What is Nebivolol (beta-blocker)?

Nebivolol: A Third-Generation Beta-Blocker with Unique Properties

Nebivolol is a third-generation beta-blocker with unique vasodilatory properties that make it particularly valuable for treating hypertension and heart failure, especially in patients who cannot tolerate traditional beta-blockers. 1, 2

Pharmacological Properties

• Nebivolol is a lipophilic beta₁-selective adrenergic receptor blocker that, unlike traditional beta-blockers, has nitric oxide (NO)-mediated vasodilatory effects 2, 3
• It is administered as a racemic mixture of d- and l-enantiomers, with the d-isomer providing beta-blocking activity and the l-isomer primarily responsible for NO-mediated vasodilation 1, 2
• At doses ≤10 mg, nebivolol is preferentially beta₁-selective in extensive metabolizers (most of the population), while at higher doses or in poor metabolizers, it inhibits both beta₁ and beta₂ receptors 1
• Nebivolol lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutic doses 1

Clinical Applications

Hypertension

• Nebivolol is FDA-approved for the treatment of hypertension at a recommended dosage of 5 mg once daily 1
• It reduces blood pressure as effectively as other beta-blockers (atenolol, metoprolol), ACE inhibitors (lisinopril, enalapril), and calcium channel blockers (nifedipine) 4, 5
• Its antihypertensive effect works through multiple mechanisms: decreased heart rate, decreased myocardial contractility, diminished sympathetic outflow, suppression of renin activity, and vasodilation 1

Heart Failure

• The European Society of Cardiology and American College of Cardiology recognize nebivolol as effective for patients with coronary artery disease and heart failure with reduced ejection fraction 3
• Nebivolol demonstrated a modest reduction in the combined endpoint of all-cause mortality or cardiovascular hospitalization in elderly heart failure patients 3
• It may be considered for decreasing hospitalization in heart failure with preserved ejection fraction patients 3

Advantages Over Traditional Beta-Blockers

• Nebivolol reduces central pulse pressure and aortic stiffness better than atenolol or metoprolol 6
• It has minimal impact on glucose tolerance compared to other beta-blockers, making it more suitable for patients with metabolic disorders 6, 7
• Nebivolol does not worsen glucose tolerance when used alone or in combination with hydrochlorothiazide 6
• It has a favorable side effect profile with lower incidence of fatigue, sexual dysfunction, and other common beta-blocker side effects 4, 5
• Unlike traditional beta-blockers, nebivolol does not significantly affect plasma lipid metabolism 4, 7

Pharmacokinetics

• Nebivolol is extensively metabolized by multiple routes, including glucuronidation and hydroxylation by CYP2D6 1
• The active isomer (d-nebivolol) has an effective half-life of about 12 hours in extensive metabolizers and 19 hours in poor metabolizers 1
• Food does not significantly alter the pharmacokinetics, allowing administration without regard to meals 1
• Plasma protein binding is approximately 98%, mostly to albumin 1

Side Effects and Precautions

• Most common adverse events include headache, fatigue, paresthesias, and dizziness 1, 5
• Contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated heart failure, severe hepatic impairment, or hypersensitivity 1
• Should not be abruptly discontinued due to risk of exacerbation of angina and potential myocardial infarction 1
• Use with caution in patients with hepatic impairment as exposure may increase significantly 1

Special Populations

• Particularly beneficial for elderly patients with heart failure as demonstrated in the SENIORS trial 3
• May be preferred in patients with metabolic syndrome or diabetes due to its neutral effect on glucose metabolism 6, 7
• Beneficial in patients with COPD, as beta-blockers have been shown to reduce exacerbations and mortality in these patients 6

Nebivolol represents an important advancement in beta-blocker therapy with its unique combination of high beta₁-selectivity and nitric oxide-mediated vasodilation, offering effective blood pressure control with fewer metabolic side effects than traditional beta-blockers 6, 8.