metabolite M8 (Tert-butyl hydroxy nelfinavir). This may lead to a loss of virologic response and possible resistance to nelfinavir

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

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

Potent inducers of CYP3A4 (e.g., rifampicin, phenobarbital and carbamazepine) may reduce nelfinavir plasma concentrations and their coadministration is contraindicated

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

No dose adjustment for nelfinavir is recommended. Nelfinavir may lead to decreased AUC of phenytoin; therefore phenytoin concentrations should be monitored during concomitant use with nelfinavir.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Nelfinavir should be given during pregnancy only if the expected benefit justifies the possible risk to the foetus.

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

Caution is recommended when nelfinavir is co-administered with other proton pump inhibitors (concomitant use with omeprazole is contraindicated)

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Increased AUC values of rifabutin and decreased AUC values of nelfinavir

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

Potent inducers of CYP3A4 (e.g., rifampicin, phenobarbital and carbamazepine) may reduce nelfinavir plasma concentrations and their coadministration is contraindicated

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

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

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

Increased AUC of saquinavir.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated. Combination contraindicated if sildenafil is used to treat pulmonary arterial hypertension

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

Coadministration of nelfinavir with simvastatin may result in significant increases in simvastatin plasma concentrations and is contraindicated product

Nelfinavir [1], St. John's wort ---> SmPC of [1] of EMA

Herbal preparations containing St. John's wort (Hypericum perforatum) must not be used while taking nelfinavir due to the risk of decreased plasma concentrations and reduced clinical effects of nelfinavir

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

HMG-CoA reductase inhibitors may interact with protease inhibitors and increase the risk of myopathy, including rhabdomyolysis.

Nelfinavir [1], strong CYP2C19 inhibitors ---> SmPC of [1] of EMA

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

Potent inducers of CYP3A4 (e.g., rifampicin, phenobarbital and carbamazepine) may reduce nelfinavir plasma concentrations and their coadministration is contraindicated

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

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

Concomitant use of tadalafil and nelfinavir may increase plasma levels of tadalafil. Co-administration of tadalafil for the treatment of pulmonary arterial hypertension with nelfinavir is not recommended.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Concomitant use of trazodone and nelfinavir may increase plasma concentrations of trazodone and a lower dose of trazodone should be considered.

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

Co-administration of nelfinavir with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 is contraindicated.

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

Concomitant use of vardenafil and nelfinavir may increase plasma levels of vardenafil. Use with increased monitoring for adverse events associated with increased exposure to vardenafil.

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

Coadministration of warfarin and nelfinavir may affect concentrations of warfarin. It is recommended that the international normalized ratio (INR) be monitored carefully during treatment with nelfinavir, especially when commencing therapy.

Nelfinavir, neratinib [2] ---> SmPC of [2] of EMA

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

Nelfinavir, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

Nelfinavir, nisoldipine

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

Nelfinavir, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Nelfinavir, norgestimate

The CYP3A4 induction may accelerate the norgestimate metabolism and decrease its plasma levels and effect. The induction lasts at least 4 weeks after dose interruption

Nelfinavir, olaparib [2] ---> SmPC of [2] of EMA

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

Nelfinavir, paclitaxel [2] ---> SmPC of [2] of EMA

The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4.

Nelfinavir, palbociclib [2] ---> SmPC of [2] of EMA

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

Nelfinavir, pazopanib [2] ---> SmPC of [2] of EMA

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

Nelfinavir, piperaquine/artenimol [2] ---> SmPC of [2] of EMA

Concomitant treatment with medicinal products which inhibit CYP3A4 may lead to a marked increase of piperaquine plasma concentration resulting in an exacerbation of the effect on QTc

Nelfinavir, pixantrone [2] ---> SmPC of [2] of EMA

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

Nelfinavir, ponatinib [2] ---> SmPC of [2] of EMA

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

Nelfinavir, primidone [2] ---> SmPC of [2] of eMC

Nelfinavir, CYP3A4 inhibitor, may increase the primidone plasma levels. Primidone, enzymatic inductor, may decrease the nelfinavir plasma levels

Nelfinavir, protease inhibitors

Generally, dual therapy with protease inhibitors is not recommended

Nelfinavir, ribociclib [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

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

Not studied. Increased exposure (inhibition of CYP3A enzymes) of rilpivirine is expected. No dose adjustment is required.

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

Ritonavir increases the serum levels of nelfinavir as a result of CYP3A4 inhibition.

Nelfinavir, ruxolitinib [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase ruxolitinib exposition. When co-administering with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced

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

Increased AUC of saquinavir. Combination not recommended.

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

The CYP3A4 enzyme induction or inhibition may alter plasma concentrations of simeprevir. It is not recommended to co-administer simeprevir with any HIV PI, with or without ritonavir.

Nelfinavir, sitaxentan [2] ---> SmPC of [2] of EMA

Clinical interaction studies with nelfinavir, a moderately potent OATP inhibitor, did not result in clinically significant changes in sitaxentan plasma levels.

Nelfinavir, solifenacin [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma levels of solifenacin. Simultaneous treatment of solifenacin and a potent CYP3A4 inhibitor is contra-indicated in patients with severe renal impairment or moderate hepatic impairment

Nelfinavir, steroid hormones ---> SmPC of [estradiol] of eMC

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

Nelfinavir, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

Nelfinavir, temsirolimus [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.

Nelfinavir, toremifene [2] ---> SmPC of [2] of EMA

Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways. Concomitant use should be carefully considered.

Nelfinavir, trastuzumab emtansine [2] ---> SmPC of [2] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Nelfinavir, trofosfamide

The inhibition of CYP3A4 may increase the formation of a trofosfamide metabolite which is related with nephrotoxicity and CNS toxicity

Nelfinavir, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Nelfinavir, vincristine [2] ---> SmPC of [2] of eMC

The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily. This metabolic pathway may be impaired in patients who are taking concomitant potent inhibitors of these isoenzymes

Nelfinavir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Nelfinavir, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that voriconazole may inhibit the metabolism of HIV protease inhibitors and the metabolism of voriconazole may also be inhibited by HIV protease inhibitors.

Protease inhibitors, sildenafil ---> SmPC of [nelfinavir] of EMA

Co-administration of a PI with sildenafil is expected to substantially increase sildenafil concentration and may result in an increase in sildenafil associated adverse events, including hypotension, visual changes, and priapism.

CONTRAINDICATIONS of Nelfinavir

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

- Co-administration with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 [e.g., terfenadine, astemizole, cisapride, amiodarone, quinidine, pimozide, triazolam, orally administered midazolam (for caution on parenterally administered midazolam, see section 4.5), ergot derivatives, alfuzosin, and sildenafil when used for treatment of pulmonary arterial hypertension (for the use of sildenafil and other PDE-5 inhibitors in patients with erectile dysfunction, see section 4.5)].

- Potent inducers of CYP3A (e.g., rifampicin, phenobarbital and carbamazepine) reduce nelfinavir plasma concentrations.

- Co-administration with rifampicin is contra-indicated due to a reduction in exposure to nelfinavir.

- Physicians should not use potent inducers of CYP 3A4 in combination with nelfinavir and should consider using alternatives when a patient is taking VIRACEPT

- Herbal preparations containing St. John's wort (Hypericum perforatum) must not be used while taking nelfinavir due to the risk of decreased plasma concentrations and reduced clinical effects of nelfinavir

- VIRACEPT should not be co-administered with omeprazole due to a reduction in exposure to nelfinavir and its active metabolite M8 (Tert-butyl hydroxy nelfinavir). This may lead to a loss of virologic response and possible resistance to VIRACEPT

http://www.ema.europa.eu/

Nemolizumab (Nemluvio)

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

Consequently, transfer of IgG antibodies to the newborns through milk, may happen during the first few days. In this short period, a risk to the breastfed child cannot be excluded.

Cytochrome P450, nemolizumab [2] ---> SmPC of [2] of EMA

No clinically significant changes in the exposure of CYP450 substrates were observed compared to prior to nemolizumab treatment. No dose adjustment is necessary.

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

Animal studies showed no impairment of fertility (see section 5.3).

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

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

Nemolizumab [1], vaccinations ---> SmPC of [1] of EMA

It is recommended that patients complete all age-appropriate vaccinations in agreement with current immunisation guidelines prior to initiating treatment.

Nemolizumab [1], vaccinations with live organism vaccines ---> SmPC of [1] of EMA

Concurrent use of live vaccines in patients treated with nemolizumab should be avoided.

CONTRAINDICATIONS of Nemolizumab (Nemluvio)

- 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/nemluvio-epar-product-information_en.pdf 14/01/2026

Nepafenac (Nevanac)

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

Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines.

Bleeding time, nepafenac [2] ---> SmPC of [2] of EMA

Concomitant use of nepafenac with medications that prolong bleeding time may increase the risk of haemorrhage

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

NEVANAC can be used during breastfeeding.

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

There are no data on the effect of NEVANAC on human fertility.

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

Nevertheless, as inhibition of prostaglandin synthesis may negatively affect pregnancy and/or embryonal/foetal development and/or parturition and/or postnatal development. NEVANAC is not recommended during pregnancy.

Nepafenac [1], prostaglandin analogues ---> SmPC of [1] of EMA

There are very limited data on the concomitant use of prostaglandin analogues and NEVANAC. Considering their mechanism of action, the concomitant use of these medicinal products is not recommended.

Nepafenac [1], protein binding ---> SmPC of [1] of EMA

In vitro studies have demonstrated a very low potential for interaction with other medicinal products and protein binding interactions (see section 5.2).

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

NEVANAC should not be used by women of child bearing potential not using contraception.

NSAID, steroids ---> SmPC of [nepafenac] of EMA

Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.

CONTRAINDICATIONS of Nepafenac (Nevanac)

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

- Hypersensitivity to other nonsteroidal anti-inflammatory drugs (NSAIDs).

- Patients in whom attacks of asthma, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other NSAIDs.

https://www.ema.europa.eu/en/documents/product-information/nevanac-epar-product-information_en.pdf 29/02/2024

Neratinib (Nerlynx)

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

The clinical status of the patient should be considered when assessing the patient's ability to perform tasks that require judgment, motor, or cognitive skills.

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

Separate dosing of Nerlynx and antacids by at least 3 hours (see sections 4.2, 4.4 and 5.2).

Atazanavir, neratinib [2] ---> SmPC of [2] of EMA

Concomitant use of strong or moderate CYP3A4/P-gp inhibitors significantly increased neratinib systemic exposure, therefore, concomitant use of neratinib with strong and moderate CYP3A4/P-gp inhibitors is not recommended

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

As co-administration of neratinib with BCRP substrates may lead to an increase of their exposure, patients who are treated with BCRP substrates (e.g., rosuvastatin, sulfasalazine and irinotecan) should be monitored carefully (see section 5.2).

Bosentan, neratinib [2] ---> SmPC of [2] of EMA

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

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

A decision must be made whether to discontinue breast-feeding or to discontinue Nerlynx, taking into account the importance of Nerlynx to the mother and the benefit of breast-feeding to the child.

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

Concomitant use of strong CYP3A4/P-gp inducers significantly decreased neratinib exposure, therefore concurrent use of neratinib with strong CYP3A4/P-gp inducers is contraindicated

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

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

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

Colchicine, neratinib [2] ---> SmPC of [2] of EMA

This might be clinically relevant for patients who are treated concomitantly with therapeutic agents with a narrow therapeutic window whose absorption involves P-gp transporters in the gastrointestinal tract

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

Dabigatran, neratinib [2] ---> SmPC of [2] of EMA

This pre-systemic interaction of neratinib with digoxin might be clinically relevant for P-gp substrates with a narrow therapeutic window (e.g. dabigatran, digoxin, and fexofenadine).

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

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

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

Diltiazem, neratinib [2] ---> SmPC of [2] of EMA

Efavirenz, neratinib [2] ---> SmPC of [2] of EMA

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

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

Etravirine, neratinib [2] ---> SmPC of [2] of EMA

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

Everolimus, neratinib [2] ---> SmPC of [2] of EMA

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

No fertility studies in women or men have been conducted. No significant changes in fertility parameters in male and female rats were detected in dosing up to 12 mg/kg/day (see section 5.3).

Fexofenadine, neratinib [2] ---> SmPC of [2] of EMA

This pre-systemic interaction of neratinib with digoxin might be clinically relevant for P-gp substrates with a narrow therapeutic window (e.g. dabigatran, digoxin, and fexofenadine).

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

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

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

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

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

Grapefruit/pomegranate or grapefruit/pomegranate juice may also increase neratinib plasma concentrations and should be avoided (see section 4.2 and 4.4).

Grapefruit, neratinib [2] ---> SmPC of [2] of EMA

Grapefruit/pomegranate or grapefruit/pomegranate juice may also increase neratinib plasma concentrations and should be avoided (see section 4.2 and 4.4).

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

Nerlynx should be taken at least 2 hours before or 10 hours after the intake of the H2-receptor antagonist (see sections 4.2, 4.4 and 5.2).

Hormonal contraceptives, neratinib [2] ---> SmPC of [2] of EMA

It is currently unknown whether Nerlynx reduces the effectiveness of systemically acting hormonal contraceptives. Therefore, women using systemically acting hormonal contraceptives should add a barrier method (see section 4.6).

Indinavir, neratinib [2] ---> SmPC of [2] of EMA

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

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

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

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

Coadministration with proton pump inhibitors (PPIs) is not recommended (e.g. omeprazole or lansoprazole) (see sections 4.4 and 5.2).

Loperamide, neratinib [2] ---> SmPC of [2] of EMA

A clinical study has demonstrated that there were no clinically significant differences in the exposure of subjects to neratinib with or without concurrent dosing with loperamide (see section 5.2).

Lopinavir, neratinib [2] ---> SmPC of [2] of EMA

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

Concomitant use of neratinib with Kaletra is contraindicated due to serious and/or life-threatening potential reactions including hepatotoxicity

Men, neratinib [2] ---> SmPC of [2] of EMA

Men should use a barrier method of contraception during treatment and for 3 months after stopping treatment.

Moderate CYP3A4 inductors, neratinib [2] ---> SmPC of [2] of EMA

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

Moderate CYP3A4 inhibitors, neratinib [2] ---> SmPC of [2] of EMA

Co-administration of neratinib with moderate CYP3A4/P-gp inhibitors is contraindicated

Moderate P-gp inhibitors, neratinib [2] ---> SmPC of [2] of EMA

Co-administration of neratinib with moderate CYP3A4/P-gp inhibitors is contraindicated

Nefazodone, neratinib [2] ---> SmPC of [2] of EMA

Nelfinavir, neratinib [2] ---> SmPC of [2] of EMA

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

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

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

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

Concomitant use of strong CYP3A4/P-gp inducers significantly decreased neratinib exposure, therefore concurrent use of neratinib with strong CYP3A4/P-gp inducers is contraindicated

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

Grapefruit/pomegranate or grapefruit/pomegranate juice may also increase neratinib plasma concentrations and should be avoided (see section 4.2 and 4.4).

Neratinib [1], pomegranate juice ---> SmPC of [1] of EMA

Grapefruit/pomegranate or grapefruit/pomegranate juice may also increase neratinib plasma concentrations and should be avoided (see section 4.2 and 4.4).

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

The potential risk for humans is unknown. Nerlynx should not be used during pregnancy unless the clinical condition of the woman requires treatment with neratinib.

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

If neratinib is used during pregnancy, or if the patient becomes pregnant while taking Nerlynx, the patient should be informed of the potential hazard to the foetus.

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

Coadministration with proton pump inhibitors (PPIs) is not recommended (e.g. omeprazole or lansoprazole) (see sections 4.4 and 5.2).

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

Concomitant use of strong CYP3A4/P-gp inducers significantly decreased neratinib exposure, therefore concurrent use of neratinib with strong CYP3A4/P-gp inducers is contraindicated

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

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

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

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

Neratinib [1], St. John's wort ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4/P-gp inducers significantly decreased neratinib exposure, therefore concurrent use of neratinib with strong CYP3A4/P-gp inducers is contraindicated

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

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

Concomitant use of strong CYP3A4/P-gp inducers significantly decreased neratinib exposure, therefore concurrent use of neratinib with strong CYP3A4/P-gp inducers is contraindicated

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

Concomitant treatment with strong CYP3A4 and P-gp inhibitors should be avoided due to risk of increased exposure to neratinib

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

Concomitant treatment with strong CYP3A4 and P-gp inhibitors should be avoided due to risk of increased exposure to neratinib

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

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

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

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

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

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

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

Therefore, women of child-bearing potential must use highly effective contraceptive measures while taking Nerlynx and for 1 month after stopping treatment.

Neratinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased due to CYP3A4 inhibition by ritonavir. Concomitant use of neratinib with Paxlovid is contraindicated due to serious and/or life-threatening potential reactions including hepatotoxicity

Neratinib, omeprazole

Coadministration with proton pump inhibitors (PPIs) is not recommended (e.g. omeprazole or lansoprazole) (see sections 4.4 and 5.2).

Neratinib, primidone [2] ---> SmPC of [2] of EMA

Concurrent use of neratinib with moderate CYP3A4/P-gp inducers is not recommended as it may also lead to loss of efficacy

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

Serum concentrations may be increased due to CYP3A4 inhibition by ritonavir. Concomitant use of neratinib with Norvir is contraindicated due to serious and/or life-threatening potential reactions including hepatotoxicity (see section 4.3).

CONTRAINDICATIONS of Neratinib (Nerlynx)

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

- Co-administration with the following medical products that are strong inducers of the CYP3A4/P-gp isoform of cytochrome P450, such as (see sections 4.5 and 5.2):

carbamazepine, phenytoin (antiepileptics)

St John's wort (Hypericum perforatum) (herbal product)

rifampicin (antimycobacterial)

- Severe hepatic impairment (Child-Pugh C) (see section 5.2).

https://www.ema.europa.eu/en/documents/product-information/nerlynx-epar-product-information_en.pdf 23/05/2025

Netarsudil (Rhokiinsa)

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

Decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Rhokiinsa therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

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

There are no data on the effects of netarsudil on male or female fertility. However, no effects are anticipated, since systemic exposure to netarsudil is negligible (see section 5.2).

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

Rhokiinsa should not be used during pregnancy unless the clinical condition of the woman requires treatment with netarsudil.

CONTRAINDICATIONS of Netarsudil (Rhokiinsa)

- 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/rhokiinsa-epar-product-information_en.pdf 24/10/2025

Netupitant/palonosetron (Akynzeo)

5-HT3 receptor antagonists, citalopram ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, duloxetine ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, escitalopram ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, fluoxetine ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, fluvoxamine ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, paroxetine ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, sertraline ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, SNRIs ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, SSRI ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

5-HT3 receptor antagonists, venlafaxine ---> SmPC of [netupitant/palonosetron] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Ability to drive, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Akynzeo has moderate influence on the ability to drive and use machines. Since it may induce dizziness, somnolence or fatigue, patients should be cautioned not to drive or use machines if such symptoms occur.

Alfentanyl, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant/palonosetron should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range

Alprazolam, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

The potential effects of increased plasma concentrations of benzodiazepines metabolized via CYP3A4 should be considered when coadministering these active substances with netupitant/palonosetron.

BCRP inhibitors, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

In vitro data suggests that netupitant inhibits the efflux of transporter BCRP. The clinical relevance of this effect is not established.

Benzodiazepine primarily metabolised by CYP3A4, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

The potential effects of increased plasma concentrations of benzodiazepines metabolized via CYP3A4 should be considered when coadministering these active substances with netupitant/palonosetron.

Breast-feeding, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Breast-feeding should be discontinued during treatment with Akynzeo and for 1 month after the last dose.

Chemotherapeutic agents that are substrates for CYP3A4, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant is a moderate CYP3A4 inhibitor and can increase the exposure of chemotherapeutic agents that are substrates for CYP3A4. Therefore, patients should be monitored for increased toxicity of chemotherapeutic agents that are substrates for CYP3A4

Colchicine, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

In vitro data show that netupitant is a P-gp inhibitor. Caution is recommended when netupitant is combined with digoxin or with other P-gp substrates such as dabigatran, or colchicine.

Cyclophosphamide, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

No consistent effect was seen with cyclophosphamide after netupitant co-administration.

Cyclosporine, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Dabigatran, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

In vitro data show that netupitant is a P-gp inhibitor. Caution is recommended when netupitant is combined with digoxin or with other P-gp substrates such as dabigatran, or colchicine.

Dexamethasone, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Co-administration of a single dose of 300 mg netupitant with a dexamethasone regimen (20 mg on Day 1, followed by 8 mg twice daily from Day 2 to Day 4) significantly increased the exposure to dexamethasone in a time and dose dependent manner.

Digoxin, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

In vitro data show that netupitant is a P-gp inhibitor. Caution is recommended when netupitant is combined with digoxin or with other P-gp substrates such as dabigatran, or colchicine.

Docetaxel, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Drugs metabolised by CYP3A4, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

This product can increase plasma concentrations of concomitantly administered medicinal products that are metabolized via CYP3A4.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, netupitant/palonosetron [2] ---> SmPC of [2]

Drugs primarily metabolised by UGT2B7, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

In vitro data shows that netupitant inhibits UGT2B7, the magnitude of such an effect in the clinical setting is not established. Caution is recommended when netupitant is combined with an oral substrate of this enzyme

Electrolyte imbalance, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Caution should be exercised in concomitant use of netupitant/palonosetron with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval.

Ergotamine, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Erythromycin, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Exposure to erythromycin and midazolam was increased, when each was co-administered with netupitant. These effects were not considered clinically important. The pharmacokinetic profile of netupitant was unaffected

Etoposide, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Exposure to docetaxel and etoposide was increased 37% and 21%, respectively, when co-administered with netupitant/palonosetron. No consistent effect was seen with cyclophosphamide after netupitant coadministration.

Everolimus, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Fentanyl, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Fertility, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant: In tierexperimentellen Studien wurden keine Auswirkungen auf die Fertilität beobachtet. Palonosetron: In einer Studie an Ratten wurde eine Degeneration des Epithels der Samenkanälchen beobachtet (siehe Abschnitt 5.3).

Irinotecan, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Ketoconazole, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant is mainly metabolized by CYP3A4; therefore, co-administration with medicinal products that inhibit CYP3A4 may increase netupitant plasma levels. Consequently, co-administration with strong CYP3A4 inhibitors should be approached with caution

Ketoconazole, palonosetron ---> SmPC of [netupitant/palonosetron] of EMA

Co-administration with ketoconazole did not affect the pharmacokinetics of palonosetron.

Midazolam, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Morphine, netupitant/palonosetron [2] ---> SmPC of [2] of EMA

Netupitant/palonosetron [1], oral contraceptives ---> SmPC of [1] of EMA

Clinical effects on the efficacy of hormonal contraception are unlikely. No relevant changes of netupitant and palonosetron pharmacokinetics were observed.

Netupitant/palonosetron [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

In vitro data show that netupitant is a P-gp inhibitor. Caution is recommended when netupitant is combined with digoxin or with other P-gp substrates such as dabigatran, or colchicine.

Netupitant/palonosetron [1], pregnancy ---> SmPC of [1] of EMA

Netupitant/palonosetron capsules are contraindicated during pregnancy (see section 4.3).

Netupitant/palonosetron [1], QT interval prolonging drugs ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], quinidine ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], rifampicin ---> SmPC of [1] of EMA

Netupitant is mainly metabolized by CYP3A4; therefore, co-administration with medicinal products that induce CYP3A4 may decrease netupitant plasma concentrations. Consequently, concomitant administration with strong CYP3A4 inducers should be avoided.

Netupitant/palonosetron [1], serotonergic medicines ---> SmPC of [1] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Netupitant/palonosetron [1], sirolimus ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], SNRIs ---> SmPC of [1] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Netupitant/palonosetron [1], SSRI ---> SmPC of [1] of EMA

There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic drugs (including SSRIs and SNRIs).

