Caspofungin acetate (Cancidas ®)

Mechanism of Action
Caspofungin acetate, an echinocandin, is an antifungal agent.
Caspofungin acetate, the active ingredient of CANCIDAS, inhibits the synthesis of ß (1,3)-D-glucan, an essential component of the cell wall of susceptible Aspergillus species and Candida species. ß (1,3)-D-glucan is not present in mammalian cells. Caspofungin has shown activity against Candida species and in regions of active cell growth of the hyphae of Aspergillus fumigatus.

Activity in vitro
Caspofungin has been shown to be active both in vitro and in clinical infections against most strains of the following microorganisms:

Aspergillus fumigatus

Aspergillus flavus

Aspergillus terreus

Candida albicans

Candida glabrata

Candida guilliermondii

Candida krusei

Candida parapsilosis

Candida tropicalis

INDICATIONS AND USAGE
CANCIDAS is indicated in adults and pediatric patients (3 months and older) for:

1.1 Empirical therapy for presumed fungal infections in febrile, neutropenic patients

1.2 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.

1.3 Treatment of Esophageal Candidiasis [see package insert for Clinical Studies (14.3)]

1.4 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.

2.1 Instructions for Use in All Patients
CANCIDAS should be administered by slow intravenous infusion (IV) over approximately 1 hour. CANCIDAS should not be administered by IV bolus 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.

2.2 Recommended Dosing in Adult Patients [>=18 years of age]
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 [see package insert Clinical Studies (14.2)]:
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 [see see package insert Clinical Studies (14.3)]. 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.

2.3 Recommended Dosing in Pediatric Patients [3 months to 17 years of age]
For all indications, a single 70-mg/m2 loading dose should be administered on Day 1, followed by 50 mg/m2 daily thereafter. The maximum loading dose and the daily maintenance dose should not exceed 70 mg, regardless of the patient's calculated dose. Dosing in pediatric patients (3 months to 17 years of age) should be based on the patient’s Body Surface Area (BSA) as calculated by the following formula (Mosteller Formula)
       Equation:  BSA (m²) = SQR RT ( [Height(cm) x Weight(kg) ]/ 3600 )

Following calculation of the patient’s BSA, the loading dose in milligrams should be calculated as BSA (m2) X 70 mg/m2. The maintenance dose in milligrams should be calculated as BSA (m2) X 50 mg/m2.

Duration of treatment should be individualized to the indication, as described for each indication in adults [see Dosage and Administration (2.2)]. If the 50-mg/m2 daily dose is well tolerated but does not provide an adequate clinical response, the daily dose can be increased to 70 mg/m2 daily (not to exceed 70 mg). Although an increase in efficacy with 70 mg/m2 daily has not been demonstrated, limited safety data suggest that an increase in dose to 70 mg/m2 daily is well tolerated.

2.4 Patients with Hepatic Insufficiency
Adult patients with mild hepatic insufficiency (Child-Pugh score 5 to 6) do not need a dosage adjustment. For adult patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), CANCIDAS 35 mg daily is recommended based upon pharmacokinetic data [see Clinical Pharmacology (12.3)]. However, where recommended, a 70-mg loading dose should still be administered on Day 1. There is no clinical experience in adult patients with severe hepatic insufficiency (Child-Pugh score >9) and in pediatric patients with any degree of hepatic insufficiency.

2.5 Patients Receiving Concomitant Inducers of Drug Clearance
Adult patients on rifampin should receive 70 mg of CANCIDAS daily. Adult patients on nevirapine, efavirenz, carbamazepine, dexamethasone, or phenytoin may require an increase in dose to 70 mg of CANCIDAS daily.

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 70 mg) should be considered [see package insert - Drug Interactions].