Azathioprine Pregnancy and Breastfeeding Warnings
Azathioprine Pregnancy Warnings
Azathioprine and its metabolites, 6-mercaptopurine and thiouric acid, are known to cross the placenta. In one small study, 35S-azathioprine was administered one time to three women at 9, 14, and 15 weeks' gestation. The ratio of radioactivity in fetal blood to maternal blood ranged from 0.64 to 0.93. In maternal blood, 27% to 41% of the administered radioactivity was present as thiouric acid, 14% to 27% as 6-MP, and 21% to 28% as azathioprine. In fetal blood, 48% to 63% of radioactivity present was due to thiouric acid. The majority of radioactivity in amniotic fluid and in the placenta was also due to thiouric acid. One study evaluated outcomes of 133 pregnancies in renal transplant recipients. Thirteen pregnancies ended in spontaneous abortion and 21 were aborted therapeutically. Of the 99 remaining pregnancies (103 fetuses), 46 ended before term. There were eight stillbirths and three early neonatal deaths, representing a perinatal mortality rate of 10.7%. Four cases of minor malformations occurred, including hypoplasia of the leg, umbilical hernia, hypospadias, and polydactyly. Detailed information was available for 66 pregnancies, 58 of which reached 28 weeks' gestation or more. Premature birth occurred in 48%, intrauterine growth retardation occurred in 29%, and infants weighed less than 2.5 kg in 50% of pregnancies. Other studies involving transplant recipients as well as those involving patients with inflammatory bowel disease or systemic lupus erythematosus have not found evidence of azathioprine-induced congenital anomalies. However, data from some of these studies suggest a possible increased risk of intrauterine growth retardation and prematurity. The true risk of azathioprine use during pregnancy has been difficult to establish as maternal disease often requires use of multiple immunosuppressive agents and other medications. In addition, maternal comorbid conditions cannot be excluded from the assessment of causality. The manufacturer recommends against using azathioprine for treating rheumatoid arthritis in pregnant women. 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).
Azathioprine has been assigned to pregnancy category D by the FDA. Some animal studies have revealed evidence of teratogenicity. There are no controlled data in human pregnancy. However, azathioprine has been used during pregnancy in the setting of renal transplantation as well as inflammatory bowel disease and systemic lupus erythematosus. While most outcomes are good, congenital anomalies, including polydactyly, plagiocephaly, congenital heart disease, hypospadias, and bilateral talipes equinovarus have occurred. Chromosomal aberrations and neonatal bone marrow suppression have also been reported. Lastly, some data suggest an increased risk of intrauterine growth retardation and prematurity. Azathioprine is only recommended for use during pregnancy when there are no alternatives and benefit outweighs risk.
Azathioprine Breastfeeding Warnings
Azathioprine and its metabolites (e.g., 6-MP) are excreted into human milk in small amounts. It is not recommended for use in nursing mothers. The manufacturer recommends that due to the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
A study on the breast milk of four women with the wild-type TPMT genotype taking azathioprine reported that azathioprine may be safe during breast-feeding in patients with the wild-type TPMT genotype taking "normal" doses. The excretion of 6-MP, the active metabolite of azathioprine, into human milk was evaluated in two women on immunosuppressive therapy following renal transplantation. Breast milk concentrations ranged from less than 1 to 4.5 ng/mL in one patient following oral administration of azathioprine 75 mg. Breast milk concentrations in another patient ranged from 8 to 18 ng/mL following oral administration of azathioprine 25 mg. The first patient elected to breast-feed her infant. The infant's growth and development were normal as were the hemoglobin levels, leukocyte counts, and platelet counts over a 3 month follow up period.
Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Wolters Kluwer Health and Drugs.com is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective, or appropriate for any given patient. Multum Information Services, Inc. does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. Copyright 2000-2008 Multum Information Services, Inc. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.