Carmustine 100 mg/vial

INDICATIONS

Carmustine 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.

PHARMACOLOGY

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.

DOSAGE & ADMINISTRATION

Recommended Dosage: As a single agent, 150 to 200 mg/m2 carmustine intravenously every 6 weeks as a single dose or divided into daily injections such as 75 to 100 mg/m2 on 2 successive days. Adjust dose for combination therapy or in patients with reduced bone marrow reserveAdminister reconstituted solution only as a slow intravenous infusion over at least 2 hours.

INTERACTION

Effects of Other Drugs on Carmustine-

Cimetidine: Greater myelosuppression (e.g., leukopenia and neutropenia) has been reported when oral cimetidine has been coadministered with carmustine. Consider alternative drugs to cimetidine.
Phenobarbital: Phenobarbital induces the metabolism of carmustine and may compromise antitumor activity of Carmustine. Consider alternative drugs to phenobarbital.

Effects of Carmustine on Other Drugs-

Phenytoin: Carmustine when coadministered with phenytoin may reduce phenytoin serum concentrations. Consider alternative drugs to phenytoin.

SIDE EFFECTS

Most common adverse reactions (>1%) are nausea, vomiting, renal toxicity, pneumonitis, pulmonary toxicity, myelosuppression

PREGNANCY & LACTATION

Pregnancy: Carmustine injection can cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings in animals. Limited available data with Carmustine injection use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Carmustine was embryotoxic in rats and rabbits and teratogenic in rats (thoracoabdominal closure, neural tube, and eye defects and malformations of the skeletal system of the fetus) when given in doses lower than the maximum cumulative human dose based on body surface area. Consider the benefits and risks of Carmustine for the mother and possible risks to the fetus when prescribing Carmustine injection to a pregnant woman. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Lactation: There is no information regarding the presence of carmustine in human milk, the effects on the breastfed infant, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse events (e.g., carcinogenicity and myelosuppression) in nursing infants, nursing should be discontinued while taking Carmustine.

PRECAUTIONS & WARNINGS

Administration Reactions: Extravasation may occur; monitor infusion site closely during administration.Carcinogenicity: Potentially carcinogenic to humans. Monitor patient periodically for such signs and apprise the patient of the symptoms for which they need to seek medical help.Ocular Toxicity: Has occurred when administered via unapproved intraarterial intracarotid route.Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to avoid pregnancy.

USE IN SPECIAL POPULATIONS

Pediatric Use: Safety and effectiveness in children have not been established. Delayed onset pulmonary fibrosis occurring up to 17 years after treatment has been reported in a long-term study of patients who received carmustine in childhood and early adolescence (1-16 years). Eight out of the 17 patients (47%) who survived childhood brain tumors, including all the 5 patients initially treated at less than 5 years of age, died of pulmonary fibrosis.Geriatric Use: Clinical studies of carmustine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Carmustine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

THERAPEUTIC CLASS

Cytotoxic Chemotherapy

STORAGE CONDITIONS

Store product and diluent in a refrigerator (2°-8°C). Store the unopened vial of the dry drug in a refrigerator (2°-8°C). Store the diluent vials in a refrigerator (2°-8°C). The recommended storage of unopened Carmustine vials provides a stable product for up to 3 years.