MajorBenzodiazepines. Short-to-medium-acting anxiolytics×HIV protease inhibitor / pharmacokinetic booster
Updated · Methodology
Mechanism
Ritonavir is the most potent CYP3A4 inhibitor available – the main alprazolam metabolic route. Alprazolam plasma levels rise 4-fold. Marked sedation, ataxia, and respiratory depression risk emerge.
Symptoms
Deep sedation, drowsiness, marked ataxia. Older patients: fall and fracture risk. With high alprazolam doses and high ritonavir doses: respiratory depression risk.
Management
Avoid the combination. Alternative benzodiazepines without CYP3A4 dependence: lorazepam or oxazepam (metabolised by glucuronidation, weakly affected by ritonavir). If alprazolam is needed, reduce the dose 4-fold.
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.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Norvir (ritonavir) prescribing information contraindications (2018)– ; DailyMed setid 2849298e-de6e-47bb-8194-56e075b33fc3
- AEMPS: Ficha técnica: Ritonavir (nº registro 81039), sección 4.5 (2025)– AEMPS, CIMA, nº registro 81039, sección 4.5
- AEMPS: Ficha técnica: Alprazolam (nº registro 61880), sección 4.5 (2026)– AEMPS, CIMA, nº registro 61880, revisión 09/2026, sección 4.5