Nebivolol

• Hypertension treatment
• Blood pressure control in patients with diabetes or metabolic syndrome
• Alternative beta-blocker for patients concerned about erectile dysfunction
• Patients requiring beta-blocker with favorable metabolic profile

Nebivolol is a third-generation, highly selective beta-1 adrenergic receptor blocker with unique vasodilating properties mediated through nitric oxide. This combination of cardioselective beta-blockade and nitric oxide-mediated vasodilation makes it particularly useful for hypertension treatment, with a favorable metabolic and tolerability profile compared to older beta-blockers.

Mechanism of Action

Nebivolol works through two distinct mechanisms that together provide effective blood pressure control with excellent tolerability. First, it blocks beta-1 adrenergic receptors in the heart with exceptional selectivity (approximately 320-fold greater affinity for beta-1 than beta-2 receptors), reducing heart rate and cardiac output. Second, it stimulates endothelial nitric oxide synthase, promoting nitric oxide release and causing vasodilation. This vasodilating property is unique among beta-blockers and contributes to blood pressure lowering without the peripheral vasoconstriction seen with traditional beta-blockers.

The nitric oxide pathway also provides potential benefits including improved endothelial function, reduced oxidative stress, and favorable effects on insulin sensitivity. These properties may make nebivolol particularly suitable for patients with diabetes, metabolic syndrome, or erectile dysfunction who require beta-blocker therapy.

Available Formulations

Nebivolol (Bystolic) is available as tablets in multiple strengths including 2.5 mg, 5 mg, 10 mg, and 20 mg. The tablets are scored for flexible dosing. Generic versions are now available, making this medication more accessible for patients requiring long-term therapy.

FDA-Approved Indications

Nebivolol is FDA-approved for the treatment of hypertension in adults. It may be used alone or in combination with other antihypertensive agents. While not FDA-approved for heart failure in the United States, clinical trial evidence (SENIORS trial) supports its use in elderly patients with heart failure, and it is approved for this indication in some other countries.

Dosing Guidelines

The recommended starting dose for hypertension is 5 mg once daily. The dose may be increased at 2-week intervals up to a maximum of 40 mg once daily as needed for blood pressure control. For patients with moderate hepatic impairment or severe renal impairment (CrCl less than 30 mL/min), the recommended starting dose is 2.5 mg once daily, with careful upward titration as needed. The medication can be taken with or without food and should be administered at approximately the same time each day.

Cardioselectivity and Metabolic Advantages

The high beta-1 selectivity of nebivolol provides several clinical advantages compared to non-selective beta-blockers. It is less likely to cause bronchospasm and may be used more safely in patients with mild asthma or COPD, although caution is still warranted. Unlike older beta-blockers, nebivolol does not significantly impair glucose metabolism or worsen lipid profiles. Clinical studies have shown neutral to favorable effects on insulin sensitivity, making it a preferred choice when beta-blocker therapy is needed in patients with diabetes or metabolic syndrome.

Important Safety Considerations

Nebivolol should not be discontinued abruptly, as this may exacerbate angina or precipitate myocardial infarction. Dose should be gradually reduced over 1-2 weeks when discontinuing. The medication is contraindicated in severe bradycardia, heart block greater than first degree (without pacemaker), cardiogenic shock, decompensated heart failure, and severe hepatic impairment. While more cardioselective than older agents, caution is still advised in patients with bronchospastic disease.

Drug Interactions

CYP2D6 inhibitors such as fluoxetine, paroxetine, and quinidine can significantly increase nebivolol levels and should be used with caution. Beta-blockers can mask hypoglycemia symptoms in diabetic patients. Additive bradycardia may occur with digoxin, diltiazem, or verapamil. Catecholamine-depleting drugs like reserpine may have additive effects. Sildenafil and other PDE5 inhibitors may enhance hypotensive effects.

Special Populations

In patients who are CYP2D6 poor metabolizers (approximately 10% of Caucasians), nebivolol exposure is increased, potentially requiring lower doses. Elderly patients may require lower initial doses and careful titration. Use during pregnancy should be avoided if possible, as beta-blockers may cause fetal bradycardia. Safety in pediatric patients has not been established.

Learn more at MedlinePlus