Pregnancy: Risk Summary: BiCNU (carmustine for injection) can cause fetal harm when administered to a pregnant woman based on the mechanism of action [see Pharmacology under Actions] and findings in animals [see Data as follows]. Limited available data with BiCNU 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 BiCNU for the mother and possible risks to the fetus when prescribing BiCNU 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.
Lactation: 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 BiCNU.
Females and Males of Reproductive Potential: Contraception: Advise female patients to avoid pregnancy during treatment with BiCNU because of the risk of fetal harm [see as follows].
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 BiCNU treatment and for at least three months after the final dose of BiCNU [see Pharmacology: Toxicology: Nonclinical Toxicology under Actions].
Infertility: Based on nonclinical findings, male fertility may be compromised by treatment with BiCNU [see Pharmacology: Toxicology: Nonclinical Toxicology under Actions].