Cancidas

Caspofungin acetate

In vitro studies have shown that caspofungin acetate does not inhibit any enzyme in the cytochrome P450 (CYP) system. In clinical studies, caspofungin did not induce changes in the metabolism of other drugs by CYP3A4. Caspofungin is not a substrate for P-glycoprotein. For cytochrome P450, Cosacet does not increase the plasma concentration of cyclosporine. When Cosacet is used concomitantly with cyclosporine, a transient increase in the levels of liver enzymes ALT and AST occurs. In clinical studies conducted in healthy subjects, the pharmacokinetics of Cosacet were not affected by itraconazole, amphotericin B, mycophenolate, nelfinavir or tacrolimus. Cosacet also had no effect on the pharmacokinetics of itraconazole, amphotericin B, rifampicin or active mycophenolate metabolites. Cosacet can reduce the 12-hour blood concentration (C12hr) of tacrolimus (FK-506) by 26%. For patients receiving these two drugs simultaneously, standard monitoring of tacrolimus blood concentrations is recommended, and tacrolimus dosage should be adjusted appropriately. Two clinical drug interaction studies have shown that rifampicin both induces and inhibits the elimination of caspofungin, with a net induction effect at steady state. When caspofungin was added to ongoing rifampicin therapy, no such inhibition was found, and caspofungin concentrations did not increase. In addition, the results of population pharmacokinetic studies suggest that when Cosacet is used simultaneously with other drug elimination inducers (efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine), a clinically significant decrease in caspofungin concentrations may occur. The data currently available show that the inducible drug elimination mechanism in the elimination of caspofungin is more like an uptake transport process than metabolism. Therefore, when Cosacet is used concomitantly with drug elimination inducers such as efavirenz, nevirapine, rifampin, dexamethasone, phenytoin, or carbamazepine, a daily dose of Cosacet of 70 mg should be considered (see Dosage and Administration).

The main ingredients of this product are caspofungin acetate and excipients: sucrose, mannitol, glacial acetic acid and sodium hydroxide (a small amount is used to adjust the pH value).

In vitro studies have shown that caspofungin acetate does not inhibit any enzyme in the cytochrome P450 (CYP) system. In clinical studies, caspofungin did not induce changes in the metabolism of other drugs by CYP3A4. Caspofungin is not a substrate for P-glycoprotein. Caspofungin is a poor substrate for cytochrome P450. In two adult clinical studies, cyclosporine (4 mg/kg-dose or 3 mg/kg twice-dose) was found to increase the AUC of caspofungin by approximately 35%. The increase in AUC may be due to reduced uptake of caspofungin by the liver. This product does not increase the plasma concentration of cyclosporine. When this product is used simultaneously with cyclosporine, a transient increase in the levels of liver enzymes ALT and AST may occur. In a retrospective study of 40 patients using this product and cyclosporine for 1 to 290 days (average 17.5 days), no serious liver adverse events were found (see Precautions). Clinical studies conducted in adult healthy subjects showed that the pharmacokinetics of this product were not affected by itraconazole, amphotericin B, mycophenolate, nelfinavir or tacrolimus. This product also had no effect on the pharmacokinetics of itraconazole, amphotericin B, rifampicin or active mycophenolate metabolites. This product can reduce the 12-hour blood concentration (C12hr) of tacrolimus (FK-506) in adult healthy subjects by 26%. For patients receiving these two drugs at the same time, it is recommended to conduct standard monitoring of tacrolimus blood concentrations and adjust the tacrolimus dose appropriately. Two clinical drug interaction studies in adult healthy subjects showed that rifampicin both induced and inhibited the elimination of caspofungin, and steady-state showed a net induction effect. In one of the studies, rifampicin and caspofungin were given together for 14 days starting on the same day. In the second study, rifampicin was given alone for 14 days to allow the induction effect to reach steady state, and then rifampicin and caspofungin were given together for another 14 days. When the induction effect of rifampicin reaches steady state, there is little change in the AUC or end-of-infusion concentration of caspofungin, but the trough concentration of caspofungin is reduced by approximately 30%. The inhibitory effect of rifampicin is manifested by a transient increase in caspofungin plasma concentrations on the first day (AUC increase of approximately 60%) when rifampicin and caspofungin are started on the same day. When caspofungin is added to ongoing rifampicin treatment, this inhibitory effect is not observed and caspofungin concentrations do not increase. In addition, the results of the pharmacokinetic studies in the adult population suggest that clinically significant decreases in caspofungin concentrations may occur when this product is used concomitantly with other inducers of drug elimination (efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine). The data currently available suggest that the inducible drug clearance mechanism in the elimination of caspofungin is more like an uptake transport process than metabolism. Therefore, when adult patients use this product simultaneously with drug elimination inducers such as efavirenz, nevirapine, rifampicin, dexamethasone, phenytoin or carbamazepine, a daily dose of 70 mg of this product should be considered (see Dosage and Administration). In pediatric patients, the regression analysis results of pharmacokinetic data showed that the combined use of dexamethasone and this product can cause a clinically significant decrease in the trough concentration of caspofungin. This result suggests that the decrease in pediatric patients under the action of inducers is similar to that of adults. In pediatric patients, when this product is used in combination with drug elimination inducers such as rifampicin, efavirenz, nevirapine, phenytoin, dexamethasone or carbamazepine, the daily dose of this product can be adjusted to 70 mg/m2 (the actual daily dose does not exceed 70 mg).