Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of nebivolol, which is primarily metabolized by the isoenzyme The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity. Several studies have shown that coadministration of CYP450 2D6 inhibitors increases the peak plasma concentration (Cmax) and systemic exposure (AUC) of nebivolol. When the potent CYP450 2D6 inhibitor paroxetine (20-40 mg daily) was coadministered with nebivolol (5 mg) in 23 healthy subjects, nebivolol's Cmax and AUC increased by 5.7-fold and 6.1-fold, respectively. Similarly, when bupropion (300 mg), a potent CYP450 2D6 inhibitor, was coadministered with nebivolol in 18 healthy volunteers, the Cmax and AUC increased by 2.3-fold and 7.2-fold, respectively. Fluoxetine (20 mg daily), a potent CYP450 2D6 inhibitor, increased nebivolol's Cmax and AUC by approximately 2.3-fold and 6-fold in 10 patients. Fluvoxamine, a mild CYP450 2D6 inhibitor, increased Cmax and AUC by 1.41-fold and 1.44-fold in 18 healthy volunteers. However, no data resulted in significant changes to heart rate or blood pressure.

MANAGEMENT: Caution is advised when nebivolol is used concomitantly with CYP450 2D6 inhibitors. Additional caution and monitoring are advised if the coadministered CYP450 2D6 inhibitor may potentiate the blood pressure lowering effects of nebivolol (e.g., phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents). Patients should be monitored closely for adverse effects such as bradycardia, diarrhea, nausea, fatigue, chest pain, peripheral edema, headache, dizziness, insomnia, dyspnea and rash, and the nebivolol dose should be adjusted according to blood pressure response.

DULoxetine may cause liver damage, and taking it with alcohol may increase that risk. You should avoid or limit the use of alcohol while being treated with DULoxetine. Call your doctor immediately if you have fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, dark colored urine, or yellowing of the skin or the whites of your eyes, as these may be symptoms of liver damage. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.