Moderate
Amitriptyline × Metoprolol
Tricyclic antidepressants (TCA)×Selective β1-adrenoceptor blockers
Mechanism
Amitriptyline is a CYP2D6 substrate, as is metoprolol. Enzyme competition raises both drug levels. Plus additive anticholinergic effect on the heart (bradycardia, PR prolongation).
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: PR prolongation. Older patients: delirium and fall risk.
Management
In older patients, check pulse and ECG 1–2 weeks after starting amitriptyline. Alternative beta-blocker without CYP2D6 dependence: bisoprolol or carvedilol. For neuropathic pain, alternative: gabapentin or pregabalin.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.