CriticalSystemic antimycotics. Imidazole derivatives×Selective immunosuppressant, mTOR inhibitor
Updated · Methodology
Mechanism
Ketoconazole strongly inhibits CYP3A4 and P-glycoprotein, the routes that clear sirolimus. In the sirolimus SmPC (Rapamune), repeated ketoconazole doses raised sirolimus AUC 10.9-fold and Cmax 4.4-fold. The EMA label for oral ketoconazole (Ketoconazole Esteve) lists sirolimus among contraindicated combinations. The sirolimus SmPC does not recommend the pair, and the FDA sirolimus label says to avoid it.
Symptoms
Severe immunosuppression.
Management
Combination contraindicated.
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: Rapamune (sirolimus) prescribing information (2017)
- EMA: Ketoconazole Esteve 200 mg tablets (ex Ketoconazole HRA): Summary of Product Characteristics (2026)– EMA, EPAR product information, EU/1/14/965/001, sections 4.3 and 4.5
- AEMPS: Ficha técnica de Rapamune 0,5 mg comprimidos recubiertos (sirolimus) (2026)– AEMPS, CIMA (texto EMA), nº registro 01171013, secciones 4.4 y 4.5