Moderate
Alprazolam × diltiazem
Benzodiazepines. Short-to-medium-acting anxiolytics×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Mechanism
Diltiazem moderately inhibits CYP3A4; alprazolam is a CYP3A4 substrate. Alprazolam AUC rises by 30–50%, prolonging sedation.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk. Morning sedation is especially pronounced (alprazolam half-life is extended).
Management
On starting the combination, reduce alprazolam by 25–50%. In older patients, start at 0.125 mg at bedtime. Antihypertensive alternatives: amlodipine or a beta-blocker without CYP3A4 effect (metoprolol, bisoprolol). Anxiolytic alternatives: lorazepam or oxazepam (CYP3A4-independent), or buspirone.