Targeted Aspergillus Prophylaxis With Voriconazole in Heart Transplant Patients: A Focus on the Interaction With Tacrolimus

Abstract

Background: Voriconazole is a commonly used agent for the treatment and prophylaxis of invasive aspergillosis (IA) in heart transplant recipients. Complicating its use with this population is its significant interaction with the calcineurin inhibitors tacrolimus and cyclosporine. Most primary literature pertaining to this interaction focuses on use of voriconazole in allogeneic hematopoietic stem cell recipients. There is little information pertaining to the efficacy of voriconazole for IA prophylaxis or its effects on tacrolimus pharmacokinetics in heart transplant patients. Objective: Evaluate the use of voriconazole for invasive Aspergillus (IA) targeted prophylaxis in heart transplant recipients with a focus on the drug-drug interaction between voriconazole and tacrolimus and its impact on tacrolimus dose after discontinuation of voriconazole. Methods: This single-center, nonrandomized, retrospective, sequential study reviewed the use of targeted prophylaxis protocol in heart transplant recipients at Abbott Northwestern Hospital from January 2015 through May 2017. Results: Patients screened for targeted prophylaxis protocol from 2015 through 2017 had a 0% incidence of IA. This was in comparison to a 7% incidence of IA for a historical group of recipients from 2010 to 2014 prior to the use of the protocol. Additionally, patients on voriconazole needed on average a 67% reduction in tacrolimus dose (mg/kg/day) while on voriconazole compared with similar patients not on voriconazole to stay within the tacrolimus trough level protocol range. On discontinuation of voriconazole, a preemptive 100% tacrolimus dose increase resulted in 55% of tacrolimus trough levels within protocol range on first check. Overall, after 1-month post-voriconazole discontinuation, a 215% average increased tacrolimus dose was needed to maintain a level within the protocol trough range. Conclusion and Relevance: This study corroborates that targeted IA prophylaxis with oral voriconazole for up to 90 days is associated with a reduction in the incidence of IA in new heart transplant recipients. The pharmacokinetic analysis was able to provide more details on the effects of the interaction between voriconazole and tacrolimus in heart transplant recipients. Application of these data will better aid transplant centers to handle the effects of voriconazole discontinuation on patients on tacrolimus.