par Gustot, Thierry ;Heine, Rob Ter;Brauns, Elisa ;Cotton, Frédéric ;Jacobs, Frédérique ;Brüggemann, Roger Johannes
Référence Journal of antimicrobial chemotherapy, 73, 9, page (2493-2496)
Publication Publié, 2018
Référence Journal of antimicrobial chemotherapy, 73, 9, page (2493-2496)
Publication Publié, 2018
Article révisé par les pairs
Résumé : | 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. |