Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child–Pugh B or C Liver Disease: A Case–Control Retrospective Study

Abstract

Introduction: To assess the association between exposure to micafungin, other echinocandins, or azoles and the development of short-term liver injury (STLI) or long-term liver injury (LTLI) in patients with Child-Pugh B or C liver disease. Methods: Multicenter case-control study of patients with Child-Pugh B or C liver disease who received antifungals (AF) for C 72 h (May 2009-May 2015) in six Spanish and Italian hospitals. All micafungin patients were randomly matched with one patient who received another echinocandin and with one patient who received azole treatment. Primary outcome was development of STLI or LTLI (development of any type of liver tumor during the follow-up period). Results: Of 2335 patients with chronic liver disease admitted to the six centers, 20 (0.85%) were found to have Child-Pugh B or C liver disease and received micafungin for C 72 h. During AF treatment, the frequency of STLI was 10% in each group. Most cases of STLI were asymptomatic, and AFs had to be switched to another class of AF in only two patients (one micafungin and one azole). No patients developed acute liver insufficiency, were admitted to the ICU, or had to undergo transplantation. Follow-up data (median of 1.3 years) were Enhanced digital features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11550816.

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“…In analyses stratified on comparing to echinocandins, no signal of increased hepatic dysfunction event reporting was found (ROR<1). In previous studies, the echinocandins were considered to have a lower hepatotoxicity when compared with triazoles [14]. A network meta-analysis and systematic review on adverse reactions of antifungal drugs also showed that caspofungin was more significantly associated with a lower incidence of hepatobiliary disorders [15].…”

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“…71,72 Although, caspofungin and micafungin undergo substantial hepatic metabolism, apparently, in two smaller clinical experiences only minimal changes in pharmacokinetics of caspofungin has been reported in patients with liver failure, apparently with no clinical impact, even in patients with Child-Pugh B or C liver disease. 75,76 On the other hand, an increase of the AUC in patients with chronic liver insufficiency during caspofungin treatment, resulted in a manufactory dose reduction recommendation for patients with CHILD Pugh B or C liver disease. 77 Nevertheless, Gustot et al 78 recently showed that dose reduction of caspofungin to 35 mg in cirrhotic patients resulted in lower drug exposure than that obtained by non-cirrhotic patients using the conventional approved dose.…”