Caspofungin dosage adjustments are not required for patients with Child-Pugh B or C cirrhosis

Thierry Gustot, Rob Ter Heine, Elisa Brauns, Frédéric Cotton, Frédérique Jacobs, Roger J. Brüggemann

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: Controversies remain over caspofungin dosage adjustments in cirrhosis, particularly Child-Pugh (CP) B or C. The product information for of caspofungin recommends a maintenance dose reduction from 50 to 35mg for patients with CP-B cirrhosis. Objectives: To quantify the impact of cirrhosis and the severity of hepatic impairment on the pharmacokinetics (PK) of caspofungin. Patients and methods: We performed PK studies of a single 70mg dose of caspofungin in patients with decompensated CP-B (n = 10) or CP-C (n = 10) cirrhosis and of multiple doses in 21 non-cirrhotic ICU patients with hypoalbuminaemia. A Monte Carlo simulation was performed to investigate the impact of amaintenance dose reduction from 50 to 35mg on the steady-state area under the 24 h concentration-time curve. Results: We observed a marginal reduction of caspofungin clearance in a PK study in patients with decompensated CP-B or CP-C cirrhosis. Dose reduction to 35mg in cirrhotic patients resulted in lower drug exposure than with the approved dose in non-cirrhotic patients. Conclusions: In contrast to the product information, we recommend giving the full dose of caspofungin regardless of the presence and severity of cirrhosis to avoid a subtherapeutic exposure.

Original languageEnglish
Pages (from-to)2493-2496
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number9
DOIs
Publication statusPublished - 1 Sept 2018
Externally publishedYes

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