Pharmacodynamic interactions: The following interactions apply to beta-adrenergic antagonists in general.
Combinations not recommended: Class I antiarrhythmics (quinidine, hydroquinidine, cibenzoline, flecainide, disopyramide, lidocaine, mexiletine, propafenone): effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased (see Precautions).
Calcium channel antagonists of verapamil/diltiazem type: negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients with β-blocker treatment may lead to profound hypotension and atrio-ventricular block (see Precautions).
Centrally-acting antihypertensives (clonidine, guanfacine, moxonidine, methyldopa, rilmenidine): concomitant use of centrally acting antihypertensive drugs may worsen heart failure by a decrease in the central sympathetic tones (reduction of heart rate and cardiac output, vasodilation) (see Precautions). Abrupt withdrawal, particularly if prior to beta-blocker discontinuation, may increase risk of "rebound hypertension".
Combinations to be used with caution: Class III antiarrhythmic drugs (Amiodarone): effect on atrio-ventricular conduction time may be potentiated.
Anaesthetics - volatile halogenated: concomitant use of beta-adrenergic antagonists and anaesthetics may attenuate reflex tachycardia and increase the risk of hypotension (see Precautions). As a general rule, avoid sudden withdrawal of beta-blocker treatment. The anaesthesiologist should be informed when the patient is receiving Nebilet.
Insulin and oral antidiabetic drugs: although nebivolol does not affect glucose level, concomitant use may mask certain symptoms of hypoglycaemia (palpitations, tachycardia).
Baclofen (antispastic agent), amifostine (antineoplastic adjunct): concomitant use with antihypertensives is likely to increase the fall in blood pressure, therefore the dosage of the antihypertensive medication should be adjusted accordingly.
Combinations to be considered: Digitalis glycosides: concomitant use may increase atrio-ventricular conduction time. Clinical trials with nebivolol have not shown any clinical evidence of an interaction. Nebivolol does not influence the kinetics of digoxin.
Calcium antagonists of the dihydropyridine type (amlodipine, felodipine, lacidipine, nifedipine, nicardipine, nimodipine, nitrendipine): concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.
Antipsychotics, antidepressants (tricyclics, barbiturates and phenothiazines): concomitant use may enhance the hypotensive effect of the beta-blockers (additive effect).
Non steroidal anti-inflammatory drugs (NSAIDs): no effect on the blood pressure lowering effect of nebivolol.
Sympathomimetic agents: concomitant use may counteract the effect of beta-adrenergic antagonists. Beta-adrenergic agents may lead to unopposed alpha-adrenergic activity of sympathomimetic agents with both alpha- and beta-adrenergic effects (risk of hypertension, severe bradycardia and heart block).
Pharmacokinetic interactions: As nebivolol metabolism involves the CYP2D6 isoenzyme, co-administration with substances inhibiting this enzyme, especially paroxetine, fluoxetine, thioridazine and quinidine may lead to increased plasma levels of nebivolol associated with an increased risk of excessive bradycardia and adverse events.
Co-administration of cimetidine increased the plasma levels of nebivolol, without changing the clinical effect. Co-administration of ranitidine did not affect the pharmacokinetics of nebivolol. Provided Nebilet is taken with the meal, and an antacid between meals, the two treatments can be co-prescribed.
Combining nebivolol with nicardipine slightly increased the plasma levels of both drugs, without changing the clinical effect. Co-administration of alcohol, furosemide or hydrochlorothiazide did not affect the pharmacokinetics of nebivolol. Nebivolol does not affect the pharmacokinetics and pharmacodynamics of warfarin.