Last update March 8, 2022

Methotrexate (obstetric and immunosuppressive use)

Likely Compatibility

Fairly safe. Mild or unlikely adverse effects. Compatible under certain circumstances. Follow-up recommended. Read Commentary.

Methotrexate (MTX) is an antineoplastic antimetabolite and folic acid analogue and antagonist with antineoplastic and immunosuppressive properties from interfering with the synthesis and cellular replication of DNA. Indicated in the treatment of certain neoplasms, rheumatic problems: arthritis, severe psoriasis, Reiter’s syndrome, inflammatory bowel disease (Pfizer 2019 & 2008, AEMPS 2018, EMA 2017) and, off-label, in multiple sclerosis and in some obstetric procedures: abortion, ectopic pregnancy, placenta accreta. (Practice Committee of the American Society for Reproductive Medicine 2013, Kulier 2011).


  • Administration in obstetrics, single or 3-day intramuscular doses of 50 mg/m2 of body surface area (mg/m2 BS) are administered for expulsion purposes.
  • Administration in rheumatic and autoimmune processes: oral (also subcutaneous or intramuscular) 7.5 to 20 mg (10-15 mg/m2 of body surface) once a week.

Excretion in breastmilk is very low (Brown 2017, Østensen 2006, Johns 1972), perhaps due to a high volume of distribution and a very low pKa that makes it very insoluble in liquids at physiological pH. (Götestam 2016)

After isolated doses of 50 mg/m2 BS for obstetric purposes, even after doses of 92 mg daily for 4 days, undetectable or negligible levels have been found in breastmilk (Baker 2018, Tanaka 2009). Zero or negligible transfer to milk has also been found when used in low weekly doses (25 mg) during the maintenance treatment of rheumatoid arthritis and other autoimmune diseases. (Delaney 2017, Thorne 2014)

No problems have been recorded or observed in infants whose mothers were taking it. (Thorne 2014).

The recommendations of experts and the practical attitude among clinicians about maintaining treatment during breastfeedingn are divided. (Huang 2016, Götestam 2016, Martínez 2009, Weber 2008, Østensen 2007)

Several authors consider isolated or weekly use in low doses during breastfeeding to be safe. (Anderson 2018, Delaney 2017, Noviani 2016, Thorne 2014, Koren 2013, Østensen 2009, Tanaka 2009, Weber 2008, Moretti 2000, Goldsmith 1989, Johns 1972)

Some recommend clinical or hematologic monitoring or of MTX levels in the infant (Rademaker 2017, Almas 2016, Østensen 2009) and administering folic acid to the infant. (Almas 2016).

Exposure can be reduced by almost half by interrupting breastfeeding 24 hours after taking the drug, expressing and discarding the milk in the meantime (CRAT 2020, Delaney 2017, Hale 2017 p628, Noviani 2016), which in practice means not breastfeeding the day MTX is taken and breastfeeding the rest of the week.

Other authors and expert consensus discourage its use during lactation. (Bermas 2017, Flint 2016, Nguyen 2016, Götestam 2016, Kavanaugh 2015, van der Woude 2015, Mahadevan 2015, Grunewald 2015, Samaritano 2014, Mervic 2014, Huang 2014, Sammaritano 2014, Mottet 2007, Temprano 2005, WHO 2002, AAP 2001, Janssen 2001)

See below the information of this related product:

  • Methotrexate (anticancer drug) (Unsafe. Moderate/severe adverse effects. Compatible under certain circumstances. Follow-up recommended. Use safer alternative or discontinue breastfeeding from 5 to 7 T ½ . Read Commentary.)


  • Etanercept (Safe substance and/or breastfeeding is the best option.)
  • Hydroxychloroquine Sulfate (Safe substance and/or breastfeeding is the best option.)
  • Infliximab (Safe substance and/or breastfeeding is the best option.)
  • Penicillamine (Safe substance and/or breastfeeding is the best option.)
  • Sulfasalazine (Safe substance and/or breastfeeding is the best option.)

Suggestions made at e-lactancia are done by APILAM team of health professionals, and are based on updated scientific publications. It is not intended to replace the relationship you have with your doctor but to compound it. The pharmaceutical industry contraindicates breastfeeding, mistakenly and without scientific reasons, in most of the drug data sheets.

Jose Maria Paricio, Founder & President of APILAM/e-Lactancia

Your contribution is essential for this service to continue to exist. We need the generosity of people like you who believe in the benefits of breastfeeding.

Thank you for helping to protect and promote breastfeeding.

José María Paricio, founder of e-lactancia.

