Animal studies have revealed evidence of teratogenicity. There are no controlled data in human pregnancy. Congenital anomalies, including polydactyly, plagiocephaly, congenital heart disease, hypospadias, and bilateral talipes equinovarus have occurred. Leucopenia and/or thrombocytopenia have been reported in a proportion of neonates whose mothers took azathioprine throughout their pregnancies. There have been reports of premature birth and low birth weight (especially in combination with corticosteroids), and spontaneous abortion after either maternal or paternal exposure; some data suggest an increased risk of intrauterine growth retardation and prematurity. Chromosomal aberrations have also been reported.

Azathioprine has been reported to cause temporary depression of spermatogenesis in mice.

Benefit versus risk must be weighed carefully before using azathioprine in patients of reproductive potential. The patient should be apprised of the potential hazard to the fetus if azathioprine is used during pregnancy or if the patient becomes pregnant while taking this drug. Extra hematologic monitoring should be considered during pregnancy.

A National Transplantation Pregnancy Registry (NTPR) has been established to monitor maternal-fetal outcomes of pregnant women exposed to immunosuppressant drugs, including azathioprine. Physicians are encouraged to register patients by calling 1-215-955-4820 (USA).

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use is considered contraindicated unless the benefits outweigh the risks.

Rheumatoid arthritis: Contraindicated (US)

AU TGA pregnancy category: D
US FDA pregnancy category: D

Comments: Adequate methods of contraception should be encouraged in both male and female patients of reproductive age during, and for at least 3 months after treatment cessation.

See references

UK: Use is contraindicated.
AU and US: Caution is recommended.

Excreted into human milk: Yes

Drugs and lactation database (LactMed): Breastfeeding is considered acceptable.

Studies in women taking azathioprine at doses up to 200 mg per day for immunosuppression in inflammatory bowel disease, systemic lupus erythematosus, or transplantation have found either low or undetectable levels of its active metabolites in milk and infant serum. Cases of mild, asymptomatic neutropenia have been reported; however, long-term data for carcinogenesis are not available. Women with decreased activity of the enzyme that detoxifies azathioprine metabolites may pass on higher levels of drug to their infants via breast milk.

If the decision is made to use azathioprine during breastfeeding, it may be advisable to monitor the complete blood count with differential, and liver function tests in exclusively breastfed infants. Avoiding breastfeeding for 4 to 6 hours after a dose should significantly reduce the dose received by the infant in breast milk.

See references