Pharmacodynamic Interactions: The following interactions apply to β-adrenergic antagonists in general.
Combinations Not Recommended: Class I Antiarrhythmics (Quinidine, Hydroquinidine, Cibenzoline, Flecainide, Disopyramide, Lidocaine, Mexiletine, Propafenone): Effect on atrioventricular conduction time may be potentiated and negative inotropic effect increased.
Calcium Channel Antagonists of Verapamil/Diltiazem Type: Negative influence on contractility and atrioventricular conduction. Intravenous administration of verapamil in patients with β-blocker treatment may lead to profound hypotension and atrioventricular block.
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 tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to β-blocker discontinuation, may increase risk of rebound hypertension.
Combinations to be Used with Caution: Class III Antiarrhythmic Drugs (Amiodarone): Effect on atrioventricular conduction time may be potentiated.
Anesthetics - Volatile Halogenated: Concomitant use of β-adrenergic antagonists and anesthetics may attenuate reflex tachycardia and increase the risk of hypotension. As a general rule, avoid sudden withdrawal of β-blocker treatment. The anesthesiologist 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 hypoglycemia (palpitations, tachycardia).
Combinations to be Considered: Digitalis Glycosides: Concomitant use may increase atrioventricular 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 β-blockers (additive effect).
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): No effect on the blood pressure lowering effect of nebivolol.
Sympathicomimetic Agents: Concomitant use may counteract the effect of β-adrenergic antagonists. Beta-adrenergic agents may lead to unopposed α-adrenergic activity of sympathicomimetic agents with both α- and β-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 meal and an antacid between meals, the 2 treatments can be prescribed.
Combining Nebivolol with nicardipine slightly inceased 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.