Netupitant/palonosetron [1], strong CYP3A4 inductors ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], tacrolimus ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], triazolam ---> SmPC of [1] of EMA

The potential effects of increased plasma concentrations of benzodiazepines metabolized via CYP3A4 should be considered when coadministering these active substances with netupitant/palonosetron.

Netupitant/palonosetron [1], UGT2B7 substrates ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], valproic acid ---> SmPC of [1] of EMA

Netupitant/palonosetron [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should not be pregnant or become pregnant while on treatment with netupitant/palonosetron capsules.

Netupitant/palonosetron [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during therapy and up to one month after treatment with this medicinal product.

Netupitant/palonosetron [1], zidovudine ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Netupitant/palonosetron (Akynzeo)

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

- Pregnancy

https://www.ema.europa.eu/en/documents/product-information/akynzeo-epar-product-information_en.pdf 05/01/2024

Nevirapine (Viramune)

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

Abacavir and Viramune can be coadministered without dose adjustments.

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

However, patients should be advised that they may experience adverse reactions such as fatigue during treatment with Viramune.

Acenocoumarol, nevirapine

Nevirapine may decrease the anticoagulant effect of acenocoumarol

Adefovir dipivoxil, nevirapine [2] ---> SmPC of [2] of EMA

Adefovir and nevirapine can be co-administered without dose adjustments

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

The effect of nevirapine on other protease inhibitors and the limited evidence available suggest that nevirapine may decrease the serum concentrations of amprenavir.

Anisindione, nevirapine

Nevirapine may decrease the anticoagulant effect of anisindione

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

The absorption of nevirapine is not affected by food, antacids or medicinal products which are formulated with an alkaline buffering agent.

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

Concomitant administration of aripiprazole and inducers of CYP3A4 may be expected to reduce the geometric means of Cmax and AUC for aripiprazole. The concomitant use of CYP3A4 inducers with aripiprazole should be avoided

Artesunate [1], nevirapine ---> SmPC of [1] of EMA

Co-administration of Artesunate Amivas with UGT inducers (e.g. nevirapine, ritonavir, rifampicin, carbamazepine, phenytoin) may decrease DHA exposures, leading to a reduction in, or loss of, efficacy. Co-administration should be avoided.

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

The mechanism of nevirapine/atazanavir interaction is CYP3A4 induction. Co-administration of nevirapine and REYATAZ is not recommended

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

Coadministration (not recommended) of EVOTAZ with moderate to weak inducers of CYP3A may result in decreased plasma concentrations of atazanavir and/or cobicistat, leading to loss of therapeutic effect and possible development of resistance to atazanavir

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

Co-administration of nevirapine with atazanavir/ritonavir is not recommended

Atorvastatin [1], nevirapine ---> SmPC of [1] of eMC

Concomitant administration of atorvastatin with inducers of cytochrome P450 3A can lead to variable reductions in plasma concentrations of atorvastatin.

Bedaquiline [1], nevirapine ---> SmPC of [1] of EMA

Co-administration of single-dose bedaquiline and multiple-dose nevirapine did not result in clinically relevant changes in the exposure to bedaquiline.

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

It is not recommended to co-administer boceprevir and nevirapine

Bosentan [1], nevirapine ---> SmPC of [1] of EMA

Due to the marked hepatotoxicity of nevirapine, which could add to bosentan liver toxicity, this combination is not recommended

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

Nevirapine is found in breast milk. It is recommended that HIV-infected mothers do not breast-feed their infants to avoid risking postnatal transmission of HIV and that mothers should discontinue breast-feeding if they are receiving nevirapine.

Brotizolam, nevirapine

The strong CYP3A4 induction may decrease the plasma concentrations of brotizolam

Bupropion, nevirapine

The CYP3A and CYP2B6 inductions may decrease the plasma levels of bupropion

Caspofungin [1], nevirapine ---> SmPC of [1] of EMA

When co-administering inducers of metabolic enzymes, an increase in the daily dose of caspofungin to 70 mg, following the 70 mg loading dose, should be considered in adult patients (see section 4.2).

Cerivastatin, nevirapine

The strong CYP3A4 induction may decrease the plasma concentrations of cerivastatin

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

Cimetidine and nevirapine can be co-administered without dose adjustments.

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

Clarithromycin exposure was significantly decreased, 14-OH metabolite exposure increased. Alternatives to clarithromycin, such as azithromycin should be considered.

Clopidogrel, nevirapine

The CYP3A and CYP2B6 inductions may decrease the plasma levels of clopidogrel

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

Co-administration of cobicistat with medicinal products that are moderate inducers of CYP3A may result in decreased plasma concentration of cobicistat. Concomitant use not recommended

Conjugated oestrogens/bazedoxifene [1], nevirapine ---> SmPC of [1] of EMA

The metabolism of oestrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

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

Oral hormonal contraceptives should not be used as the sole method of contraception in women taking Viramune (see section 4.4).

Cyclophosphamide, nevirapine

The CYP2B6 and CYP3A4 inhibition may decrease the efficacy of cyclophosphamide (prodrug)

CYP3A4 and CYP2B6 inductors, nevirapine [2] ---> SmPC of [2] of EMA

Nevirapine is an inducer of CYP3A and potentially CYP2B6, with maximal induction occurring within 2-4 weeks of initiating multiple-dose therapy.

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

Compounds using this metabolic pathway may have decreased plasma concentrations when co-administered with nevirapine.

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

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

Induction of CYP3A4 by etravirine may decrease the daclatasvir concentration. Due to the lack of data, coadministration of daclatasvir and nevirapine is not recommended.

Darunavir/cobicistat, nevirapine ---> SmPC of [darunavir] of EMA

Concomitant use of darunavir/cobicistat with weak to moderate CYP3A4 inductors may result in subtherapeutic plasma exposure to darunavir. Co-administration of darunavir/cobicistat with weak to moderate CYP3A inducers is not recommended

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

Increased AUC of nevirapine from CYP3A inhibition. The combination can be used without dose adjustments.

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

Possibly decreases plasma concentrations of dasabuvir, ombitasvir and paritaprevir. Concomitant use is contraindicated

Dasabuvir [1], nevirapine ---> SmPC of [1] of EMA

Co-administration (contraindicated) of dasabuvir with medicinal products that are strong or moderate enzyme inducers is expected to decrease dasabuvir plasma concentrations and reduce its therapeutic effect

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

The concomitant administration of nevirapine with non-nucleoside reverse transcriptase inhibitors is not recommended.

Dicoumarol, nevirapine

Nevirapine may decrease the anticoagulant effect of dicoumarol

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

Didanosine and Viramune can be coadministered without dose adjustments.

Dienogest, nevirapine

The enzymatic induction may decrease the plasma levels of dienogest

Dolutegravir [1], nevirapine ---> SmPC of [1] of EMA

Nevirapine, enzymatic inductor, may decrease dolutegravir plasma levels. In the presence of integrase class resistance alternative combinations that do not include nevirapine should be considered

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

Co-administration with nevirapine may decrease dolutegravir plasma concentration due to enzyme induction and has not been studied.

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

As Dovato is a fixed-dose tablet, an additional 50 mg tablet of dolutegravir should be administered, approximately 12 hours after Dovato for the duration of the nevirapine co-administration. Induction of UGT1A1 and CYP3A enzymes

Drospirenone/estetrol [1], nevirapine ---> SmPC of [1] of EMA

Medicinal products increasing the clearance of CHCs

Drugs primarily metabolised by CYP3A4, nevirapine

Nevirapine, strong CYP3A4 inductor, may decrease the plasma concentrations of the medicinal products mainly metabolized by CYP3A4

Dydrogesterone/estradiol [1], nevirapine ---> SmPC of [1] of eMC

The metabolism of oestrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

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

It is not recommended to co-administer efavirenz and nevirapine, because of additive toxicity and no benefit in terms of efficacy over either NNRTI alone

Elvitegravir [1], nevirapine ---> SmPC of [1] of EMA

Co-administration of nevirapine and elvitegravir is expected to decrease elvitegravir plasma concentrations which may result in loss of therapeutic effect and possible development of resistance. Co-administration is not recommended

Elvitegravir/cobicistat, nevirapine [2] ---> SmPC of [2] of EMA

Coadministration of nevirapine with elvitegravir in combination with cobicistat is not recommended

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

Emtricitabine and Viramune can be coadministered without dose adjustments.

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

Tenofovir alafenamide exposure is not expected to be affected by maraviroc, nevirapine or raltegravir, nor is it expected to affect the metabolic and excretion pathways relevant to maraviroc, nevirapine or raltegravir.

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

Enfuvirtide and nevirapine can be co-administered without dose adjustments

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

Entecavir and nevirapine can be co-administered without dose adjustments

Estradiol valerate/norgestrel [1], nevirapine ---> SmPC of [1] of eMC

The metabolism of oestrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estradiol [1], nevirapine ---> SmPC of [1] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estradiol/norethisterone [1], nevirapine ---> SmPC of [1] of eMC

The metabolism of oestrogens and progestogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estriol [1], nevirapine ---> SmPC of [1] of eMC

The metabolism of estrogens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

Estrogens, nevirapine ---> SmPC of [estradiol] of eMC

The metabolism of oestrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

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

Decreased AUC of ethinylestradiol. Should not be used as the sole method of contraception

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

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones

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

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

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

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones

Ethinylestradiol/gestodene [1], nevirapine ---> SmPC of [1] of eMC

Drugs which induce hepatic enzymes (especially cytochrome P450 3A4) increase the metabolism of contraceptive steroids and hence may result in breakthrough bleeding and pregnancy.

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

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

Interactions can occur with medicinal products that induce microsomal enzymes, specifically cytochrome P450 enzymes, which can result in increased clearance of sex hormones

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

Concomitant use of etravirine with nevirapine may cause a significant decrease in the plasma concentrations of etravirine and loss of therapeutic effect of etravirine. The concomitant administration of nevirapine with NNRTIs is not recommended

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

Decreased exposure of everolimus expected. Avoid the use of concomitant potent CYP3A4 inducers.

Felodipine, nevirapine ---> SmPC of [felodipine/metoprolol] of eMC

The enzymatic induction may decrease the plasma levels of felodipine

Felodipine/metoprolol, nevirapine

It has been shown that inductors of cytochrome P450-3A4 system decrease the plasma concentrations of felodipine. The concomitant use with strong CYP3A4 inductors should be avoided

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

In reproductive toxicology studies, evidence of impaired fertility was seen in rats.

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

Because of the risk of increased exposure to nevirapine, caution should be exercised if the medicinal products are given concomitantly and patients should be monitored closely

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

The absorption of nevirapine is not affected by food, antacids or medicinal products which are formulated with an alkaline buffering agent.

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

It is not recommended to co-administer fosamprenavir and nevirapine if fosamprenavir is not co-administered with ritonavir

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

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

Gestagens, nevirapine ---> SmPC of [estradiol] of eMC

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes

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

There was a significant decrease in the rate and extent of guanfacine exposure when co-administered with rifampin, a CYP3A4 inducer. Other CYP3A4 inducers may have a comparable effect

Hydrocortisone [1], nevirapine ---> SmPC of [1] of EMA

Potent CYP 3A4 inducers can enhance the metabolic clearance of cortisol, decrease terminal half-life and thus reduce circulating levels and increase fluctuations of cortisol (due to shorter terminal half-life).

Ifosfamide, nevirapine

The CYP3A and CYP2B6 inductions may decrease the plasma levels of ifosfamide

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

The CYP3A4 induction may decrease the plasma concentrations of indinavir. A dose increase of indinavir should be considered if given with nevirapine.

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

Interferon and nevirapine can be co-administered without dose adjustments

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

No CRESEMBA dose adjustment necessary. NNRTIs: careful monitoring for any occurrence of drug toxicity and/or lack of anti-viral efficacy, and dose adjustment if required.

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

A dose increase for itraconazole should be considered when these two agents are administered concomitantly.

Ketoconazole [1], nevirapine ---> SmPC of [1] of EMA

Ketoconazole HRA is mainly metabolised by cytochrome CYP3A4. Enzyme-inducing drugs may significantly reduce the bioavailability of ketoconazole. Use of Ketoconazole HRA with potent enzyme inducers is not recommended.

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

Lamivudine and Viramune can be coadministered without dose adjustments.

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

Letermovir [1], nevirapine ---> SmPC of [1] of EMA

These antivirals may decrease plasma concentrations of letermovir. Co-administration of PREVYMIS with these antivirals is not recommended.

Levonorgestrel [1], nevirapine ---> SmPC of [1] of eMC

The metabolism of levonorgestrel is enhanced by concomitant use of liver enzyme inducers.

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

Decreased plasma levels of lopinavir. No dosage adjustment necessary.

Lopinavir/ritonavir, nevirapine [2] ---> SmPC of [2] of EMA

Decreased plasma levels of lopinavir. The Kaletra dosage should be increased when co-administered with nevirapine.

Lovastatine, nevirapine

The strong CYP3A4 induction may decrease the plasma concentrations of lovastatin

Macimorelin [1], nevirapine ---> SmPC of [1] of EMA

Administration of a CYP3A4 inducer may reduce the plasma macimorelin concentrations and may affect the diagnostic performance of the test and therefore should be avoided.

Macrolide antibiotics, nevirapine

Increased plasma levels of nevirapine.

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

Maraviroc and nevirapine can be co-administered without dose adjustments

Maribavir [1], nevirapine ---> SmPC of [1] of EMA

A dose adjustment of maribavir to 1 200 mg twice daily is recommended when co-administration with these a non-nucleoside reverse transcriptase inhibitors.

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

Medroxyprogesterone and nevirapine can be co-administered without dose adjustments

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

Decreased methadone exposition. Methadone-maintained patients beginning nevirapine therapy should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly.

Methylergometrine, nevirapine

Strong CYP3A4 inhibitors may weaken the pharmacological effect of methylergometrine

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

Nelfinavir and nevirapine can be co-administered without dose adjustments.

Nevirapine [1], non-nucleoside reverse transcriptase inhibitors ---> SmPC of [1] of EMA

The concomitant administration of nevirapine with non-nucleoside reverse transcriptase inhibitors is not recommended.

Nevirapine [1], norethindrone ---> SmPC of [1] of EMA

Decreased AUC of norethindrone. Should not be used as the sole method of contraception

Nevirapine [1], P450 metabolised medicinal products ---> SmPC of [1] of EMA

Careful monitoring of the therapeutic effectiveness of P450 metabolised medicinal products is recommended when taken in combination with nevirapine.

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

Nevirapine readily crosses the placenta. Caution should be exercised when prescribing nevirapine to pregnant women

Nevirapine [1], raltegravir ---> SmPC of [1] of EMA

Raltegravir and nevirapine can be co-administered without dose adjustments

Nevirapine [1], ribavirin ---> SmPC of [1] of EMA

Ribavirin and nevirapine can be co-administered without dose adjustments

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

Rifabutin and nevirapine can be co-administered without dose adjustments. However, due to the high interpatient variability some patients may experience large increases in rifabutin exposure and may be at higher risk for rifabutin toxicity.

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

It is not recommended to co-administer rifampicin and nevirapine. Physicians may consider coadministration of rifabutin instead.

Nevirapine [1], rilpivirine ---> SmPC of [1] of EMA

The concomitant administration of nevirapine with non-nucleoside reverse transcriptase inhibitors is not recommended.

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

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

Nevirapine [1], St. John's wort ---> SmPC of [1] of EMA

Coadministration of nevirapine with herbal preparations containing St. John's wort (Hypericum perforatum) is contraindicated due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine

Nevirapine [1], stavudine ---> SmPC of [1] of EMA

Stavudine and Viramune can be coadministered without dose adjustments.

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

Nevirapine is an inducer of CYP3A. Compounds using this metabolic pathway may have decreased plasma concentrations when co-administered with nevirapine.

Nevirapine [1], telaprevir ---> SmPC of [1] of EMA

Caution should be exercised when co-administering telaprevir with nevirapine. If co-administered with nevirapine, an adjustment in the telaprevir dose should be considered.

Nevirapine [1], telbivudine ---> SmPC of [1] of EMA

Telbivudine and nevirapine can be co-administered without dose adjustments

Nevirapine [1], tenofovir ---> SmPC of [1] of EMA

Tenofovir and Viramune can be coadministered without dose adjustments.

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

The interaction between nevirapine and the antithrombotic agent warfarin is complex, with the potential for both increases and decreases in coagulation time when used concomitantly. Close monitoring of anticoagulation levels is warranted.

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

Women of childbearing potential should not use oral contraceptives as the sole method for birth control, since nevirapine might lower the plasma concentrations of these medicinal products (see sections 4.4 & 4.5).

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

Zidovudine and nevirapine can be co-administered without dose adjustments. Granulocytopenia is commonly associated with zidovudine. In such patients haematological parameters should be carefully monitored.

Nevirapine, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

Known strong inducers of this isozyme (CYP3A) are not recommended with Lynparza, as it is possible that the efficacy of Lynparza could be substantially reduced.

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

Coadministration of Viekirax with/without dasabuvir with drugs that are strong or moderate enzyme inducers is expected to decrease ombitasvir, paritaprevir, and ritonavir plasma levels and reduce their therapeutic effect. Concomitant use contraindicated

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

Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

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

The possible induction of CYP3A4 and P-glycoprotein may decrease the plasma concentrations of pazopanib. The combination should be avoided

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

Co-administration of ritonavir with nevirapine does not lead to clinically relevant changes in the pharmacokinetics of either nevirapine or ritonavir.

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

No dose adjustment required.

Nevirapine, selegiline

The CYP3A and CYP2B6 inductions may decrease the plasma levels of selegiline

Nevirapine, sertraline

The CYP3A and CYP2B6 inductions may decrease the plasma levels of sertraline

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

The CYP3A4 enzyme induction [etravirine or nevirapine] or inhibition [delavirdine] altered plasma concentrations of simeprevir. It is not recommended to co-administer OLYSIO with delavirdine, etravirine or nevirapine.

Nevirapine, simvastatine

The strong CYP3A4 induction may decrease the plasma concentrations of simvastatin

Nevirapine, sorafenib

The CYP3A and CYP2B6 inductions may decrease the plasma levels of sorafenib

Nevirapine, tamoxifen

The CYP3A and CYP2B6 inductions may decrease the plasma levels of tamoxifen

Nevirapine, tenofovir alafenamide [2] ---> SmPC of [2] of EMA

No dose adjustment of Vemlidy or nevirapine is required.

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

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

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

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

Nevirapine, tramadol

Nevirapine may decrease the effect of tramadol by increasing tramadol metabolism and clearance

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

Administration of the potent CYP3A4 inducers markedly decreased Cmax and AUC of ulipristal acetate and its active metabolite. Concomitant use of ulipristal acetate and potent CYP3A4 inducers is not recommended

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

In vitro studies show that the metabolism of voriconazole may be inhibited by NNRTIs and voriconazole may inhibit the metabolism of NNRTIs. Careful monitoring for any occurrence of drug toxicity and/or lack of efficacy

CONTRAINDICATIONS of Nevirapine (Viramune)

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

- Readministration to patients who have required permanent discontinuation for severe rash, rash accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to nevirapine.

- Patients with severe hepatic impairment (Child-Pugh C) or pre-treatment ASAT or ALAT > 5 ULN until baseline ASAT/ALAT are stabilised < 5 ULN.

- Readministration to patients who previously had ASAT or ALAT > 5 ULN during nevirapine therapy and had recurrence of liver function abnormalities upon readministration of nevirapine

- Coadministration with herbal preparations containing St. John's wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of nevirapine

https://www.ema.europa.eu/en/documents/product-information/viramune-epar-product-information_en.pdf 17/10/2024

Other trade names: Nevirapina Actavis, Nevirapina Aurobindo, Nevirapina Combino, Nevirapina Kern Pharma, Nevirapina Mylan, Nevirapina Normon, Nevirapina Panluetol, Nevirapina Sandoz, Nevirapina Teva,

Nicardipine

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

Caution should be exercised because the hypotensive effects of this drug may cause dizziness.

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

Nicardipine may be used in combination with beta-blocking and other anti-hypertensive drugs but the possibility of an additive effect resulting in postural hypotension should be considered.

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

Concentrations of the calcium channel blocker may be increased when co-administered with EVOTAZ. The mechanism of interaction is inhibition of CYP3A4 by atazanavir and cobicistat. Caution is warranted.

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

Nicardipine may be used in combination with beta-blocking and other anti-hypertensive drugs but the possibility of an additive effect resulting in postural hypotension should be considered.

Boceprevir [1], nicardipine ---> SmPC of [1] of EMA

Boceprevir, CYP3A4 inhibitor, may increase the plasma concentrations of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

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

Nicardipine is contraindicated during breastfeeding

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

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inductors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

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

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inhibitors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

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

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat. Clinical monitoring of therapeutic effect and adverse events is recommended when these medicinal products are co-administered with Tybost.

Cyclosporine [1], nicardipine ---> SmPC of [1] of eMC

Inhibitors of CYP3A4 may lead to increased levels of cyclosporine.

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

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

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

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

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

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

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

Boosted darunavir can be expected to increase the plasma concentrations of calcium channel blocker. (CYP3A and/or CYP2D6 inhibition)

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

Careful monitoring of serum digoxin levels is advised in patients also receiving nicardipine as levels may be increased.

Dihydropyridines, rifampicin

Rifampicin, strong CYP3A4 inductor, may decrease the plasma levels of dihydropyridine.

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

If used nicardipine in combination with diuretics or beta-blockers, careful titration of nicardipine is advised.

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

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of calcium antagonist

Efavirenz/emtricitabine/tenofovir disoproxil [1], nicardipine ---> SmPC of [1] of EMA

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of calcium antagonist

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

Concentrations of calcium channel blocker may be increased when co-administered with cobicistat.

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

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat.

Enzalutamide [1], nicardipine ---> SmPC of [1] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of nicardipine and decrease its plasma levels and effect

Fentanyl, nicardipine [2] ---> SmPC of [2] of eMC

Severe hypotension has been reported during fentanyl anaesthesia with concomitant use of a beta-blocker and calcium blockade.

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

Blood levels and/or effects of nicardipine may be altered by phenytoin (CYP3A4 induction)

Grapefruit juice, nicardipine [2] ---> SmPC of [2] of eMC

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inhibitors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

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

The co-administration of idelalisib with nicardipine may increase the serum concentrations of nicardipine. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

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

Increased dihydropyridine calcium channel blocker concentration. Calcium channel blockers are metabolized by CYP3A4 which is inhibited by indinavir. Caution is warranted and clinical monitoring of patients is recommended.

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

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of nicardipine. Clinical monitoring is recommended

Nebivolol [1], nicardipine ---> SmPC of [1] of eMC

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

Nicardipine is contraindicated during pregnancy

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

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inductors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

Nicardipine, phenytoin

Phenytoin may decrease the plasma concentrations of nicardipine

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

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

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

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Nicardipine, sirolimus [2] ---> SmPC of [2] of EMA

Inhibitors of CYP3A4 may decrease the metabolism of sirolimus and increase sirolimus blood levels.

Nicardipine, strong CYP3A4 inductors [2] ---> SmPC of [2] of eMC

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inductors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

Nicardipine, strong CYP3A4 inhibitors [2] ---> SmPC of [2] of eMC

Nicardipine is metabolized by cytochrome P450 3A4. Concomitant administration of nicardipine with inhibitors of cytochrome P450 3A4 may alter the plasma levels of nicardipine.

Nicardipine, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

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

Inhibition of CYP3A and/or effect on P-gp transport in the gut increases plasma concentration of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Nicardipine, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Nicardipine, vasodilators

Nicardipine should not be administered with other vasodilatators in order to avoid the synergistic effects

CONTRAINDICATIONS of Nicardipine

1) Pregnancy and lactation.

2) Hypersensitivity to nicardipine hydrochloride or other dihydropyridines because of the theoretical risk of cross reactivity.

3) Because part of the effect of nicardipine is secondary to reduced afterload, the drug should not be given to patients with severe aortic stenosis. Reduction of diastolic pressure in these patients may worsen rather than improve myocardial infarction.

4) Cardene should not be used in cardiogenic shock, clinically significant aortic stenosis, unstable angina, and during or within one month of a myocardial infarction.

