Caspofungin drug interactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]
Drug Interactions
Studies in vitro show that caspofungin acetate is not an inhibitor of any enzyme in the cytochrome P450 (CYP) system. In clinical studies, caspofungin did not induce the CYP3A4 metabolism of other drugs. Caspofungin is not a substrate for P-glycoprotein and is a poor substrate for cytochrome P450 enzymes.
Clinical studies in adult healthy volunteers show that the pharmacokinetics of CANCIDAS are not altered by itraconazole, amphotericin B, mycophenolate, nelfinavir, or tacrolimus. CANCIDAS has no effect on the pharmacokinetics of itraconazole, amphotericin B, or the active metabolite of mycophenolate.
Cyclosporine: In two adult clinical studies, cyclosporine (one 4 mg/kg dose or two 3 mg/kg doses) increased the AUC of caspofungin by approximately 35%. CANCIDAS did not increase the plasma levels of cyclosporine. There were transient increases in liver ALT and AST when CANCIDAS and cyclosporine were co-administered [see Warnings and Precautions (5.2)].
Tacrolimus: CANCIDAS reduced the blood AUC0-12 of tacrolimus (FK-506, Prograf®) by approximately 20%, peak blood concentration (Cmax) by 16%, and 12-hour blood concentration (C12hr) by 26% in healthy adult subjects when tacrolimus (2 doses of 0.1 mg/kg 12 hours apart) was administered on the 10th day of CANCIDAS 70 mg daily, as compared to results from a control period in which tacrolimus was administered alone. For patients receiving both therapies, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended.
Rifampin: A drug-drug interaction study with rifampin in adult healthy volunteers has shown a 30% decrease in caspofungin trough concentrations. Adult patients on rifampin should receive 70 mg of CANCIDAS daily.
Other inducers of drug clearance
Adults
In addition, results from regression analyses of adult patient pharmacokinetic data suggest that co-administration of other inducers of drug clearance (efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine) with CANCIDAS may result in clinically meaningful reductions in caspofungin concentrations. It is not known which drug clearance mechanism involved in caspofungin disposition may be inducible. When CANCIDAS is co-administered to adult patients with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, use of a daily dose of 70 mg of CANCIDAS should be considered.
Pediatric patients
In pediatric patients, results from regression analyses of pharmacokinetic data suggest that co-administration of dexamethasone with CANCIDAS may result in clinically meaningful reductions in caspofungin trough concentrations. This finding may indicate that pediatric patients will have similar reductions with inducers as seen in adults. When CANCIDAS is co-administered to pediatric patients with inducers of drug clearance, such as rifampin, efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a CANCIDAS dose of 70 mg/m2 daily (not to exceed an actual daily dose of 70 mg) should be considered. [1]
References
Adapted from the FDA Package Insert.