*Purpose: Provide guidance on tacrolimus (TAC) dose adjustments during glecaprevir/pibrentasvir (GLE/PIB) initiation and discontinuation in patients on triazole antifungals by comparing changes in TAC concentration-dose ratio (C/D) with or without triazole antifungal therapy.

*Methods: A single-center retrospective study of adults transplanted between January 1^st, 2017 and August 1^st, 2021 who received concomitant TAC and GLE/PIB for 12 weeks was conducted. TAC C/D was compared between groups based on degree of CYP3A inhibition by triazole used during GLE/PIB therapy: strong (posaconazole or voriconazole), moderate (fluconazole), and no triazole. Kruskal-Wallis and Wilcoxon Signed Ranks tests were used to assess outcomes.

*Results: A total of 81 patients who received concomitant tacrolimus and GLE/PIB were included: 13 (16.0%) also received posaconazole or voriconazole, 9 (11.1%) fluconazole, and 59 (72.8%) no triazole. TAC C/D differed significantly at all time points in the no triazole group (p < 0.001), from end of GLE/PIB therapy to 30 days post-discontinuation in the posaconazole/voriconazole group (p = 0.023), and from baseline to day 7 and end of therapy to 7 days post-discontinuation in the fluconazole group (p = 0.011 and 0.012, respectively). Percent change in TAC C/D from baseline to day 14 was numerically higher in the posaconazole/voriconazole group albeit not statistically significant (64.0 vs. 20.7 [fluconazole] vs. 38.8 [no triazole], p = 0.737). Percent change in TAC C/D at GLE/PIB initiation and discontinuation and time to hepatitis C virus clearance did not differ significantly among groups (Table 2).

*Conclusions: Increased TAC monitoring may be required at initiation and discontinuation of GLE/PIB, regardless of triazole use. Hepatitis C clearance did not change significantly with the addition of a triazole. Further research in a larger cohort is needed to determine impact of posaconazole and voriconazole on this interaction.

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