Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands
Caspofungin should be initiated by a physician experienced in the management of invasive fungal infections.
A single 70 mg loading dose should be administered on Day-1, followed by 50 mg daily thereafter. In patients weighing more than 80 kg, after the initial 70 mg loading dose, caspofungin 70 mg daily is recommended (see section 5.2). No dosage adjustment is necessary based on gender or race (see section 5.2).
In paediatric patients (12 months to 17 years of age), dosing should be based on the patient’s body surface area (see Instructions for Use in Paediatric Patients, Mosteller1 Formula). For all indications, a single 70-mg/m² loading dose (not to exceed an actual dose of 70 mg) should be administered on Day 1, followed by 50 mg/m² daily thereafter (not to exceed an actual dose of 70 mg daily). 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 an actual daily dose of 70 mg).
The safety and efficacy of caspofungin have not been sufficiently studied in clinical trials involving neonates and infants below 12 months of age. Caution is advised when treating this age group. Limited data suggest that caspofungin at 25 mg/m² daily in neonates and infants (less than 3 months of age) and 50 mg/m² daily in young children (3 to 11 months of age) can be considered (see section 5.2).
Duration of empirical therapy should be based on the patient’s clinical response. Therapy should be continued until up to 72 hours after resolution of neutropaenia (ANC>500). Patients found to have a fungal infection should be treated for a minimum of 14 days and treatment should continue for at least 7 days after both neutropaenia and clinical symptoms are resolved.
Duration of treatment of invasive candidiasis should be based upon the patient’s clinical and microbiological response. After signs and symptoms of invasive candidiasis have improved and cultures have become negative, a switch to oral antifungal therapy may be considered. In general, antifungal therapy should continue for at least 14 days after the last positive culture.
Duration of treatment of invasive aspergillosis is determined on a case by case basis and should be based upon the severity of the patient’s underlying disease, recovery from immunosuppression, and clinical response. In general, treatment should continue for at least 7 days after resolution of symptoms.
The safety information on treatment durations longer than 4 weeks is limited. However, available data suggest that caspofungin continues to be well tolerated with longer courses of therapy (up to 162 days in adult patients and up to 87 days in paediatric patients).
In elderly patients (65 years of age or more), the area under the curve (AUC) is increased by approximately 30 %. However, no systematic dosage adjustment is required. There is limited treatment experience in patients 65 years of age and older (see section 5.2).
No dosage adjustment is necessary based on renal impairment (see section 5.2).
For adult patients with mild hepaticimpairment (Child-Pugh score 5 to 6), no dosage adjustment is needed. For adult patients with moderate hepatic impairment (Child-Pugh score 7 to 9), caspofungin 35 mg daily is recommended based upon pharmacokinetic data. An initial 70 mg loading dose should be administered on Day-1. There is no clinical experience in adult patients with severe hepatic impairment (Child-Pugh score greater than 9) and in paediatric patients with any degree of hepatic impairment (see section 4.4).
Limited data suggest that an increase in the daily dose of caspofungin to 70 mg, following the 70 mg loading dose, should be considered when co-administering caspofungin in adult patients with certain inducers of metabolic enzymes (see section 4.5). When caspofungin is co-administered to paediatric patients (12 months to 17 years of age) with these same inducers of metabolic enzymes (see
section 4.5), a caspofungin dose of 70-mg/m² daily (not to exceed an actual daily dose of 70 mg) should be considered.
After reconstitution and dilution, the solution should be administered by slow intravenous infusion over approximately 1 hour. For reconstitution directions see section 6.6.
Both 70 mg and 50 mg vials are available. Caspofungin should be given as a single daily infusion.
Inadvertent administration of up to 400 mg of caspofungin in one day has been reported. These occurrences did not result in clinically important adverse reactions. Caspofungin is not dialysable.
Shelf life: 2 years.
Reconstituted concentrate: should be used immediately. Stability data have shown that the concentrate for solution for infusion can be stored for up to 24 hours when the vial is stored at 25°C or less and reconstituted with water for injection.
Diluted patient infusion solution: should be used immediately. Stability data have shown that the product can be used within 24 hours when stored at 25°C or less, or within 48 hours when the intravenous infusion bag (bottle) is stored refrigerated (2 to 8°C) and diluted with sodium chloride solution 9 mg/ml (0.9%), 4.5 mg/ml (0.45%), or 2.25 mg/ml (0.225%) for infusion, or lactated Ringer’s solution.
CANCIDAS contains no preservatives. From a microbiological point of view, the product should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution and dilution have taken place in controlled validated aseptic conditions.
Unopened vials: store in a refrigerator (2°C-8°C).
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
CANCIDAS 50 mg powder for concentrate for solution for infusion: 10 ml Type I glass vial with a grey butyl stopper and a plastic cap with a red aluminium band.
CANCIDAS 70 mg powder for concentrate for solution for infusion: 10 ml Type I glass vial with a grey butyl stopper and a plastic cap with an orange aluminium band.
