Assessing the Impact of Posaconazole Cessation on Tacrolimus Serum Concentrations and Incident Cardiac Allograft Rejection: Take Caution

Abstract

Invasive aspergillosis (IA) is a rare and often fatal complication of immunosuppression following orthotopic heart transplant. Prophylaxis plays a crucial role in preventing the emergence of this opportunistic infection. The azole class of medications are the bellwether agents utilized in this patient population. Unfortunately, given their impact on the Cytochrome P450 enzyme system, significant fluctuations in serum tacrolimus concentrations occur when initiating and stopping azole therapy, increasing the risk for prolonged periods of sub-optimal immunosuppression. While there are recommended dosing adjustments for these transition periods based on small data sets primarily with fluconazole, there is no published literature on recommended dosing adjustments for posaconazole. Given our institution utilizes posaconazole as the primary therapeutic for aspergillosis prophylaxis, we aimed to explore and report our local data to better guide dosing decisions during these transition periods.