The Basics
What is Azathioprine?
prevent organ rejection after a transplant. It can also treat rheumatoid arthritis
Brand names for Azathioprine
Imuran
How Azathioprine is classified
Immunosuppressive Agents
Azathioprine During Pregnancy
Azathioprine pregnancy category
Category DNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Azathioprine while pregnant
IMURAN can cause fetal harm when administered to a pregnant woman. IMURAN should not be given during pregnancy without careful weighing of risk versus benefit. Whenever possible, use of IMURAN in pregnant patients should be avoided. This drug should not be used for treating rheumatoid arthritis in pregnant women.12 IMURAN is teratogenic in rabbits and mice when given in doses equivalent to the human dose (5 mg/kg daily). Abnormalities included skeletal malformations and visceral anomalies.11 Limited immunologic and other abnormalities have occurred in a few infants born of renal allograft recipients on IMURAN. In a detailed case report,13 documented lymphopenia, diminished IgG and IgM levels, CMV infection, and a decreased thymic shadow were noted in an infant born to a mother receiving 150 mg azathioprine and 30 mg prednisone daily throughout pregnancy. At 10 weeks most features were normalized. DeWitte et al reported pancytopenia and severe immune deficiency in a preterm infant whose mother received 125 mg azathioprine and 12.5 mg prednisone daily.14 There have been two published reports of abnormal physical findings. Williamson and Karp described an infant born with preaxial polydactyly whose mother received azathioprine 200 mg daily and prednisone 20 mg every other day during pregnancy.15 Tallent et al described an infant with a large myelomeningocele in the upper lumbar region, bilateral dislocated hips, and bilateral talipes equinovarus. The father was on long-term azathioprine therapy.16 Benefit versus risk must be weighed carefully before use of IMURAN in patients of reproductive potential. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing age should be advised to avoid becoming pregnant.
Taking Azathioprine While Breastfeeding
What are recommendations for lactation if you're taking Azathioprine?
Most experts consider breastfeeding during azathioprine to be acceptable.[1][2][3][4][5][6][7][8] Studies in women with inflammatory bowel disease, systemic lupus erythematosus or transplantation taking doses of azathioprine up to 200 mg daily for immunosuppression have found either low or unmeasurable levels of the active metabolites in milk and infant serum. Some evidence indicates a lack of adverse effects on the health and development of infants exposed to azathioprine during breastfeeding up to 3.5 years of age, but long-term follow-up for effects such as carcinogenesis have not been performed. Mothers with decreased activity of the enzyme that detoxifies azathioprine metabolites may transmit higher levels of drug to their infants in breastmilk. Cases of mild, asymptomatic neutropenia have been reported, so it might be desirable to monitor exclusively breastfed infants with a complete blood count with differential, and liver function tests if azathioprine is used during lactation, although some authors feel that monitoring is unnecessary.[9] Avoiding breastfeeding for 4 hours after a dose should markedly decrease the dose received by the infant in breastmilk.[10]
Maternal / infant drug levels
Most experts consider breastfeeding during azathioprine to be acceptable.[1][2][3][4][5][6][7][8] Studies in women with inflammatory bowel disease, systemic lupus erythematosus or transplantation taking doses of azathioprine up to 200 mg daily for immunosuppression have found either low or unmeasurable levels of the active metabolites in milk and infant serum. Some evidence indicates a lack of adverse effects on the health and development of infants exposed to azathioprine during breastfeeding up to 3.5 years of age, but long-term follow-up for effects such as carcinogenesis have not been performed. Mothers with decreased activity of the enzyme that detoxifies azathioprine metabolites may transmit higher levels of drug to their infants in breastmilk. Cases of mild, asymptomatic neutropenia have been reported, so it might be desirable to monitor exclusively breastfed infants with a complete blood count with differential, and liver function tests if azathioprine is used during lactation, although some authors feel that monitoring is unnecessary.[9] Avoiding breastfeeding for 4 hours after a dose should markedly decrease the dose received by the infant in breastmilk.[10]
Possible effects of Azathioprine on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Azathioprine
(Immunosuppression) Cyclosporine, Tacrolimus; (Inflammatory Bowel Disease) Budesonide, Infliximab, Mesalamine, Prednisone; (Systemic Lupus Erythematosus) Hydroxychloroquine, Prednisone.
