Adverse drug interactions as a high-risk factor for lethal post-transplant complications in Chinese population

Metabolism of triazole antifungal agents is highly competitive to conventional post-transplant immunosuppressants like cyclosporine A (CsA) via the cytochrome P450-dependent pathway. We present the first report on lethal complications that may arise due to this type of drug interaction. A retrospective survey identified 10 of 104 cases (9.62%) that suffered life-threatening complications associated with the interaction between CsA and itraconazole or voriconazole following allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center. According to the close drug monitoring, all 10 patients experienced supratherapeutic levels of CsA even with a preemptive CsA dosage reduction and prompt dose adjustment. Six patients developed grade I to III acute graft-versus-host disease (aGVHD) and eventually died from either idiopathic pneumonia syndrome or diffuse alveolar hemorrhage; another four patients died from CSA-associated neurological complications. Impaired hepatic and renal function was noted in only one of these 10 cases. The high frequency as well as the unpredictability of severe complications lead us to suggest that triazole should always be replaced by another antifungal medication (e.g., amphotericin B or Echincandins) while patients receive CsA after HSCT, especially in the Chinese population.