⛔ FDA 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 until blood counts recover. Pulmonary Toxicity Carmustine for Injection causes dose-related pulmonary toxicity. Patients receiving greater than 1400 mg /m 2 cumulative dose are at significantly higher risk than those receiving less. Delayed pulmonary toxicity can occur years after treatment, and can result in death, particularly in patients treated in childhood [see Adverse Reactions (6) and Use in Specific Populations (8.4) ] . 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. Monitor blood counts. (5, 6). • Pulmonary toxicity from Carmustine for Injection appears to be dose related. Patients receiving greater than 1400 mg/m 2 cumulative dose are at significantly higher risk than those receiving less (5, 6).
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Carmustine for Injection 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 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 for the mother and possible risks to the fetus when prescribing Carmustine for 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. 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