Major
Alprazolam × Fluoxetine
Benzodiazepines. Short-to-medium-acting anxiolytics×Selective serotonin reuptake inhibitors
Mechanism
Fluoxetine and its active metabolite norfluoxetine moderately block CYP3A4. Alprazolam plasma levels rise by 30–50%; deep sedation and fall risk in older patients emerge.
Symptoms
Deep sedation, drowsiness, ataxia. Older patients: fall and fracture risk. Symptoms appear within 1–2 weeks of combination.
Management
Reduce alprazolam by 30–50% when combined. Alternative benzodiazepines without CYP3A4 dependence: lorazepam or oxazepam.