Biolet Drug Interactions

Drugs Affecting Hepatic Microsomal Enzymes: Nebivolol is metabolized by cytochrome P-450 (CYP) isoenzyme 2D6 but does not inhibit CYP isoenzymes at clinically relevant concentrations.
Potent inhibitors of CYP2D6 (e.g., quinidine, propafenone, fluoxetine, paroxetine): Potential pharmacokinetic interaction (increased plasma concentrations of nebivolol). Monitor patient carefully; adjust nebivolol dosage according to blood pressure response.
Drugs Affecting Cardiac Conduction: Antiarrhythmic Agents: Possible conduction disturbance when nebivolol is used concomitantly with antiarrhythmic agents (e.g., amiodarone, disopyramide). Use concomitantly with caution.
β-Adrenergic Blocking Agents: Possible additive negative effects on AV conduction and heart rate. Concomitant use of nebivolol with other β-adrenergic blocking agents (β-blockers) is not recommended.
Calcium-channel Blocking Agents: Possible conduction disturbance when nebivolol is used concomitantly with nondihydropyridine calcium-channel blocking agents (e.g., diltiazem, verapamil). Use concomitantly with caution; monitor blood pressure and ECG with concomitant use.
Digoxin: Possible additive negative effects on AV conduction and heart rate; increased risk of bradycardia. Use concomitantly with caution. Concomitant use of digoxin (0.25 mg once daily) and nebivolol (10 mg once daily) for 10 days in healthy adults did not affect the pharmacokinetics of either drug.
Catecholamine-depleting Agents: Potential additive effects (e.g., hypotension, bradycardia) with catecholamine-depleting agents (e.g., reserpine, guanethidine). Monitor closely for symptoms (e.g., vertigo, syncope, postural hypotension).
Other Cardiovascular Drugs: Clonidine: Potential pharmacologic interaction (increased rebound hypertension following discontinuance of clonidine). When clonidine is to be discontinued in patients receiving clonidine and nebivolol concurrently, nebivolol should be discontinued several days before gradual withdrawal of clonidine.
Diuretics: No pharmacokinetic interactions observed in healthy individuals receiving nebivolol (10 mg daily for 10 days) and a diuretic (single 40-mg dose of furosemide, hydrochlorothiazide 25 mg once daily for 10 days, or spironolactone 25 mg once daily for 10 days).
Losartan: No pharmacokinetic interaction observed following single-dose administration of nebivolol (10 mg) and losartan potassium (50 mg).
Propafenone: Potential pharmacokinetic interaction (increased plasma concentrations of nebivolol). Use concomitantly with caution.
Quinidine: Potential pharmacokinetic interaction (increased plasma concentrations of nebivolol). Use concomitantly with caution.
Ramipril: No pharmacokinetic interaction observed following concomitant administration of nebivolol (10 mg once daily) and ramipril (5 mg once daily) for 10 days.
Sildenafil: Potential pharmacokinetic interaction (modest [21-23%] decrease in peak plasma concentration and area under the plasma concentration-time curve [AUC] of sildenafil, modest [less than 20%] effect on peak plasma concentration and AUC of d-nebivolol). Nebivolol and sildenafil have additive effects on blood pressure and pulse.
GI Drugs: Activated Charcoal: No effect on nebivolol pharmacokinetics following single-dose administration of nebivolol (10 mg) and repeated-dose administration of activated charcoal over 48 hours.
Cimetidine: Potential pharmacokinetic interaction (modest [21-23%] increase in plasma nebivolol concentrations) observed following concomitant administration of nebivolol (single 5-mg dose) and cimetidine (400 mg twice daily for 3 days). No apparent change in pharmacodynamics of nebivolol (e.g., blood pressure, heart rate).
Ranitidine: No effect on nebivolol pharmacokinetics or pharmacodynamics (e.g., blood pressure, heart rate) observed following concomitant administration of nebivolol (single 5-mg dose) and ranitidine (150 mg twice daily for 3 days).
Psychotherapeutic Agents: Fluoxetine: Potential pharmacokinetic interaction (increased plasma concentrations of nebivolol). Eightfold increase in AUC and threefold increase in peak plasma concentration of d-nebivolol observed in healthy individuals receiving a single 10-mg dose of nebivolol following administration of fluoxetine 20 mg daily for 21 days. Use concomitantly with caution.
Paroxetine: Potential pharmacokinetic interaction (increased plasma concentrations of nebivolol). Use concomitantly with caution.
Warfarin: No effect on warfarin or nebivolol pharmacokinetics observed in individuals receiving warfarin (single 10-mg dose) and nebivolol (10 mg once daily for 10 days); no effect on prothrombin times after a single warfarin dose.