Busulfex Use In Pregnancy & Lactation

Pregnancy: Risk Summary: BUSULFEX can cause fetal harm when administered to a pregnant woman based on animal data. Busulfan was teratogenic in mice, rats, and rabbits following administration during organogenesis. The solvent, DMA, may also cause fetal harm when administered to a pregnant woman. In rats, DMA doses of approximately 40% of the daily dose of DMA in the BUSULFEX dose on a mg/m² basis given during organogenesis caused significant developmental anomalies [see Data]. There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
Animal Data: Following administration during organogenesis in animals, busulfan caused malformations and anomalies, including significant alterations in the musculoskeletal system, body weight gain, and size. In pregnant rats, busulfan produced sterility in both male and female offspring due to the absence of germinal cells in the testes and ovaries. The solvent, N,N- dimethylacetamide (DMA), administered to rats at doses of 400 mg/kg/day (about 40% of the daily dose of DMA in the BUSULFEX dose on a mg/m² basis) during organogenesis caused significant developmental anomalies. The most striking abnormalities included anasarca, cleft palate, vertebral anomalies, rib anomalies, and serious anomalies of the vessels of the heart.
Lactation: Risk Summary: It is not known whether BUSULFEX is present in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for busulfan in human and animal studies, discontinue breastfeeding during treatment with BUSULFEX. The safety of Busulfex in nursing women has not been established.
Females and Males of Reproductive Potential: Contraception: Females: BUSULFEX can cause fetal harm when administered to a pregnant woman [see Pregnancy].
Busulfex should not be administered to pregnant women or women who may possibly be pregnant. Advise females of reproductive potential to use effective contraception during treatment with BUSULFEX and for 6 months following cessation of therapy.
Males: BUSULFEX may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during treatment with BUSULFEX and for 3 months after cessation of therapy [see Pharmacology: Toxicology: Nonclinical Toxicology under Actions].
Infertility: Females: Ovarian suppression and amenorrhea commonly occur in premenopausal women undergoing chronic, low-dose busulfan therapy for chronic myelogenous leukemia. Busulfan may cause temporary or permanent infertility in prepubertal girls or in females of child-bearing potential treated with high-dose BUSULFEX in the conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation.
Males: Sterility, azoospermia, and testicular atrophy have been reported in male patients.