Caspofungin Acetate - Cancidas ®

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Stability / Miscellaneous

Storage/Stability ----

Vials
The lyophilized vials should be stored refrigerated at 2° to 8°C (36° to 46°F).

Reconstituted Concentrate
Reconstituted CANCIDAS may be stored at ≤25°C (≤77°F) for one hour prior to the preparation of the patient infusion solution.

Diluted Product
The final patient infusion solution in the IV bag or bottle can be stored at ≤25°C (≤77°F) for 24 hours or at 2 to 8°C (36 to 46°F) for 48 hours.

Label: Refrigerate.

Indications:
* 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. CANCIDAS has not been studied in endocarditis, osteomyelitis, and meningitis due to Candida.
* Treatment of Esophageal Candidiasis.
* 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). CANCIDAS has not been studied as initial therapy for invasive aspergillosis.

DOSAGE AND ADMINISTRATION
Do not mix or co-infuse CANCIDAS with other medications, as there are no data available on the compatibility of CANCIDAS with other intravenous substances, additives, or medications. DO NOT USE DILUENTS CONTAINING DEXTROSE (a-D-GLUCOSE), as CANCIDAS is not stable in diluents containing dextrose. CANCIDAS should be administered by slow IV infusion over approximately 1 hour.

Empirical Therapy
A single 70-mg loading dose should be administered on Day 1, followed by 50 mg daily thereafter. Duration of treatment should be based on the patient's clinical response. Empirical therapy should be continued until resolution of neutropenia. Patients found to have a fungal infection should be treated for a minimum of 14 days; treatment should continue for at least 7 days after both neutropenia and clinical symptoms are resolved. If the 50-mg dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70 mg. Although an increase in efficacy with 70 mg daily has not been demonstrated, limited safety data suggest that an increase in dose to 70 mg daily is well tolerated.

Candidemia and other Candida infections
A single 70-mg loading dose should be administered on Day 1, followed by 50 mg daily thereafter. Duration of treatment should be dictated by the patient's clinical and microbiological response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. Patients who remain persistently neutropenic may warrant a longer course of therapy pending resolution of the neutropenia.

Esophageal Candidiasis
The dose should be 50 mg daily. Because of the risk of relapse of oropharyngeal candidiasis in patients with HIV infections, suppressive oral therapy could be considered. A 70-mg loading dose has not been studied with this indication.

Invasive Aspergillosis
A single 70-mg loading dose should be administered on Day 1, followed by 50 mg daily thereafter. Duration of treatment should be based upon the severity of the patient's underlying disease, recovery from immunosuppression, and clinical response. The efficacy of a 70-mg dose regimen in patients who are not clinically responding to the 50-mg daily dose is not known. Limited safety data suggest that an increase in dose to 70 mg daily is well tolerated. The safety and efficacy of doses above 70 mg have not been adequately studied.

Hepatic Insufficiency
Patients with mild hepatic insufficiency (Child-Pugh score 5 to 6) do not need a dosage adjustment. For patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), CANCIDAS 35 mg daily is recommended. However, where recommended, a 70-mg loading dose should still be administered on Day 1. There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9).

Preparation of CANCIDAS for use:
Do not mix or co-infuse CANCIDAS with other medications, as there are no data available on the compatibility of CANCIDAS with other intravenous substances, additives, or medications. DO NOT USE DILUENTS CONTAINING DEXTROSE (a-D-GLUCOSE), as CANCIDAS is not stable in diluents containing dextrose.

Preparation of the 70-mg infusion
1. Equilibrate the refrigerated vial of CANCIDAS to room temperature.
2. 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. The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained. This reconstituted solution may be stored for up to one hour at ≤25°C (≤77°F). 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.
3. Aseptically transfer 10 mL of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 mL 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer's Injection. This infusion solution 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). (If a 70-mg vial is unavailable, see below: Alternative Infusion Preparation Methods, Preparation of 70-mg dose from two 50-mg vials.)

Preparation of the daily 50-mg infusion
1. Equilibrate the refrigerated vial of CANCIDAS to room temperature.
2. 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.5 This reconstituted solution may be stored for up to one hour at ≤25°C (≤77°F).6
3. Aseptically transfer 10 mL of reconstituted CANCIDAS to an IV bag (or bottle) containing 250 mL 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer's Injection. This infusion solution 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). (If a reduced infusion volume is medically necessary, see below: Alternative Infusion Preparation Methods, Preparation of 50-mg daily doses at reduced volume.)

Alternative Infusion Preparation Methods
Preparation of 70-mg dose from two 50-mg vials
Reconstitute two 50-mg vials with 10.8 mL of diluent each (see Preparation of the daily 50-mg infusion). Aseptically transfer a total of 14 mL of the reconstituted CANCIDAS from the two vials to 250 mL of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer's Injection.

Preparation of 50-mg daily doses at reduced volume
When medically necessary, the 50-mg daily doses can be prepared by adding 10 mL of reconstituted CANCIDAS to 100 mL of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer's Injection (see Preparation of the daily 50-mg infusion).

Preparation of a 35-mg daily dose for patients with moderate Hepatic Insufficiency
Reconstitute one 50-mg vial (see above: Preparation of the daily 50-mg infusion). Aseptically transfer 7 mL of the reconstituted CANCIDAS from the vial to 250 mL or, if medically necessary, to 100 mL of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection, or Lactated Ringer's Injection.

CANCIDAS Concentrations

HOW SUPPLIED
No. 3822 - CANCIDAS 50 mg is a white to off-white powder/cake for infusion in a vial with a red aluminum band and a plastic cap.
NDC 0006-3822-10 supplied as one single-use vial.
No. 3823 - CANCIDAS 70 mg is a white to off-white powder/cake for infusion in a vial with a yellow/orange aluminum band and a plastic cap.
NDC 0006-3823-10 supplied as one single-use vial.

Distributed by:
Merck & Co., Inc., Whitehouse Station, NJ 08889, USA
July 2007