Supplied in packs of 1 vial.
DO NOT USE ANY DILUENTS CONTAINING GLUCOSE, as CANCIDAS is not stable in diluents containing glucose. DO NOT MIX OR CO-INFUSE CANCIDAS WITH ANY OTHER MEDICINES, as there are no data available on the compatibility of CANCIDAS with other intravenous substances, additives, or medicinal products. Visually inspect the infusion solution for particulate matter or discolouration.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
To reconstitute the powder, bring the vial to room temperature and aseptically add 10.5 ml of water for injection. The concentrations of the reconstituted vials will be 5.2 mg/ml.
The white to off-white compact lyophilised powder will dissolve completely. Mix gently until a clear solution is obtained. Reconstituted solutions should be visually inspected for particulate matter or discolouration. This reconstituted solution may be stored for up to 24 hours at or below 25°C.
Diluents for the final solution for infusion are: sodium chloride solution for injection, or lactated Ringer’s solution. The solution for infusion is prepared by aseptically adding the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml infusion bag or bottle. Reduced volume infusions in 100 ml may be used, when medically necessary, for 50 mg or 35 mg daily doses. Do not use if the solution is cloudy or has precipitated.
PREPARATION OF THE SOLUTION FOR INFUSION IN ADULTS:
| DOSE* | Volume of reconstituted CANCIDAS for transfer to intravenous bag or bottle | Standard preparation (reconstituted CANCIDAS added to 250 ml) final concentration | Reduced volume infusion (reconstituted CANCIDAS added to 100 ml) final concentration |
|---|---|---|---|
| 50 mg | 10 ml | 0.20 mg/ml | - |
| 50 mg at reduced volume | 10 ml | - | 0.47 mg/ml |
| 35 mg for moderate hepatic impairment (from one 50 mg vial) | 7 ml | 0.14 mg/ml | - |
| 35 mg for moderate hepatic impairment (from one 50 mg vial) at reduced volume | 7 ml | - | 0.34 mg/ml |
* 10.5 ml should be used for reconstitution of all vials.
Before preparation of infusion, calculate the body surface area (BSA) of the patient using the following formula: (Mosteller Formula)
Preparation of the 70 mg/m² infusion for paediatric patients >3 months of age (using a 50-mg vial):
Preparation of the 50 mg/m² infusion for paediatric patients >3 months of age (using a 50-mg vial):
Preparation notes:
a. The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.
b. Visually inspect the reconstituted solution for particulate matter or discolouration during reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated.
c. CANCIDAS is formulated to provide the full labeled vial dose (50 mg) when 10 ml is withdrawn from the vial.
To reconstitute the powder bring the vial to room temperature and aseptically add 10.5 ml of water for injection. The concentrations of the reconstituted vials will be: 7.2 mg/ml.
The white to off-white compact lyophilised powder will dissolve completely. Mix gently until a clear solution is obtained. Reconstituted solutions should be visually inspected for particulate matter or discolouration. This reconstituted solution may be stored for up to 24 hours at or below 25°C.
Diluents for the final solution for infusion are: sodium chloride solution for injection, or lactated Ringer’s solution. The solution for infusion is prepared by aseptically adding the appropriate amount of reconstituted concentrate (as shown in the table below) to a 250 ml infusion bag or bottle. Reduced volume infusions in 100 ml may be used, when medically necessary, for 50 mg or 35 mg daily doses. Do not use if the solution is cloudy or has precipitated.
PREPARATION OF THE SOLUTION FOR INFUSION IN ADULTS:
| DOSE* | Volume of reconstituted CANCIDAS for transfer to intravenous bag or bottle | Standard preparation (reconstituted CANCIDAS added to 250 ml) final concentration | Reduced volume infusion (reconstituted CANCIDAS added to 100 ml) final concentration |
|---|---|---|---|
| 70 mg | 10 ml | 0.28 mg/ml | Not Recommended |
| 70 mg (from two 50 mg vials)** | 14 ml | 0.28 mg/ml | Not Recommended |
| 35 mg for moderate hepatic impairment (from one 70 mg vial) | 5 ml | 0.14 mg/ml | 0.34 mg/ml |
* 10.5 ml should be used for reconstitution of all vials.
** If 70 mg vial is not available, the 70 mg dose can be prepared from two 50 mg vials.
Before preparation of infusion, calculate the body surface area (BSA) of the patient using the following formula: (Mosteller Formula)
Preparation of the 70 mg/m² infusion for paediatric patients >3 months of age (using a 70-mg vial):
Preparation of the 50 mg/m² infusion for paediatric patients >3 months of age (using a 70-mg vial):
Preparation notes:
a. The white to off-white cake will dissolve completely. Mix gently until a clear solution is obtained.
b. Visually inspect the reconstituted solution for particulate matter or discolouration during reconstitution and prior to infusion. Do not use if the solution is cloudy or has precipitated.
c. CANCIDAS is formulated to provide the full labelled vial dose (70 mg) when 10 ml is withdrawn from the vial.
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