Merck’s anti-fungal caspofungin (Cancidas) to carry warning on liver problems in kids

Caspofungin, an anti-fungal drug sold in the brand name Cancidas by Merck, can cause serious liver problems in children, warned US FDA.

Caspofungin (Cancidas) cause liver problems in patients under age 17, mostly in very ill children with many competing causes for their hepatotoxicity, the US FDA alerted.

Caspofungin (Cancidas) is frequently prescribed for children with other serious illness who are taking multiple drugs, which makes “an assessment of a causation challenging.

Caspofungin (Cancidas) leads to abnormal liver function tests and of liver injury in seriously ill children, the US FDA review panel for adverse events reported.

Now in the light of these findings, Merck’s Cancidas will carry labeling changes to warn of possible liver problems in children, as recommended by US Food and Drug Administration.

When used together with cyclosporine, the transplant drug was shown to elevate AUC of caspofungin by approximately 35%.

In a clinical study, 2 of 8 healthy men developed transient ALT elevations of less than 2X ULN.

In this study, cyclosporine (4 mg/kg) was administered on Days 1 and 12, and Cancidas was administered (70 mg) daily on Days 3 through 13. In one subject, the ALT elevation occurred on Days 7 and 9 and, in the other subject, the ALT elevation occurred on Day 19. These elevations returned to normal by Day 27. In all groups, elevations in AST paralleled ALT elevations but were of lesser magnitude. In these clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35%.

In a second randomized, double-blinded invasive candidiasis study, patients received either Cancidas 50 mg/day (following a 70-mg loading dose) or Cancidas 150 mg/day. The proportion of patients who experienced any adverse reaction was similar in the 2 treatment groups; however, this study was not large enough to detect differences in rare or unexpected adverse events.

Laboratory abnormalities in liver function tests have been seen in healthy volunteers and patients treated with caspofungin (Cancidas). In some patients with serious underlying conditions who were receiving multiple concomitant medications with caspofungin (Cancidas), isolated cases of clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported; a causal relationship to CANCIDAS has not been established.
Patients who develop abnormal liver function tests during caspofungin (Cancidas) therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing caspofungin (Cancidas) therapy, Merck’s preescribing information suggests.

Caspofungin (Cancidas) is an echinocandin antifungal drug that is indicated in adults and pediatric patients 3 months and older for: empirical therapy for presumed fungal infections in febrile, neutropenic patients; treatment of Candidemia and the following Candida infections: intra-abdominal abscesses, peritonitis and pleural space infections; treatment of esophageal candidiasis and treatment of Invasive Aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole).