Posology : מינונים

2    DOSAGE AND ADMINISTRATION

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

2.2 Recommended Dosage in Adult Patients [≥18 years of age]
The dosage and duration of CANCIDAS treatment for each indication are as follows: Empirical Therapy for Presumed Fungal Infections in Febrile Neutropenic Patients
Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily thereafter. Duration of treatment should be based on the patient’s clinical response. Continue empirical therapy until resolution of neutropenia. In general, treat patients found to have a fungal infection for a minimum of 14 days after the last positive culture and continue treatment 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.
Candidemia and Other Candida Infections
Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily thereafter. Duration of treatment should be dictated by the patient’s clinical and microbiological response. In general, continue antifungal therapy for at least 14 days after the last positive culture. Patients with neutropenia who remain persistently neutropenic may warrant a longer course of therapy pending resolution of the neutropenia.
Esophageal Candidiasis
The dose is 50 mg once daily for 7 to 14 days after symptom resolution. A 70- mg loading dose has not been studied for this indication. Because of the risk of relapse of oropharyngeal candidiasis in patients with HIV infections, suppressive oral therapy could be considered [see Clinical Studies (14.3)].
Invasive Aspergillosis
Administer a single 70-mg loading dose on Day 1, followed by 50 mg once daily thereafter. Duration of treatment should be based upon the severity of the patient’s underlying disease, recovery from immunosuppression, and clinical response.

2.3 Recommended Dosing in Pediatric Patients [3 months to 17 years of age]
For all indications, administer a single 70 mg/m2 loading dose on Day 1, followed by 50 mg/m2 once 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 Mosteller Formula [see References (15)]:



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).

2.4 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 35 mg once daily is recommended based upon pharmacokinetic data [see Clinical Pharmacology (12.3)] 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.

2.5 Dosage Adjustments in Patients Receiving Concomitant Inducers of
Hepatic CYP Enzymes
Adult Patients:
Adult patients on rifampin should receive 70 mg of caspofungin once daily.
When caspofungin 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 should be considered [see Drug Interactions (7)].
Pediatric Patients:

Pediatric patients on rifampin should receive 70 mg/m2 of caspofungin daily (not to exceed an actual daily dose of 70 mg). When caspofungin is co-administered to pediatric patients with other inducers of hepatic CYP enzymes, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a caspofungin dose of 70 mg/m2 once daily (not to exceed 70 mg) should be considered [see Drug Interactions (7)].

2.6 Preparation for Administration

Reconstitution of CASPOVIDAE for Intravenous Infusion
A. Equilibrate the refrigerated vial of CASPOVIDAE to room temperature.
B. Aseptically add 10.5 mL of Sterile Water for Injection.
C. Each vial of CASPOVIDAE contains an intentional overfill of
CASPOVIDAE. Thus, the drug concentration of the resulting solution is listed in Table 1 below.

Table 1: Information for Preparation of CASPOVIDAE
CASPOVIDAE     Total Drug Content     Reconstitution Volume   Resulting Concentration vial       (including overfill)        to be added        following Reconstitution 50 mg            55.5 mg                 10.5 mL                  5.2 mg/mL 70 mg            77.7 mg                 10.5 mL                  7.2 mg/mL 
D. 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.

E. The reconstituted solution may be stored for up to 24 hours at ≤25°C.

F. CASPOVIDAE vials are for single use only; the remaining solution should be discarded.

Dilution of the Reconstituted Solution in the Intravenous Bag for Infusion A. Aseptically transfer the appropriate volume (mL) of reconstituted
CASPOVIDAE to an IV bag (or bottle) containing 250 mL of 0.9%, 0.45%, or 0.225% Sodium Chloride Injection or Lactated Ringers Injection.
B. Alternatively, the volume (mL) of reconstituted CASPOVIDAE 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/mL.
C This infusion solution must be used within 24 hours if stored at ≤ 25°C or within 48 hours if stored refrigerated at 2°C to 8°C.

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 (2.3)]. 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/mL (if reconstituted from the 70-mg vial) or a concentration of 5 mg/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/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.

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