Cardene should not be used for acute attacks of angina.

5) Cardene should not be used for secondary prevention of myocardial infarction.

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

Nicorandil

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

Blood pressure-lowering effects of nicorandil can reduce the ability to drive or to use machines.

Alcohol, nicorandil [2] ---> SmPC of [2] of eMC

If nicorandil is used concomitantly with antihypertensive agents or other medicinal products with blood-pressure-lowering effect the blood-pressure-lowering effect may be increased.

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

If nicorandil is used concomitantly with antihypertensive agents or other medicinal products with blood-pressure-lowering effect the blood-pressure-lowering effect may be increased.

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

It is not known whether nicorandil is excreted in human milk, therefore it is not recommended during breastfeeding.

Calcium antagonists, nicorandil [2] ---> SmPC of [2] of eMC

If nicorandil is used concomitantly with antihypertensive agents or other medicinal products with blood-pressure-lowering effect the blood-pressure-lowering effect may be increased.

Clopidogrel/acetylsalicylic acid [1], nicorandil ---> SmPC of [1] of EMA

In patients concomitantly receiving nicorandil and NSAIDs including ASA and LAS, there is an increased risk for severe complications such as gastrointestinal ulceration, perforation and haemorrhage

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

Gastrointestinal perforations in the context of concomitant use of nicorandil and corticosteroids have been reported. Caution is advised when concomitant use is considered.

Nicorandil [1], PDE5 inhibitors ---> SmPC of [1] of eMC

Concurrent use of nicorandil and phosphodiesterase 5 inhibitors is contraindicated, since it can lead to a serious drop in blood pressure.

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

Nicorandil must only be used in pregnant women if the anticipated benefit outweighs any potential risks.

Nicorandil [1], tadalafil ---> SmPC of [1] of eMC

Concurrent use of nicorandil and phosphodiesterase 5 inhibitors is contraindicated, since it can lead to a serious drop in blood pressure.

Nicorandil [1], tricyclic antidepressant ---> SmPC of [1] of eMC

If nicorandil is used concomitantly with antihypertensive agents or other medicinal products with blood-pressure-lowering effect the blood-pressure-lowering effect may be increased.

Nicorandil [1], vasodilators ---> SmPC of [1] of eMC

If nicorandil is used concomitantly with antihypertensive agents or other medicinal products with blood-pressure-lowering effect the blood-pressure-lowering effect may be increased.

Nicorandil, sildenafil [2] ---> SmPC of [2] of EMA

Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component it has the potential to result in a serious interaction with sildenafil.

Nicorandil, sulfonylureas

Sulphonylurea agent has the potential to close potassium channels and may thus antagonise some of the effects of nicorandil.

Nicorandil, vardenafil [2] ---> SmPC of [2] of EMA

Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component it has the potential to result in a serious interaction with sildenafil.

CONTRAINDICATIONS of Nicorandil

- Ikorel is contraindicated in patients with hypersensitivity to nicorandil or any of the excipients.

- Nicorandil must not be used in the case of cardiogenic shock, hypotension or left ventricular failure with low filling pressure.

- Concurrent use of nicorandil and phosphodiesterase 5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) is contraindicated since it can lead to a serious drop in blood pressure.

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

Nicotine

Adenosine, nicotine

Nicotine may increase the hemodynamic effects of adenosine

Adrenergic agonists, nicotine [2] ---> SmPC of [2] of eMC

Smoking and nicotine may raise the blood levels of cortisol and catecholamines, i.e. may lead to an increased effect of adrenergic agonists.

Adrenoceptor antagonists, nicotine [2] ---> SmPC of [2] of eMC

Smoking and nicotine may raise the blood levels of cortisol and catecholamines, i.e. may lead to a reduced effect of adrenergic antagonists

Agomelatine [1], nicotine ---> SmPC of [1] of EMA

Smoking induces CYP1A2 and has been shown to decrease the bioavailability of agomelatine, especially in heavy smokers (≥ 15 cigarettes/day)

Alpha-1 proteinase inhibitor, nicotine

Decreased effect of alpha-1 proteinase inhibitor

Alpha1-antytripsin, nicotine

Decreased effect of alpha1-antitrypsin

Aminophylline [1], nicotine ---> SmPC of [1] of eMC

Smoking can increase clearance of theophylline.

Benperidol [1], nicotine ---> SmPC of [1] of eMC

Smoking may theoretically enhance the metabolic breakdown of neuroleptics, necessitating an increased dose.

Betablockers, nicotine ---> SmPC of [propranolol] of eMC

Smoking tobacco may oppose the effects of beta blockers in the treatment of angina or hypotension.

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

Nicotine is excreted in breast milk in quantities that may affect the child even in therapeutic doses.

Bromperidol, nicotine

The co-administration may decrease the plasma levels of bromperidol

Bupropion, nicotine

Nicotine, administered transdermally by patches, may increase the blood pressure

Caffeine, nicotine

Nicotine, strong CYP1A2 inductor, may decrease the plasma concentrations of caffeine

Certoparin, nicotine

The co-administration may weaken the pharmacological effects of certoparin

Cilostazol [1], nicotine ---> SmPC of [1] of EMA

In clinical trials, smoking (which induces CYP1A2) decreased cilostazol plasma concentrations by 18%.

Cinacalcet [1], nicotine ---> SmPC of [1] of EMA

In vitro data indicate that cinacalcet is in part metabolised by CYP1A2. Smoking induces CYP1A2; the clearance of cinacalcet was observed to be 36-38% higher in smokers than non-smokers.

Clomipramine [1], nicotine ---> SmPC of [1] of eMC

Known inducers of CYP1A2 (e.g. nicotine/components in cigarette smoke), decrease plasma concentrations of tricyclic drugs

Clozapine [1], nicotine ---> SmPC of [1] of eMC

In cases of sudden cessation of smoking, the plasma clozapine concentration may be increased, thus leading to an increase in adverse effects.

CYP1A2 substrates with narrow therapeutic index, nicotine [2] ---> SmPC of [2] of eMC

Smoking but not nicotine is associated with increased CYP1A2 activity. After stopping smoking there may be increased plasma levels of some medicinal products of potential clinical importance because of their narrow therapeutic window

Dalteparin [1], nicotine ---> SmPC of [1] of eMC

As heparin has been shown to interact with intravenous nitroglycerine, tobacco smoking interaction cannot be ruled out for dalteparin.

Dextropropoxyphene, nicotine

Decreased analgetic effect of dextropropoxyphene

Diazepam, nicotine

The clearance of diazepam can be accelerated by smokers

Dihydroergotamine, nicotine

Concomitant use of dihydroergotamine with peripheral vasoconstrictors may enhance the vasoconstrictor effect and is contraindicated

Drugs metabolised by CYP1A2, nicotine

Nicotine, strong CYP1A2 inductor, may decrease the plasma concentrations of the medicinal products metabolized by CYP1A2

Duloxetine [1], nicotine ---> SmPC of [1] of EMA

Population pharmacokinetic studies analyses have shown that smokers (induction of CYP1A2) have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.

Enoxaparin, nicotine

The co-administration may weaken the effect of enoxaparin

Ergot derivatives, nicotine

Excessive nicotine may enhance the vasoconstriction

Ergotamine, nicotine

Concomitant use of ergotamine and nicotine (e. g. smoking) may enhance the vasoconstriction

Erlotinib [1], nicotine ---> SmPC of [1] of EMA

Results of a pharmacokinetic interaction study indicated a significant 2.8-, 1.5- and 9-fold reduced AUCinf, Cmax and plasma concentration at 24 hours, respectively, after administration of erlotinib in smokers as compared to non-smokers

Fentanyl, nicotine

Decreased plasma concentrations of fentanyl

Flecainide, nicotine

Nicotine may increase the metabolism of flecainide and decrease its plasma concentrations

Fluvoxamine, nicotine

Nicotine, strong CYP1A2 inductor, may decrease the plasma concentrations of fluvoxamine

Furosemide, nicotine [2] ---> SmPC of [2] of eMC

Smoking may lead to reduced diuretic response to furosemide

H2 antagonists, nicotine [2] ---> SmPC of [2] of eMC

Smoking may lead to reduced responder rates in ulcer healing with H2-antagonists.

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

Drugs which activate the hepatic mono-oxygenase enzyme system may accelerate the metabolism and lower plasma concentrations of imipramine, resulting in decreased efficacy.

Insulin, nicotine [2] ---> SmPC of [2] of eMC

Increased subcutaneous absorption of insulin which occurs upon smoking cessation may necessitate a reduction in insulin dose.

Isoprenaline, nicotine

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

Medazepam, nicotine

Acceleration of medazepam elimination

Melatonin [1], nicotine ---> SmPC of [1] of EMA

Cigarette smoking may decrease melatonin levels due to induction of CYP1A2.

Memantin [1], nicotine ---> SmPC of [1] of EMA

Active substances that use the same renal cationic transport system as amantadine may possibly interact with memantine leading to a potential risk of increased plasma levels.

Methylergometrine, nicotine

Methylergometrine may enhance the vasoconstrictor/vasopressor effect of other medicinal products

Methysergide [1], nicotine ---> SmPC of [1] of eMC

Concomitant use of methysergide and vasoconstrictors or vasopressors must be avoided since this may result in enhanced vasoconstriction

Nadroparin, nicotine

The co-administration may weaken the nadroparin effect

Naratriptan [1], nicotine ---> SmPC of [1] of eMC

Nicotine increases the total clearance of naratriptan. But no dosing adjustments are required.

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

In pregnant women, complete cessation of tobacco smoking should always be recommended without nicotine replacement therapy.

Nicotine [1], ropinirole ---> SmPC of [1] of eMC

Nicotine [1], tacrine ---> SmPC of [1] of eMC

Nicotine, olanzapine [2] ---> SmPC of [2] of EMA

The metabolism of olanzapine may be induced by smoking, which may lead to reduced olanzapine concentrations.

Nicotine, opiates

Smoking may lead to reduced analgesic effects of opioids (e.g. dextropropoxyphene, pentazocine)

Nicotine, pentazocine [2] ---> SmPC of [2] of eMC

Tobacco smoking appears to enhance the metabolic clearance rate of pentazocine reducing the clinical effectiveness of a standard dose.

Nicotine, pirfenidone [2] ---> SmPC of [2] of EMA

Smoking has the potential to induce hepatic enzyme (CYP1A2) production and thus increase medicinal product clearance and decrease exposure. Patients should be encouraged to stop smoking before and during treatment with pirfenidone.

Nicotine, prazosin

Decrease of circulating catecholamines. It can be necessary to reduce the dose of alfa-adrenergic antagonist

Nicotine, progesterone

Possible decrease of progesterone bioavailability

Nicotine, propranolol [2] ---> SmPC of [2] of eMC

Smoking tobacco may oppose the effects of beta blockers in the treatment of angina or hypotension.

Nicotine, rasagiline [2] ---> SmPC of [2] of EMA

There is a risk that the plasma levels of rasagiline in smoking patients could be decreased, due to induction of the metabolising enzyme CYP1A2.

Nicotine, riluzole [2] ---> SmPC of [2] of EMA

In vitro studies suggest that CYP1A2 is the principal isozyme involved in the initial oxidative metabolism of riluzole. Inducers of CYP1A2 could increase the rate of riluzole elimination.

Nicotine, riociguat [2] ---> SmPC of [2] of EMA

Plasma concentrations of riociguat in smokers are reduced compared to non-smokers. Dose adjustment may be necessary in patients who start or stop smoking during treatment with riociguat

Nicotine, salbutamol

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

Nicotine, tasimelteon [2] ---> SmPC of [2] of EMA

Tasimelteon exposure decreased by approximately 40% in smokers compared to non-smokers. This reduction in exposure is not considered clinically relevant and therefore no dose adjustment is necessary.

Nicotine, theophylline [2] ---> SmPC of [2] of eMC

Smoking can increase clearance of theophylline.

Nicotine, tizanidine

The administration of tizanidine to smokers (> 10 cigarettes/day) decreases the systemic exposition of tizanidine

Nicotine, tricyclic antidepressant ---> SmPC of [clomipramine] of eMC

Known inducers of CYP1A2 (e.g. nicotine/components in cigarette smoke), decrease plasma concentrations of tricyclic drugs

Nicotine, zafirlukast [2] ---> SmPC of [2] of eMC

The clearance of zafirlukast in smokers may be increased by approximately 20%.

CONTRAINDICATIONS of Nicotine

- Hypersensitivity to nicotine or to any of the excipients

- Boots NicAssist lozenge should not be used by non-smokers.

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

Nifedipine

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

Reactions to nifedipine may vary in intensity in patients

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

Nifedipine may be used in combined therapy with other antihypertensive agents including beta-blocker drugs, but the possibility of an additive effect resulting in postural hypotension should be borne in mind.

AIIRA, nifedipine [2] ---> SmPC of [2] of eMC

Alfa-adrenergic receptor blockers, nifedipine [2] ---> SmPC of [2] of eMC

Alpha-methyldopa, nifedipine [2] ---> SmPC of [2] of eMC

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

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

Atenolol [1], nifedipine ---> SmPC of [1] of eMC

Concomitant administration of atenolol und dihydropyridine derivatives may increase the risk of hypotension, and in patients with latent cardiac insufficiency, treatment with beta-blocking agents may lead to cardiac failure.

Atenolol/chlortalidone [1], nifedipine ---> SmPC of [1] of eMC

Concomitant therapy with dihydropyridines may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.

Atenolol/nifedipine, digoxin ---> SmPC of [nifedipine] of eMC

The administration of nifedipine and digoxin concurrently may lead to reduced digoxin clearance and therefore, bring about an increase in the plasma digoxin level.

Azithromycin, nifedipine

Azithromycin doesn't inhibit the CYP3A4

Azole antifungals, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

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

Betaxolol, nifedipine

The combination may cause strong hypotension (in individual cases cardiac failure). The sympathetic reflex reactions to strong hemodynamic episodes may be reduced

Boceprevir [1], nifedipine ---> SmPC of [1] of EMA

Boceprevir, CYP3A4 inhibitor, may increase the plasma concentrations of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

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

Nifedipine may be present in breast milk and therefore contraindicated for use in nursing mothers.

Calcium antagonists, nifedipine [2] ---> SmPC of [2] of eMC

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

Carbamazepine, strong CYP3A4 inductor, may decrease the plasma concentrations of nifedipine

Cefixime, nifedipine

Nifedipine may increase the plasma levels of cephalosporin

Celiprolol [1], nifedipine ---> SmPC of [1] of eMC

Concomitant therapy of celiprolol with dihydropyridine calcium channel antagonists may increase the risk of hypotension, and cardiac failure may occur in patients with latent or uncontrolled cardiac insufficiency.

Cephalosporins, nifedipine

Nifedipine may increase the plasma levels of cephalosporin

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

Due to its inhibition of cytochrome P450 3A4, cimetidine elevates the plasma concentrations of nifedipine and may potentiate the antihypertensive effect

Cisapride, nifedipine

Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentration of nifedipine.

Clopidogrel [1], nifedipine ---> SmPC of [1] of EMA

No clinically significant pharmacodynamic interactions were observed when clopidogrel was co-administered with atenolol, nifedipine, or both atenolol and nifedipine.

Clopidogrel/acetylsalicylic acid [1], nifedipine ---> SmPC of [1] of EMA

No clinically significant pharmacodynamic interactions were observed when clopidogrel was co-administered with atenolol, nifedipine, or both atenolol and nifedipine.

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

Cyclosporine [1], nifedipine ---> SmPC of [1] of eMC

The concurrent administration of nifedipine with ciclosporin may result in an increased rate of gingival hyperplasia compared with that observed when ciclosporin is given alone.

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

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

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

Administration of daclatasvir with nifedipine (CYP3A4 inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Dalfopristin, nifedipine [2] ---> SmPC of [2] of eMC

Simultaneous administration of quinupristin / dalfopristin and nifedipine may lead to increased plasma concentration of nifedipine.

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

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

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

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

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

Boosted darunavir can be expected to increase the plasma concentrations of calcium channel blocker. (CYP3A and/or CYP2D6 inhibition)

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

CYP3A4 inhibition. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Digitoxin, nifedipine

The CYP3A4 inhibition may increase the plasma levels of digitoxin

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

The administration of nifedipine and digoxin concurrently may lead to reduced digoxin clearance and therefore, bring about an increase in the plasma digoxin level.

Diltiazem, nifedipine

Diltiazem decreases the clearance of nifedipine

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

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

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of calcium antagonist

Efavirenz/emtricitabine/tenofovir disoproxil [1], nifedipine ---> SmPC of [1] of EMA

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of calcium antagonist

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

Eluxadoline may increase the exposure of co-administered medicinal products metabolised by Cytochrome CYP3A4. Caution should be exercised when administering such products, especially for those with a narrow therapeutic index.

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

Concentrations of calcium channel blocker may be increased when co-administered with cobicistat.

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

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat.

Enzalutamide [1], nifedipine ---> SmPC of [1] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of nifedipine and decrease its plasma levels and effect

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

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

Esmolol [1], nifedipine ---> SmPC of [1] of eMC

Calcium antagonists may increase the risk of hypotension. In patients with cardiac insufficiency and who are being treated with a calcium antagonist, treatment with beta-blocking agents may lead to cardiac failure.

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

Nifedipine is metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of amlodipine. Frequent monitoring for adverse events is recommended.

Fluoxetine, nifedipine [2] ---> SmPC of [2] of eMC

The CYP3A4 inhibition may increase the plasma concentrations of nifedipine

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

Blood levels and/or effects of nifedipine may be altered by phenytoin (CYP3A4 induction)

Grapefruit juice, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine should not be taken with grapefruit juice because bioavailability is increased.

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

The co-administration of idelalisib with nifedipine may increase the serum concentrations of nifedipine. Clinical monitoring of therapeutic effect and adverse reactions is recommended.

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

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

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

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

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

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

Lopinavir/ritonavir, CYP3A4 inhibitors, may increase the plasma concentrations of nifedipine. Clinical monitoring is recommended

Macrolide antibiotics, nifedipine

The macrolide inhibits the CYP3A4 and therefore may increase the plasma concentrations of nifedipine. Azithromycin is void of CYP3A4 inhibition.

Metformin, nifedipine

Increased absorption, plasma levels and hypoglycemic effect of metformin

Metildigoxin, nifedipine

Increased plasma levels of metildigoxin

Metoprolol [1], nifedipine ---> SmPC of [1] of eMC

Calcium channel blockers (such as dihydropyridine derivatives e.g. nifedipine) should not be given in combination with metoprolol because of the increased risk of hypotension and heart failure.

Micafungin [1], nifedipine ---> SmPC of [1] of EMA

Patients receiving nifedipine in combination with micafungin should be monitored for nifedipine toxicity and the nifedipine dosage should be reduced if necessary

Mizolastine [1], nifedipine ---> SmPC of [1] of eMC

Concurrent use of other potent inhibitors or substrates of hepatic oxidation (cytochrome P450 3A4) with mizolastine should be approached with caution.

Moderate CYP3A4 inhibitors, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs that are known to inhibit this enzyme

Nebivolol [1], nifedipine ---> SmPC of [1] of eMC

Nefazodone, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

Nelfinavir, nifedipine [2] ---> SmPC of [2] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

Nicergoline, nifedipine

Nicergoline may enhance the hypotensive effect of the coadministered hypotensive agents

Nifedipine [1], organic nitrates ---> SmPC of [1] of eMC

Nifedipine [1], PDE5 inhibitors ---> SmPC of [1] of eMC

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

The strong CYP3A4 induction may decrease the plasma concentrations of nifedipine

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

The strong CYP3A4 induction may decrease the plasma concentrations of nifedipine. The phenytoin plasma concentrations can increase

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

Nifedipine is contraindicated in woman capable of child-bearing. Safe use of nifedipine during human pregnancy has not been established.

Nifedipine [1], protease inhibitors ---> SmPC of [1] of eMC

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs known to inhibit this enzyme system.

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

It is reported that serum quinidine levels have been reduced when it is used in combination with nifedipine, irrespective of the quinidine dose taken.

Nifedipine [1], quinupristin ---> SmPC of [1] of eMC

Simultaneous administration of quinupristin / dalfopristin and nifedipine may lead to increased plasma concentration of nifedipine.

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

Nifedipine should not be administered concomitantly with rifampicin, as effective plasma levels of nifedipine may not be achieved as a result of enzyme induction.

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

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs that are known to induce this enzyme

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

Nifedipine is metabolised via the cytochrome P450 3A4 system. Therefore, there are theoretical interactions with drugs that are known to inhibit this enzyme

Nifedipine [1], valproic acid ---> SmPC of [1] of eMC

The CYP3A4 inhibition may increase the plasma concentrations of nifedipine

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

CYP3A4 inhibition. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Nifedipine, oxprenolol

The co-administration may enhance the hypotensive effect

Nifedipine, pantoprazole [2] ---> SmPC of [2] of EMA

No clinically significant interactions were observed

Nifedipine, penbutolol

The co-administration of calcium antagonists of nifedipine type with penbutolol may cause strong hypotension

Nifedipine, pindolol/clopamide [2] ---> SmPC of [2] of eMC

The concomitant use of pindolol/clopamide with dihydropyridines e.g. nifedipine may increase the risk of hypotension.

Nifedipine, posaconazole [2] ---> SmPC of [2] of EMA

Concomitant use of posaconazole with calcium channel blockers metabolised through CYP3A4 increases plasma concentrations of the calcium channel blocker.

Nifedipine, repaglinide [2] ---> SmPC of [2] of EMA

Co-administration of cimetidine, nifedipine, oestrogen, or simvastatin with repaglinide, all CYP3A4 substrates, did not significantly alter the pharmacokinetic parameters of repaglinide.

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

Ritonavir, CYP3A4 inhibitor, may increase the plasma concentrations of nifedipine. Careful monitoring of therapeutic and adverse effects is recommended.

Nifedipine, salbutamol

The co-administration may enhance the broncholytic effect of salbutamol

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

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

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

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Nifedipine, sitaxentan [2] ---> SmPC of [2] of EMA

The clearance of nifedipine was not clinically significantly changed when given concomitantly with sitaxentan. This was tested for low-dose nifedipine only. Therefore, at higher doses of nifedipine, an increase in exposure cannot be excluded.

Nifedipine, sucroferric oxyhydroxide [2] ---> SmPC of [2] of EMA

In vitro studies did not show any relevant interaction

Nifedipine, tacrolimus [2] ---> SmPC of [2] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

Nifedipine, talinolol

Concomitant therapy of talinolol with dihydropyridine calcium channel antagonists may increase the risk of hypotension, and cardiac failure may occur in patients with latent or uncontrolled cardiac insufficiency.

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

Inhibition of CYP3A and/or effect on P-gp transport in the gut increases plasma concentration of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Nifedipine, telithromycin [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of nifedipine and may result in hypotension, bradycardia or loss of consciousness, and should therefore be avoided.

Nifedipine, theophylline

The co-administration may increase the plasma levels of theophylline

Nifedipine, vardenafil [2] ---> SmPC of [2] of EMA

In a specific study, where vardenafil (20 mg) was co-administered with slow release nifedipine (30 mg or 60 mg) in hypertensive patients, there was an additional reduction on blood pressure

Nifedipine, vincristine [2] ---> SmPC of [2] of eMC

Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily

CONTRAINDICATIONS of Nifedipine

- in patients with a known hypersensitivity to the drug or other constituents of the tablets

- in patients with a known hypersensitivity to other dihydropyridines calcium antagonists, because of the theoretical risk of cross-reactivity

- in women who are or may become pregnant, are capable of child bearing or to nursing mothers

- in patients with clinically significant aortic stenosis, in cardiogenic shock or unstable angina or for the treatment of acute attacks of angina

- in patients with inflammatory bowel disease, Crohn's disease or with a history of gastrointestinal obstruction, oesophageal obstruction or with decreased diameter of the gas

- in patients with hepatic impairment

- for secondary prevention of myocardial infarction or during or within one month of a myocardial infarction

It should not be administered concomitantly with rifampicin since effective plasma levels of nifedipine may not be achieved owing to enzyme induction

The safety of nifedipine prolonged release tablets has not been established in patients with malignant hypertension.

