CriticalAntifungal, triazole×HMG-CoA reductase inhibitors (statins)
Updated · Methodology
Mechanism
Itraconazole is the strongest CYP3A4 inhibitor in clinical use. Simvastatin is a sensitive substrate; its concentration rises 10–20 fold. Risk of rhabdomyolysis with acute kidney injury is the highest among statin–azole combinations.
Symptoms
Rhabdomyolysis within 3–7 days: myalgia, weakness, dark urine. CK above 50× ULN, oliguria.
Management
Combination contraindicated. Stop simvastatin one week before starting itraconazole and resume 2 weeks after the last dose. Alternative: pravastatin or rosuvastatin.
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: Zocor (simvastatin) prescribing information – CYP3A4 contraindications (2020)– FDA Zocor label, Contraindications §4; DailyMed setid 8f55d5de-5a4f-4a39-8c84-c53976dd6af9
- FDA: Sporanox (itraconazole) prescribing information – CYP3A4 inhibition contraindications (2020)– FDA Sporanox label, Contraindications §4 and Drug Interactions §7; DailyMed setid a4d555fa-787c-40fb-bb7d-b0d4f7318fd0
- AEMPS: Ficha técnica: Simvastatina (nº registro 65199), sección 4.3 (2026)– AEMPS, CIMA, nº registro 65199, revisión 03/2026, sección 4.3