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Nielsen OH, Maxwell C, Hendel J. IBD medications during pregnancy and lactation. Nat Rev Gastroenterol Hepatol. 2014;11:116-27. PMID: 23897285
2. Constantinescu S, Pai A, Coscia LA et al. Breast-feeding after transplantation. Best Pract Res Clin Obstet Gynaecol. 2014;28:1163-73. PMID: 25271063
3. Nguyen GC, Seow CH, Maxwell C et al. The Toronto Consensus Statements for the Management of IBD in Pregnancy. Gastroenterology. 2016;150:734-57. PMID: 26688268
4. van der Woude CJ, Ardizzone S, Bengtson MB et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015;9:107-24. PMID: 25602023
5. Flint J, Panchal S, Hurrell A et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016;55:1693-7. PMID: 26750124
6. Gotestam Skorpen C, Hoeltzenbein M, Tincani A et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795-810. PMID: 26888948
7. Mottet C, Schoepfer AM, Juillerat P et al. Experts opinion on the practical use of azathioprine and 6-mercaptopurine in inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:2733-47. PMID: 27760078
8. Mahadevan U, Robinson C, Bernasko N et al. Inflammatory bowel disease in pregnancy clinical care pathway: A report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology. 2019;156:1508-24. PMID: 30658060
9. Christensen LA, Dahlerup JF, Nielsen MJ et al. Azathioprine treatment during lactation: authors’ reply. Aliment Pharmacol Ther. 2009;30:91. PMID: 19566905
10. Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya’acov A et al. Management of inflammatory bowel disease during pregnancy. Dig Dis Sci. 2016;61:2194-204. PMID: 27068171
11. Coulam CB, Moyer TP, Jiang NS et al. Breast-feeding after renal transplantation. Transplant Proc. 1982;13:605-9. PMID: 6817481
12. Kane SV, Present DH. Metabolites to immunomodulators are not detected in breast milk. Am J Gastroenterol. 2004;99 (10 Suppl S):S246-7. Abstract 761. DOI: doi:10.1111/j.1572-0241.2004.001_1.x
13. Moretti ME, Verjee Z, Ito S, Koren G. Breast-feeding during maternal use of azathioprine. Ann Pharmacother. 2006;40:2269-72. PMID: 17132809
14. Sau A, Clarke S, Bass J et al. Azathioprine and breastfeeding-is it safe? BJOG. 2007;114:498-501. PMID: 17261122
15. Christensen LA, Dahlerup JF, Nielsen MJ et al. Azathioprine treatment during lactation. Aliment Pharmacol Ther. 2008;28:1209-13. PMID: 18761704
16. Gardiner SJ, Gearry RB, Roberts RL et al. Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharmacol. 2006;62:453-6. PMID: 16995866
17. Bernard N, Garayt C, Chol F et al. Prospective clinical and biological follow-up of three breastfed babies from azathioprine-treated mothers. Fundam Clin Pharmacol. 2007;21 (Suppl 1):62-3. Abstract. DOI: doi:10.1111/j.1472-8206.2007.00481.x
18. Zelinkova Z, De Boer IP, Van Dijke MJ et al. Azathioprine treatment during lactation. Aliment Pharmacol Ther. 2009;30:90-1; author reply 91. PMID: 19566905
19. Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppresive therapy and breast-feeding after renal transplantation. Nephron. 1984;37:68. Letter. PMID: 6371564
20. Madill JE, Levy G, Greig P. Pregnancy and breast-feeding while receiving cyclosporine A. In: Williams BAH S-GD, eds. Trends in organ transplantation. New York: Springer Publishing Company, 1996:109-21.
21. Nyberg G, Haljamae U, Frisenette-Fich C et al. Breast-feeding during treatment with cyclosporine. Transplantation. 1998;65:253-5. PMID: 9458024
22. Munoz-Flores-Thiagarajan KD, Easterling T, Davis C et al. Breast-feeding by a cyclosporine-treated mother. Obstet Gynecol. 2001;97(5 pt 2):816-8. PMID: 11336764
23. Gardiner SJ, Gearry RB, Roberts RL et al. Comment: breast-feeding during maternal use of azathioprine. Ann Pharmacother. 2007. PMID: 17389671
24. Khare MM, Lott J, Currie A, Howarth E. Is it safe to continue azathioprine in breast feeding mothers? J Obstet Gynaecol. 2003;23 (Suppl 1):S48. Abstract 53. DOI: doi:10.1080/718591746
25. Werner M, Bjornsson E, Prytz H et al. Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding? Scand J Gastroenterol. 2007;42:986-91. PMID: 17613929
26. Angelberger S, Reinisch W, Messerschmidt A et al. Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding. J Crohns Colitis. 2011;5:95-100. PMID: 21453877
27. de Meij TG, Jharap B, Kneepkens CM et al. Long-term follow-up of children exposed intrauterine to maternal thiopurine therapy during pregnancy in females with inflammatory bowel disease. Aliment Pharmacol Ther. 2013;38:38-43. PMID: 23675854
28. Bernard N, Gouraud A, Paret N et al. Azathioprine and breastfeeding: long-term follow-up. Fundam Clin Pharmacol. 2013;27 (Suppl 1):12. Abstract 05-03. DOI: doi:10.1111/fcp.12025
29. Mahadevan U, Martin CF, Sandler RS et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterology. 2012;142 (5 Suppl 1):S149. Abstract 865.
30. Beswick L, Shukla D, Friedman AB et al. National audit: Assessing the use and safety of allopurinol thiopurine co-therapy in pregnant females with inflammatory bowel disease. J Gastroenterol Hepatol. 2016;31 (Suppl 2):128-9. Abstract. DOI: doi:10.1111/jgh.13521
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