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

Nilotinib (Tasigna)

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

It is recommended that patients experiencing dizziness, fatigue, visual impairment or other undesirable effects with a potential impact on the ability to drive or use machines safely should refrain from these activities as long as the undesirable effects

Alectinib [1], nilotinib ---> 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.

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

Nilotinib is a moderate CYP3A4 inhibitor. Appropriate monitoring and dose adjustment may be necessary for drugs that are CYP3A4 substrates and have a narrow therapeutic index when co-administered with nilotinib.

Aluminium hydroxide, nilotinib [2] ---> SmPC of [2] of EMA

If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of Tasigna.

Amiodarone, nilotinib [2] ---> SmPC of [2] of EMA

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with medicinal products with a known potential to prolong QT. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

Anagrelide, nilotinib [2] ---> SmPC of [2] of EMA

It may be given with hydroxyurea or anagrelide if clinically indicated.

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

If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of Tasigna.

Antiarrhythmics, nilotinib [2] ---> SmPC of [2] of EMA

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

Concentrations of the antineoplastic may be increased when coadministered with EVOTAZ resulting in the potential for increased adverse events. The mechanism of interaction is CYP3A4 inhibition by cobicistat.

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

Since a risk to the newborns/infants cannot be excluded, women should not breast-feed during Tasigna treatment and for 2 weeks after the last dose.

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

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent.

Chloroquine, nilotinib [2] ---> SmPC of [2] of EMA

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

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with strong CYP3A4 inhibitors. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

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

Concentrations of nilotinib may be increased when co-administered with cobicistat resulting in the potential for increased adverse events usually associated with this anticancer medicinal product.

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

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

Alternative concomitant medicinal products with nilotinib with no or minimal CYP3A4 inhibition should be considered.

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

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

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

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition. Caution should be exercised when combining

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

Boosted darunavir is expected to increase the antineoplastic plasma concentrations. (CYP3A inhibition)

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

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

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

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

Nilotinib is a moderate CYP3A4 inhibitor. As a result, the systemic exposure of other drugs primarily metabolised by CYP3A4 may be increased when co-administered with nilotinib.

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

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

Erythropoietin, nilotinib [2] ---> SmPC of [2] of EMA

Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated.

Esomeprazole, nilotinib [2] ---> SmPC of [2] of EMA

Nilotinib has pH dependent solubility, with lower solubility at higher pH. Nilotinib may be used concurrently with esomeprazole or other proton pump inhibitors as needed.

Famotidine, nilotinib [2] ---> SmPC of [2] of EMA

When the concurrent use of a H2 blocker is necessary, it may be administered approximately 10 hours before and approximately 2 hours after the dose of Tasigna.

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

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

Animal studies did not show an effect on fertility in male and female rats (see section 5.3).

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

The absorption and bioavailability of Tasigna are increased if it is taken with food, resulting in a higher serum concentration. Grapefruit juice and other foods that are known to inhibit CYP3A4 should be avoided.

Granulocyte colony-stimulating factor, nilotinib [2] ---> SmPC of [2] of EMA

Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated.

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

The CYP3A4 inhibition may increase the plasma concentrations of nilotinib. The intake of grapefruit/grapefruit juice should be avoided

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

When the concurrent use of a H2 blocker is necessary, it may be administered approximately 10 hours before and approximately 2 hours after the dose of Tasigna.

Halofantrine, nilotinib [2] ---> SmPC of [2] of EMA

Haloperidol, nilotinib [2] ---> SmPC of [2] of EMA

Hemopoietic growth factors, nilotinib [2] ---> SmPC of [2] of EMA

Tasigna may be given in combination with haematopoietic growth factors such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) if clinically indicated.

Hydroxyurea, nilotinib [2] ---> SmPC of [2] of EMA

It may be given with hydroxyurea or anagrelide if clinically indicated.

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

The co-administration of idelalisib with nilotinib may increase the serum concentrations of nilotinib. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Imatinib, nilotinib [2] ---> SmPC of [2] of EMA

Concomitant administration of nilotinib with imatinib (a substrate and moderator of P-gp and CYP3A4), had a slight inhibitory effect on CYP3A4 and/or P-gp. These changes are unlikely to be clinically important.

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

Ketoconazole [1], nilotinib

Not recommended due to the risk of increased exposure to these medicinal products and QT prolongation.

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

Lomitapide [1], nilotinib ---> SmPC of [1] 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.

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

Most tyrosine kinase inhibitors such as dasatinib and nilotinib, also vincristine and vinblastine: Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by Kaletra.

Magnesium hydroxide, nilotinib [2] ---> SmPC of [2] of EMA

If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of Tasigna.

Methadone, nilotinib [2] ---> SmPC of [2] of EMA

Miconazole, nilotinib

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Midazolam, nilotinib [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, nilotinib [2] ---> SmPC of [2] of EMA

Increased exposure to nilotinib might be expected with moderate CYP3A4 inhibitors. Alternative concomitant medicinal products with no or minimal CYP3A4 inhibition should be considered.

Moxifloxacin, nilotinib [2] ---> SmPC of [2] of EMA

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

Therefore, absorption and subsequent elimination of systemically absorbed nilotinib may be influenced by substances that affect CYP3A4 and/or P-gp.

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

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent.

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

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent.

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

Tasigna should not be used during pregnancy unless the clinical condition of the woman requires treatment with nilotinib. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.

Nilotinib [1], procainamide ---> SmPC of [1] of EMA

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

Nilotinib has pH dependent solubility, with lower solubility at higher pH. Nilotinib may be used concurrently with esomeprazole or other proton pump inhibitors as needed.

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

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

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

Rifampicin, a potent CYP3A4 inducer, decreases nilotinib Cmax by 64% and reduces nilotinib AUC by 80%. Rifampicin and nilotinib should not be used concomitantly.

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

Nilotinib [1], simeticone ---> SmPC of [1] of EMA

If necessary, an antacid may be administered approximately 2 hours before or approximately 2 hours after the dose of Tasigna.

Nilotinib [1], sirolimus ---> SmPC of [1] of EMA

Nilotinib [1], sotalol ---> SmPC of [1] of EMA

Nilotinib [1], St. John's wort ---> SmPC of [1] of EMA

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent.

Nilotinib [1], statins metabolised by CYP3A4 ---> SmPC of [1] of EMA

The combination of nilotinib with those statins that are mainly eliminated by CYP3A4, may increase the potential for statin-induced myopathy, including rhabdomyolysis.

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

The concomitant administration of other medicinal products that induce CYP3A4 is likely to reduce exposure to nilotinib to a clinically relevant extent.

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

Nilotinib [1], tacrolimus ---> SmPC of [1] of EMA

Nilotinib [1], telithromycin ---> SmPC of [1] of EMA

Nilotinib [1], voriconazole ---> SmPC of [1] of EMA

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

Due to lack of steady-state data, control of warfarin pharmacodynamic markers (INR or PT) following initiation of nilotinib therapy (at least during the first 2 weeks) is recommended.

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

Women of childbearing potential have to use highly effective contraception during treatment with nilotinib and for up to two weeks after ending treatment.

Nilotinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased when coadministered with ritonavir resulting in the potential for increased incidence of adverse events.

Nilotinib, sodium zirconium cyclosilicate [2] ---> SmPC of [2] of EMA

Sodium zirconium cyclosilicate should be administered at least 2 hours before or 2 hours after oral medicinal products with clinically meaningful gastric pH dependent bioavailability.

Nilotinib, 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 Nilotinib (Tasigna)

- 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/tasigna-epar-product-information_en.pdf 03/12/2024

Other trade names: Nilotinib Accord,

Nimesulide

ACE inhibitors, nimesulide

The co-administration with long-term NSAIDs may decrease the antihypertensive effect and increase the risk of renal failure

Ability to drive, nimesulide

Somnolence, dizziness or fatigue may occur

Acetylsalicylic acid, nimesulide

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Angiotensin-II receptor antagonists, nimesulide

The co-administration with long-term NSAIDs may decrease the antihypertensive effect and increase the risk of renal failure

Antihypertensives, nimesulide

The co-administration may weaken the hypotensive effect

Breast-feeding, nimesulide

Nimesulide is contraindicated during breastfeeding

Coumarin anticoagulants, nimesulide

The coagulation inhibition and the gastrointestinal adverse effects increase the bleeding risk. The co-administration should be avoided

Cyclosporine, nimesulide

Prostaglandin synthetase inhibitors like nimesulide may increase the nephrotoxicity of cyclosporine

Diuretics, nimesulide

Reduced diuretic and antihypertensive effect of diuretic

Drugs primarily metabolised by CYP2C9, nimesulide

Nimesulide, CYP2C9 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by CYP2C9

Glucocorticoids, nimesulide

Increased risk of gastrointestinal haemorrhage and ulceration. Caution is recommended

Lithium, nimesulide

The inhibition of the renal excretion of lithium may increase plasma concentrations and toxicity of lithium. Caution is recommended

Medicines with hepatotoxic effects, nimesulide

The co-administration of nimesulide with other potentially hepatotoxic products is contraindicated

Methotrexate, nimesulide

Increased haematological toxicity of methotrexate due to decrease in its renal clearance. Caution is recommended

Nimesulide, nonsteroidal antiinflammatory drugs

Concomitant use of several NSAIDs should be avoided due to an increased risk of adverse effects, particularly upper gastrointestinal disorders.

Nimesulide, platelet aggregation inhibitors

The co-administration may increase the risk of bleeding

Nimesulide, pregnancy

Strict indication in the first and second trimester. Contraindicated in the third trimester

Nimesulide, salicylic acid

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

Nimesulide, selective serotonin reuptake inhibitors

The co-administration may increase the risk of gastrointestinal haemorrhage or ulcera

Nimesulide, tolbutamide

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

Nimesulide, valproic acid

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

Nimodipine

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

In theory, the possibility of the occurrence of the side-effect dizziness may impair the patient's ability to drive or operate machinery.

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

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

AIIRA, nimodipine [2] ---> SmPC of [2] of eMC

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

Alpha-methyldopa, nimodipine [2] ---> SmPC of [2] of eMC

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

Aminoglycoside antibiotics, nimodipine

The co-administration of nimodipine with potential nephrotoxic agents may impairment the renal function

Antiadrenergics, nimodipine [2] ---> SmPC of [2] of eMC

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

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

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

Azole antifungals, nimodipine [2] ---> SmPC of [2] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

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

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

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

Nimodipine and its metabolites have been shown to be present in human milk at levels of the same order of magnitude as corresponding maternal plasma concentrations. Nursing mothers are advised not to breast-feed when taking this drug.

Calcium antagonists, nimodipine [2] ---> SmPC of [2] of eMC

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

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

The concomitant use of oral nimodipine and cytochrome P450 3A4 system-inducing carbamazepine is contraindicated. The efficacy of nimodipine could be reduced if this drug is administered concomitantly.

Cephalosporins, nimodipine

The co-administration of nimodipine with potential nephrotoxic agents may impairment the renal function

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

The simultaneous administration of nimodipine with the H2-antagonist cimetidine can lead to an increase in the plasma concentration of nimodipine

Dalfopristin, nimodipine [2] ---> SmPC of [2] of eMC

Based on experience with the calcium-antagonist nifedipine, co-administration of quinupristin/dalfopristin may lead to increased plasma concentrations of nimodipine

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

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

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

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Fluoxetine, nimodipine [2] ---> SmPC of [2] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

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

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

Furosemide, nimodipine

The co-administration of nimodipine with potential nephrotoxic agents may impairment the renal function

Grapefruit juice, nimodipine [2] ---> SmPC of [2] of eMC

The intake of grapefruit juice is not recommended in combination with nimodipine as it can result in increased plasma nimodipine concentrations due to the inhibition of the oxidative metabolism of dihydropyridines.

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

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Macrolide antibiotics, nimodipine [2] ---> SmPC of [2] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered. Azithromycin is void of CYP3A4 inhibition.

Moderate CYP3A4 inhibitors, nimodipine [2] ---> SmPC of [2] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Nebivolol [1], nimodipine ---> SmPC of [1] of eMC

Nefazodone, nimodipine [2] ---> SmPC of [2] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Nephrotoxic substances, nimodipine

The co-administration of nimodipine with potential nephrotoxic agents may impairment the renal function

Nimodipine [1], nortriptyline ---> SmPC of [1] of eMC

Concurrent administration of nimodipine and the antidepressant nortriptyline resulted in a slight decrease in nimodipine plasma levels with no effect on nortriptyline plasma levels.

Nimodipine [1], organic nitrates ---> SmPC of [1] of eMC

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

Nimodipine [1], PDE5 inhibitors ---> SmPC of [1] of eMC

Nimodipine may increase the blood pressure lowering effect of concomitant antihypertensives

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

The concomitant use of oral nimodipine and cytochrome P450 3A4 system-inducing phenobarbital is contraindicated. The efficacy of nimodipine could be reduced if this drug is administered concomitantly.

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

The concomitant use of oral nimodipine and cytochrome P450 3A4 system-inducing phenytoin is contraindicated. The efficacy of nimodipine could be reduced if this drug is administered concomitantly.

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

If nimodipine is to be administered during pregnancy, the benefits and potential risks must be carefully weighed according to the severity of the clinical picture.

Nimodipine [1], protease inhibitors ---> SmPC of [1] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Nimodipine [1], quinupristin ---> SmPC of [1] of eMC

Based on experience with the calcium-antagonist nifedipine, co-administration of quinupristin/dalfopristin may lead to increased plasma concentrations of nimodipine

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

The concomitant use of oral nimodipine and rifampicin is contraindicated. The efficacy of nimodipine could be reduced if rifampicin is administered concomitantly.

Nimodipine [1], ritonavir ---> SmPC of [1] of eMC

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Nimodipine [1], sodium valproate ---> SmPC of [1] of eMC

The simultaneous administration of nimodipine with the anticonvulsant valproic acid can lead to an increase in the plasma concentration of nimodipine

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

Upon co-administration of nimodipine with CYP3A4 inhibitors the blood pressure should be monitored and, if necessary, an adaptation in the nimodipine dose should be considered.

Nimodipine [1], valproic acid ---> SmPC of [1] of eMC

The simultaneous administration of nimodipine with the anticonvulsant valproic acid can lead to an increase in the plasma concentration of nimodipine

Nimodipine [1], zidovudine ---> SmPC of [1] of eMC

Animal studies have shown that when nimodipine and zidovudine are administered concomitantly, the AUC for zidovudine was increased, and the volume of distribution and clearance rate decreased.

Nimodipine, primidone [2] ---> SmPC of [2] of eMC

Primidone therapy may lead to altered pharmacokinetics in concomitantly administered drugs, whose metabolism may be increased and lead to lowered plasma levels and/or a shorter half-life.

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

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

Nimodipine, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma concentrations of nimodipine

CONTRAINDICATIONS of Nimodipine

- Nimodipine must not be administered in case of hypersensitivity to the active substance or to any of the excipients.

- Nimodipine should not be administered to patients during or within one month of a myocardial infarction or an episode of unstable angina.

- The use of nimodipine in combination with rifampicin or the antiepileptic drugs, phenobarbital, phenytoin or carbamazepine is contraindicated as the efficacy of Nimotop tablets could be significantly reduced when concomitantly administered.

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

Nintedanib (Vargatef)

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

Patients should be advised to be cautious when driving or using machines during treatment with Vargatef.

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

A risk to the new-borns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Vargatef.

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

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

CYP metabolism, nintedanib [2] ---> SmPC of [2] of EMA

The likelihood of drug-drug interactions with nintedanib based on CYP metabolism is therefore considered to be low.

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

Co-administration of nintedanib with docetaxel (75 mg/m ²) did not alter the pharmacokinetics of either medicinal product to a relevant extent.

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

If co-administered with nintedanib, potent P-gp inhibitors may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of nintedanib.

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

Based on preclinical investigations there is no evidence for impairment of male fertility (see section 5.3). There are no human or animal data on potential effects of nintedanib on female fertility available.

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

Nintedanib capsules must be taken orally, preferably with food, swallowed whole with water, and must not be chewed or crushed.

Hormonal contraceptives, nintedanib [2] ---> SmPC of [2] of EMA

The efficacy of oral hormonal contraceptives may be compromised by vomiting and/or diarrhoea or other conditions where the absorption may be affected.

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

If co-administered with nintedanib, potent P-gp inhibitors may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of nintedanib.

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

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

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

As nintedanib may cause foetal harm also in humans, it should not be used during pregnancy unless the clinical condition requires treatment.

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

As several other tyrosine kinase inhibitors are known to exert an effect on QT, caution should be exercised when administering nintedanib in patients who may develop QTc prolongation.

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

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

Nintedanib [1], St. John's wort ---> SmPC of [1] of EMA

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

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

Potent P-gp inducers may decrease exposure to nintedanib. Co-administration with nintedanib should be carefully considered.

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

If co-administered with nintedanib, potent P-gp inhibitors may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of nintedanib.

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

Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Vargatef and to use highly effective contraceptive methods at initiation of, during and at least 3 months after the last dose of Vargatef.

CONTRAINDICATIONS of Nintedanib (Vargatef)

- Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/vargatef-epar-product-information_en.pdf 22/08/2024

Other trade names: Nintedanib Accord, Ofev,

Niraparib (Zejula)

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

Patients who take Zejula may experience asthenia, fatigue and dizziness. Patients who experience these symptoms should observe caution when driving or using machines.

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

Caution is recommended when niraparib is combined with principles the metabolism of which is CYP3A4-dependent and, notably, those having a narrow therapeutic range (e.g. ciclosporin, tacrolimus, alfentanil, ergotamine, pimozide, quetiapine, and halofantrine

Atorvastatin, niraparib [2] ---> SmPC of [2] of EMA

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

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

No dose adjustment for Zejula is required when administered concomitantly with medicinal products known to inhibit P-gp (e.g. amiodarone, verapamil) or BCRP (e.g. osimertinib, velpatasvir, and eltrombopag).

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

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

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

It is unknown whether niraparib or its metabolites are excreted in human milk. Breast-feeding is contraindicated during administration of Zejula and for 1 month after receiving the last dose (see section 4.3).

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

No dose adjustment for Zejula is required when administered concomitantly with medicinal products known to inhibit (e.g. itraconazole, ritonavir, and clarithromycin) or induce CYP enzymes (e.g. rifampin, carbamazepine, and phenytoin)

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

Clozapine, niraparib [2] ---> SmPC of [2] of EMA

Caution is recommended when niraparib is combined with active substances the metabolism of which is CYP1A2-dependent and, notably, those having a narrow therapeutic range (e.g. clozapine, theophylline, and ropinirole).

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

CYP1A2 substrates with narrow therapeutic index, niraparib [2] ---> SmPC of [2] of EMA

Cytotoxic agents, niraparib [2] ---> SmPC of [2] of EMA

The data on niraparib in combination with cytotoxic medicinal products are limited. Therefore, caution should be taken if niraparib is used in combination with vaccines, immunosuppressant agents or with other cytotoxic medicinal products.

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

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

Enzyme inhibitors, niraparib [2] ---> SmPC of [2] of EMA

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

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

There are no clinical data on fertility. A reversible reduction of spermatogenesis was observed in rats and dogs (see section 5.3).

Halofantrine, niraparib [2] ---> SmPC of [2] of EMA

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

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

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

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

MATE1 substrates, niraparib [2] ---> SmPC of [2] of EMA

Niraparib is an inhibitor of MATE1 and MATE2. Increased plasma concentrations of co-administered medicinal products that are substrates of these transporters (e.g. metformin) cannot be excluded.

MATE2 substrates, niraparib [2] ---> SmPC of [2] of EMA

Niraparib is an inhibitor of MATE1 and MATE2. Increased plasma concentrations of co-administered medicinal products that are substrates of these transporters (e.g. metformin) cannot be excluded.

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

Niraparib is an inhibitor of MATE1 and MATE2. Increased plasma concentrations of co-administered medicinal products that are substrates of these transporters (e.g. metformin) cannot be excluded.

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

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

Niraparib [1], OAT1 inhibitors ---> SmPC of [1] of EMA

No dose adjustment for Zejula is required when administered concomitantly with medicinal products known to inhibit OAT1 (e.g. probenecid) or OAT3 (e.g. probenecid, diclofenac), or OCT2 (e.g. cimetidine, quinidine) uptake transporters

Niraparib [1], OAT3 inhibitors ---> SmPC of [1] of EMA

Niraparib [1], OATP1B1 inhibitors ---> SmPC of [1] of EMA

No dose adjustment for Zejula is required when administered concomitantly with medicinal products known to inhibit OATP1B1 or 1B3 (e.g. gemfibrozil, ritonavir), or OCT1 (e.g. dolutegravir) uptake transporters.

Niraparib [1], OCT1 inhibitors ---> SmPC of [1] of EMA

Niraparib [1], OCT1 substrates ---> SmPC of [1] of EMA

In vitro, niraparib weakly inhibits the organic cation transporter 1 (OCT1). Caution is recommended when niraparib is combined with active substances that undergo an uptake transport by OCT1 such as metformin.

Niraparib [1], OCT2 inhibitors ---> SmPC of [1] of EMA

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

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

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

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

Based on its mechanism of action, niraparib could cause embryonic or foetal harm, including embryo-lethal and teratogenic effects, when administered to a pregnant woman. Zejula should not be used during pregnancy.

Niraparib [1], quetiapine ---> SmPC of [1] of EMA

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

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

Niraparib [1], ropinirole ---> SmPC of [1] of EMA

Niraparib [1], rosuvastatin ---> SmPC of [1] of EMA

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

Niraparib [1], simvastatine ---> SmPC of [1] of EMA

Caution is recommended when niraparib is combined with substrates of BCRP (irinotecan, rosuvastatin, simvastatin, atorvastatin, and methotrexate).

Niraparib [1], tacrolimus ---> SmPC of [1] of EMA

Niraparib [1], theophylline ---> SmPC of [1] of EMA

Niraparib [1], vaccinations ---> SmPC of [1] of EMA

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

Women of childbearing potential should not become pregnant while on treatment and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to treatment.

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

Women of childbearing potential must use highly effective contraception during therapy and for 6 months after receiving the last dose of Zejula.

CONTRAINDICATIONS of Niraparib (Zejula)

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

- Breast-feeding (see section 4.6).

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

Nirmatrelvir/ritonavir (Paxlovid)

Abemaciclib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased due to CYP3A4 inhibition by ritonavir. Coadministration of abemaciclib and Paxlovid should be avoided.

Ability to drive, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Paxlovid is expected to have no influence on the ability to drive and use machines.

Afatinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased due to Breast Cancer Resistance Protein (BCRP) and acute P-gp inhibition by ritonavir.

Alfuzosin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of alfuzosin may lead to severe hypotension and is therefore contraindicated

Aliskiren, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Avoid concomitant use with Paxlovid.

Alprazolam, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Alprazolam metabolism is inhibited following the introduction of ritonavir. Caution is warranted during the first several days when alprazolam is coadministered with ritonavir before induction of alprazolam metabolism develops.

Amiodarone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Given the risk of substantial increase in amiodarone or flecainide exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Amitriptyline, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of antidepressant. Careful monitoring of therapeutic and adverse effects is recommended

Amlodipine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A4 and as a result is expected to increase the plasma levels of calcium channel antagonists. Careful monitoring of therapeutic and adverse effects is recommended when these medicines are concomitantly administered with ritonavir.

Amphetamine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of amphetamine and its derivatives.

Apalutamide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Apalutamide is a moderate to strong CYP3A4 inducer and this may lead to a decreased exposure of Nirmatrelvir/ritonavir and potential loss of virologic response. Concomitant use is not recommended.

Apixaban, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Combined P-gp and strong CYP3A4 inhibitors increase blood levels of apixaban and increase the risk of bleeding. Dosing recommendations for coadministration of apixaban with Paxlovid depend on the apixaban dose.

