Moderate
Alprazolam × fluvoxamine
Benzodiazepines. Short-to-medium-acting anxiolytics×SSRI
Mechanism
Fluvoxamine inhibits CYP3A4 and CYP1A2. Alprazolam is a CYP3A4 substrate. Alprazolam AUC rises by 50–100%; half-life doubles.
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.
Management
Avoid the combination. If unavoidable, halve the alprazolam dose and give only at bedtime. Do not prescribe in older patients. Anxiolytic alternatives: buspirone, lorazepam, or oxazepam (CYP3A4-independent). Antidepressant alternatives: sertraline or escitalopram (minimal CYP3A4 effect).