Major
carvedilol × Fluoxetine
Alpha and beta blocker (non-selective β + α1)×Selective serotonin reuptake inhibitors
Mechanism
Fluoxetine is a potent CYP2D6 inhibitor, the main carvedilol metabolic route. Carvedilol plasma levels rise 2- to 3-fold. Marked hypotension and bradycardia emerge.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall risk.
Management
Halve the carvedilol dose when combined; monitor blood pressure and pulse. Alternative beta-blockers without CYP2D6 dependence: bisoprolol or nebivolol. Alternative antidepressants without CYP2D6 inhibition: sertraline or escitalopram.