Major
Alprazolam × Fluconazole
Benzodiazepines. Short-to-medium-acting anxiolytics×Antifungals, triazole derivatives
Mechanism
Fluconazole at 200 mg/day or above blocks CYP3A4 – the main alprazolam metabolic route. Alprazolam plasma levels rise 2- to 3-fold, with stronger and longer effect.
Symptoms
Deep sedation, drowsiness, ataxia. Particularly dangerous in older patients – fall and fracture risk. Symptoms appear within 1–2 days.
Management
During fluconazole therapy, halve the alprazolam dose. Alternative antifungals: terbinafine or echinocandins. Alternative benzodiazepines without CYP3A4 dependence: lorazepam or oxazepam.