Aripiprazole, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Dosage adjustment of aripiprazole and brexpiprazole is recommended. Refer to aripiprazole or brexpiprazole SmPCs for more information.

Atorvastatin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Atorvastatin is less dependent on CYP3A for metabolism. The lowest possible doses of atorvastatin should be administered.

Atovaquone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer induces glucuronidation and as a result is expected to decrease the plasma levels of atovaquone. Careful monitoring of serum levels or therapeutic effects is recommended

Avanafil, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Concomitant use of avanafil, sildenafil, tadalafil and vardenafil with Paxlovid is contraindicated (see section 4.3).

Bedaquiline, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Due to the risk of bedaquiline related adverse events, coadministration should be avoided. If the benefit outweighs the risk, coadministration of bedaquiline with ritonavir must be done with caution.

Bictegravir/emtricitabine/tenofovir alafenamide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may significantly increase the plasma levels of bictegravir through CYP3A inhibition. Ritonavir is expected to increase the absorption of tenofovir alafenamide by inhibition of P-gp, thereby increasing the systemic level of tenofovir.

Bosentan, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration of bosentan and ritonavir may increase steady-state bosentan maximum concentrations (Cmax) and AUC.

Breast-feeding, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

A risk to the newborn/infant cannot be excluded. Breast-feeding should be discontinued during treatment and as a precautionary measure for 48 hours after completing Paxlovid.

Brexpiprazole, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Dosage adjustment of aripiprazole and brexpiprazole is recommended. Refer to aripiprazole or brexpiprazole SmPCs for more information.

Budesonide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Systemic corticosteroid effects have been reported. Therefore, concomitant administration of ritonavir with corticosteroids metabolised by CYP3A is not recommended or switch to one, which is not a substrate for CYP3A4 (e.g., beclomethasone).

Buprenorphine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

The increases of plasma levels of buprenorphine and its active metabolite did not lead to clinically significant pharmacodynamic changes in a population of opioid tolerant patients.

Bupropion, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Concurrent administration of bupropion with repeated doses of ritonavir is expected to decrease bupropion levels. The reductions in bupropion concentrations may have onset several days after initiation of ritonavir coadministration.

Buspirone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A and as a result is expected to increase the plasma concentrations of buspirone. Careful monitoring of therapeutic and adverse effects is recommended when buspirone concomitantly administered with ritonavir.

Carbamazepine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Concomitant use of carbamazepine, phenobarbital, phenytoin and primidone with Paxlovid is contraindicated (see section 4.3).

Cariprazine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration is contraindicated due to increased plasma exposure of cariprazine and its active metabolites (see section 4.3).

Ceritinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations of ceritinib may be increased due to CYP3A and P-gp inhibition by ritonavir. Caution should be exercised in administering ceritinib with Paxlovid.

Cilostazol, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Dosage adjustment of cilostazol is recommended. Refer to the cilostazol SmPC for more information.

Cisapride, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Increased plasma concentrations of cisapride. Thereby, increasing the risk of serious arrhythmias from this agent and therefore concomitant use with Paxlovid is contraindicated

Clarithromycin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Clarithromycin doses greater than 1 g per day should not be coadministered with ritonavir dosed as a pharmacokinetic enhancer.

Clonazepam, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

A dose decrease may be needed for clonazepam when coadministered with Paxlovid and clinical monitoring is recommended.

Clopidogrel, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration with clopidogrel may decrease levels of clopidogrel active metabolite. Avoid concomitant use with Paxlovid.

Clorazepate, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of clorazepate, diazepam, estazolam, and flurazepam and is therefore contraindicated (see section 4.3).

Clozapine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Given the risk of increase in clozapine exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Colchicine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine and ritonavir (CYP3A4 and P-gp inhibition). Concomitant use of colchicine with Paxlovid is contraindicated

Corticosteroids metabolized by CYP3A4, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Cyclosporine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of cyclosporine, tacrolimus or everolimus.

CYP3A4 inductors, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Nirmatrelvir and ritonavir are CYP3A substrates; therefore, medicinal products that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce Paxlovid therapeutic effect.

CYP3A4 inhibitors, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration of Paxlovid with medicinal product that inhibits CYP3A4 may increase nirmatrelvir and ritonavir plasma concentrations.

Dabigatran, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Concomitant administration of Paxlovid is expected to increase dabigatran concentrations resulting in increased risk of bleeding. Reduce dose of dabigatran or avoid concomitant use.

Darifenacin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Given the risk of substantial increase in darifenacin exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Dasatinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased when coadministered with ritonavir resulting in the potential for increased incidence of adverse events.

Delamanid, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Due to the risk of QTc prolongation associated with DM-6705, if coadministration is considered necessary, very frequent ECG monitoring throughout the full delamanid treatment period is recommended

Desipramine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

The AUC and Cmax of the 2-hydroxy metabolite were decreased 15% and 67%, respectively. Dosage reduction of desipramine is recommended when coadministered with ritonavir.

Dexamethasone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A and as a result is expected to increase the plasma concentrations of dexamethasone. Careful monitoring of therapeutic and adverse effects is recommended when dexamethasone is concomitantly administered with ritonavir.

Diazepam, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of clorazepate, diazepam, estazolam, and flurazepam and is therefore contraindicated (see section 4.3).

Digoxin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

This interaction may be due to modification of P-gp mediated digoxin efflux by ritonavir dosed as a pharmacokinetic enhancer.

Dihydroergotamine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Diltiazem, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Disopyramide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may increase plasma concentrations of disopyramide, which could result in an increased risk of adverse events such as cardiac arrhythmias. Caution is warranted and therapeutic concentration monitoring is recommended

Divalproex sodium, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer induces oxidation by CYP2C9 and glucuronidation and as a result is expected to decrease the plasma concentrations of anticonvulsants. Careful monitoring of therapeutic and adverse effects is recommended

Dronedarone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of dronedarone, propafenone and quinidine and is therefore contraindicated (see section 4.3).

Drugs primarily metabolised by CYP1A2, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways

Drugs primarily metabolised by CYP2C19, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways

Drugs primarily metabolised by CYP2C8, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways

Drugs primarily metabolised by CYP2C9, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways

Drugs primarily metabolised by CYP2D6, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration of Paxlovid with drug substrates of CYP2D6 may increase the CYP2D6 substrate concentration.

Drugs primarily metabolised by CYP3A4, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Thus, coadministration of nirmatrelvir/ritonavir with medicinal products highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated (see Table 1).

Efavirenz, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

A higher frequency of adverse reactions (e.g., dizziness, nausea, paraesthesia) and laboratory abnormalities (elevated liver enzymes) have been observed when efavirenz is coadministered with ritonavir.

Eletriptan, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration of eletriptan within at least 72 hours of Paxlovid is contraindicated due to potential for serious adverse reactions including cardiovascular and cerebrovascular events (see section 4.3).

Elexacaftor, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Reduce dosage when coadministered with Paxlovid. Refer to individual SmPCs for more information.

Encorafenib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations of encorafenib or ivosidenib may be increased when coadministered with ritonavir which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation

Enzalutamide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Enzalutamide is a strong CYP3A4 inducer, and this may lead to decreased exposure of Paxlovid, potential loss of virologic response, and possible resistance. Concomitant use of enzalutamide with Paxlovid is contraindicated

Eplerenone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration with eplerenone is contraindicated due to potential for hyperkalemia (see section 4.3).

Ergonovine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Ergot derivatives, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Ergotamine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Erythromycin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer inhibits CYP3A4 and as a result is expected to increase the plasma levels of itraconazole and erythromycin. Careful monitoring of therapeutic and adverse effects is recommended.

Estazolam, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of clorazepate, diazepam, estazolam, and flurazepam and is therefore contraindicated (see section 4.3).

Estradiol, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir is likely to change the uterine bleeding profile and reduce the effectiveness of estradiol-containing contraceptives.

Ethinyl estradiol, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Due to reductions in ethinyl estradiol concentrations, barrier or other non-hormonal methods of contraception should be considered with concomitant ritonavir use when dosed as an antiretroviral agent or as a pharmacokinetic enhancer.

Everolimus, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Felodipine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Fentanyl, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

If concomitant use with Paxlovid is necessary, consider a dosage reduction of these narcotic analgesics and closely monitor therapeutic and adverse effects (including respiratory depression).

Fertility, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

There are no human data on the effect of Paxlovid (nirmatrelvir and ritonavir) or ritonavir alone on fertility. Both nirmatrelvir and ritonavir, tested separately, produced no effects on fertility in rats (see section 5.3).

Fexofenadine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir may modify P-gp mediated fexofenadine efflux when dosed as a pharmacokinetic enhancer resulting in increased concentrations of fexofenadine.

Finerenone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration contraindicated due to potential for serious adverse reactions including hyperkalemia, hypotension and hyponatremia (see section 4.3).

Flecainide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Fluoxetine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Flurazepam, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of clorazepate, diazepam, estazolam, and flurazepam and is therefore contraindicated (see section 4.3).

Fluticasone propionate, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Fluvastatin, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

While not dependent on CYP3A for metabolism, pravastatin and fluvastatin exposure may be increased due to transporter inhibition. Consider temporary discontinuation of pravastatin and fluvastatin during treatment with Paxlovid.

Fostamatinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration of fostamatinib with ritonavir may increase fostamatinib metabolite R406 exposure resulting in dose-related adverse events such as hepatotoxicity, neutropenia, hypertension or diarrhoea.

Fusidic acid [1], nirmatrelvir/ritonavir ---> SmPC of [1] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of both fusidic acid and ritonavir and is therefore contraindicated

Fusidic acid, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Given the risk of substantial increase in fusidic acid (systemic route) exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Glecaprevir/pibrentasvir, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum levels may be increased due to P-gp, BCRP and OATP1B inhibition by ritonavir. Coadministration is not recommended due to an increased risk of ALT elevations associated with increased glecaprevir exposure

Haloperidol, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of haloperidol, risperidone and thioridazine. Careful monitoring of therapeutic and adverse effects is recommended

Ibrutinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations of ibrutinib may be increased due to CYP3A inhibition by ritonavir, resulting in increased risk for toxicity including risk of tumour lysis syndrome. Coadministration of ibrutinib and ritonavir should be avoided.

Imipramine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Itraconazol, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ivabradine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration with ivabradine is contraindicated due to potential for bradycardia or conduction disturbances (see section 4.3).

Ivosidenib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ketoconazole, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir inhibits CYP3A-mediated metabolism of ketoconazole. Due to an increased incidence of gastrointestinal and hepatic adverse reactions, a dose reduction of ketoconazole should be considered when coadministered with ritonavir.

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

Lercanidipine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Given the risk of significant increase in lercanidipine exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Levothyroxine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Thyroid-stimulating hormone (TSH) should be monitored in patients treated with levothyroxine at least the first month after starting and/or ending ritonavir treatment.

Lomitapide, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Due to CYP3A inhibition by ritonavir, concentrations of lomitapide are expected to increase. Concomitant use of Paxlovid with lomitapide is contraindicated

Loratadine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as a pharmacokinetic enhancer inhibits CYP3A and as a result is expected to increase the plasma levels of loratadine. Careful monitoring of therapeutic and adverse effects is recommended when loratadine is coadministered with ritonavir.

Lovastatine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Since increased concentrations of lovastatin and simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of these medicinal products with ritonavir is contraindicated

Lumacaftor/ivacaftor, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration contraindicated due to potential loss of virologic response and possible resistance (see section 4.3).

Lurasidone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Due to CYP3A inhibition by ritonavir, concentrations of lurasidone are expected to increase. The concomitant administration with lurasidone is contraindicated

Maraviroc, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir increases the serum levels of maraviroc as a result of CYP3A inhibition. Maraviroc may be given with ritonavir to increase the maraviroc exposure. For further information, refer to the Summary of Product Characteristics for maraviroc.

Medicines extensively metabolised by CYP3A and have high first pass metabolism, nirmatrelvir/ritonavir [2] ---> Sm

Medicinal products that are extensively metabolised by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in exposure when coadministered with nirmatrelvir/ritonavir.

Methadone, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Increased methadone dose may be necessary when coadministered with ritonavir dosed as a pharmacokinetic enhancer due to induction of glucuronidation. Dose adjustment should be considered based on the patient's clinical response to methadone therapy.

Methylergonovine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of ergot derivatives and is therefore contraindicated

Midazolam, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Paxlovid should not be coadministered with orally administered midazolam, whereas caution should be used with coadministration of Paxlovid and parenteral midazolam: possible 3- to 4-fold increase in midazolam plasma levels.

Morphine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Morphine levels may be decreased due to induction of glucuronidation by coadministered ritonavir dosed as a pharmacokinetic enhancer.

Naloxegol, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Coadministration contraindicated due to the potential for opioid withdrawal symptoms (see section 4.3).

Neratinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Nicardipine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Nifedipine, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Nilotinib, nirmatrelvir/ritonavir [2] ---> SmPC of [2] of EMA

Serum concentrations may be increased when coadministered with ritonavir resulting in the potential for increased incidence of adverse events.

Nirmatrelvir/ritonavir [1], norbuprenorphine ---> SmPC of [1] of EMA

The increases of plasma levels of buprenorphine and its active metabolite did not lead to clinically significant pharmacodynamic changes in a population of opioid tolerant patients.

Nirmatrelvir/ritonavir [1], nortriptyline ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], oral contraceptives ---> SmPC of [1] of EMA

Use of ritonavir may reduce the efficacy of combined hormonal contraceptives.

Nirmatrelvir/ritonavir [1], oxycodone ---> SmPC of [1] of EMA

If concomitant use with Paxlovid is necessary, consider a dosage reduction of these narcotic analgesics and closely monitor therapeutic and adverse effects (including respiratory depression).

Nirmatrelvir/ritonavir [1], P-glycoprotein substrates ---> SmPC of [1] of EMA

Paxlovid also has a high affinity for P-glycoprotein (P-gp) and inhibits this transporter; caution should thus be exercised in case of concomitant treatment.

Nirmatrelvir/ritonavir [1], paroxetine ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], pethidine ---> SmPC of [1] of EMA

Coadministration could result in increased or prolonged opioid effects. If concomitant use is necessary, consider dosage reduction of pethidine. Monitor for respiratory depression and sedation.

Nirmatrelvir/ritonavir [1], pharmacological interactions ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], phenobarbital ---> SmPC of [1] of EMA

Concomitant use of carbamazepine, phenobarbital, phenytoin and primidone with Paxlovid is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], phenytoin ---> SmPC of [1] of EMA

Concomitant use of carbamazepine, phenobarbital, phenytoin and primidone with Paxlovid is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], pimozide ---> SmPC of [1] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of pimozide and is therefore contraindicated

Nirmatrelvir/ritonavir [1], piroxicam ---> SmPC of [1] of EMA

Decreased piroxicam exposure due to CYP2C9 induction by Paxlovid.

Nirmatrelvir/ritonavir [1], pravastatine ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], prednisolone ---> SmPC of [1] of EMA

Careful monitoring of therapeutic and adverse effects is recommended when prednisolone is concomitantly administered with ritonavir. The AUC of the metabolite prednisolone increased by 37% and 28% after 4 and 14 days ritonavir, respectively.

Nirmatrelvir/ritonavir [1], pregnancy ---> SmPC of [1] of EMA

Paxlovid is not recommended during pregnancy and in women of childbearing potential not using contraception unless the clinical condition requires treatment with Paxlovid.

Nirmatrelvir/ritonavir [1], primidone ---> SmPC of [1] of EMA

Concomitant use of carbamazepine, phenobarbital, phenytoin and primidone with Paxlovid is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], propafenone ---> SmPC of [1] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of dronedarone, propafenone and quinidine and is therefore contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], propoxyphene ---> SmPC of [1] of EMA

Increased plasma concentrations of norpethidine, piroxicam and propoxyphene may result in serious respiratory depression or haematologic abnormalities and are therefore contraindicated

Nirmatrelvir/ritonavir [1], quetiapine ---> SmPC of [1] of EMA

Due to CYP3A inhibition by ritonavir, concentrations of quetiapine are expected to increase. Concomitant administration of Paxlovid and quetiapine is contraindicated as it may increase quetiapine-related toxicity

Nirmatrelvir/ritonavir [1], quinidine ---> SmPC of [1] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of dronedarone, propafenone and quinidine and is therefore contraindicated (see section 4.3).

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

Coadministration of ritonavir and raltegravir results in a minor reduction in raltegravir levels

Nirmatrelvir/ritonavir [1], ranolazine ---> SmPC of [1] of EMA

Due to CYP3A inhibition by ritonavir, concentrations of ranolazine are expected to increase. The concomitant administration with ranolazine is contraindicated

Nirmatrelvir/ritonavir [1], rifabutin ---> SmPC of [1] of EMA

An increase in rifabutin exposure is expected due to the inhibition of CYP3A4 by ritonavir. The consultation of a multidisciplinary group is recommended to safely guide the co-administration and the need of a reduction of the rifabutin dose.

Nirmatrelvir/ritonavir [1], rifampicin ---> SmPC of [1] of EMA

Rifampicin and rifapentine are strong CYP3A4 inducers, and this may lead to a decreased exposure of nirmatrelvir/ritonavir, potential loss of virologic response and possible resistance. Concomitant use is contraindicated

Nirmatrelvir/ritonavir [1], rifapentine ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], rimegepant ---> SmPC of [1] of EMA

Avoid concomitant use with Paxlovid.

Nirmatrelvir/ritonavir [1], riociguat ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A and P-gp inhibition by ritonavir. The coadministration of riociguat with Paxlovid is not recommended (refer to riociguat SmPC).

Nirmatrelvir/ritonavir [1], risperidone ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], rivaroxaban ---> SmPC of [1] of EMA

Inhibition of CYP3A and P-gp lead to increased plasma levels and pharmacodynamic effects of rivaroxaban which may lead to an increased bleeding risk. Therefore, the use of ritonavir is not recommended in patients receiving rivaroxaban.

Nirmatrelvir/ritonavir [1], rosuvastatin ---> SmPC of [1] of EMA

While rosuvastatin elimination is not dependent on CYP3A, an elevation of rosuvastatin exposure has been reported with ritonavir coadministration. The lowest possible doses of rosuvastatin should be administered.

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

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

Nirmatrelvir/ritonavir [1], saxagliptin ---> SmPC of [1] of EMA

Dosage adjustment of saxagliptin to 2.5 mg once daily is recommended.

Nirmatrelvir/ritonavir [1], sertraline ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], sildenafil ---> SmPC of [1] of EMA

Concomitant use of avanafil, sildenafil, tadalafil and vardenafil with Paxlovid is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], silodosin ---> SmPC of [1] of EMA

Coadministration is contraindicated due to potential for postural hypotension (see section 4.3).

Nirmatrelvir/ritonavir [1], simvastatine ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], sofosbuvir/velpatasvir/voxilaprevir ---> SmPC of [1] of EMA

Serum concentrations may be increased due to OATP1B inhibition by ritonavir. Concomitant administration of sofosbuvir/velpatasvir/voxilaprevir and Paxlovid is not recommended.

Nirmatrelvir/ritonavir [1], solifenacin ---> SmPC of [1] of EMA

Given the risk of substantial increase in solifenacin exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Nirmatrelvir/ritonavir [1], St. John's wort ---> SmPC of [1] of EMA

Herbal preparations containing St John's wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of nirmatrelvir and ritonavir and therefore concomitant use with Paxlovid is contraindicated

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

Dose alteration of sulfamethoxazole/trimethoprim during concomitant ritonavir therapy should not be necessary.

Nirmatrelvir/ritonavir [1], tacrolimus ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], tadalafil ---> SmPC of [1] of EMA

Concomitant use of avanafil, sildenafil, tadalafil and vardenafil with Paxlovid is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], tamsulosin ---> SmPC of [1] of EMA

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6, both of which are inhibited by ritonavir. Avoid concomitant use with Paxlovid.

Nirmatrelvir/ritonavir [1], terfenadine ---> SmPC of [1] of EMA

Increased plasma concentrations of terfenadine. Thereby, increasing the risk of serious arrhythmias from these agents and therefore concomitant use with Paxlovid is contraindicated

Nirmatrelvir/ritonavir [1], tezacaftor/ivacaftor ---> SmPC of [1] of EMA

Reduce dosage when coadministered with Paxlovid. Refer to individual SmPCs for more information.

Nirmatrelvir/ritonavir [1], theophylline ---> SmPC of [1] of EMA

An increased dose of theophylline may be required when coadministered with ritonavir, due to induction of CYP1A2.

Nirmatrelvir/ritonavir [1], thioridazine ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], ticagrelor ---> SmPC of [1] of EMA

Given the risk of substantial increase in ticagrelor exposure and thus of its related adverse events, coadministration should not be used unless a multidisciplinary consultation could be obtained to safely guide it.

Nirmatrelvir/ritonavir [1], tofacitinib ---> SmPC of [1] of EMA

Dosage adjustment of tofacitinib is recommended. Refer to the tofacitinib SmPC for more information.

Nirmatrelvir/ritonavir [1], tolvaptan ---> SmPC of [1] of EMA

Coadministration is contraindicated due to potential for dehydration, hypovolemia and hyperkalemia (see section 4.3).

Nirmatrelvir/ritonavir [1], triamcinolone ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], triazolam ---> SmPC of [1] of EMA

Ritonavir coadministration is likely to result in increased plasma concentrations of triazolam and is therefore contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], upadacitinib ---> SmPC of [1] of EMA

Dosing recommendations for coadministration of upadacitinib with Paxlovid depends on the upadacitinib indication. Refer to the upadacitinib SmPC for more information.

Nirmatrelvir/ritonavir [1], vardenafil ---> SmPC of [1] of EMA

Concomitant use of avanafil, sildenafil, tadalafil and vardenafil with Paxlovid is contraindicated (see section 4.3).

Nirmatrelvir/ritonavir [1], venetoclax ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by ritonavir, resulting in increased risk of tumour lysis syndrome at the dose initiation and during the ramp-up phase and is therefore contraindicated

Nirmatrelvir/ritonavir [1], verapamil ---> SmPC of [1] of EMA

Nirmatrelvir/ritonavir [1], vinblastine ---> SmPC of [1] of EMA

Serum concentrations may be increased when coadministered with ritonavir resulting in the potential for increased incidence of adverse events.

Nirmatrelvir/ritonavir [1], vincristine ---> SmPC of [1] of EMA

Serum concentrations may be increased when coadministered with ritonavir resulting in the potential for increased incidence of adverse events.

Nirmatrelvir/ritonavir [1], voclosporine ---> SmPC of [1] of EMA

Coadministration is contraindicated due to potential for acute and/or chronic nephrotoxicity (see section 4.3).

Nirmatrelvir/ritonavir [1], vorapaxar ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by ritonavir. The coadministration of vorapaxar with Paxlovid is not recommended (refer to the vorapaxar SmPC).

Nirmatrelvir/ritonavir [1], voriconazole ---> SmPC of [1] of EMA

Coadministration of voriconazole and ritonavir dosed as a pharmacokinetic enhancer should be avoided unless an assessment of the benefit/risk to the patient justifies the use of voriconazole.

Nirmatrelvir/ritonavir [1], warfarin ---> SmPC of [1] of EMA

Induction of CYP1A2 and CYP2C9 lead to decreased levels of R-warfarin while little pharmacokinetic effect is noted on S-warfarin when coadministered with ritonavir. Decreased R-warfarin levels may lead to reduced anticoagulation

Nirmatrelvir/ritonavir [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should avoid becoming pregnant during treatment with Paxlovid and as a precautionary measure for 7 days after completing Paxlovid.

Nirmatrelvir/ritonavir [1], zidovudine ---> SmPC of [1] of EMA

Ritonavir may induce the glucuronidation of zidovudine, resulting in slightly decreased levels of zidovudine. Dose alterations should not be necessary.

Nirmatrelvir/ritonavir [1], zolpidem ---> SmPC of [1] of EMA

Zolpidem and ritonavir may be coadministered with careful monitoring for excessive sedative effects.

