Tacrolimus Dosage Adjustments after Posaconazole Discontinuation in Lung Transplant Recipients

Abstract

Purpose Posaconazole is commonly used in lung transplant recipients (LTRs) as prophylaxis against invasive fungal infections. Due to CYP3A4 drug interactions, tacrolimus (TAC) dose adjustments are required after discontinuing posaconazole. Current data has assessed tacrolimus dose adjustments only with posaconazole initiation. This study's purpose was to assess TAC dose adjustment requirements following posaconazole discontinuation in LTRs. Methods This was a single-center, retrospective review of LTRs between Jan and Dec 2019. The primary outcome was the change in TAC dose‐corrected trough concentration (∆C/D) from pre- to post-posaconazole discontinuation. Secondary outcomes included the time to first therapeutic TAC level post-posaconazole discontinuation and the number of TAC dose changes to achieve the first therapeutic TAC level after stopping posaconazole. Results 19 LTRs were included, the majority of which were Caucasian and CYP3A5 poor metabolizers [Table 1]. The median (IQR) TAC ∆C/D was 3.1 (2.3-4.4). Following posaconazole discontinuation, the median (IQR) time to the first therapeutic TAC level was 19 (14-26) days, and a median (IQR) of 3 (1-4) dose changes were required to achieve the first therapeutic TAC level. There was a trend towards the one CYP3A5 extensive metabolizer having a higher TAC ∆C/D (11.2), compared with poor (3.1) and intermediate metabolizers (3.3), although non-significant (p=0.25). Baseline posaconazole trough level did not impact the TAC ∆C/D (p=0.57). Similarly, baseline TAC trough level did not impact the time to first therapeutic TAC level post-posaconazole discontinuation (p=0.42). Conclusion In this cohort, LTRs required a 3-fold increase in TAC dose to obtain a trough level within goal after posaconazole discontinuation. Further studies are warranted to assess the impact of posaconazole discontinuation on TAC dose adjustments in various CYP3A5 pharmacogenomic phenotypes, cystic fibrosis LTRs, and those receiving TAC extended-release.