Also known as Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, MTX, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexat, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, Méthotrexate, Novatrex, Rheumatrex, Texate, Tremetex, Trexall, Trexeron, Trixilem, WR-19039

An antimetabolite and antifolate agent with antineoplastic and immunosuppressant activities. Methotrexate binds to and inhibits the enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis and, subsequently, inhibition of DNA and RNA syntheses. Methotrexate also exhibits potent immunosuppressant activity although the mechanism(s) of actions is unclear.

Originator: NCI Thesaurus | Source: The website of the National Cancer Institute (http://www.cancer.gov)

Can I take Methotrexate while breastfeeding?

Most sources consider breastfeeding to be contraindicated during maternal high-dose antineoplastic drug therapy with methotrexate. An abstinence period of at least 1 week after chemotherapy doses of methotrexate has been suggested.[1]

Limited information indicates that a maternal dose of methotrexate up to 65 mg (or 50 mg/square meter) produces low levels in milk, leading some authors to state that low single or weekly doses, such as those used for ectopic pregnancy or rheumatoid arthritis, are of low risk to the breastfed infant,[2][3][4][5][6] although some expert opinion warns against this use.[7][8][9][10][11] If breastfeeding during long-term, low-dose methotrexate use is undertaken, monitoring of the infant’s complete blood count and differential could be considered.

Drug levels

Maternal Levels. One patient who was 1 month postpartum given 22.5 mg (15 mg/square meter) methotrexate daily by mouth for choriocarcinoma. Milk was collected at various times of the first 12 days of therapy. A peak milk level of 2.3 mcg/L occurred 10 hours after the first dose. However, the milk level was relatively constant during the period from 4 to 10 hours after the dose, after which it began to drop. Peak milk levels on the second and third days of administration were 2.7 mcg/L. The authors estimated that a cumulative amount of 0.32 mcg would be excreted in milk during the first 12 hours after this dose.[2]

A woman was given a single intramuscular dose of 65 mg (50 mg/square meter) of methotrexate for ectopic pregnancy. Six milk samples were obtained from 1 to 24 hours after the dose. Methotrexate was undetectable (<22.7 mcg/L) in all milk samples.[5] A woman with rheumatoid arthritis received hydroxychloroquine, sulfasalazine and prednisone 10 mg daily during pregnancy and postpartum. On day 151 postpartum, methotrexate 25 mg was given subcutaneously. Breastmilk samples were obtained at 2, 12 and 24 hours after the dose. Milk levels were 0.05 micromolar (22.7 mcg/L) in all samples which was considered detectable, but not quantifiable. A fully breastfed infant would receive 3.4 mcg/kg in the first 24 hours after administration, or about 1% of the weight-adjusted maternal dosage.[6] Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

Maternal Levels. One patient who was 1 month postpartum given 22.5 mg (15 mg/square meter) methotrexate daily by mouth for choriocarcinoma. Milk was collected at various times of the first 12 days of therapy. A peak milk level of 2.3 mcg/L occurred 10 hours after the first dose. However, the milk level was relatively constant during the period from 4 to 10 hours after the dose, after which it began to drop. Peak milk levels on the second and third days of administration were 2.7 mcg/L. The authors estimated that a cumulative amount of 0.32 mcg would be excreted in milk during the first 12 hours after this dose.[2]

A woman was given a single intramuscular dose of 65 mg (50 mg/square meter) of methotrexate for ectopic pregnancy. Six milk samples were obtained from 1 to 24 hours after the dose. Methotrexate was undetectable (<22.7 mcg/L) in all milk samples.[5] A woman with rheumatoid arthritis received hydroxychloroquine, sulfasalazine and prednisone 10 mg daily during pregnancy and postpartum. On day 151 postpartum, methotrexate 25 mg was given subcutaneously. Breastmilk samples were obtained at 2, 12 and 24 hours after the dose. Milk levels were 0.05 micromolar (22.7 mcg/L) in all samples which was considered detectable, but not quantifiable. A fully breastfed infant would receive 3.4 mcg/kg in the first 24 hours after administration, or about 1% of the weight-adjusted maternal dosage.[6] Infant Levels. Relevant published information was not found as of the revision date.

Possible effects on lactation

Relevant published information was not found as of the revision date.

Alternate drugs to consider

Auranofin, Etanercept, Gold Sodium Thiomalate, Hydroxychloroquine, Infliximab, Penicillamine, Sulfasalazine

References

1. Pistilli B, Bellettini G, Giovannetti E et al. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: How should we counsel cancer patients about breastfeeding? Cancer Treat Rev. 2013;39:207-11. PMID: 23199900

2. Johns DG, Rutherford LD et al. Secretion of methotrexate in human milk. Am J Obstet Gynecol. 1972;112:978-80. PMID: 5042796

3. Moretti ME, Lee A, Ito S. Which drugs are contraindicated during breastfeeding? Can Fam Physician. 2000;46:1753-7. PMID: 11013791

4. Ostensen M. Management of early aggressive rheumatoid arthritis during pregnancy and lactation. Expert Opin Pharmacother. 2009;10:1469-79. PMID: 19505214

5. Tanaka T, Walsh W, Verjee Z et al. Methotrexate use in a lactating woman with an ectopic pregnancy. Birth Defects Res A Clin Mol Teratol. 2009;85:494. Abstract. Assay sensitivity per Shinya Ito, MD.

6. Thorne JC, Nadarajah T, Moretti M, Ito S. Methotrexate use in a breastfeeding patient with rheumatoid arthritis. J Rheumatol. 2014;41:2332. PMID: 25362724

7. 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

8. Mahadevan U, Matro R. Care of the pregnant patient with inflammatory bowel disease. Obstet Gynecol. 2015;126:401-12. PMID: 26241432

9. Kavanaugh A , Cush JJ, Ahmed MS et al. 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;67:313-25. PMID: 25385050

10. 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

11. 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. PMID: 26750124

Last Revision Date

20160401

Disclaimer:Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

Source: LactMed – National Library of Medicine (NLM)

3D Model of the Methotrexate molecule

MolView – data visualization platform