CriticalSecond-generation systemic triazole antifungal×Selective immunosuppressant, mTOR inhibitor
Updated · Methodology
Mechanism
Posaconazole strongly inhibits CYP3A4, the enzyme that clears sirolimus. In the posaconazole SmPC (Noxafil), repeated posaconazole doses raised sirolimus Cmax a mean 6.7-fold and AUC 8.9-fold, with a range of 3.1 to 17.5-fold. The FDA posaconazole label lists sirolimus as a contraindication. The EMA does not recommend the combination and asks to avoid it whenever possible.
Symptoms
Rising creatinine, thrombocytopenia, hepatotoxicity within 5 days.
Management
The combination is not used. If a transplant patient on sirolimus needs posaconazole, a transplant specialist reviews the immunosuppressive regimen. For unavoidable co-administration the posaconazole SmPC advises a large immediate cut in the sirolimus dose and very frequent trough monitoring: at baseline, during co-administration and when posaconazole stops. If the patient is switched to tacrolimus, its dose also depends on posaconazole: per the SmPC it is reduced to about one third of the current dose and then adjusted by blood levels.
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Sources
- EMA: Noxafil (posaconazole) Summary of Product Characteristics (2024)– EMA EPAR Noxafil
- FDA: Noxafil (posaconazole) prescribing information (2026)– FDA, DailyMed, Noxafil, setid b073b082-7b57-4423-8c06-4fd4263d6f84, revisión 02/2026, secciones 4.2 y 7.2
- AEMPS: Ficha técnica de Noxafil 100 mg comprimidos gastrorresistentes (posaconazol) (2026)– AEMPS, CIMA (texto EMA), nº registro 105320002, secciones 4.3 y 4.5