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• W4362579862 abstract "PurposeWith the expansion of the donor pool through Hepatitis C viremic donors (HCV+), the use of DAA agents for treatment and prophylaxis has expanded in cardiothoracic transplant (CTT). Azole antifungal prophylaxis (AAF) is common in CTT to prevent systemic fungal infections, and has several drug drug interactions (DDI) such as PGP inhibition. Glecaprevir/pibrentasvir (GP) is a common agent used for HCV+ donors, utilizing a PGP pathway. While available drug interaction resources identify some DDI with GP and AAF, not all are well described.MethodsThis single-center, case series describes adult patients that received a CTT from HCV+ donors treated with prophylactic GP (protocolized day 0-56) as well as AAF agents after transplant. The primary outcome was peak hyperbilirubinemia (HB) on GP therapy alone as compared to GP+AAF therapy. Secondary outcomes included time to peak HB, time to normalization of HB after AAF discontinuation, time to AAF initiation, and transaminitis on GP+AAF therapy.ResultsFive HCV+ donor CTT patients experienced HB in combination with AAF. All patients started on GP post-operative day 0 and were subsequently started on AAF a median of 3.5 (2-9) days later. After addition of strong PGP inhibitors posaconazole and itraconazole, median and peak total bilirubin demonstrated the most significant increases from baseline (Table 1). Elevations in HB were less prominent with weaker PGP inhibitor isavuconazole, as well as with voriconazole. No patients had concomitant transaminitis.ConclusionHB is a side effect of GP and several AAF agents. Combination therapy of these agents should be done with careful monitoring for HB, particularly with itraconazole and posaconazole due to PGP inhibiting effects increasing GP concentrations, making adverse effects more probable. With the expansion of the donor pool through Hepatitis C viremic donors (HCV+), the use of DAA agents for treatment and prophylaxis has expanded in cardiothoracic transplant (CTT). Azole antifungal prophylaxis (AAF) is common in CTT to prevent systemic fungal infections, and has several drug drug interactions (DDI) such as PGP inhibition. Glecaprevir/pibrentasvir (GP) is a common agent used for HCV+ donors, utilizing a PGP pathway. While available drug interaction resources identify some DDI with GP and AAF, not all are well described. This single-center, case series describes adult patients that received a CTT from HCV+ donors treated with prophylactic GP (protocolized day 0-56) as well as AAF agents after transplant. The primary outcome was peak hyperbilirubinemia (HB) on GP therapy alone as compared to GP+AAF therapy. Secondary outcomes included time to peak HB, time to normalization of HB after AAF discontinuation, time to AAF initiation, and transaminitis on GP+AAF therapy. Five HCV+ donor CTT patients experienced HB in combination with AAF. All patients started on GP post-operative day 0 and were subsequently started on AAF a median of 3.5 (2-9) days later. After addition of strong PGP inhibitors posaconazole and itraconazole, median and peak total bilirubin demonstrated the most significant increases from baseline (Table 1). Elevations in HB were less prominent with weaker PGP inhibitor isavuconazole, as well as with voriconazole. No patients had concomitant transaminitis. HB is a side effect of GP and several AAF agents. Combination therapy of these agents should be done with careful monitoring for HB, particularly with itraconazole and posaconazole due to PGP inhibiting effects increasing GP concentrations, making adverse effects more probable." @default.
• W4362579862 created "2023-04-06" @default.
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• W4362579862 date "2023-04-01" @default.
• W4362579862 modified "2023-09-27" @default.
• W4362579862 title "(1157) Evaluation of Hyperbilirubinemia During Glecaprevir/pibrentasvir and Azole Antifungal Coadministration after Cardiothoracic Transplant" @default.
• W4362579862 doi "https://doi.org/10.1016/j.healun.2023.02.1368" @default.
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