Company:

Forest

Cardioselective β-blocker

Nebivolol (as HCl) 2.5mg, 5mg, 10mg; tabs.

Hypertension, alone or with other antihypertensives.

Nebivolol is a once-daily β-adrenergic blocking agent that, at doses up to 10mg, is primarily β₁-selective. In poor metabolizers (those with reduced activity of CYP2D6) and at higher doses, however, it may inhibit β₂ adrenergic receptors as well. β₂ 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 which 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 1716 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 anti-hypertensive regimen of up to two other agents, including ACEIs, ARBs, 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 2 weeks after starting therapy and was maintained over the 24-hour dosing interval.

≥18yrs: initially 5mg once daily. Individualize; may increase at 2-week intervals; max 40mg/day. Severe renal or moderate hepatic impairment: initially 2.5mg once daily.

<18yrs: not recommended.

Severe hepatic impairment (Child-Pugh >B). Severe bradycardia. 2nd- or 3rd degree AV block. Cardiogenic shock. Overt heart failure. Sick sinus syndrome (unless paced).

CHF. Angina. Recent MI. Bronchospastic disease. Diabetes. Hyperthyroidism. Severe renal impairment. Moderate hepatic impairment. Avoid abrupt cessation (taper over 1–2 weeks). Surgery. Peripheral vascular disease. Pheochromocytoma. Pregnancy (Cat.C). Nursing mothers: not recommended.

Caution with phenylalkylamine and benzothiazepine calcium channel blockers (eg, verapamil, diltiazem), antiarrhythmics (eg disopyramide), digoxin, reserpine, guanethidine; monitor. May be potentiated by CYP2D6 inhibitors (eg, 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.

Tabs—30, 100

1/18/08