Major
Alprazolam × Clarithromycin
Benzodiazepines. Short-to-medium-acting anxiolytics×Macrolide antibiotic
Mechanism
Clarithromycin blocks CYP3A4 – the main alprazolam metabolic route. Alprazolam plasma levels rise 2- to 3-fold, with prolonged and stronger effect.
Symptoms
Prolonged sedation, drowsiness, dizziness, ataxia. Falls and fracture risk in older patients. Symptoms appear within 1–2 days.
Management
During clarithromycin therapy, halve the alprazolam dose. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 impact). Alternative benzodiazepines without CYP3A4 dependence: lorazepam, oxazepam.