What is the interaction between Nebivolol (Beta blocker) and Fluoxetine (Selective serotonin reuptake inhibitor)?

From the Guidelines

Nebivolol and fluoxetine can be used together, but this combination requires careful monitoring due to potential interactions. When taking these medications concurrently, patients should be aware that fluoxetine may increase nebivolol blood levels, potentially enhancing its blood pressure-lowering effects and side effects like dizziness or fatigue. This interaction occurs because fluoxetine inhibits the CYP2D6 enzyme that metabolizes nebivolol 1. Patients should report any unusual symptoms such as significant dizziness, unusual fatigue, or pronounced bradycardia (slow heart rate) to their healthcare provider.

Key Considerations

• Blood pressure should be monitored more frequently when starting this combination or when changing doses of either medication.
• Typically, no initial dose adjustment is needed, but the nebivolol dose may need to be reduced if side effects occur, as indicated in the guidelines for the management of high blood pressure in adults 1.
• Neither medication should be stopped abruptly; nebivolol requires gradual tapering to avoid rebound hypertension, while fluoxetine needs gradual discontinuation to prevent withdrawal symptoms.

Monitoring and Adjustments

• The combination of nebivolol and fluoxetine is generally acceptable when medically necessary, but requires appropriate monitoring and potential dose adjustments.
• Patients with certain conditions, such as heart failure or ischemic heart disease, may require closer monitoring due to the potential effects of nebivolol on these conditions 1.
• The guidelines for the prevention, detection, evaluation, and management of high blood pressure in adults provide recommendations for the use of beta blockers, including nebivolol, in the treatment of hypertension 1.

From the FDA Drug Label

Fluoxetine, a CYP2D6 inhibitor, administered at 20 mg per day for 21 days prior to a single 10 mg dose of nebivolol to 10 healthy adults, led to an 8-fold increase in the AUC and 3-fold increase in Cmax for d-nebivolol [see Drug Interactions (7)] Use caution when nebivolol tablets are co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc.) [see Clinical Pharmacology (12.5)]

Key Points:

• Fluoxetine increases the plasma levels of nebivolol by inhibiting CYP2D6.
• The AUC of d-nebivolol increases 8-fold and Cmax increases 3-fold when co-administered with fluoxetine.
• Caution is advised when co-administering nebivolol with fluoxetine due to the potential for increased nebivolol levels 2, 2.

From the Research

Nebivolol and Fluoxetine Interaction

• The interaction between nebivolol and fluoxetine has been studied in the context of drug-drug interactions, particularly with regards to the cytochrome P450 2D6 (CYP2D6) enzyme 3.
• Fluoxetine, a potent inhibitor of CYP2D6, can increase the plasma concentrations of certain beta-blockers, including nebivolol, when administered concomitantly 4.
• A study found that coadministration of fluoxetine with nebivolol in extensive CYP2D6 metabolizers impeded the apparent clearance of nebivolol 3.
• Another study investigated the potential pharmacokinetic interaction between nebivolol and fluvoxamine, a similar antidepressant to fluoxetine, and found that fluvoxamine increased the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers 5.
• However, the clinical relevance of this drug interaction is still unclear and requires further investigation in actual patients 5.
• It is essential to consider the potential risks of combining nebivolol with fluoxetine, including increased risk of hemodynamic adverse events such as hypotension, bradycardia, and falls 4.

Pharmacokinetic and Pharmacodynamic Effects

• The pharmacokinetic parameters of nebivolol, including Cmax and AUC0-∞, were increased when coadministered with fluvoxamine 5.
• The pharmacodynamic effects of nebivolol, including blood pressure and heart rate lowering, were not significantly affected by fluvoxamine coadministration in healthy volunteers 5.
• However, the study noted that more detailed studies involving actual patients are required to further investigate the clinical relevance of this drug interaction 5.

Clinical Implications

• The combination of nebivolol and fluoxetine should be used with caution, particularly in patients with hypertension or heart disease 3, 4.
• Healthcare providers should monitor patients closely for signs of hemodynamic adverse events when coadministering these medications 4.
• Further studies are needed to fully understand the clinical implications of this drug interaction and to provide guidance for healthcare providers 5.