Voriconazole is a strong CYP3A4 inhibitor, the main enzyme for sirolimus. Sirolimus levels rise 11-fold causing severe toxicity: nephrotoxicity, hepatotoxicity, cytopenias, thrombotic microangiopathy. FDA Vfend Section 4.3 – strict contraindication.
Symptoms
Within 3–7 days – rising creatinine and transaminases, thrombocytopenia, oedema, haematuria.
Management
Combination contraindicated. For severe aspergillosis in a transplant patient, switch sirolimus to tacrolimus with a 50% dose reduction and blood-level monitoring. Alternative antifungal: isavuconazole with weaker CYP3A4 inhibition.
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.