What are the interactions between nebivolol and performance pills (phosphodiesterase type 5 inhibitors), such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra)?

Nebivolol and Phosphodiesterase Type 5 Inhibitors Interaction

The co-administration of nebivolol with phosphodiesterase type 5 inhibitors (PDE5i) like sildenafil, tadalafil, or vardenafil is generally safe with minimal pharmacokinetic interactions, but requires caution due to potential additive hypotensive effects. 1

Pharmacokinetic Interactions

• According to the FDA drug label, the co-administration of nebivolol and sildenafil decreased AUC and Cmax of sildenafil by 21% and 23% respectively, with small effects (<20%) on nebivolol levels 1
• Nebivolol does not significantly inhibit any cytochrome P450 pathways at therapeutically relevant concentrations, limiting major drug-drug interactions with PDE5 inhibitors 1
• Population pharmacokinetic analyses have shown that sildenafil does not have a significant effect on the pharmacokinetics of nebivolol 1

Hemodynamic Considerations

• The combined effect on vital signs (pulse and blood pressure) when nebivolol and sildenafil are co-administered is approximately the sum of the individual effects of each drug 1
• PDE5 inhibitors are mild vasodilators that cause small decreases in blood pressure which may be additive to the blood pressure-lowering effects of beta-blockers like nebivolol 2
• Patients may experience additive decreases in blood pressure without a significant increase in adverse events when PDE5 inhibitors are used with most antihypertensive agents 2

Critical Safety Warnings

• The most important contraindication to be aware of is that PDE5 inhibitors should NEVER be used concomitantly with nitrate medications due to risk of severe hypotension, which can be life-threatening 3
• After using sildenafil or vardenafil, patients should avoid taking nitroglycerin for at least 24 hours 3
• After using tadalafil, patients should avoid taking nitroglycerin for at least 48 hours due to its longer half-life of 17.5 hours 3, 4
• The suitable delay before nitrate administration after vardenafil use has not been definitively determined, but blood pressure generally returns to baseline by 24 hours 3

Specific PDE5 Inhibitor Considerations

Sildenafil

• Has a half-life of approximately 4 hours 4, 2
• Maximum effects observed after 60 minutes 3
• Most side effects are mild to moderate and mainly related to vasodilation (headache, flushing, epistaxis) 3

Tadalafil

• Has a significantly longer half-life of 17.5 hours 4, 2
• Maximum effects observed after 75-90 minutes 3
• The longer duration of action means patients should wait at least 48 hours after their last tadalafil dose before using nitrates 3, 4

Vardenafil

• Has a half-life similar to sildenafil 2, 5
• Maximum effects observed after 40-45 minutes 3
• Side effect profile similar to sildenafil 3

Clinical Recommendations

• Monitor blood pressure when initiating combined therapy of nebivolol with any PDE5 inhibitor 1, 2
• Start with lower doses of PDE5 inhibitors when used concomitantly with nebivolol to assess individual response 2, 6
• Educate patients about potential symptoms of hypotension (dizziness, lightheadedness) and when to seek medical attention 2, 6
• Emphasize the absolute contraindication of nitrate use with PDE5 inhibitors, regardless of nebivolol use 3
• Schedule follow-up within 4-12 weeks after initiating combination therapy to assess efficacy and tolerability 4

Special Considerations

• Be aware that some herbal erectile dysfunction products may be contaminated with undeclared PDE5 inhibitors, which could lead to unexpected drug interactions 7
• Patients with cardiovascular disease should be assessed for risk before using PDE5 inhibitors with nebivolol 4, 2
• Patients with well-controlled hypertension on stable doses of nebivolol are generally at lower risk for significant hypotension when adding a PDE5 inhibitor 2, 6