BACKGROUND: Mild, transient alanine aminotransferase (ALT) elevations were seen in Phase I studies of caspofungin and cyclosporin A (CsA). METHODS: We conducted a retrospective chart review at four sites to characterize the hepatic safety in patients receiving > or =1 day of both drugs over a 20-month period. Investigators assessed reasons for discontinuing concomitant therapy and the presence/etiology of any hepatotoxicity. RESULTS: Forty patients receiving concomitant therapy for 1-290 days (median 17.5 days) were identified. Although common, liver enzyme abnormalities were frequently attributed to other comorbidities or medications. ALT and/or aspartate aminotransferase (AST) elevations occurred in 14 patients (35%). Five had AST elevations at least possibly related to caspofungin/CsA, but none were >3.6 times the normal upper limit. No ALT elevations were related to caspofungin/CsA. Two of 4 patients had discontinuation of therapy because of hepatotoxicity possibly related to caspofungin/CsA. No serious adverse events occurred because of caspofungin. CONCLUSIONS: These data do not suggest a significant risk of clinically relevant hepatotoxicity with concomitant caspofungin/CsA.
BACKGROUND: Mild, transient alanine aminotransferase (ALT) elevations were seen in Phase I studies of caspofungin and cyclosporin A (CsA). METHODS: We conducted a retrospective chart review at four sites to characterize the hepatic safety in patients receiving > or =1 day of both drugs over a 20-month period. Investigators assessed reasons for discontinuing concomitant therapy and the presence/etiology of any hepatotoxicity. RESULTS: Forty patients receiving concomitant therapy for 1-290 days (median 17.5 days) were identified. Although common, liver enzyme abnormalities were frequently attributed to other comorbidities or medications. ALT and/or aspartate aminotransferase (AST) elevations occurred in 14 patients (35%). Five had AST elevations at least possibly related to caspofungin/CsA, but none were >3.6 times the normal upper limit. No ALT elevations were related to caspofungin/CsA. Two of 4 patients had discontinuation of therapy because of hepatotoxicity possibly related to caspofungin/CsA. No serious adverse events occurred because of caspofungin. CONCLUSIONS: These data do not suggest a significant risk of clinically relevant hepatotoxicity with concomitant caspofungin/CsA.
Authors: Andreas H Groll; Gerda Silling; Charlotte Young; Rainer Schwerdtfeger; Helmut Ostermann; Werner J Heinz; Joachim Gerss; Hedwig Kolve; Claudia Lanvers-Kaminsky; João Paulo Vieira Pinheiro; Sibylle Gammelin; Oliver A Cornely; Gudrun Wuerthwein Journal: Antimicrob Agents Chemother Date: 2010-07-26 Impact factor: 5.191