CARMUSTINE- carmustine kit

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CARMUSTINE (UNII: U68WG3173Y) (CARMUSTINE - UNII:U68WG3173Y)

Available from:

Zydus Pharmaceuticals USA Inc.

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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. Carmustine for injection, USP is contraindicated in patients with previous hypersensitivity to carmustine for injection, USP or its components. Risk Summary Carmustine for injection, USP can cause fetal harm when administered to a pregnant woman based on the mechanism of action [see Clinical Pharmacology (12.1)] and findings in animals [see Data ]. Limited available data with carmustine for injection, USP 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 injection, USP for the mother and possible risks to the fetus when prescribing carmustine for injection, USP 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. Data Animal Data Intraperitoneal (IP) administration of carmustine to pregnant rats 14 days prior to mating and during the period of organogenesis at cumulative doses ≥ 26 mg/kg (158 mg/ m2 ), approximately 0.1 times the maximum cumulative human dose of 1400 mg/m2 , resulted in pre-implantation loss, increased resorptions (including completely resorbed litters), and reduced the number of live births in the presence of maternal toxicity. Carmustine administered IP to pregnant rats during the period of organogenesis at cumulative doses ≥ 4 mg/kg (24 mg/m2 ), approximately 0.02 times the maximum cumulative human dose based on a mg/m2 basis, resulted in reduced fetal weight and various malformations, which included thoracoabdominal closure defects, neural tube defects, and eye defects, including microphthalmia/anophthalmia, and skeletal anomalies in the skull, sternebra, vertebrae and ribs, and reduced skeletal ossification) in the presence of maternal toxicity. Embryo-fetal death was observed at cumulative doses ≥ 8 mg/kg (48 mg/m2 ), approximately 0.03 times the maximum cumulative human dose on a mg/ m2 basis. Intravenous (IV) administration of carmustine to rats at a cumulative dose of 50 mg/kg (300 mg/ m2 ), approximately 0.2 times the maximum cumulative human dose on a mg/m2 basis, during the last quarter of pregnancy resulted in the death of offspring within 4 months. Carmustine administered IV to rabbits during the period of organogenesis resulted in spontaneous abortions in mothers and growth defects in the fetus, mainly at cumulative doses ≥ 13 mg/kg (156 mg/ m2 ), approximately 0.1 times the maximum cumulative human dose on a mg/ m2 basis. Risk Summary 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 for injection, USP. Contraception Advise female patients to avoid pregnancy during treatment with carmustine for injection, USP because of the risk of fetal harm [see Use in Specific Populations (8.1)] . Advise female patients of reproductive potential to use highly effective contraception during and for up to six months after completion of treatment. Advise males with female sexual partners of reproductive potential to use effective contraception during carmustine for injection, USP treatment and for at least three months after the final dose of carmustine for injection, USP [see Nonclinical Toxicology (13.1)]. Infertility Based on nonclinical findings, male fertility may be compromised by treatment with carmustine for injection, USP [see Nonclinical Toxicology (13.1)]. 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 for injection, USP 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. [see Adverse Reactions (6.1)]. Clinical studies of carmustine for injection, USP 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 for injection, USP 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.

Product summary:

Carmustine for injection, USP. Each package includes a vial containing 100 mg carmustine and a vial containing 3 mL sterile diluent. NDC 70710-1525-9 Store product and diluent in a refrigerator (2°-8°C, 36°-46°F). Stability Store the unopened vial of the dry drug in a refrigerator (2°-8°C, 36°-46°F). Store the diluent vials in a refrigerator (2°-8°C, 36°-46°F). The recommended storage of unopened carmustine for injection, USP vials provides a stable product for up to 3 Years. Compatibility/ Incompatibility with Containers The intravenous solution is unstable in polyvinyl chloride container. DO NOT USE PVC Containers . Administer carmustine for injection, USP solution from the glass bottles or polypropylene container only. Ensure the polypropylene containers used are PVC free and DEHP free. Important Note Carmustine for injection, USP has a low melting point (30.5°-32.0°C or 86.9°-89.6°F). Exposure of the drug to this temperature or above will cause the drug to liquefy and appear as an oil film on the vials. This is a sign of decomposition and vials should be discarded. If there is a question of adequate refrigeration upon receipt of this product, immediately inspect the vial in each individual carton. Hold the vial to a bright light for inspection. The carmustine for injection, USP will appear as a very small amount of dry flakes or dry congealed mass. If this is evident, the carmustine for injection, USP is suitable for use and should be refrigerated immediately.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

CARMUSTINE - CARMUSTINE
ZYDUS PHARMACEUTICALS USA INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CARMUSTINE FOR INJECTION,
USP SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
CARMUSTINE FOR INJECTION,
USP. CARMUSTINE FOR INJECTION, USP, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL:1977
WARNING: MYELOSUPPRESSION AND PULMONARY TOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
SUPPRESSION OF MARROW FUNCTION, NOTABLY THROMBOCYTOPENIA AND
LEUKOPENIA, IS THE
MOST COMMON AND SEVERE OF THE TOXIC EFFECTS OF CARMUSTINE FOR
INJECTION, USP.
MONITOR BLOOD COUNTS. (5, 6).
PULMONARY TOXICITY FROM CARMUSTINE FOR INJECTION, USP APPEARS TO BE
DOSE RELATED.
PATIENTS RECEIVING GREATER THAN 1400 MG/M CUMULATIVE DOSE ARE AT
SIGNIFICANTLY
HIGHER RISK THAN THOSE RECEIVING LESS (5, 6).
INDICATIONS AND USAGE
Carmustine for injection, USP is a nitrosourea indicated as palliative
therapy as a single agent or in
established combination therapy with other approved chemotherapeutic
agents in the following: (1)
Brain tumors glioblastoma, brainstem glioma, medulloblastoma,
astrocytoma, ependymoma, and
metastatic brain tumors (1)
Multiple myeloma-in combination with prednisone (1)
Relapsed or refractory Hodgkin's lymphoma in combination with other
approved drugs (1)
Relapsed or refractory Non-Hodgkin's lymphomas in combination with
other approved drugs (1)
DOSAGE AND ADMINISTRATION
Recommended Dosage: As a single agent, 150 to 200 mg/m carmustine for
injection, USP
intravenously every 6 weeks as a single dose or divided into daily
injections such as 75 to 100 mg/m 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)
DOSAGE FORMS AND STRENGTHS
For injection: 100 mg of carmustine lyophilized powder in a
single-dose vial for reconstitution and a vial
containing 3mL sterile diluent (Dehydrated