Carmustine Drug Information

The following serious adverse reactions are described elsewhere in the labeling: Myelosuppression Pulmonary toxicity Administration Reactions Carcinogenicity Ocular Toxicity The following adverse reactions associated with the use of carmustine for injection, USP were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders Tachycardia and chest pain.

Eye Disorders Conjunctival edema, conjunctival hemorrhage, blurred vision and loss of depth perception Gastrointestinal Toxicity Nausea, vomiting, anorexia, and diarrhea Hepatotoxicity Increased transaminase, increased alkaline phosphatase, increased bilirubin levels Infections and Infestations Opportunistic infection (including with fatal outcome). Neoplasms Benign, Malignant and Unspecified (including cysts and polyps) Acute leukemia, bone marrow dysplasias. Nephrotoxicity Progressive azotemia, decrease in kidney size, renal failure Nervous System Disorders Headaches, encephalopathy, and seizures Pulmonary Toxicity Pneumonitis, interstitial lung disease Reproductive System and Breast Disorders Gynecomastia Skin and Subcutaneous Tissue Disorders Burning sensation, hyperpigmentation, swelling, pain, erythema, skin necrosis, alopecia, allergic reaction Vascular Disorders Veno-occlusive disease. Most common adverse reactions (>1%) are nausea, vomiting, renal toxicity, pneumonitis, pulmonary toxicity, myelosuppression To report SUSPECTED ADVERSE REACTIONS, contact Navinta LLC, Ewing NJ 08618 at +1-609-883-1135 or FDA at +1-800-FDA-1088 or www.fda.gov/medwatch.

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. Phenobarbital: Phenobarbital induces the metabolism of carmustine and may compromise antitumor activity of carmustine for injection, USP. Consider alternative drugs to phenobarbital.

Effects of carmustine for injection

USP on other drugs Phenytoin: Carmustine for injection, USP when coadministered with phenytoin may reduce phenytoin serum concentrations. Consider alternative drugs to phenytoin.

Pregnancy Risk Summary Carmustine for injection, USP 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 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/ m 2 ), approximately 0.1 times the maximum cumulative human dose of 1400 mg/m 2, 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/m 2 ), approximately 0.02 times the maximum cumulative human dose based on a mg/m 2 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/m 2 ), approximately 0.03 times the maximum cumulative human dose on a mg/ m 2 basis.

Intravenous (IV) administration of carmustine to rats at a cumulative dose of 50 mg/kg (300 mg/ m 2 ), approximately 0.2 times the maximum cumulative human dose on a mg/m 2 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/ m 2 ), approximately 0.1 times the maximum cumulative human dose on a mg/ m 2 basis.

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 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..

Carmustine for injection, USP is contraindicated in patients with previous hypersensitivity to carmustine for injection, USP or its components. Hypersensitivity

The main result of overdose is myeloablation. No proven antidotes have been established for carmustine for injection, USP overdosage.