*Purpose: Posaconazole (POSA) is a strong CYP3A4 inhibitor known to increase tacrolimus exposure by up to 4-fold. Initiation requires empiric tacrolimus dose adjustment and close monitoring upon discontinuation (d/c) to avoid low levels that may contribute to graft rejection. We describe our experience with a posaconazole prophylaxis protocol (PPP) in heart transplant recipients receiving tacrolimus.

*Methods: All patients at our center who received an orthotopic heart transplant patients (OHT) after September 2019 were enrolled in the PPP. POSA was typically initiated within the first 3 days post-operatively with doses adjusted to maintain a target trough of 1000-2000 ng/mL for 3 months. Patients unable to swallow the oral delayed release formulation received the intravenous formulation. At the time of POSA d/c, tacrolimus doses were doubled with bi-weekly monitoring to maintain goal levels.

*Results: 50 patients underwent OHT with PPP. Four patients were not initiated on POSA due to drug-drug interactions. Of the 46 patients included in analysis, 18 (39%) experienced a tacrolimus level > 15 ng/mL within the first 7 days of POSA initiation. Early discontinuation was necessary in 15% of patients (Table 1). Therapy was extended beyond 3 months in 3 patients due to rejection episodes necessitating pulse steroids. Six (15%) patients experienced >2R rejection within one month of POSA d/c. Half of these patients had no prior rejection episodes, while half had prior rejection with a negative biopsy immediately prior to the 2R diagnosis. Four (66%) of these patients had subtherapeutic tacrolimus levels at time of rejection. No patients have experienced fungal infections since initiation of PPP.

*Conclusions: Use of PPP in the first 3 months after heart transplant can be used to prevent fungal infections; however, this practice requires close monitoring upon discontinuation to prevent low tacrolimus levels that may contribute to rejection risk.

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