Moderate
Amitriptyline × diltiazem
Tricyclic antidepressants (TCA)×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Mechanism
Diltiazem weakly inhibits CYP2D6 and CYP3A4; amitriptyline is metabolised by both. TCA levels can rise, amplifying anticholinergic, sedative, and QT effects. Bradycardia is additive.
Symptoms
Dry mouth, constipation, urinary retention, accommodation disturbance, tachycardia. In older patients: delirium and confusion risk. Postural dizziness, syncope, fatigue. Older patients: fall and fracture risk.
Management
On the combination, begin amitriptyline at 10 mg at bedtime. Avoid the combination in older patients — orthostatic hypotension and arrhythmia risk. For neuropathic pain, alternatives: gabapentin or pregabalin. Antihypertensive alternatives: amlodipine or a beta-blocker without CYP effect.
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.