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

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 35 mg 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 70 mg 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 a maintenance dose reduction from 50 to 35 mg 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 35 mg 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.