ModerateBenzodiazepines. Short-to-medium-acting anxiolytics×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Updated · Methodology
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.
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Sources
- FDA: Cardizem section 7 (2014)– ; DailyMed setid f3e7ecef-f360-4987-a4f5-933214130ab2
- AEMPS: Ficha técnica: Alprazolam (nº registro 61880), sección 4.5 (2026)– AEMPS, CIMA, nº registro 61880, revisión 09/2026, sección 4.5