Major
Fluoxetine × Metoprolol
Selective serotonin reuptake inhibitors×Selective β1-adrenoceptor blockers
Mechanism
Fluoxetine is a potent CYP2D6 inhibitor, the main metoprolol metabolic route. Metoprolol plasma levels rise 4- to 5-fold. Risk of marked bradycardia, hypotension, and AV block emerges.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope, orthostatic hypotension. In heart failure: worsening dyspnoea and oedema.
Management
Reduce metoprolol 2- to 3-fold when combined; monitor pulse and blood pressure. Alternative beta-blockers without CYP2D6 dependence: bisoprolol or carvedilol. Alternative antidepressants without CYP2D6 inhibition: sertraline or escitalopram.