Pregnancy & Lactation : הריון/הנקה

4.6      FERTILITY, PREGNANCY AND LACTATION

Effects on fertility
Busulfan can impair fertility. Impotence, sterility, azoospermia, and testicular atrophy have been reported in male patients. Therefore, men treated with Busulfex are advised not to father a child during and up to 6 months after treatment and to seek advice on cryo-conservation of sperm prior to treatment because of the possibility of irreversible infertility due to therapy with Busulfex.
Ovarian suppression and amenorrhoea with menopausal symptoms commonly occur in pre- menopausal patients. Busulfan treatment in a pre- adolescent girl prevented the onset of puberty due to ovarian failure. Busulfan may cause temporary or permanent infertility in females.

Busulfan disrupted spermatogenesis in rats, guinea-pigs, rabbits and monkeys, depleted oocytes and impaired fertility in female mice, and induced sterility in male rats and male hamsters. The solvent dimethylacetamide (DMA) was found to impair fertility in studies with male and female rodents.

Use in pregnancy – Category D

Busulfex is contraindicated during pregnancy. Busulfan and DMA reduced fetal weight and caused embryofetal lethality and malformations in various animal species in pre-clinical studies.
For busulfan, terata were observed in the musculoskeletal system of mice, rats and rabbits, while DMA-induced malformations occurred in the heart, major vessels and oral cavity in the rat.
Administration of busulfan to pregnant rats caused sterility in male and female offspring due to the destruction of germinal cells in the testes and ovaries.


There are no adequate and well-controlled studies of either busulfan or DMA in pregnant women.
A few cases of congenital abnormalities have been reported with low-dose oral busulfan, not necessarily attributable to the drug, and third trimester exposure may be associated with impaired intrauterine growth.

Women of childbearing potential must use effective contraception during and up to 6 months after treatment.

Use in lactation

Patients who are taking Busulfex must be advised not to breast-feed. It is not known whether busulfan and DMA are excreted in human milk. Because of the potential for severe adverse effects, including tumourigenicity, breast-feeding should be discontinued at the start of therapy.