At what dose is Nebivolol (beta blocker) cardioselective?

Nebivolol Cardioselectivity and Dosing

Nebivolol maintains β1-selectivity (cardioselectivity) at doses ≤10 mg daily in extensive metabolizers, which represents most of the population; at higher doses or in poor metabolizers, it loses selectivity and inhibits both β1- and β2-adrenergic receptors. 1

Dose-Dependent Selectivity Profile

The FDA label clearly defines the cardioselectivity threshold for nebivolol:

• At doses ≤10 mg: Nebivolol is preferentially β1-selective in extensive metabolizers (most people) 1
• At doses >10 mg: Selectivity is lost, and the drug inhibits both β1- and β2-adrenergic receptors 1
• In poor CYP2D6 metabolizers: Cardioselectivity is compromised even at lower doses due to 5-fold higher peak concentrations and 10-fold higher drug exposure 1

Clinical Dosing Recommendations

The evidence-based dosing from major guidelines consistently supports staying within the cardioselective range:

Heart Failure with Reduced Ejection Fraction

• Starting dose: 1.25 mg once daily 2
• Target dose: 10 mg once daily 2
• Titration: Increase gradually (doubling every 1-2 weeks) over weeks to months 2

This target dose of 10 mg represents the upper limit of cardioselectivity and was the dose used in major heart failure trials 2.

Hypertension

• Recommended dose: 5 mg once daily 3, 4
• Range: 1-10 mg daily, though 5 mg is most commonly effective 3, 5, 4
• No significant additional blood pressure reduction occurs with doses above 5 mg in most patients 4

Atrial Fibrillation Rate Control

• Dose range: 2.5-10 mg once daily 2

Important Clinical Considerations

The 10 mg threshold is critical because nebivolol's unique nitric oxide-mediated vasodilatory properties and superior β1-selectivity—which distinguish it from other beta-blockers—are preserved only at doses ≤10 mg. 1, 6

Metabolizer Status Impact

• Extensive metabolizers (most patients): Maintain cardioselectivity up to 10 mg 1
• Poor CYP2D6 metabolizers: Experience 5-fold higher peak concentrations and may lose selectivity at lower doses 1
• Poor metabolizers represent a small percentage of the population but require particular caution with dosing 1

Practical Pitfalls to Avoid

1. Do not exceed 10 mg in an attempt to achieve greater efficacy—you will lose cardioselectivity and the unique vasodilatory benefits without meaningful additional therapeutic effect 1, 4

2. In elderly patients or those with severe renal impairment, dosage adjustments are recommended, typically starting at lower doses 4

3. Patients with bronchospastic disease should be managed with doses ≤10 mg to maintain β1-selectivity and minimize β2-blockade effects 2, 6

4. At the 5 mg dose, nebivolol uniquely does not inhibit exercise-induced heart rate increases, a property lost at higher doses 6