CriticalBenzodiazepines. Short-to-medium-acting anxiolytics×Systemic antimycotics. Imidazole derivatives
Updated · Methodology
Mechanism
Ketoconazole strongly inhibits CYP3A4, the enzyme that breaks down alprazolam in the liver. Alprazolam levels rise and its sedative effect is enhanced (FDA labels of both drugs).
Symptoms
Drowsiness, deep sedation, slowed thinking, impaired coordination and speech; in older people, a risk of falls.
Management
The combination is contraindicated: the FDA alprazolam label prohibits use with strong CYP3A4 inhibitors, including ketoconazole, and the FDA ketoconazole label lists alprazolam among contraindicated drugs. The Spanish alprazolam SmPC does not recommend it with ketoconazole and other azole antifungals (alprazolam SmPC). If a patient on alprazolam needs a systemic antifungal, choose one that does not inhibit CYP3A4.
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Sources
- AEMPS: Ficha técnica: Alprazolam (nº registro 61880), sección 4.5 (2026)– AEMPS, CIMA, nº registro 61880, revisión 09/2026, sección 4.5
- FDA: Xanax (alprazolam) tablets prescribing information (Pharmacia & Upjohn) (2023)– FDA label, DailyMed setid 388e249d-b9b6-44c3-9f8f-880eced0239f, revised 01/2023, section 7.1 (CNS Depressants) and 17
- FDA: Ketoconazole Tablets USP 200 mg prescribing information (2026)– FDA label, DailyMed setid 1d598696-c6f3-4b7c-ad73-949d2089df35, revised 08/2026, Contraindications