L01BA01; L04AX03

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).}

OBSTETRIC AND IMMUNOSUPPRESSANT USES:

• 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.)