CONTRAINDICATIONS of Nirmatrelvir/ritonavir (Paxlovid)

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

- Medicinal products listed below are a guide and not considered a comprehensive list of all possible medicinal products that are contraindicated with Paxlovid.

- Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions.

- Alpha1-adrenoreceptor antagonist: alfuzosin

- Antianginal: ranolazine

- Antiarrhythmic: dronedarone, propafenone, quinidine

- Anticancer drugs: neratinib, venetoclax

- Anti-gout: colchicine

- Antihistamines: terfenadine

- Antipsychotics/neuroleptics: lurasidone, pimozide, quetiapine

- Benign prostatic hyperplasia medicinal products: silodosin

- Cardiovascular medicinal products: eplerenone, ivabradine

- Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine

- GI motility agents: cisapride

- Immunosuppressants: voclosporin

- Lipid-modifying agents:

- HMG Co-A reductase inhibitors: lovastatin, simvastatin

- Microsomal triglyceride transfer protein (MTTP) inhibitor: lomitapide

- Migraine medicinal products: eletriptan

- Mineralocorticoid receptor antagonists: finerenone

- Neuropsychiatric agents: cariprazine

- Opioid antagonists: naloxegol

- PDE5 inhibitor: avanafil, sildenafil, tadalafil, vardenafil

- Sedative/hypnotics: clorazepate, diazepam, estazolam, flurazepam, oral midazolam and triazolam

- Vasopressin receptor antagonists: tolvaptan

- Medicinal products that are potent CYP3A inducers where significantly reduced nirmatrelvir/ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.

- Antibiotics: rifampicin, rifapentine

- Anticancer drugs: apalutamide, enzalutamide

- Anticonvulsants: carbamazepine, phenobarbital, phenytoin, primidone

- Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor

- Herbal products: St. John's wort (Hypericum perforatum)

- Paxlovid cannot be started immediately after discontinuation of CYP3A4 inducers due to the delayed offset of the recently discontinued CYP3A4 inducer (see section 4.5).

- A multi-disciplinary approach (e.g., involving physicians and specialists in clinical pharmacology) should be considered to determine the adequate timing for Paxlovid initiation taking into account the delayed offset of the recently discontinued CYP3A inducer and the need to initiate Paxlovid within 5 days of symptom onset.

https://www.ema.europa.eu/en/documents/product-information/paxlovid-epar-product-information_en.pdf 27/05/2025

Nirogacestat (Ogsiveo)

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

Since fatigue and dizziness may occur in patients taking nirogacestat (see section 4.8), caution should be observed by patients who experience those adverse reactions when driving or operating machinery.

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

However, if concomitant use with acid reducing agents cannot be avoided, Ogsiveo can be staggered with antacids by administering Ogsiveo 2 hours before or 2 hours after antacid use.

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

Because of the potential for serious adverse reactions in a breastfed child, women must not breastfeed during treatment with Ogsiveo and for 1 week after the last dose of Ogsiveo (see section 4.3).

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

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

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

Concomitant use with strong inhibitors of CYP3A4 (e.g., clarithromycin, oral ketoconazole, itraconazole) and moderate inhibitors of CYP3A4 (e.g., erythromycin and fluconazole) should therefore be avoided.

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

Ogsiveo should not be used with concomitant administration of CYP3A4 substrates that have narrow therapeutic indices (e.g., cyclosporine, tacrolimus, digitoxin, warfarin, carbamazepine).

CYP2C8 substrates, nirogacestat [2] ---> SmPC of [2] of EMA

When substrates of CYP2C8, CYP2C9, CYP2C19, and CYP2B6 are administered with Ogsiveo, evaluation for reduced efficacy of the substrate should be performed and dose adjustment of the substrate may be required to maintain optimal plasma concentrations.

CYP3A4 substrates with narrow therapeutic index, nirogacestat [2] ---> SmPC of [2] of EMA

Ogsiveo should not be used with concomitant administration of CYP3A4 substrates that have narrow therapeutic indices (e.g., cyclosporine, tacrolimus, digitoxin, warfarin, carbamazepine).

Dabigatran, nirogacestat [2] ---> SmPC of [2] of EMA

A single-dose drug-drug interaction study demonstrated that nirogacestat did not affect the exposure of dabigatran, a P-gp substrate, which supports the absence of clinically meaningful P-gp inhibition by nirogacestat.

Diarrhoe, nirogacestat [2] ---> SmPC of [2] of EMA

Diarrhoea was reported in patients receiving nirogacestat (see section 4.8). Patients who experience diarrhoea during treatment with nirogacestat should be monitored and managed using anti-diarrhoeal medicinal products.

Digitoxin, nirogacestat [2] ---> SmPC of [2] of EMA

Ogsiveo should not be used with concomitant administration of CYP3A4 substrates that have narrow therapeutic indices (e.g., cyclosporine, tacrolimus, digitoxin, warfarin, carbamazepine).

Efavirenz, nirogacestat [2] ---> SmPC of [2] of EMA

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

Electrolyte imbalance, nirogacestat [2] ---> SmPC of [2] of EMA

Electrolyte abnormalities, including hypophosphataemia and hypokalaemia, were reported in patients receiving nirogacestat (see section 4.8).

Etravirine, nirogacestat [2] ---> SmPC of [2] of EMA

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

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

Fertility studies were not conducted in humans. The effect of Ogsiveo on fertility in humans is not known. Based on findings from animal studies, male and female fertility may be impaired (see section 5.3).

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

Patients should avoid consuming grapefruit and grapefruit juice when taking Ogsiveo since they include inhibitors of CYP3A4 (see section 4.2).

Grapefruit, nirogacestat [2] ---> SmPC of [2] of EMA

Patients should avoid consuming grapefruit and grapefruit juice when taking Ogsiveo since they include inhibitors of CYP3A4 (see section 4.2).

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

However, co-administration of these medicinal products may reduce the bioavailability of nirogacestat. Concomitant use of Ogsiveo with proton pump inhibitors and H2 blockers is not recommended.

Hepatic function, nirogacestat [2] ---> SmPC of [2] of EMA

ALT or AST elevations were reported in patients who received nirogacestat (see section 4.8). Liver function tests should be monitored regularly.

Hidradenitis, nirogacestat [2] ---> SmPC of [2] of EMA

Dermatologic reactions, including maculopapular rash, folliculitis, and hidradenitis, were reported in patients receiving nirogacestat (see section 4.8).

Hormonal contraceptives, nirogacestat [2] ---> SmPC of [2] of EMA

Since no study has been performed investigating the effect of nirogacestat on systemic contraceptive steroid exposure, it is unknown whether nirogacestat reduces the effectiveness of systemically acting hormonal contraceptives.

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

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

Men, nirogacestat [2] ---> SmPC of [2] of EMA

Male patients with female partners of childbearing potential should be advised to use highly effective contraceptive methods during treatment with nirogacestat and for 1 week after the last dose of nirogacestat (see section 4.6).

Moderate CYP3A4 inductors, nirogacestat [2] ---> SmPC of [2] of EMA

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

Moderate CYP3A4 inhibitors, nirogacestat [2] ---> SmPC of [2] of EMA

Nirogacestat [1], non-melanoma skin cancers ---> SmPC of [1] of EMA

Non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) were reported in patients receiving nirogacestat (see section 4.8).

Nirogacestat [1], ovarian toxicity ---> SmPC of [1] of EMA

Ovarian toxicity was reported in female patients of childbearing potential receiving nirogacestat (see section 4.8).

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

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

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

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

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

Based on findings from animal studies and its mechanism of action, Ogsiveo may cause foetal harm when administered to a pregnant woman. Ogsiveo is contraindicated in pregnant women (see sections 4.3 and 5.3).

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

However, co-administration of these medicinal products may reduce the bioavailability of nirogacestat. Concomitant use of Ogsiveo with proton pump inhibitors and H2 blockers is not recommended.

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

Therefore, no clinically significant prolongation in QTcF interval is associated with therapeutic dosing of Ogsiveo.

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

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

Nirogacestat [1], St. John's wort ---> SmPC of [1] of EMA

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

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

Moderate and strong inducers are expected to result in clinically relevant decreases in exposure of nirogacestat that could lead to reduced efficacy.

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

Nirogacestat [1], tacrolimus ---> SmPC of [1] of EMA

Ogsiveo should not be used with concomitant administration of CYP3A4 substrates that have narrow therapeutic indices (e.g., cyclosporine, tacrolimus, digitoxin, warfarin, carbamazepine).

Nirogacestat [1], treatment alternatives ---> SmPC of [1] of EMA

If therapeutic alternatives are not available, Ogsiveo should be immediately interrupted for the period of time in which a strong or moderate CYP3A4 inhibitor is given.

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

Ogsiveo should not be used with concomitant administration of CYP3A4 substrates that have narrow therapeutic indices (e.g., cyclosporine, tacrolimus, digitoxin, warfarin, carbamazepine).

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

Patients should be monitored for changes in menstrual cycle regularity or the development of symptoms of oestrogen deficiency, including hot flashes, night sweats, and vaginal dryness.

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

Women of childbearing potential receiving nirogacestat must use highly effective contraceptive methods during treatment with nirogacestat and for 1 week after the last dose of nirogacestat (see section 4.6).

CONTRAINDICATIONS of Nirogacestat (Ogsiveo)

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

- Pregnancy (see sections 4.4 and 4.6)

- Women of childbearing potential not using highly effective contraception (see sections 4.4 and 4.6)

- Breast-feeding (see section 4.6)

https://www.ema.europa.eu/en/documents/product-information/ogsiveo-epar-product-information_en.pdf 03/10/2025

Nirsevimab (Beyfortus)

Ability to drive [1], nirsevimab ---> SmPC of [1] of EMA

Not applicable.

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

Not applicable.

Cytochrome P450, monoclonal antibodies

Monoclonal antibodies do not typically have significant interaction potential, as they do not directly affect cytochrome P450 enzymes and are not substrates of hepatic or renal transporters.

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

Not applicable.

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

Not applicable.

Nirsevimab [1], vaccinations ---> SmPC of [1] of EMA

Nirsevimab should not be mixed with any vaccine in the same syringe or vial (see section 6.2). When administered concomitantly with injectable vaccines, they should be given with separate syringes and at different injection sites.

CONTRAINDICATIONS of Nirsevimab (Beyfortus)

- 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/beyfortus-epar-product-information_en.pdf 23/02/2026

Nisoldipine

Ability to drive, nisoldipine

Nisoldipine may alter the capacity to react

ACE inhibitors, nisoldipine

The co-administration may potentiate the hypotensive effect

AIIRA, nisoldipine

The co-administration may potentiate the hypotensive effect

Allopurinol/lesinurad [1], nisoldipine ---> SmPC of [1] of EMA

Patients using lipid lowering or anti-hypertensive medicinal products that were CYP3A substrates required concomitant medicinal product change when treated with lesinurad 200 mg in combination with a xanthine oxidase inhibitor

Alpha-methyldopa, nisoldipine

The co-administration may potentiate the hypotensive effect

Antiadrenergics, nisoldipine

The co-administration may potentiate the hypotensive effect

Antihypertensives, nisoldipine

The co-administration may potentiate the hypotensive effect

Azole antifungals, nisoldipine

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

Betablockers, nisoldipine

The co-administration may cause heart failure.

Boceprevir [1], nisoldipine ---> SmPC of [1] of EMA

Boceprevir, CYP3A4 inhibitor, may increase the plasma concentrations of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Breast-feeding, nisoldipine

Nisoldipine is contraindicated during breast-feeding

Calcium antagonists, nisoldipine

The co-administration may potentiate the hypotensive effect

Carbamazepine, nisoldipine

Carbamazepine, strong CYP3A4 inductor, may decrease the plasma concentrations of nisoldipine. The co-administration is contraindicated

Cimetidine, nisoldipine

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

Dalfopristin, nisoldipine

The CYP3A4 inhibition may increase the plasma concentrations of nisoldipine

Diuretics, nisoldipine

The co-administration may potentiate the hypotensive effect

Erythromycin, nisoldipine

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

Fluconazole, nisoldipine

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

Fluoxetine, nisoldipine

The CYP3A4 inhibition may increase the plasma concentrations of nisoldipine

Grapefruit juice, nisoldipine

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

Indinavir, nisoldipine

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

Itraconazol, nisoldipine

Concomitant use of itraconazol and nisoldipine is contraindicated

Ketoconazole [1], nisoldipine ---> SmPC of [1] of EMA

Concomitant therapy of ketoconazole with nisoldipine is contraindicated due to an increased risk of oedema and congestive heart failure

Macrolide antibiotics, nisoldipine

The macrolide inhibits the CYP3A4 and may increase the plasma levels of nisoldipine (the co-administration is contraindicated). Azithromycin is void of CYP3A4 inhibition.

Moderate CYP3A4 inhibitors, nisoldipine

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

Nefazodone, nisoldipine

Nefazodone, strong CYP3A4 inhibitor, may increase the plasma levels of nisoldipine.

Nelfinavir, nisoldipine

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

Nisoldipine, organic nitrates

The co-administration may potentiate the hypotensive effect

Nisoldipine, PDE5 inhibitors

The co-administration may potentiate the hypotensive effect

Nisoldipine, phenobarbital

The strong CYP3A4 induction may decrease the plasma concentrations of nisoldipine. The co-administration is contraindicated

Nisoldipine, phenytoin

The strong CYP3A4 induction may decrease the plasma concentrations of nisoldipine. The co-administration is contraindicated

Nisoldipine, posaconazole [2] ---> SmPC of [2] of EMA

Concomitant use of posaconazole with calcium channel blockers metabolised through CYP3A4 increases plasma concentrations of the calcium channel blocker.

Nisoldipine, pregnancy

Nisoldipine is contraindicated during pregnancy

Nisoldipine, protease inhibitors

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

Nisoldipine, quinupristin

The CYP3A4 inhibition may increase the plasma concentrations of nisoldipine

Nisoldipine, rifampicin

Rifampicin, strong CYP3A4 inductor, may decrease the plasma levels of nisoldipine. The co-administration is contraindicated.

Nisoldipine, ritonavir

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

Nisoldipine, saquinavir

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

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

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

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

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Caution is warranted

Nisoldipine, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma concentrations of nisoldipine

Nisoldipine, strong CYP3A4 inhibitors

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

Nisoldipine, tacrolimus

The CYP3A4 inhibition may increase the plasma concentrations of nisoldipine

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

Inhibition of CYP3A and/or effect on P-gp transport in the gut increases plasma concentration of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Nisoldipine, valproic acid

The CYP3A4 inhibition may increase the plasma concentrations of nisoldipine

Nitisinone (Orfadin)

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

Adverse reactions involving the eyes can affect the vision.

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

Mothers receiving nitisinone must not breast-feed, since a risk to the suckling child cannot be excluded

Drugs primarily metabolised by CYP2C9, nitisinone [2] ---> SmPC of [2] of EMA

Therefore nitisinone treatment may result in increased plasma concentrations of co-administered medicinal products metabolized primarily via CYP2C9 (see section 4.4).

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

Nitisinone has been co-administered with food during the generation of efficacy and safety data. Therefore, it is recommended that if nitisinone treatment with Orfadin hard capsules is initiated with food, this should be maintained on a routine basis

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

Orfadin should not be used during pregnancy unless the clinical condition of the woman requires treatment with nitisinone. Nitisinone crosses the human placenta.

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

Nitisinone is metabolised in vitro by CYP 3A4 and dose-adjustment may therefore be needed when nitisinone is co-administered with inducers of this enzyme.

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

Nitisinone is metabolised in vitro by CYP 3A4 and dose-adjustment may therefore be needed when nitisinone is co-administered with inhibitors of this enzyme.

CONTRAINDICATIONS of Nitisinone (Orfadin)

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

- Mothers receiving nitisinone must not breast-feed

https://www.ema.europa.eu/en/documents/product-information/orfadin-epar-product-information_en.pdf 04/07/2025

Other trade names: Nitisinone (Orfadin) Nityr, Nitisinone MDK (previously Nitisinone MendeliKABS),

Nitrendipine

Ability to drive, nitrendipine

Nitrendipine may impair your ability to drive or operate machines.

ACE inhibitors, nitrendipine

The co-administration may potentiate the hypotensive effect

AIIRA, nitrendipine

The co-administration may potentiate the hypotensive effect

Alpha-methyldopa, nitrendipine

The co-administration may potentiate the hypotensive effect

Amiodarone, nitrendipine

Calcium antagonist may potentiate the negative inotrope effect of antiarrthymics leading to sinus arrest and AV block

Antiadrenergics, nitrendipine

The co-administration may potentiate the hypotensive effect

Antiarrhythmics, nitrendipine

Calcium antagonist may potentiate the negative inotrope effect of antiarrthymics leading to sinus arrest and AV block

Antihypertensives, nitrendipine

The co-administration may potentiate the hypotensive effect

Azole antifungals, nitrendipine

The strong CYP3A4 inhibition may increase the plasma concentrations of nitrendipine. Caution is recommended

Betablockers, nitrendipine

The co-administration may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency

Breast-feeding, nitrendipine

Nitrendipine is contraindicated during breast-feeding

Calcium antagonists, nitrendipine

The co-administration may potentiate the hypotensive effect

Carbamazepine, nitrendipine

Carbamazepine, strong CYP3A4 inductor, may decrease the bioavailability and effect of nitrendipine

Cimetidine, nitrendipine

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

Dalfopristin, nitrendipine

The CYP3A4 inhibition may increase the plasma concentrations of nitrendipine.

Digoxin, nitrendipine

The co-administration may increase the plasma levels of digoxin

Diuretics, nitrendipine

The co-administration may potentiate the hypotensive effect

Erythromycin, nitrendipine

The moderate CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

Fluoxetine, nitrendipine

The CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

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.

Ketoconazole, nitrendipine

The strong CYP3A4 inhibition may increase the plasma concentrations of nitrendipine. Caution is recommended

Macrolide antibiotics, nitrendipine

The macrolide inhibits the CYP3A4 and therefore may increase the plasma concentrations of nitrendipine. Azithromycin is void of CYP3A4 inhibition.

Moderate CYP3A4 inhibitors, nitrendipine

The moderate CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

Nebivolol [1], nitrendipine ---> SmPC of [1] of eMC

Nefazodone, nitrendipine

Nefazodone, strong CYP3A4 inhibitor, may increase the plasma levels of nitrendipine.

Nitrendipine, organic nitrates

The co-administration may potentiate the hypotensive effect

Nitrendipine, pancuronium

Possible enhancement of pancuronium effect and the intensity of neuromuscular block

Nitrendipine, PDE5 inhibitors

The co-administration may potentiate the hypotensive effect

Nitrendipine, phenobarbital

The strong CYP3A4 induction may decrease the bioavailability and effect of nitrendipine

Nitrendipine, phenytoin

The strong CYP3A4 induction may decrease the bioavailability and effect of nitrendipine

Nitrendipine, posaconazole [2] ---> SmPC of [2] of EMA

Concomitant use of posaconazole with calcium channel blockers metabolised through CYP3A4 increases plasma concentrations of the calcium channel blocker.

Nitrendipine, prazosin

The co-administration of nitrendipine and prazosin may cause severe hypotension

Nitrendipine, pregnancy

Nitrendipine is contraindicated in pregnancy

Nitrendipine, protease inhibitors

The strong CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

Nitrendipine, quinidine

Calcium antagonist may potentiate the negative inotrope effect of antiarrthymics leading to sinus arrest and AV block

Nitrendipine, quinupristin

The CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

Nitrendipine, ranitidine

The CYP3A4 inhibition may increase the plasma levels of nitrendipine

Nitrendipine, rifampicin

Rifampicin, strong CYP3A4 inductor, may decrease the plasma levels of nitrendipine. The co-administration is contraindicated.

Nitrendipine, ritonavir

The CYP3A4 inhibition may increase the plasma levels of nitrendipine

Nitrendipine, strong CYP3A4 inductors

The strong CYP3A4 induction may decrease the plasma concentrations of nitrendipine

Nitrendipine, strong CYP3A4 inhibitors

The strong CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

Nitrendipine, ursodeoxycholic acid [2] ---> SmPC of [2] of eMC

Ursodeoxycholic acid has been shown to reduce the plasma peak concentrations (Cmax) and the area under the curve (AUC) of the calcium antagonist nitrendipine.

Nitrendipine, valproic acid

The CYP3A4 inhibition may increase the plasma concentrations of nitrendipine

Nitrendipine, vecuronium

The duration and intensity of action of muscle relaxants may be enhanced.

Nitric oxide (INOmax)

Alkyl nitrates, nitric oxide [2] ---> SmPC of [2] of EMA

There is an increased risk of methaemoglobin formation if substances with a known tendency to increase methaemoglobin concentrations are administered concomitantly with nitric oxide

Breast-feeding, nitric oxide [2] ---> SmPC of [2] of EMA

INOmax should not be used during breastfeeding.

Fertility, nitric oxide [2] ---> SmPC of [2] of EMA

No fertility studies have been performed.

Glycerol trinitrate, nitric oxide [2] ---> SmPC of [2] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Hypoxic respiratory insufficiency, nitric oxide [2] ---> SmPC of [2] of EMA

For patients who are to be referred to another hospital, to prevent worsening of their condition on acute discontinuation of INOmax, the availability of nitric oxide during transport should be assured.

Ibuprofen [1], nitric oxide ---> SmPC of [1] of EMA

Since both medicinal products inhibit platelet function, their combination may in theory increase the risk of bleeding.

Local anaesthetics, nitric oxide ---> SmPC of [liposomal bupivacaine] of EMA

Patients that are administered local anaesthetics may be at increased risk of developing methaemoglobinamia when concurrently exposed to these oxidizing medicinal products

Methemoglobinemia, nitric oxide [2] ---> SmPC of [2] of EMA

There is an increased risk of methaemoglobin formation if substances with a known tendency to increase methaemoglobin concentrations are administered concomitantly with nitric oxide

Nitric oxide [1], nitric oxide donors ---> SmPC of [1] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Nitric oxide [1], nitroglycerine ---> SmPC of [1] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Nitric oxide [1], nitroprussiate ---> SmPC of [1] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Nitric oxide [1], oxygen ---> SmPC of [1] of EMA

In the presence of oxygen, nitric oxide is rapidly oxidised to derivatives which are toxic to the bronchial epithelium and alveolo-capillary membrane.

Nitric oxide [1], pregnancy ---> SmPC of [1] of EMA

INOmax should not be used during pregnancy

Nitric oxide [1], prilocaine ---> SmPC of [1] of EMA

Prilocaine, whether administered as oral, parenteral, or topical formulations may cause methaemoglobinaemia. Care must be taken when INOmax is given at the same time as medicinal products containing prilocaine.

Nitric oxide [1], sodium nitroprusside ---> SmPC of [1] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Nitric oxide [1], sulphonamides ---> SmPC of [1] of EMA

There is an increased risk of methaemoglobin formation if substances with a known tendency to increase methaemoglobin concentrations are administered concomitantly with nitric oxide

Nitric oxide [1], susceptibility to infections ---> SmPC of [1] of EMA

There are also animal data suggesting an increased susceptibility to airway infections upon exposure to low levels of NO2.

Nitric oxide [1], tolazoline ---> SmPC of [1] of EMA

INOmax has been safely administered with tolazoline, dopamine, dobutamine, steroids, surfactant, and high-frequency ventilation.

Nitric oxide [1], vasodilators ---> SmPC of [1] of EMA

Available data suggest additive effects on central circulation, pulmonary artery pressure and right ventricular performance. Inhaled nitric oxide combination with other vasodilators acting by the cGMP or cAMP systems should be done with caution.

Nitric oxide, sildenafil [2] ---> SmPC of [2] of EMA

The combined used with other vasodilators (e.g. sildenafil) is not extensively studied.

