Amneal Pharmaceuticals LLC
Carmustine for injection causes suppression of marrow function (including thrombocytopenia and leukopenia), which may contribute to bleeding and overwhelming infections [see Warnings and Precautions (5.1) and Adverse Reactions (6)]. Monitor blood counts weekly for at least 6 weeks after each dose. Adjust dosage based on nadir blood counts from the prior dose [see Dosage and Administration (2.1)]. Do not administer a repeat course of carmustine for injection until blood counts recover.
C armustine for injection causes dose-related pulmonary toxicity. Patients receiving greater than 1,400 mg/m2 cumulative dose are at significantly higher risk than those receiving less. Delayed pulmonary toxicity can occur years after treatment, and can result in death, particularly in patients treated in childhood [see Adverse Reactions (6) and Use in Specific Populations (8.4)].
Carmustine for injection is indicated as palliative therapy as a single agent or in established combination therapy in the following:
– Brain tumors glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors.
– Multiple myeloma in combination with prednisone.
– Relapsed or refractory Hodgkin’s lymphoma in combination with other approved drugs.
– Relapsed or refractory Non-Hodgkin’s lymphomas in combination with other approved drugs.
The recommended dose of carmustine for injection as a single agent in previously untreated patients is 150 mg/m2 to 200 mg/m2 intravenously every 6 weeks. Administer as a single-dose or divided into daily injections such as 75 mg/m2 to 100 mg/m2 on two successive days. Lower the dose when carmustine for injection is used with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted. Administer carmustine for injection, for the duration according to the established regimen. Premedicate each dose with anti-emetics.
Adjust doses subsequent to the initial dose according to the hematologic response of the patient to the preceding dose. The following schedule is suggested as a guide to dosage adjustment:
Nadir After Prior Dose
Percentage of Prior Dose to be Given
3,000 to 3,999
75,000 to 99,999
2,000 to 2,999
25,000 to 74,999
The hematologic toxicity can be delayed and cumulative. Monitor blood counts weekly. Do not administer a repeat course of carmustine for injection until circulating blood elements have returned to acceptable levels (platelets above 100 Gi/L, leukocytes above 4 Gi/L and absolute neutrophil count above 1 Gi/L). The usual interval between courses is 6 weeks.
Evaluate renal function prior to administration and periodically during treatment. For patients with compromised renal function, monitor for toxicity more frequently. Discontinue carmustine for injection if the creatinine clearance is less than 10 mL/min. Do not administer carmustine for injection to patients with compromised renal function. Monitor transaminases and bilirubin periodically during treatment [see Adverse Reactions (6)].
- Dissolve carmustine for injection with 3 mL of the supplied sterile diluent (Dehydrated Alcohol Injection, USP).
- Aseptically add 27 mL Sterile Water for Injection, USP.
- Each mL of resulting solution contains 3.3 mg of carmustine for injection in 10% ethanol. Such solutions should be protected from light.
- The reconstituted solution is a clear, colorless to yellowish solution.
- Once reconstituted, the solution must be further diluted with Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.
- Examine reconstituted vials for crystal formation prior to use. If crystals are observed, they may be re-dissolved by warming the vial to room temperature with agitation.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- After reconstitution as recommended, carmustine for injection is stable for 24 hours under refrigeration 2° to 8°C, (36° to 46°F) in glass container. Examine reconstituted vials for crystal formation prior to use. If crystals are observed, they may be redissolved by warming the vial to room temperature with agitation.
- Vials reconstituted as directed and further diluted with 500 mL Sodium Chloride Injection, USP or 5% Dextrose Injection, USP, in glass or polypropylene containers to a concentration of 0.2 mg/mL, should be stored at room temperature, protected from light and utilized within 8 hours. These solutions are also stable 24 hours under refrigeration 2° to 8°C, (36° to 46°F) and an additional 6 hours at room temperature protected from light.
- Administer reconstituted solution by slow intravenous infusion over at least two hours. Administration of carmustine for injection over a period of less than two hours can lead to pain and burning at the site of injection. Monitor the injected area during the administration. The rate of administration of the intravenous infusion should not be more than 1.66 mg/m2 /min.
- See Section 16.2 for important instructions on the storage and handling of the injection. Carmustine for injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
- The lyophilized dosage formulation contains no preservatives and is not intended for use as a multiple dose vial.
Accidental contact of reconstituted carmustine for injection with the skin has caused transient hyperpigmentation of the affected areas. Wear impervious gloves to minimize the risk of dermal exposure impervious gloves when handling vials containing carmustine for injection. Immediately wash the skin or mucosa thoroughly with soap and water if carmustine for injection lyophilized material or solution contacts the skin or mucosa1.
Carmustine for Injection, USP is a lyophilized pale yellow flakes or congealed mass containing 100 mg carmustine, USP in an amber colored glass vial for single-dose use. It is supplied with 3 mL of dehydrated alcohol injection, USP (sterile diluent for carmustine for injection) for reconstitution.
Carmustine for injection is contraindicated in patients with previous hypersensitivity to carmustine for injection or its components.
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