Last update March 8, 2022

Methotrexate (anticancer drug)

High Risk

Poorly safe. Evaluate carefully. Use safer alternative or interrupt breastfeeding 3 to 7 T ½ (elimination half-lives). Read the Comment.

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).

ONCOLOGIC USE:

Administration can be intramuscular, intravenous or intrathecal and the dose can vary from 15 mg to 3 g per day, with highly variable duration and cycles depending on the type of cancer. (Pfizer 2019 & 2008)

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)

Although the levels found in breastmilk are very low (Johns 1972), during cancer treatment it is recommended to stop breastfeeding due to potentially serious side effects for the infant. (Rademaker 2017, Moretti 2000)

Chemotherapy does not affect milk production during or after treatment. Abrupt weaning can be psychologically traumatic for both the mother and the infant. (Pistilli 2013)

If the mother wishes, the production of milk can be maintained by regular expressing from the breast, being able to return to breastfeeding in the periods in which no significant traces of the drug remain in the milk (Anderson 2016) or at the end of the treatment. (Pistilli 2013)

It is known from pharmacokinetics that after 3 elimination half-lives (T½) 87.5% of the drug is eliminated from the body; after 4 T½ it is 94%, after 5 T½, 96.9%, after 6 T½, 98.4% and after 7 T½ it is 99%. From 7 T½ the plasma concentrations of the drug in the body are negligible. In general, a period of at least five half-lives can be considered a safe waiting period before breastfeeding again.(Anderson 2016)

Taking as reference the longest published T½ (15 hours), these 5 T½ would correspond to 3 days and 7 T½ would be 4 days, which is what expert authors recommend waiting after the last dose to restart breastfeeding (Hale). Meanwhile, express and discard milk from the breast regularly.

When it is possible to do so, detections in the breastmilk of each patient to determine the total elimination of the drug would be the best indicator of resuming breastfeeding between two cycles of chemotherapy.

Some chemotherapeutic agents with antibiotic effects can alter the composition of the microbiota (bacterial cluster or bacterial flora) of the milk and the concentration of some of its components (Urbaniak 2014). This possibly occurs temporarily with subsequent recovery, although no harmful effects are expected nor have been reported in breastfed infants.

Women undergoing chemotherapy during pregnancy have lower rates of breastfeeding due to experiencing difficulties with breastfeeding (Stopenski 2017), needing more support to achieve it.

Given the strong evidence that exists regarding the benefits of breastfeeding for the development of babies and the health of mothers, it is advisable to evaluate the risk-benefit of any maternal treatment, including chemotherapy, individually advising each mother who wishes to continue with breastfeeding.(Koren 2013)


See below the information of this related product:

Alternatives

We do not have alternatives for Methotrexate (anticancer drug).

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 (anticancer drug) is also known as


Methotrexate (anticancer drug) in other languages or writings:

Groups

Methotrexate (anticancer drug) belongs to these groups or families:

Pharmacokinetics

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
8 - 15 (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 %

References

  1. 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
  2. AEMPS-Wyeth. Metotrexato. Ficha técnica. 2018 Full text (in our servers)
  3. 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
  4. 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
  5. EMA-Therakind Ltd. Methotrexate. Drug Summary 2017 Full text (in our servers)
  6. 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
  7. Anderson PO. Cancer Chemotherapy. Breastfeed Med. 2016 May;11:164-5. Abstract Full text (link to original source) Full text (in our servers)
  8. 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)
  9. 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)
  10. 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)
  11. 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
  12. Practice Committee of American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril. 2013 Abstract
  13. Kulier R, Kapp N, Gülmezoglu AM, Hofmeyr GJ, Cheng L, Campana A. Medical methods for first trimester abortion. Cochrane Database Syst Rev. 2011 Abstract
  14. 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
  15. 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)
  16. 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)
  17. Johns DG, Rutherford LD, Leighton PC, Vogel CL. Secretion of methotrexate into human milk. Am J Obstet Gynecol. 1972 Abstract

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