Nebivolol (as HCl) 2.5 mg, 5 mg, 10 mg; tabs.
Hypertension, alone or with other antihypertensives.
Nebivolol is a once-daily beta-adrenergic blocking agent that, at doses up to 10 mg, is primarily beta1-selective. In poor metabolizers (those with reduced activity of CYP2D6) and at higher doses, however, it may inhibit beta2 adrenergic receptors as well. Beta2 blockade may lead to bronchoconstrictive effects. Nebivolol does not have intrinsic sympathomimetic effects or membrane stabilizing activity at therapeutic doses. It has several active metabolites that are the product of glucuronidation and hydroxylation by the oxidative enzyme CYP2D6.
Possible factors that may contribute to nebivolol antihypertensive activity include decreased heart rate and myocardial contractility, reduced sympathetic tone, suppression of renin activity, and vasodilation and reduced peripheral vascular resistance.
Three double-blind, placebo-controlled, 12-week studies were conducted to demonstrate the effectiveness of nebivolol as monotherapy in the treatment of hypertension. Two of these trials studied 1,716 patients in the general hypertensive population (26% non-Caucasian), and a third studied 300 black (African-American) patients. Another study, which enrolled 669 patients, evaluated the effect of adding nebivolol to a background antihypertensive regimen of up to two other agents and thiazide diuretics. In each study, nebivolol was shown to be effective in lowering both systolic and diastolic BP. Effectiveness was established in black patients, but as monotherapy, the magnitude of effect was somewhat less than in Caucasians.
The BP-lowering effect was seen at two weeks after starting therapy and was maintained over the 24-hour dosing interval.
≥18 years: initially 5 mg once daily. Individualize; may increase at two-week intervals; max 40 mg/day. Severe renal or moderate hepatic impairment: initially 2.5 mg once daily.
<18 years: not recommended.
Severe hepatic impairment (Child-Pugh >B). Severe bradycardia. Second- or third-degree atrioventricular block. Cardiogenic shock. Overt heart failure. Sick sinus syndrome (unless paced).
Congestive heart failure. Angina. Recent MI. Bronchospastic disease. Diabetes. Hyperthyroidism. Severe renal impairment. Moderate hepatic impairment. Avoid abrupt cessation (taper over one to two weeks). Surgery. Peripheral vascular disease. Pheochromocytoma. Pregnancy (Cat. C). Nursing mothers: not recommended.
Caution with phenylalkylamine and benzothiazepine calcium channel blockers (e.g., verapamil, diltiazem), anti-arrhythmics (e.g., disopyramide), digoxin, reserpine, guanethidine; monitor. May be potentiated by CYP2D6 inhibitors (e.g., quinidine, propafenone, paroxetine, fluoxetine); may need to reduce dose. If on both nebivolol and clonidine, discontinue nebivolol before tapering clonidine. May block epinephrine.
Headache, fatigue, dizziness, GI upset.
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