CONTRAINDICATIONS of Nitric oxide (INOmax)

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

- Neonates known to be dependent on right-to-left, or significant left-to-right, shunting of blood.

https://www.ema.europa.eu/en/documents/product-information/inomax-epar-product-information_en.pdf 15/05/2025

Other trade names: Nomixgen, Noxap, Vasokinox,

Nitrofural

Breast-feeding, nitrofural

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

Nitrofural, pregnancy

Nitrofural is contraindicated in pregnancy

Nitroglycerine

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

As glyceryl trinitrate can cause dizziness patients should make sure they are not affected before driving or operating machinery.

Acetylcysteine, nitroglycerine [2] ---> SmPC of [2] of eMC

N-acetylcysteine may potentiate the vasodilator effects of glyceryl trinitrate.

Acetylsalicylic acid, nitroglycerine

The col-administration of glycerol trinitrate with acetylsalicylic acid may decrease the clearance of glycerol trinitrate

Alcohol, nitroglycerine [2] ---> SmPC of [2] of eMC

The risk of hypotension and syncope with use of glyceryl trinitrate may be enhanced by alcohol.

Alcohol, organic nitrates

The risk of hypotension and syncope with use of organic nitrates may be enhanced by alcohol.

Alteplase, nitroglycerine

It has been shown that IV nitroglycerin decreases the thrombolytic effect of alteplase.

Amitriptyline, nitroglycerine [2] ---> SmPC of [2] of eMC

There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

Amitriptyline, organic nitrates ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth to reduce the effectiveness of sublingual nitrates.

Anticholinergics, nitroglycerine [2] ---> SmPC of [2] of eMC

There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

Anticholinergics, organic nitrates ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth to reduce the effectiveness of sublingual nitrates.

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

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

Antimuscarinic agents, organic nitrates ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth to reduce the effectiveness of sublingual nitrates.

Atropine, organic nitrates ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth to reduce the effectiveness of sublingual nitrates.

Bemiparin, nitroglycerine

Interaction of heparin with intravenous nitroglycerine (which can result in a decrease in efficacy) cannot be ruled out for bemiparin.

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

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

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

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

Calcium antagonists, nitroglycerine [2] ---> SmPC of [2] of eMC

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

Cangrelor [1], nitroglycerine ---> SmPC of [1] of EMA

No pharmacokinetic or pharmacodynamic interaction with cangrelor was observed in an interaction study with acetylsalicylic acid, heparin, or nitroglycerin.

Captopril [1], nitroglycerine ---> SmPC of [1] of eMC

Treatment of captopril with nitroglycerine and other nitrates, or other vasodilators, should be used with caution.

Certoparin, nitroglycerine

The co-administration may weaken the pharmacological effects of certoparin

Dalteparin, nitroglycerine

Nitroglycerin i.v. decreases the anticoagulant effect

Dapsone, nitroglycerine

The methemoglobin reductase inhibition may increase the formation of methemoglobin

Desipramine, nitroglycerine [2] ---> SmPC of [2] of eMC

There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

Dihydroergotamine, nitroglycerine [2] ---> SmPC of [2] of eMC

Glyceryl trinitrate can reduce the first pass hepatic metabolism of dihydroergotamine.

Doubutamine, nitroglycerine

Concomitant use of dobutamine and vasodilatators may cause more pronounced increase in cardiac output and decrease in pulmonary arterial pressure than when either medicinal product was given alone

Doxepin, nitroglycerine [2] ---> SmPC of [2] of eMC

There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

Enalapril [1], nitroglycerine ---> SmPC of [1] of eMC

Concomitant use of enalapril and nitrates may further reduce blood pressure.

Enalapril/hydrochlorothiazide [1], nitroglycerine ---> SmPC of [1] of eMC

Concomitant use of enalapril/hydrochlorothiazide with nitroglycerine and other nitrates may further reduce blood pressure.

Fosinopril [1], nitroglycerine ---> SmPC of [1] of eMC

The co-administration of fosinopril with glycerol trinitrate and other nitrates or other vasodilatators may further decrease the blood pressure

Glycerol trinitrate, organic nitrates ---> SmPC of [nitroglycerine] of eMC

The possibility of tolerance to the effects of glyceryl trinitrate should be considered when used in conjunction with long-acting nitrate preparations.

Heparin, nitroglycerine [2] ---> SmPC of [2] of eMC

There is evidence that systemic nitrates may interfere with the anticoagulant effects of heparin.

Heparin, organic nitrates ---> SmPC of [nitroglycerine] of eMC

There is evidence that systemic nitrates may interfere with the anticoagulant effects of heparin.

Hydroxycobalamin, nitroglycerine

Physical incompatibility (particle formation). These medicinal products must not be administered simultaneously through the same intravenous line as hydroxocobalamine

Imidapril [1], nitroglycerine ---> SmPC of [1] of eMC

Concomitant use of imidapril with nitroglycerin and other nitrates may further reduce blood pressure.

Indometacin, nitroglycerine

Weaken of hypotensive effect of nitroglycerin

Labetalol, nitroglycerine

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

Lidocaine/prilocaine [1], nitroglycerine ---> SmPC of [1] of EMA

Methaemoglobinaemia may be accentuated in patients already taking medicinal products known to induce the condition

Lisinopril [1], nitroglycerine ---> SmPC of [1] of eMC

Concomitant use of lisinopril with nitrates may further reduce blood pressure.

Lofepramine, organic nitrates ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth to reduce the effectiveness of sublingual nitrates.

Methemoglobin reductase inhibitors, nitroglycerine

The methemoglobin reductase inhibition may increase the formation of methemoglobin

Methylergometrine, nitroglycerine

Methylergometrine has a vasoconstrictor effect and can weaken the effect of antianginal drugs

Neuroleptics, nitroglycerine [2] ---> SmPC of [2] of eMC

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

Nitric oxide [1], nitroglycerine ---> SmPC of [1] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Nitroglycerine [1], organic nitrates ---> SmPC of [1] of eMC

The possibility of tolerance to the effects of glyceryl trinitrate should be considered when used in conjunction with long-acting nitrate preparations.

Nitroglycerine [1], PDE5 inhibitors ---> SmPC of [1] of eMC

Phosphodiesterase type 5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and coadministration with glyceryl trinitrate is therefore contraindicated

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

The administration of glyceryl trinitrate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

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

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

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

Phosphodiesterase type 5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and coadministration with glyceryl trinitrate is therefore contraindicated

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

Phosphodiesterase type 5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and coadministration with glyceryl trinitrate is therefore contraindicated

Nitroglycerine [1], tricyclic antidepressant ---> SmPC of [1] of eMC

Treatment with other agents with hypotensive effects may potentiate the hypotensive effect of glyceryl trinitrate. There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effective

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

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

Nitroglycerine, NSAID

Concurrent administration may potentiate the blood pressure lowering effects of nitroglycerin.

Nitroglycerine, pancuronium [2] ---> SmPC of [2] of eMC

Potentiation of the duration of action of pancuronium and the intensity of neuromuscular block.

Nitroglycerine, perindopril [2] ---> SmPC of [2] of eMC

Concomitant use of perindopril with nitroglycerin may further reduce blood pressure.

Nitroglycerine, reviparin

The intravenous nitroglycerine reduces the heparin effect

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

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

Nitroglycerine, sodium heparin

The anticoagulant effect of heparin may decrease in patients treated with iv nitroglycerin

Nitroglycerine, vardenafil [2] ---> SmPC of [2] of EMA

The co-administration of vardenafil with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated

Organic nitrates, procyclidine ---> SmPC of [nitroglycerine] of eMC

Drugs with anticholinergic properties may decrease salivation causing dry mouth and, in theory, may reduce the absorption and therefore the therapeutic effect of sublingual or buccal nitrate tablets.

Organic nitrates, tricyclic antidepressant ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth (eg anticholinergic, antimuscarinics, tricyclic antidepressants) to reduce the effectiveness of sublingual nitrates.

Organic nitrates, trihexyphenidyl ---> SmPC of [nitroglycerine] of eMC

There is a potential for drugs that cause dry mouth to reduce the effectiveness of sublingual nitrates.

CONTRAINDICATIONS of Nitroglycerine

- Glyceryl trinitrate is contraindicated in patients taking phosphodiesterase type 5 inhibitors (e.g. sildenafil, vardenafil, tadalafil)

- Glyceryl trinitrate is contraindicated in angina caused by hypertrophic obstructive cardiomyopathy as it may exaggerate outflow obstruction.

- Hypersensitivity to the active substance, to other nitro compounds, or to any of the excipients.

- Glyceryl trinitrate should not be used in patients with possible increased intracranial pressure (e.g. cerebral haemorrhage or head trauma).

- Marked anaemia

- Closed angle glaucoma

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

Nitroprussiate

Ability to drive, nitroprussiate

Disorientation, dizziness and blurred vision may occur

Ability to drive, sodium nitroprusside

Disorientation, dizziness and blurred vision may occur

Anaesthetics, nitroprussiate

Enhanced blood pressure lowering

Antihypertensives, nitroprussiate

Concomitant use of sodium nitroprusside with other antihypertensive agents may increase the antihypertensive effect

Antihypertensives, sodium nitroprusside

Concomitant use of sodium nitroprusside with other antihypertensive agents may increase the antihypertensive effect

Breast-feeding, nitroprussiate

It is not recommended for women who are breast feeding.

Breast-feeding, sodium nitroprusside

It is not recommended for women who are breast feeding.

Dapsone, nitroprussiate

The methemoglobin reductase inhibition may increase the formation of methemoglobin

Diazepam [1], nitroprussiate ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Doubutamine, nitroprussiate

Concomitant use of dobutamine and vasodilatators may cause more pronounced increase in cardiac output and decrease in pulmonary arterial pressure than when either medicinal product was given alone

Lidocaine/prilocaine [1], nitroprussiate ---> SmPC of [1] of EMA

Methaemoglobinaemia may be accentuated in patients already taking medicinal products known to induce the condition

Lorazepam [1], nitroprussiate ---> SmPC of [1] of eMC

Enhanced hypotensive effect

Methemoglobin reductase inhibitors, nitroprussiate

The methemoglobin reductase inhibition may increase the formation of methemoglobin

Midazolam, nitroprussiate

Enhanced hypotensive effect

Midazolam, sodium nitroprusside

Enhanced hypotensive effect

Nitric oxide [1], nitroprussiate ---> SmPC of [1] of EMA

There may be an additive effect with nitric oxide on the risk of developing methaemoglobinemia with nitric oxide donor substances, including sodium nitroprusside and nitroglycerin.

Nitroprussiate, PDE5 inhibitors

Enhanced blood pressure lowering

Nitroprussiate, pregnancy

The use should be considered only when the potential benefits outweigh the possible risks.

Nitroprussiate, sedatives

Enhanced blood pressure lowering

Nitroprussiate, sildenafil [2] ---> SmPC of [2] of EMA

Studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside in vitro.

Nitroprussiate, sodium iodide

The withdrawal period prior to administration of sodium [131I]iodine is 1 week

Nitroprussiate, vasodilators

Enhanced blood pressure lowering

Pregnancy, sodium nitroprusside

The use should be considered only when the potential benefits outweigh the possible risks.

Nivolumab (Opdivo)

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

Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that nivolumab does not adversely affect them.

Ability to drive, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

Because of potential adverse reactions such as fatigue and dizziness (see section 4.8), patients should be advised to use caution when driving or operating machines until they are certain that Opdualag does not adversely affect them.

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

A decision must be made whether to discontinue breast-feeding or to discontinue from nivolumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Breast-feeding, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

A risk to the breast-fed infant cannot be excluded during this short period. Afterwards, Opdualag could be used during breast-feeding if clinically needed.

Corticosteroids, nivolumab [2] ---> SmPC of [2] of EMA

The use of systemic corticosteroids and other immunosuppressants at baseline, before starting nivolumab, should be avoided because of their potential interference with the pharmacodynamic activity.

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

Studies to evaluate the effect of nivolumab on fertility have not been performed. Thus, the effect of nivolumab on male and female fertility is unknown.

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

The use of systemic corticosteroids and other immunosuppressants at baseline, before starting nivolumab, should be avoided because of their potential interference with the pharmacodynamic activity.

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

Nivolumab is a human monoclonal antibody, as such pharmacokinetic interaction studies have not been conducted

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

Nivolumab is not recommended during pregnancy and in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk.

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

Effective contraception should be used for at least 5 months following the last dose of nivolumab.

Nivolumab/relatlimab [1], pregnancy ---> SmPC of [1] of EMA

Opdualag is not recommended during pregnancy and in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk.

CONTRAINDICATIONS of Nivolumab (Opdivo)

- 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/opdivo-epar-product-information_en.pdf 21/01/2026

Other trade names: Nivolumab BMS,

Nivolumab/relatlimab (Opdualag)

Ability to drive, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

Antibodies, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other active substances metabolising enzymes, inhibition or induction of these enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetic

Breast-feeding, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

A risk to the breast-fed infant cannot be excluded during this short period. Afterwards, Opdualag could be used during breast-feeding if clinically needed.

Cytochrome P450, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

Nivolumab and relatlimab are not expected to affect the pharmacokinetics of other active substances that are metabolised by CYP enzymes

Fertility, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

Studies to evaluate the effect of nivolumab and/or relatlimab on fertility have not been performed. Thus, the effect of nivolumab and/or relatlimab on male and female fertility is unknown.

Immunosuppressives, nivolumab/relatlimab [2] ---> SmPC of [2] of EMA

The use of systemic corticosteroids and other immunosuppressants at baseline, before starting nivolumab in combination with relatlimab, should be avoided because of their potential interference with the pharmacodynamic activity.

Nivolumab/relatlimab [1], pregnancy ---> SmPC of [1] of EMA

Opdualag is not recommended during pregnancy and in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk.

Nivolumab/relatlimab [1], women of childbearing potential ---> SmPC of [1] of EMA

Opdualag is not recommended in women of childbearing potential not using effective contraception unless the clinical benefit outweighs the potential risk.

Nivolumab/relatlimab [1], women of childbearing potential ---> SmPC of [1] of EMA

Effective contraception should be used for at least 5 months following the last dose of Opdualag.

CONTRAINDICATIONS of Nivolumab/relatlimab (Opdualag)

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

https://www.ema.europa.eu/en/documents/product-information/opdualag-epar-product-information_en.pdf 06/01/2025

Nomegestrol/estradiol (Zoely)

Anti-infective, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Bosentan, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Breast-feeding, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Therefore, the use of COCs should not be recommended until the breastfeeding mother has completely weaned her child and an alternative method of contraception should be proposed to women wishing to breastfeed.

Carbamazepine, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Clarithromycin, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of oestrogens or progestogens.

Diltiazem, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Efavirenz, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Enzyme inductors, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions between oral contraceptives and enzyme-inducing medicinal products may lead to breakthrough bleeding and even contraceptive failure.

Erythromycin, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Felbamate, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Fertility, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Zoely is indicated for the prevention of pregnancy. For information on return to fertility, see section 5.1.

Fluconazole, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Griseofulvin, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Itraconazol, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Ketoconazole, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

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.

Moderate CYP3A4 inhibitors, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Nevirapine, nomegestrol/estradiol [2] ---> SmPC of [2] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], oral contraceptives ---> SmPC of [1] of EMA

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

Nomegestrol/estradiol [1], oxcarbazepine ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], phenobarbital ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], phenytoin ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], pregnancy ---> SmPC of [1] of EMA

Zoely is not indicated during pregnancy.

Nomegestrol/estradiol [1], primidone ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], rifampicin ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], ritonavir ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], St. John's wort ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

Nomegestrol/estradiol [1], strong CYP3A4 inhibitors ---> SmPC of [1] of EMA

Nomegestrol/estradiol [1], topiramate ---> SmPC of [1] of EMA

Interactions can occur with substances that induce CYP450 enzymes, resulting in reduced concentrations of sex hormones and decreased effectiveness of combined oral contraceptives, including Zoely.

CONTRAINDICATIONS of Nomegestrol/estradiol (Zoely)

CHCs must not be used in the following conditions. Should any of the conditions appear for the first time during Zoely use, the medicinal product should be stopped immediately.

- Presence or risk of venous thromboembolism (VTE)

. Venous thromboembolism -current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]).

. Known hereditary or acquired predisposition for venous thromboembolism, such as activated protein C (APC)-resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency.

. Major surgery with prolonged immobilisation (see section 4.4).

. A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4).

- Presence or risk of arterial thromboembolism (ATE)

. Arterial thromboembolism -current ATE, history of ATE (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris).

. Cerebrovascular disease - current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack [TIA]).

. Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant).

. History of migraine with focal neurological symptoms.

. A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence of one serious risk factor such as:

- diabetes mellitus with vascular symptoms;

- severe hypertension;

- severe dyslipoproteinaemia.

- Pancreatitis or a history thereof if associated with severe hypertriglyceridaemia.

- Presence or history of severe hepatic disease as long as liver function values have not returned to normal.

- Presence or history of liver tumours (benign or malignant).

- Known or suspected sex steroid-influenced malignancies (e.g., of the genital organs or the breasts).

- Meningioma or history of meningioma.

- Undiagnosed vaginal bleeding.

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

https://www.ema.europa.eu/en/documents/product-information/zoely-epar-product-information_en.pdf 25/09/2024

Nonacog alfa (BeneFIX)

Breast-feeding, nonacog alfa [2] ---> SmPC of [2] of EMA

Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breastfeeding is not available. Therefore, factor IX should be used during pregnancy and breast-feeding only if clearly indicated.

Fertility, nonacog alfa [2] ---> SmPC of [2] of EMA

The effect of BeneFIX on fertility has not been established.

Nonacog alfa [1], pregnancy ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Nonacog alfa (BeneFIX)

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

- Known allergic reaction to hamster proteins.

https://www.ema.europa.eu/en/documents/product-information/benefix-epar-product-information_en.pdf 07/03/2025

Nonacog beta pegol (Refixia)

Breast-feeding, nonacog beta pegol [2] ---> SmPC of [2] of EMA

Factor IX should be used during pregnancy and lactation only if clearly indicated.

Nonacog beta pegol [1], pregnancy ---> SmPC of [1] of EMA

Factor IX should be used during pregnancy and lactation only if clearly indicated.

CONTRAINDICATIONS of Nonacog beta pegol (Refixia)

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

- Known allergic reaction to hamster protein.

https://www.ema.europa.eu/en/documents/product-information/refixia-epar-product-information_en.pdf 06/11/2023

Nonacog gamma (Rixubis)

Breast-feeding, nonacog gamma [2] ---> SmPC of [2] of EMA

It is unknown whether Factor IX/metabolites are excreted in human milk.

Fertility, nonacog gamma [2] ---> SmPC of [2] of EMA

There is no information on the effects of factor IX on fertility.

Medicinal products, nonacog gamma [2] ---> SmPC of [2] of EMA

No interactions of human coagulation factor IX (rDNA) products with other medicinal products have been reported.

Nonacog gamma [1], pregnancy ---> SmPC of [1] of EMA

Factor IX should be used during pregnancy and breast-feeding only if clearly indicated.

CONTRAINDICATIONS of Nonacog gamma (Rixubis)

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

- Known allergic reaction to hamster protein.

https://www.ema.europa.eu/en/documents/product-information/rixubis-epar-product-information_en.pdf 27/11/2024

Norelgestromin/ethinylestradiol (Evra)

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

The use of EVRA is not to be recommended until the breastfeeding mother has completely weaned her child.

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

The plasma and tissue levels of cyclosporine may increase up to toxic levels

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Estrogens, non-nucleoside reverse transcriptase inhibitors ---> SmPC of [norelgestromin/ethinylestradiol] of EMA

When co-administered with CHCs, many combinations of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors can increase or decrease plasma concentrations of estrogen or progestins.

Estrogens, protease inhibitors ---> SmPC of [norelgestromin/ethinylestradiol] of EMA

Ethinyl estradiol, etoricoxib ---> SmPC of [norelgestromin/ethinylestradiol] of EMA

It is thought that etoricoxib increases ethinyl estradiol levels because it inhibits sulfotransferase activity thereby inhibiting ethinyl estradiol metabolism.

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

Etoricoxib has been shown to increase plasma levels of ethinyl estradiol (50 to 60%) when taken concomitantly with an oral triphasic hormonal contraceptive.

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

Women may experience a delay in conception following discontinuation of EVRA.

Gestagens, non-nucleoside reverse transcriptase inhibitors ---> SmPC of [norelgestromin/ethinylestradiol] of EMA

Gestagens, protease inhibitors ---> SmPC of [norelgestromin/ethinylestradiol] of EMA

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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.

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

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

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], oxcarbazepine ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], penicillins ---> SmPC of [1] of EMA

Contraceptive failures have been reported with antibiotics, such as penicillins and tetracyclines.

Norelgestromin/ethinylestradiol [1], phenobarbital ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], phenytoin ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], pregnancy ---> SmPC of [1] of EMA

EVRA is not indicated during pregnancy. If pregnancy occurs during use of EVRA, EVRA should be stopped immediately.

Norelgestromin/ethinylestradiol [1], primidone ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], rifabutin ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], rifampicin ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], ritonavir ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], rufinamide ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], St. John's wort ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

Norelgestromin/ethinylestradiol [1], tetracyclines ---> SmPC of [1] of EMA

Contraceptive failures have been reported with antibiotics, such as penicillins and tetracyclines.

Norelgestromin/ethinylestradiol [1], topiramate ---> SmPC of [1] of EMA

Interactions can occur with medicinal products that induce hepatic enzymes which can result in increased clearance of sex hormones

CONTRAINDICATIONS of Norelgestromin/ethinylestradiol (Evra)

Combined hormonal contraceptives (CHCs) should not be used in the following conditions. If one of these disorders occurs during the use of EVRA, EVRA must be discontinued immediately.

- Presence or risk of venous thromboembolism (VTE)

- Venous thromboembolism - current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]);

- Known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance, (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency;

- Major surgery with prolonged immobilisation (see section 4.4);

- A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4);

- Presence or risk of arterial thromboembolism (ATE)

- Arterial thromboembolism - current arterial thromboembolism, history of arterial thromboembolism (e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris);

- Cerebrovascular disease - current stroke, history of stroke or prodromal condition (e.g. transient ischaemic attack, TIA);

- Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant);

- History of migraine with focal neurological symptoms;

- A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence of one serious risk factor such as:

- diabetes mellitus with vascular symptoms

- severe hypertension

- severe dyslipoproteinaemia

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

- Known or suspected carcinoma of the breast

- Carcinoma of the endometrium or other known or suspected oestrogen-dependent neoplasia

- Abnormal liver function related to acute or chronic hepatocellular disease

- Hepatic adenomas or carcinomas

- Undiagnosed abnormal genital bleeding

- Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, medicinal products containing glecaprevir/pibrentasvir or sofosbuvir/velpatasvir/voxilaprevir (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/evra-epar-product-information_en.pdf 09/11/2022

Norepinephrine

Alcohol, norepinephrine

The use of noradrenaline with alcohol is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Alfa-adrenergic receptor blockers, norepinephrine

The co-administration of noradrenaline with alfa-adrenergic antagonists may reverse the adrenaline effect (= hypotension)

Anticholinergics, norepinephrine

The use of noradrenaline with parasympatholytic drugs is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Antidiabetics, norepinephrine

Noradrenaline reduces the hypoglycemic effect of antidiabetic agent

Antihistamines, noradrenaline

Some antihistaminics may block the catecholamine uptake by peripheral tissues and increase the toxicity of the injected noradrenalin

Antihistamines, norepinephrine

Some antihistaminics may block the catecholamine uptake by peripheral tissues and increase the toxicity of the injected noradrenalin

Antihypertensives, noradrenaline

Decreased antihypertensive effect

Antihypertensives, norepinephrine

Decreased antihypertensive effect

Atomoxetine, norepinephrine

Drugs that affect noradrenaline should be used cautiously when co-administered with atomoxetine because of the potential for additive or synergistic pharmacological effects.