Other names

Methotrexate (obstetric and immunosuppressive use) is also known as

Methotrexate (obstetric and immunosuppressive use) in other languages or writings:


Methotrexate (obstetric and immunosuppressive use) belongs to this group or family:


Main tradenames from several countries containing Methotrexate (obstetric and immunosuppressive use) in its composition:


Variable Value Unit
Oral Bioavail. 60 (20 - 95) %
Molecular weight 454 daltons
Protein Binding 50 %
VD 0.4 - 0.8 l/Kg
pKa 3.41 -
Tmax oral: 1 - 2; IM: 0.5 -1 hours
3 - 10 (dos. < 30 mg/m2) hours
M/P ratio 0.08 - 0.1 -
Theoretical Dose 0.0013 - 0.0034 mg/Kg/d
Relative Dose 0.08 - 0.81 %
Ped.Relat.Dose 0.04 - 0.1 %


  1. CRAT - Centre de Référence sur les Agents Tératogènes. Méthotrexate - Grossesse et allaitement. 2020 Full text (link to original source) Full text (in our servers)
  2. Anderson PO. Drug Treatment of Rheumatoid Arthritis During Breastfeeding. Breastfeed Med. 2018 Nov;13(9):575-577. Abstract
  3. Baker T, Datta P, Rewers-Felkins K, Hale TW. High-Dose Methotrexate Treatment in a Breastfeeding Mother with Placenta Accreta: A Case Report. Breastfeed Med. 2018 Abstract
  4. Rademaker M, Agnew K, Andrews M, Armour K, Baker C, Foley P, Frew J, Gebauer K, Gupta M, Kennedy D, Marshman G, Sullivan J. Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration. Australas J Dermatol. 2018 May;59(2):86-100. Abstract
  5. AEMPS-Wyeth. Metotrexato. Ficha técnica. 2018 Full text (in our servers)
  6. Bermas BL. Lactation and Management of Postpartum Disease. Rheum Dis Clin North Am. 2017 May;43(2):249-262. Abstract
  7. Brown SM, Aljefri KA, Waas R, Hampton PJ. Systemic medications used in treatment of common dermatological conditions: Safety profile with respect to pregnancy, breast feeding and content in seminal fluid. J Dermatolog Treat. 2017 Abstract
  8. EMA-Therakind Ltd. Methotrexate. Drug Summary 2017 Full text (in our servers)
  9. Delaney S, Colantonio D, Ito S. Methotrexate in breast milk. 30 Annual Education Meeting of the Organization of Teratology Information Specialist (OTIS) and MotherToBaby Affiliates. Birth Defects Res. 2017;109 (SI):711. Poster-Abstract 7. 2017
  10. Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, Arthanari S, Cunningham J, Flanders L, Moore L, Crossley A, Purushotham N, Desai A, Piper M, Nisar M, Khamashta M, Williams D, Gordon C, Giles I; BSR and BHPR Standards, Guidelines and Audit Working Group. 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 Sep;55(9):1693-7. Abstract Full text (link to original source) Full text (in our servers)
  11. McConnell RA, Mahadevan U. Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications. Gastroenterol Clin North Am. 2016 Abstract
  12. Huang VW, Chang HJ, Kroeker KI, Goodman KJ, Hegadoren KM, Dieleman LA, Fedorak RN. Management of Inflammatory Bowel Disease during Pregnancy and Breastfeeding Varies Widely: A Need for Further Education. Can J Gastroenterol Hepatol. 2016;2016:6193275. Epub 2016 Sep 20. Abstract Full text (link to original source) Full text (in our servers)
  13. Almas S, Vance J, Baker T, Hale T. Management of Multiple Sclerosis in the Breastfeeding Mother. Mult Scler Int. 2016;2016:6527458. Abstract Full text (link to original source) Full text (in our servers)
  14. Noviani M, Wasserman S, Clowse ME. Breastfeeding in mothers with systemic lupus erythematosus. Lupus. 2016 Aug;25(9):973-9. Abstract
  15. Nguyen GC, Seow CH, Maxwell C, Huang V, Leung Y, Jones J, Leontiadis GI, Tse F, Mahadevan U, van der Woude CJ; IBD in Pregnancy Consensus Group. The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. Gastroenterology. 2016 Mar;150(3):734-757.e1. Abstract Full text (link to original source) Full text (in our servers)
  16. Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Förger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbühl C, Østensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795-810. Abstract Full text (link to original source) Full text (in our servers)
  17. Grunewald S, Jank A. New systemic agents in dermatology with respect to fertility, pregnancy, and lactation. J Dtsch Dermatol Ges. 2015 Abstract Full text (link to original source) Full text (in our servers)
  18. Kavanaugh A, Cush JJ, Ahmed MS, Bermas BL, Chakravarty E, Chambers C, Clowse M, Curtis JR, Dao K, Hankins GD, Koren G, Kim SC, Lapteva L, Mahadevan U, Moore T, Nolan M, Ren Z, Sammaritano LR, Seymour S, Weisman MH. Proceedings from the American College of Rheumatology Reproductive Health Summit: the management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res (Hoboken). 2015 Mar;67(3):313-25. Abstract Full text (link to original source) Full text (in our servers)
