nebivolol (Rx)

1-10%

Headache (6-9%)

Fatigue (2-5%)

Dizziness (2-4%)

Diarrhea (2-3%)

Nausea (1-3%)

Increased triglyceride levels and insulin resistance, decreased high-density lipoprotein (HDL) levels (1%)

Insomnia (1%)

Peripheral edema (1%)

Weakness (1%)

<1%

Bradycardia

Chest pain

Dyspnea

Contraindications

Hypersensitivity

Severe hepatic impairment

Cardiogenic shock

Sick sinus syndrome (if no pacemaker)

2°/3° heart block (if no pacemaker)

Bradycardia (HR <50 beats/min)

Decompensated heart failure

Severe hepatic impairment (Child-Pugh Class C)

Cautions

Anesthetics that cause myocardial depression, bradycardia, 1° heart block, ischemic heart disease, Prinzmetal angina, untreated congestive heart failure (CHF)

Patients with bronchospastic disease should not receive beta-blockers; patients with bronchospastic disease who do not respond to other therapies, initial low doses may be employed and used cautiously; monitor closely; patient should have immediate access to beta2-agonist

May mask hyperthyroidism, including tachycardia; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm; if thyrotoxicosis suspected, carefully manage and treat

Severe renal impairment decreases clearance; adjust dose in severe renal failure

Moderate hepatic impairment decreases metabolism ; adjust dose in moderate hepatic impairment (Child-Pugh class B); contraindicated in severe hepatic impairment (Child-Pugh class C)

May potentiate hypoglycemia in patients with hypoglycemia and/or mask signs and symptoms

Sudden discontinuance can exacerbate angina and lead to MI; to discontinue therapy, taper gradually over 1-2 weeks to avoid acute tachycardia, ischemia, and/or hypertension; temporary but prompt resumption of beta-blocker therapy may be necessary if angina symptoms or acute coronary insufficiency symptoms worsen

Can precipitate or worsen symptoms of arterial insufficiency in patients with peripheral and Raynaud disease (intermittent claudication); use caution; monitor for progression of arterial obstruction

Renal disease, cerebrovascular insufficiency, use in pheochromocytoma (alpha blocker should be started before beta blocker)

Increased risk of stroke after surgery; routine withdrawal of chronic beta-blocker therapy not recommended prior to major surgery

Use with caution in patients with myasthenia gravis

Use with caution in patients taking calcium-channel blockers or cardiac glycosides or using inhaled anesthetics

Drug loses receptor selectivity in poor metabolizers and in high doses (blocks both beta1 and beta2)

Excerbation or induction of psoriasis associated with psoriasis; use caution

Not shown to reduce morbidity or mortality in heart failure population; bisoprolol, carvedilol, and extended release metoprolol only beta blockers proven to reduce mortality; use caution in patients with compensated heart failure and monitor for worsening of condition; temporarily discontinue or reduce dose if condition worsens; stabilize patients on heart failure regimen before initiating beta-blocker therapy; initiate therapy at very low doses; may require adjustment of other medications, including ACE inhibitors and/or diuretics

May cause or exacerbate CNS depression; use caution in patient with psychiatric disorder

Pregnancy category: C

Lactation: Not known whether drug is excreted into breast milk; use not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Competitive and selective beta1-receptor antagonist; has little or no effect on beta2 receptors at doses <10 mg; possesses mild vasodilating properties; reduces systemic vascular resistance

Absorption

Bioavailability: Extensive metabolizers, 12%; poor metabolizers, 96%

Peak plasma time: 1.5-4 hr

Distribution

Protein bound: 98%

Vd: 8-12 L/kg

Metabolism

Metabolized by CYP2D6 via alicyclic and aromatic hydroxylation, N-dealkylation, glucuronidation

Elimination

Half-life: Extensive metabolizers, 10-12 hr; poor metabolizers, 19-32 hr

Excretion: Urine (38-67%), feces (13-44%)