Caspofungin

Patients with Renal Impairment No dosage adjustment is necessary for patients with renal impairment. Caspofungin is not dialyzable; thus, supplementary dosing is not required following hemodialysis [see Clinical Pharmacology].

Dosage Adjustments in Patients with Hepatic Impairment Adult patients with mild hepatic impairment (Child-Pugh score 5 to 6) do not need a dosage adjustment. For adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9), caspofungin acetate for injection 35 mg once daily is recommended based upon pharmacokinetic data [see Clinical Pharmacology] with a 70 mg loading dose administered on Day 1 where appropriate.

There is no clinical experience in adult patients with severe hepatic impairment (Child-Pugh score greater than 9) and in pediatric patients with any degree of hepatic impairment.

Dosage Adjustments in Patients Receiving Concomitant Inducers of Hepatic CYP Enzymes Adult Patients : Adult patients on rifampin should receive 70 mg of caspofungin acetate for injection once daily. When caspofungin acetate for injection is co-administered to adult patients with other inducers of hepatic CYP enzymes such as nevirapine, efavirenz, carbamazepine, dexamethasone, or phenytoin, administration of a daily dose of 70 mg of caspofungin acetate for injection should be considered [see Drug Interactions].

Pediatric Patients : Pediatric patients on rifampin should receive 70 mg/m 2 of caspofungin acetate for injection daily (not to exceed an actual daily dose of 70 mg). When caspofungin acetate for injection is co-administered to pediatric patients with other inducers of hepatic CYP enzymes, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a caspofungin acetate for injection dose of 70 mg/m 2 once daily (not to exceed 70 mg) should be considered [see Drug Interactions].

Important Administration Instructions for Use in All Patients Administer caspofungin acetate for injection by slow intravenous (IV) infusion over approximately 1 hour. Do not administer caspofungin acetate for injection by IV bolus administration.

Preparation for Administration Reconstitution of Caspofungin for Intravenous Infusion Equilibrate the refrigerated vial of caspofungin acetate for injection to room temperature. Aseptically add 10.8 mL of 0.9% Sodium Chloride Injection, Sterile Water for Injection, Bacteriostatic Water for Injection with methylparaben and propylparaben, or Bacteriostatic Water for Injection with 0.9% benzyl alcohol to the vial.

Each vial of caspofungin acetate for injection contains an intentional overfill of caspofungin acetate for injection. Thus, the volume of diluent to be added to each vial and the drug concentration of the resulting solution is listed in Table 1 below. [See table below.] The white to off-white cake will dissolve completely.

Mix gently until a clear solution is obtained. Visually inspect the reconstituted solution for particulate matter or discoloration during reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated. The reconstituted solution of caspofungin acetate for injection in the vial may be stored for up to one hour at ≤25°C (≤77°F) prior to the preparation of the infusion solution in the intravenous bag or bottle.

Caspofungin acetate for injection vials are for single-dose only. Discard unused portion. Dilution of the Reconstituted Solution in the Intravenous Bag for Infusion Aseptically transfer the appropriate volume (mL) of reconstituted caspofungin acetate for injection to an intravenous (IV) bag (or bottle) containing 250 mL of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection.

Alternatively, the volume (mL) of reconstituted caspofungin acetate for injection can be added to a reduced volume of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection, not to exceed a final concentration of 0.5 mg per mL. This diluted infusion solution in the intravenous bag or bottle must be used within 24 hours if stored at ≤25°C (≤77°F) or within 48 hours if stored refrigerated at 2 to 8°C (36 to 46°F).

Important Reconstitution and Dilution Instructions for Pediatric Patients 3 Months of Age and Older Follow the reconstitution procedures described above using either the 70 mg or 50 mg vial to create the reconstituted solution [see Dosage and Administration]. From the reconstituted solution in the vial, remove the volume of drug equal to the calculated loading dose or calculated maintenance dose based on a concentration of 7 mg per mL (if reconstituted from the 70 mg vial) or a concentration of 5 mg per mL (if reconstituted from the 50 mg vial).

The choice of vial should be based on total milligram dose of drug to be administered to the pediatric patient. To help ensure accurate dosing, it is recommended for pediatric doses less than 50 mg that 50 mg vials (with a concentration of 5 mg per mL) be used if available. The 70 mg vial should be reserved for pediatric patients requiring doses greater than 50 mg.

The maximum loading dose and the daily maintenance dose should not exceed 70 mg, regardless of the patient's calculated dose .

Drug Incompatibilities Do not mix or co-infuse caspofungin acetate for injection with other medications, as there are no data available on the compatibility of caspofungin acetate for injection with other intravenous substances, additives, or medications. Do not use diluents containing dextrose (α-D-glucose), as caspofungin acetate for injection is not stable in diluents containing dextrose.