  19. van der Woude CJ, Ardizzone S, Bengtson MB, Fiorino G, Fraser G, Katsanos K, Kolacek S, Juillerat P, Mulders AG, Pedersen N, Selinger C, Sebastian S, Sturm A, Zelinkova Z, Magro F; European Crohn’s and Colitis Organization. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015 Feb;9(2):107-24. Review. Abstract Full text (link to original source) Full text (in our servers)
  20. Mahadevan U, Matro R. Care of the Pregnant Patient With Inflammatory Bowel Disease. Obstet Gynecol. 2015 Aug;126(2):401-12. Abstract
  21. Huang VW, Habal FM. From conception to delivery: managing the pregnant inflammatory bowel disease patient. World J Gastroenterol. 2014 Abstract Full text (link to original source) Full text (in our servers)
  22. Mervic L. Management of moderate to severe plaque psoriasis in pregnancy and lactation in the era of biologics. Acta Dermatovenerol Alp Pannonica Adriat. 2014;23(2):27-31. Abstract Full text (link to original source) Full text (in our servers)
  23. Thorne JC, Nadarajah T, Moretti M, Ito S. Methotrexate use in a breastfeeding patient with rheumatoid arthritis. J Rheumatol. 2014 Abstract Full text (link to original source) Full text (in our servers)
  24. Sammaritano LR, Bermas BL. Rheumatoid arthritis medications and lactation. Curr Opin Rheumatol. 2014 Abstract
  25. Koren G, Carey N, Gagnon R, Maxwell C, Nulman I, Senikas V; Society of Obstetricians and Gynaecologists of Canada. Cancer chemotherapy and pregnancy. J Obstet Gynaecol Can. 2013 Mar;35(3):263-278. Abstract Full text (link to original source) Full text (in our servers)
  26. Practice Committee of American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril. 2013 Abstract
  27. Pistilli B, Bellettini G, Giovannetti E, Codacci-Pisanelli G, Azim HA Jr, Benedetti G, Sarno MA, Peccatori FA. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: how should we counsel cancer patients about breastfeeding? Cancer Treat Rev. 2013 May;39(3):207-11. Abstract
  28. Kulier R, Kapp N, Gülmezoglu AM, Hofmeyr GJ, Cheng L, Campana A. Medical methods for first trimester abortion. Cochrane Database Syst Rev. 2011 Abstract
  29. Tanaka T, Walsh W, Verjee Z, Ratnapalan S, Sharma K, Ito S. Methotrexate use in a lactating woman with an ectopic pregnancy. 22 International Conference of the Organization of Teratology Information Specialist (OTIS). Birth Defects Res;85:494 Abstract 4. 2009
  30. Ostensen M. Management of early aggressive rheumatoid arthritis during pregnancy and lactation. Expert Opin Pharmacother. 2009 Abstract
  31. Weber JC, Kuhnert C. Traitements de fond des affections inflammatoires systémiques au cours de l’allaitement. [Breastfeeding and drug management in connective tissue and rheumatic diseases]. Rev Med Interne. 2008 Dec;29(12):1017-23. Abstract
  32. Mottet C, Juillerat P, Pittet V, Gonvers JJ, Froehlich F, Vader JP, Michetti P, Felley C. Pregnancy and breastfeeding in patients with Crohn's disease. Digestion. 2007 Abstract
  33. Østensen M, Motta M. Therapy insight: the use of antirheumatic drugs during nursing. Nat Clin Pract Rheumatol. 2007 Abstract
  34. Østensen M, Khamashta M, Lockshin M, Parke A, Brucato A, Carp H, Doria A, Rai R, Meroni P, Cetin I, Derksen R, Branch W, Motta M, Gordon C, Ruiz-Irastorza G, Spinillo A, Friedman D, Cimaz R, Czeizel A, Piette JC, Cervera R, Levy RA, et al. Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther. 2006 Abstract Full text (link to original source) Full text (in our servers)
  35. Temprano KK, Bandlamudi R, Moore TL. Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum. 2005 Abstract
  36. WHO / UNICEF. BREASTFEEDING AND MATERNAL MEDICATION Recommendations for Drugs in the Eleventh WHO Model List of Essential Drugs. Department of Child and Adolescent Health and Development (WHO/UNICEF) 2002 Abstract Full text (link to original source) Full text (in our servers)
  37. AAP - American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89. Abstract Full text (link to original source) Full text (in our servers)
  38. Moretti ME, Lee A, Ito S. Which drugs are contraindicated during breastfeeding? Practice guidelines. Can Fam Physician. 2000 Sep;46:1753-7. Review. Abstract Full text (link to original source) Full text (in our servers)
  39. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med. 2000 Abstract Full text (link to original source) Full text (in our servers)
  40. Goldsmith DP. Neonatal rheumatic disorders. View of the pediatrician. Rheum Dis Clin North Am. 1989 Abstract
  41. Johns DG, Rutherford LD, Leighton PC, Vogel CL. Secretion of methotrexate into human milk. Am J Obstet Gynecol. 1972 Abstract

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