Drug Interaction Between Fluvoxamine and Bystolic (Nebivolol)
Yes, fluvoxamine can interact with nebivolol (Bystolic), primarily through cytochrome P450-mediated metabolism, though this interaction is generally manageable with appropriate monitoring and dose adjustments.
Mechanism of Interaction
Fluvoxamine is a potent inhibitor of cytochrome P450 1A2 and a moderate inhibitor of other CYP enzymes, which can increase plasma concentrations of drugs metabolized through these pathways. 1 While nebivolol is primarily metabolized by CYP2D6, fluvoxamine's broad CYP inhibition profile creates potential for pharmacokinetic interactions. 1
Clinical Significance in Cardiovascular Disease
Beta-Blocker Importance
- Beta-blockers like nebivolol are essential therapy for patients with cardiovascular disease, particularly those with prior myocardial infarction, heart failure with reduced ejection fraction, or acute coronary syndrome, as they reduce mortality and prevent recurrent events. 2
- Nebivolol is a cardioselective (beta-1 selective) beta-blocker with vasodilatory properties, though it is not the preferred beta-blocker for heart failure with reduced ejection fraction compared to carvedilol, metoprolol succinate, or bisoprolol. 2, 3
Fluvoxamine's Cardiovascular Safety Profile
- Fluvoxamine has minimal direct cardiovascular effects and causes no clinically significant alterations in cardiac conduction, repolarization, or blood pressure. 4, 5
- The only cardiovascular effect is a statistically (but not clinically) significant slowing of heart rate, which could theoretically be additive with beta-blocker effects. 4
- Fluvoxamine is particularly valuable in patients with cardiovascular disease because it lacks the anticholinergic and quinidine-like properties of tricyclic antidepressants that cause tachycardia, postural hypotension, and conduction abnormalities. 6, 5
Management Strategy
Monitoring Requirements
- Monitor for excessive bradycardia (heart rate <50 bpm) or symptomatic hypotension when initiating or adjusting doses of either medication. 4, 5
- Check blood pressure and heart rate at baseline, 1-2 weeks after starting combination therapy, and after any dose adjustments. 5
- Assess for signs of beta-blocker toxicity including fatigue, dizziness, or worsening heart failure symptoms. 2
Dose Adjustments
- Start with standard doses of both medications but be prepared to reduce nebivolol dose by 25-50% if excessive bradycardia or hypotension develops. 1
- The overall reporting rate of drug-drug interactions with fluvoxamine is very low (73 cases from over 8 million patients), suggesting clinical significance is limited in most patients. 1
Common Pitfalls to Avoid
- Do not discontinue beta-blocker therapy in patients with established cardiovascular disease due to concerns about drug interactions—the mortality benefit of beta-blockers far outweighs theoretical interaction risks. 2
- Avoid combining nebivolol with non-selective beta-blockers or other heart rate-lowering agents (verapamil, diltiazem) as this creates redundancy and increases bradycardia risk. 7, 8
- Do not use labetalol as an alternative if the patient has reactive airway disease, as it is contraindicated due to non-selective beta-2 blockade. 3
Special Considerations
Drug Interaction Profile
- Fluvoxamine's most clinically significant interactions occur with drugs metabolized by CYP1A2, including some tricyclic antidepressants (clomipramine levels increased up to 8-fold), anticoagulants, and certain antiepileptic drugs. 1
- Nebivolol is not primarily metabolized by CYP1A2, making this a lower-risk combination compared to fluvoxamine with other cardiovascular medications. 1
Alternative Beta-Blockers
- If interaction concerns persist, consider metoprolol succinate or bisoprolol, which are also cardioselective and have proven mortality benefits in heart failure. 2, 3
- Carvedilol is preferred in patients with heart failure and refractory hypertension due to combined alpha-beta blocking properties. 2, 7