Overview
11 DESCRIPTION The active ingredient in carmustine for injection, USP is a nitrosourea with the chemical name 1,3-bis(2-chloroethyl)-1-nitrosourea and a molecular weight of 214.06. The drug product is supplied as sterile lyophilized pale yellow flakes or a congealed mass, and it is highly soluble in alcohol and lipids, and poorly soluble in water.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of carmustine is not fully understood. While carmustine alkylates DNA and RNA, it is not cross-resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins. The metabolites may contribute to antitumor activity and toxicities of carmustine. 12.2 Pharmacodynamics The exposure-response relationship for efficacy or safety is unknown. 12.3 Pharmacokinetics Distribution Carmustine crosses the blood-brain barrier. Levels of radioactivity in the CSF are greater than or equal to 50% of those measured concurrently in plasma.
Indications
- 1 INDICATIONS AND USAGE Carmustine for injection, USP 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.
Common Doses
- 200 mg
- 100 mg
- 10 mL
- 3 mL
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage: As a single agent, 150 to 200 mg/m 2 carmustine for injection, USP intravenously every 6 weeks as a single dose or divided into daily injections such as 75 to 100 mg/m 2 on 2 successive days. Adjust dose for combination therapy or in patients with reduced bone marrow reserve (2.1) Administer reconstituted solution only as a slow intravenous infusion over at least 2 hours. (2.2) 2.1 Dosage The recommended dose of carmustine for injection, USP as a single agent in previously untreated patients is 150 to 200 mg/m 2 intravenously every 6 weeks.
Black Box Warning
WARNING: MYELOSUPPRESSION and PULMONARY TOXICITY Myelosuppression Carmustine for injection, USP 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, USP until blood counts recover.
Contraindications
- 4 CONTRAINDICATIONS Carmustine for injection, USP is contraindicated in patients with previous hypersensitivity to carmustine for injection, USP or its components. Hypersensitivity
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Pulmonary toxicity [see Warnings and Precautions (5.2) ] Administration Reactions [see Warnings and Precautions (5.3) ] Carcinogenicity [see Warnings and Precautions (5.4) ] Ocular Toxicity [see Warnings and Precautions (5.5) ] The following adverse reactions associated with the use of carmustine for injection, USP were identified in clinical studies or postmarketing reports.
Interactions
- 7 DRUG INTERACTIONS Cimetidine: Increased myelosuppression with concomitant use. (7.1) Phenobarbital: Induces carmustine metabolism, reducing exposure. May lead to reduced efficacy. (7.1) Phenytoin: Carmustine for injection, USP may reduce the efficacy of phenytoin. (7.2) 7.1 Effects of other drugs on carmustine for injection, USP Cimetidine: Greater myelosuppression (e.g., leukopenia and neutropenia) has been reported when oral cimetidine has been coadministered with carmustine. Consider alternative drugs to cimetidine.