Major
Alprazolam × Ketoconazole
Benzodiazepines. Short-to-medium-acting anxiolytics×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole strongly blocks CYP3A4 – the main alprazolam metabolic route. Alprazolam plasma levels rise 3- to 4-fold. Particularly dangerous in older patients: deep sedation and fall risk.
Symptoms
Deep sedation, drowsiness, marked ataxia, cognitive impairment. In older patients: fall and fracture risk. Symptoms appear within 1–2 days.
Management
Avoid the combination. Alternative antifungals: terbinafine (no CYP3A4 effect) for dermatophytosis or echinocandins for systemic mycoses. Alternative benzodiazepines without CYP3A4 dependence: lorazepam, oxazepam.
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.