Major
Metoprolol × Verapamil
Selective β1-adrenoceptor blockers×Non-dihydropyridine calcium channel blocker
Mechanism
Non-dihydropyridine calcium channel blocker (verapamil) + beta-blocker (metoprolol) – additive AV node blockade and negative inotropic effect. Verapamil also blocks CYP2D6 and raises metoprolol plasma levels.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block. Older patients: fall risk.
Management
Avoid the combination. For atrial fibrillation rate control: metoprolol + digoxin (without verapamil) or verapamil with metoprolol withdrawn. Alternative beta-blockers without CYP2D6 dependence: bisoprolol or carvedilol.