Major
diltiazem × Metoprolol
Calcium channel blocker, non-DHP (benzothiazepine derivative)×Selective β1-adrenoceptor blockers
Mechanism
Non-dihydropyridine calcium channel blocker (diltiazem) + beta-blocker (metoprolol) – additive AV node blockade and negative inotropic effect. Diltiazem also raises metoprolol levels via a minor CYP route.
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 For atrial fibrillation rate control: metoprolol + digoxin (without diltiazem) or diltiazem with metoprolol withdrawn. Alternative beta-blockers without CYP2D6 dependence: bisoprolol or carvedilol.