Atropine, norepinephrine

The use of noradrenaline with parasympatholytic drugs is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Bendroflumethiazide, norepinephrine

Decreased sympathomimetic effect

Betablockers, noradrenaline

The co-administration of noradrenaline with beta-blockers may decrease the hypertensive effect of noradrenaline

Betablockers, norepinephrine

The co-administration of noradrenaline with beta-blockers may decrease the hypertensive effect of noradrenaline

Bisoprolol [1], norepinephrine ---> SmPC of [1] of eMC

Combination with bisoprolol may unmask the alfa-adrenoceptor-mediated vasoconstrictor effects leading to blood pressure increase and exacerbated intermittent claudication.

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

No information is available on the use of noradrenaline in lactation.

Carbazochrome, norepinephrine

The use of noradrenaline with carbazochrome is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Catecholamine-O-methyltransferase inhibitors, norepinephrine

The use of noradrenaline with catecholamine-O-methyltransferase inhibitors is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Celiprolol, norepinephrine

Noradrenaline may counteract the effects of celiprolol

Chlorphenamine, norepinephrine [2] ---> SmPC of [2] of eMC

The use of noradrenaline with chlorphenamine is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Chlortalidone, norepinephrine

Decreased sympathomimetic effect

Clozapine [1], norepinephrine ---> SmPC of [1] of eMC

Owing to its anti-alpha-adrenergic properties, clozapine may reduce the blood-pressure-increasing effect of norepinephrine

Desipramine, noradrenaline

Desipramine increases significantly the toxicity of noradrenalin

Desipramine, norepinephrine

Desipramine increases significantly the toxicity of noradrenalin

Desmopressin, noradrenaline

Decreased antidiuretic effect

Desmopressin, norepinephrine

Decreased antidiuretic effect

Digital glycosides, norepinephrine [2] ---> SmPC of [2] of eMC

The use of noradrenaline with any cardiac sensitizing agents is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Dihydroergotamine, noradrenaline

Dihydroergotamine may increase the noradrenaline effects

Dihydroergotamine, norepinephrine

Dihydroergotamine may increase the noradrenaline effects

Diuretics, norepinephrine

Possible severe, prolonged hypertension and heart rhythm disorders. The combination is not recommended

Doubutamine, norepinephrine

The co-administration may increase the blood pressure

Ergometrine, noradrenaline

Ergometrine may increase the noradrenaline effects

Ergometrine, norepinephrine

Ergometrine may increase the noradrenaline effects

Furosemide, norepinephrine

The co-administration may weaken the effect of pressor amine

Guanethidine, norepinephrine [2] ---> SmPC of [2] of eMC

The use of noradrenaline with guanethidine is not recommended because severe, prolonged hypertension and possible arrhythmias may result

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

The use of noradrenaline with volatile halogenated anaesthetic agents is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Hydrochlorothiazide, norepinephrine ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

Hydrochlorothiazide may reduce the response to pressor amines. The clinical significance of this effect is uncertain and not sufficient to preclude their use.

Hypokalemia, norepinephrine

The use of noradrenaline with drugs which may cause hypokaliemia is not recommended because severe, prolonged hypertension and possible arrhythmias may result

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

The use of noradrenaline with monoamine oxidase inhibitors is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Isoniazid, norepinephrine

Increased adverse effects of sympathomimetic agent

Kaliuretic medicines, norepinephrine

Possible severe, prolonged hypertension and heart rhythm disorders. The combination is not recommended

Levodopa, noradrenaline

The use of noradrenaline with levodopa is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Levodopa, norepinephrine

The use of noradrenaline with levodopa is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Levodopa/benserazide [1], norepinephrine ---> SmPC of [1] of eMC

Sympathomimetics may increase the cardiovascular side-effects of levodopa.

Linezolid [1], norepinephrine ---> SmPC of [1] of eMC

The co-administration is contraindicated, unless there are facilities available for close observation and monitoring of blood pressure

Lithium, noradrenaline

Decreased norepinephrine effect

Lithium, norepinephrine

Decreased norepinephrine effect

Local anaesthetics, norepinephrine

The co-administration of noradrenaline with local anaesthetic agents may cause a mutual potentiation of effects

Mefruside, norepinephrine

Decreased sympathomimetic effect

Methyldopa, norepinephrine [2] ---> SmPC of [2] of eMC

The use of noradrenaline with methyldopa is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Methylergometrine, noradrenaline

Methylergometrine may increase the noradrenaline effects

Methylergometrine, norepinephrine

Methylergometrine may increase the noradrenaline effects

Methylphenidate, noradrenaline

Methylphenidate may increase the noradrenaline effects

Methylphenidate, norepinephrine

Methylphenidate may increase the noradrenaline effects

Methysergide, noradrenaline

Methysergide may increase the noradrenaline effects

Methysergide, norepinephrine

Methysergide may increase the noradrenaline effects

Metoprolol [1], norepinephrine ---> SmPC of [1] of eMC

The administration of adrenaline (epinephrine) or noradrenaline (norepinephrine) to patients undergoing beta-blockade can result in an increase in blood pressure and bradycardia, although this is less likely to occur with beta1-selective drugs.

Noradrenaline, thyroid hormones

Thyroid hormones may increase the noradrenaline effects

Noradrenaline, vasopressin

Decreased antidiuretic effect

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

It may impair placental perfusion and induce fetal bradycardia. It may also exert a contractile effect on the pregnant uterus and lead to fetal asphyxia in late pregnancy.

Norepinephrine [1], reserpine ---> SmPC of [1] of eMC

The use of noradrenaline with reserpine is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norepinephrine [1], tricyclic antidepressant ---> SmPC of [1] of eMC

The use of noradrenaline with antidepressants is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norepinephrine, ornipressin

The use of noradrenaline with ornipressin is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norepinephrine, phenothiazines

The co-administration of noradrenaline with phenothiazines may decrease the hypertensive effect of noradrenaline

Norepinephrine, sotalol

Significant blood pressure increase

Norepinephrine, tetracyclic antidepressant

The use of noradrenaline with antidepressants is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norepinephrine, theophylline

The use of noradrenaline with theophylline is not recommended because severe, prolonged hypertension and possible arrhythmias may result

Norepinephrine, thiazides

Decreased sympathomimetic effect

Norepinephrine, thyroid hormones

Thyroid hormones may increase the noradrenaline effects

Norepinephrine, trimipramine [2] ---> SmPC of [2] of eMC

Trimipramine should not be given with sympathomimetic agents

Norepinephrine, vasopressin

Decreased antidiuretic effect

CONTRAINDICATIONS of Norepinephrine

- Hypersensitivity to noradrenaline tartrate or to any of the excipients.

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

Norethisterone acetate

Barbiturates, norethisterone acetate

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Breast-feeding, norethisterone acetate

Norethisterone acetate is contraindicated in lactation

Carbamazepine, norethisterone acetate

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Enzyme inductors, norethisterone acetate

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Griseofulvin, norethisterone acetate

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone acetate, phenylbutazone

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone acetate, phenytoin

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone acetate, pregnancy

Norethisterone acetate is contraindicated in pregnancy

Norethisterone acetate, primidone

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone acetate, rifabutin

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone acetate, rifampicin

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norethisterone acetate, St. John's wort

Reduced contraceptive efficacy with hepatic enzyme-inducing drugs

Norfloxacin

Ability to drive, norfloxacin

Norfloxacin may alter the capacity to react

Algeldrate/magnesium hydroxide, norfloxacin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs by chelate formation

Aluminium hydroxide, norfloxacin

Concomitant use of aluminium hydroxide may decrease the absorption and effect of quinolones. Separate administration by at least 4 hours

Aluminium oxide/magnesium hydroxide, norfloxacin

The co-administration of aluminium-containing antacids with other drugs may decrease the absorption of these drugs by chelate formation

Aluminium, enoxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the aluminium hydroxide

Aluminium, lomefloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the aluminium preparation

Aluminium, norfloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the other active principle.

Aluminium, prulifloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the aluminium preparation

Aluminium, quinolones

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the aluminium preparation

Antacids, norfloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the other active principle.

Antacids, prulifloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of antacid

Antacids, quinolones

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of antacid

Antacids, rufloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of antacid

Breast-feeding, norfloxacin

Contraindicated

Caffeine, norfloxacin

Quinolone may inhibit the metabolism, decrease the elimination and prolong the plasma half-life of caffeine. The caffeine intake should be avoided.

Caffeine, quinolones

Quinolone may inhibit the metabolism, decrease the elimination and prolong the plasma half-life of caffeine. The caffeine intake should be avoided.

Calcium, norfloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the other active principle.

Class IA antiarrhythmic agents, norfloxacin [2] ---> SmPC of [2] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Class IA antiarrhythmic agents, quinolones ---> SmPC of [norfloxacin] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Class III antiarrhythmic agents, norfloxacin [2] ---> SmPC of [2] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Class III antiarrhythmic agents, quinolones ---> SmPC of [norfloxacin] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Colistimethate [1], norfloxacin ---> SmPC of [1] of EMA

Co-treatment should be undertaken with caution in patients with myasthenia gravis

Cyclosporine, norfloxacin

The co-administration may increase the plasma levels of cyclosporine.

Didanosine, norfloxacin

Decreased absorption of norfloxacin. Separate administration at least 2 hours

Drugs metabolised by CYP1A2, norfloxacin

Norfloxacin, strong CYP1A2 inhibitor, may increase the plasma concentrations of the medicinal products metabolized by CYP1A2

Drugs primarily metabolised by CYP1A2, norfloxacin

Norfloxacin, strong CYP1A2 inhibitor, may increase the plasma concentrations of the medicinal products mainly metabolized by CYP1A2

Fenbufen, norfloxacin

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Fenbufen, quinolones

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold

Ferric maltol [1], norfloxacin ---> SmPC of [1] of EMA

Oral iron is known to reduce the absorption of norfloxacin. This medicinal product should be given at least 2 hours apart from Feraccru.

Glyburide, norfloxacin

The co-administration may cause severe hypoglycaemia

Hydrotalcite, norfloxacin

The co-administration of hydrotalcite with other drugs may decrease the absorption of these drugs. It is recommended to separate the times of administration by at least 1-2 hours

Iron, lomefloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the other active principle.

Iron, norfloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the other active principle.

Iron, prulifloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the iron preparation

Iron, quinolones

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the iron preparation

Lomefloxacin, magnesium

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the magnesium preparation

Macrolide antibiotics, norfloxacin [2] ---> SmPC of [2] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Magaldrate, norfloxacin

Considerable decrease in the absorption of quinolone. During the treatment with a quinolone is not recommended la administration of magaldrate

Magnesium, norfloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the other active principle.

Magnesium, prulifloxacin

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the magnesium preparation

Magnesium, quinolones

Decreased absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of the magnesium preparation

Mycophenolate mofetil [1], norfloxacin ---> SmPC of [1] of EMA

In healthy volunteers, no significant interaction was observed when mycophenolate mofetil was concomitantly administered with norfloxacin and metronidazole separately.

Mycophenolate [1], norfloxacin ---> SmPC of [1] of EMA

In healthy volunteers, no significant interaction was observed when mycophenolate mofetil was concomitantly administered with norfloxacin and metronidazole separately.

Nitrofurantoin, norfloxacin [2] ---> SmPC of [2] of eMC

Anti-bacterial antagonism by quinolone anti-infectives.

Norfloxacin [1], QT interval prolonging drugs ---> SmPC of [1] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Norfloxacin [1], tricyclic antidepressant ---> SmPC of [1] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Norfloxacin, NSAID

The NSAID can increase the risk of convulsions associated with quinolone antibiotic.

Norfloxacin, oral anticoagulants

The co-administration may enhance the effect of oral anticoagulant

Norfloxacin, oral contraceptives

It is reported that some antibiotics reduce the effect of oral contraceptives

Norfloxacin, oxetacaine

Decreased absorption of norfloxacin

Norfloxacin, pregnancy

Norfloxacin must not be used during breast-feeding

Norfloxacin, probenecide

Probenecid decreases the elimination of norfloxacin

Norfloxacin, ropinirole [2] ---> SmPC of [2] of eMC

The CYP1A2 inhibition may increase plasma concentrations of ropinirol

Norfloxacin, sucralfate [2] ---> SmPC of [2] of eMC

The co-administration may decrease the absorption of quinolone. The quinolone should be administered 2 hours before or 4 hours after the administration of sucralfate.

Norfloxacin, sun

Patients should be advised to minimise exposure to sunlight during therapy, as norfloxacin may potentially have a photosensitizing effect.

Norfloxacin, tacrine

Norfloxacin, strong CYP1A2 inhibitor, may increase the plasma concentrations of tacrine

Norfloxacin, theophylline [2] ---> SmPC of [2] of eMC

Quinolone reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Norfloxacin, tizanidine [2] ---> SmPC of [2] of eMC

Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine. Co-administration of tizanidine inhibitors of CYP1A2 is not recommended

Norfloxacin, tolterodine

The co-administration may increase the plasma concentrations of tolterodine

Norfloxacin, vitamin K antagonists

Quinolone antibiotic may enhance the anticoagulant effect

Norfloxacin, warfarin

Quinolone may increase the effect anticoagulant of warfarin

Quinolones, sun

Patients should be advised to avoid extensive exposure to either UV irradiation or sunlight.

Quinolones, tricyclic antidepressant ---> SmPC of [norfloxacin] of eMC

The fluoroquinolones should be used with caution in patients receiving drugs known to prolong the QT interval

Quinolones, warfarin

Quinolone may increase the effect anticoagulant of warfarin

Nortriptyline

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

Nortriptyline may impair the mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a car; therefore the patient should be warned accordingly.

Alcohol, nortriptyline [2] ---> SmPC of [2] of eMC

Tricyclic antidepressants may potentiate the CNS depressant effect of alcohol.

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

Careful monitoring of the therapeutic and adverse reactions of tricyclic antidepressants is recommended when they are concomitantly administered with amprenavir

Analgesics, nortriptyline

The co-administration of nortriptyline and CNS depressants may increase the depressive effects on the CNS

Antacids, nortriptyline

Possible decrease of plasma levels of nortriptyline

Anticholinergics, nortriptyline [2] ---> SmPC of [2] of eMC

Supervision and adjustment of dosage may be required when nortriptyline is used with other anticholinergic drugs.

Antidyskinetic drugs, nortriptyline

Supervision and adjustment of dosage may be required when nortriptyline is used with other anticholinergic drugs.

Antiepileptics, nortriptyline

Nortriptyline decreases the effects of anticonvulsivant drugs

Antihistamines, nortriptyline [2] ---> SmPC of [2] of eMC

Supervision and adjustment of dosage may be required when nortriptyline is used with other anticholinergic drugs.

Antimalarial agents, nortriptyline

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Antithyroid medicines, nortriptyline

The co-administration of nortriptyline with antithyroid drugs may increase the risk of agranulocytosis

Astemizole, nortriptyline

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Barbiturates, nortriptyline [2] ---> SmPC of [2] of eMC

Barbiturates may increase the rate of metabolism of nortriptyline.

Betanidine, nortriptyline

Nortriptyline may decrease the antihypertensive effect of betanidine

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

Nortriptyline is contra-indicated for the nursing mother

Carbamazepine [1], nortriptyline ---> SmPC of [1] of eMC

Carbamazepine may lower the plasma level of tricyclic antidepressant

Centrally-acting antihypertensives, nortriptyline

Nortriptyline may decrease the antihypertensive effect

Cimetidine, nortriptyline

Cimetidine inhibit nortriptyline metabolism and increases its toxicity

Cinacalcet [1], nortriptyline ---> SmPC of [1] of EMA

Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments of concomitant medicinal products may be required when cinacalcet is administered with narrow therapeutic index substances that are predominantly metabolised by CYP2D6

Cisapride, nortriptyline

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

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

Caution is recommended when citalopram is co-administered with medicinal products that are mainly metabolised by CYP2D6, and that have a narrow therapeutic index

Class IA antiarrhythmic agents, nortriptyline

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Class III antiarrhythmic agents, nortriptyline

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Clonidine, nortriptyline [2] ---> SmPC of [2] of eMC

Nortriptyline may decrease the antihypertensive effect of clonidine. Risk of hypertension rebound

CNS depressants, nortriptyline

The co-administration of nortriptyline and CNS depressants may increase the depressive effects on the CNS

Coumarin anticoagulants, nortriptyline

Nortriptyline may enhance the anticoagulant effects of coumarine derivatives or of indandione

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

Concomitant use of boosted darunavir/cobicistat (CYP2D6 and/or CYP3A inhibition) and this antidepressant may increase concentrations of the antidepressant.

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

It is expected to increase these anti-depressant plasma concentrations. CYP2D6 and/or CYP3A inhibition. If this anti-depressant is to be used with Symtuza clinical monitoring is recommended and a dose adjustment of the anti-depressant may be needed.

Debrisoquine, nortriptyline [2] ---> SmPC of [2] of eMC

Nortriptyline may decrease the antihypertensive effect of debrisoquine

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

Quinidine is a potent inhibitor of CYP2D6. Treatment with dextromethorphan/quinidine may therefore result in elevated plasma levels and accumulation of co-administered medicinal products that undergo extensive CYP2D6 metabolism.

Drugs primarily metabolised by CYP2D6, nortriptyline

La co-administration with substances metabolized by CYP2D6 may increase the plasma levels of nortriptyline. It may be necessary to decrease the dose

Duloxetine [1], nortriptyline ---> SmPC of [1] of EMA

Duloxetine is a moderate inhibitor of CYP2D6. Caution is advised if duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6

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

Concomitant administration of eliglustat with CYP2D6 substrates may increase the exposition of these substrates. Lower doses of medicinal products that are CYP2D6 substrates may be required.

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

Caution should be observed when co-administering escitalopram (CYP2D6 inhibitor) and drugs that are mainly metabolised by CYP2D6 and that have a narrow therapeutic index. Dosage adjustment may be warranted.

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

Fluconazole increases the effect of nortriptyline. Dosage of nortriptyline should be adjusted, if necessary

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

Careful monitoring of the therapeutic and adverse reactions of tricyclic antidepressants is recommended when they are concomitantly administered with amprenavir

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

Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension

Griseofulvin, nortriptyline

Possible decrease of plasma levels of nortriptyline

Guanadrel, nortriptyline [2] ---> SmPC of [2] of eMC

Nortriptyline may decrease the antihypertensive effect of guanadrel

Guanethidine, nortriptyline [2] ---> SmPC of [2] of eMC

Nortriptyline may decrease the antihypertensive effect of guanethidine

Guanidine derivatives, nortriptyline

Nortriptyline may decrease the antihypertensive effect

Halofantrine, nortriptyline

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Hypokalemia, nortriptyline

The co-administration of nortriptyline with drugs that can cause hypokaliemia should be avoided

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

Under no circumstances should nortriptyline be given concurrently with, or within 2 weeks of cessation of, therapy with MAO inhibitors. Hyperpyretic crises, severe convulsions and fatalities have occurred

Indandione, nortriptyline

Nortriptyline may enhance the anticoagulant effects of coumarine derivatives or of indandione

Insulin, nortriptyline

Nortriptyline may enhance the blood-glucose reducing effect of insulin and oral antidiabetic drugs

Interferon, nortriptyline

Caution should be used when administering interferon with medicines mainly metabolised by hepatic cytochrome P450 and have a narrow therapeutic window

Isocarboxazid [1], nortriptyline ---> SmPC of [1] of eMC

Isocarboxazid should not be administered together with nortriptyline. Hypotensive and other adverse reactions are likely to be increased.

Methyldopa, nortriptyline [2] ---> SmPC of [2] of eMC

Nortriptyline may decrease the antihypertensive effect of methyldopa

Nimodipine [1], nortriptyline ---> SmPC of [1] of eMC

Concurrent administration of nimodipine and the antidepressant nortriptyline resulted in a slight decrease in nimodipine plasma levels with no effect on nortriptyline plasma levels.

Non-potassium-sparing diuretics, nortriptyline

The co-administration of nortriptyline with drugs that can cause hypokaliemia should be avoided

Nortriptyline [1], phenindione ---> SmPC of [1] of eMC

Nortriptyline potentiates the effect of phenindione

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

Barbiturates may increase the rate of metabolism of nortriptyline.

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

The drug should not be administered to pregnant patients or women of childbearing age unless the potential benefits clearly outweigh any potential risk.

Nortriptyline [1], reserpine ---> SmPC of [1] of eMC

Nortriptyline may decrease the antihypertensive effect of reserpine

Nortriptyline [1], sympathomimetics ---> SmPC of [1] of eMC

Nortriptyline should not be given with sympathomimetic agents

Nortriptyline [1], thyroid hormones ---> SmPC of [1] of eMC

Great care is necessary if nortriptyline is administered to patients receiving thyroid medication, since cardiac arrhythmias may develop.

Nortriptyline, opioid analgesics

The co-administration of nortriptyline and CNS depressants may increase the depressive effects on the CNS

Nortriptyline, oral antidiabetics

Nortriptyline may enhance the blood-glucose reducing effect of insulin and oral antidiabetic drugs

Nortriptyline, paroxetine [2] ---> SmPC of [2] of eMC

Paroxetine inhibits the hepatic cytochrome P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of co-administered drugs metabolised by this enzyme.

Nortriptyline, pimozide

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Nortriptyline, propafenone

La co-administration with substances metabolized by CYP2D6 may increase the plasma levels of nortriptyline. It may be necessary to decrease the dose

Nortriptyline, QT interval prolonging drugs

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Nortriptyline, quinidine ---> SmPC of [dextromethorphan/quinidine] of EMA

Quinidine, strong CYP2D6 inhibitor, may increase the plasma concentrations of nortriptyline

Nortriptyline, rifampicin [2] ---> SmPC of [2] of eMC

Rifampicin is a potent inducer of certain cytochrome P-450 enzymes. Coadministration of rifampicin with drugs that are also metabolised through these cytochrome P-450 enzymes may accelerate the metabolism and reduce the activity of these other drugs.

Nortriptyline, ritonavir [2] ---> SmPC of [2] of EMA

Ritonavir dosed as an antiretroviral agent is likely to inhibit CYP2D6 and as a result is expected to increase concentrations of imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine or sertraline.

Nortriptyline, sertindole

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Nortriptyline, sotalol

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

Nortriptyline, SSRI

La co-administration of selective serotonin reuptake inhibitors may increase the plasma levels of nortriptyline. It may be necessary to decrease the dose

Nortriptyline, St. John's wort

Saint John's wort may decrease the plasma levels of nortriptyline

Nortriptyline, strong CYP2D6 inhibitors

Concomitant use of nortriptyline with drugs increasing the metabolism and plasma levels of nortriptyline should be avoided

Nortriptyline, terfenadine

Concomitant use of nortriptyline with drugs known to prolong the QT interval should be avoided

CONTRAINDICATIONS of Nortriptyline

- Hypersensitivity to nortriptyline.

- Recent myocardial infarction, any degree of heart block or other cardiac arrhythmias.

- Severe liver disease.

- Mania.

- Nortriptyline is contra-indicated for the nursing mother and for children under the age of six years.

- Please also refer to 'Drug interactions' section.

http://www.medicines.org.uk/emc/

Nusinersen (Spinraza)

Breast-feeding, nusinersen [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from nusinersen therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Cytochrome P450, nusinersen [2] ---> SmPC of [2] of EMA

No interaction studies have been performed. In vitro studies indicated that nusinersen is not an inducer or inhibitor of CYP450 mediated metabolism.

Drugs with high protein binding, nusinersen [2] ---> SmPC of [2] of EMA

In vitro studies indicate that the likelihood for interactions with nusinersen due to competition for plasma protein binding, or competition with or inhibition of transporters is low.

Fertility, nusinersen [2] ---> SmPC of [2] of EMA

In toxicity studies in animals no effects on male or female fertility were observed (see section 5.3). There are no data available on the potential effects on fertility in humans.

Nusinersen [1], pregnancy ---> SmPC of [1] of EMA

As a precautionary measure, it is preferable to avoid the use of nusinersen during pregnancy.

Nusinersen, risdiplam [2] ---> SmPC of [2] of EMA

There is no efficacy or safety data to support the concomitant use of risdiplam and nusinersen.

CONTRAINDICATIONS of Nusinersen (Spinraza)

- 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/spinraza-epar-product-information_en.pdf 29/01/2026

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