Can you take methotrexate while breastfeeding?

What LactMed would consider instead

LactMed ends this record by naming the drugs it would consider in place of methotrexate. Whether any of them fits depends on what you are treating — this is the database’s list, not a recommendation from us.

• Auranofin
• Etanercept
• Gold Sodium Thiomalate
• Hydroxychloroquine
• Infliximab
• Penicillamine
• Sulfasalazine
• Adalimumab
• Certolizumab Pegol
• Phototherapy
• Tretinoin

How much methotrexate gets into breastmilk

Methotrexate is partially metabolized to the active metabolite, 7-hydroxymethotrexate, which is detectable in breastmilk.

Maternal Levels. One patient who was 1 month postpartum was 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 and measured using an old bioassay. 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. Assuming a maternal weight of 60 kg and using the highest milk level, the worst-case relative infant dose would be about 0.1%

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.

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.

Two lactating women receiving subcutaneous methotrexate 25 mg once weekly donated 4 to 7 milk samples over a 1-week period between doses. Peak breastmilk methotrexate milk concentrations occurred between 1 and 12 hours after the dose and were 4 nmol/L (1.8 mcg/L). Peak breastmilk milk concentrations of the active metabolite, 7-hydroxymethotrexate, occurred at 24 hours after the dose and were 1.8 nmol/L (846 ng/L). Milk methotrexate concentrations were less than 2.5 nmol/L (1.1 mcg/L) during the rest of the dosing interval after the peak. One patient had undetectable (<91 ng/L) milk levels between 5 and 7 days after the dose. The authors estimated that if the peak methotrexate level were sustained throughout the feeding, the relative infant dose would be 0.5% of the weight-adjusted maternal dose and if breastfeeding were withheld for the first 24 hours after the dose, this value would decrease to 0.3% of the weight-adjusted maternal dose.

A woman with placenta accretia received intramuscular methotrexate 92 mg (1.12 mg/kg) daily for 4 days, beginning on day 5 postpartum. On day 2 of therapy, she provided samples of breastmilk at baseline and 1, 2, 4, 8, 12, and 24 hours after the dose. The peak methotrexate milk concentration of 16.9 mcg/L occurred at 2 hours after the dose, which decreased to 4.9 mcg/L at 24 hours. The average methotrexate milk level over the 24-hour period was 8.6 mcg/L. The peak 7-hydroxymethotrexate milk concentration of 3 mcg/L occurred at 1 hour after the dose. The average 7-hydroxymethotrexate milk level over the 24-hour period was 1.5 mcg/L. The estimated daily dosages of methotrexate and 7-hydroxymethotrexate were estimated to be 1.2 mcg/kg and 0.2 mcg/kg, respectively. These represent infant dosages of 0.11% and 0.02% of maternal weight-adjusted dosages.

Milk samples from 7 women receiving methotrexate weekly for inflammatory conditions were used to construct a physiologically based pharmacokinetic (PBPK) model for methotrexate in doses of 10 to 25 mg weekly. An infant PBPK model was used to simulate infant plasma concentrations from methotrexate in breastmilk. Infants breastfed by women during low-dose weekly methotrexate therapy are predicted to have less than 1% of the corresponding maternal exposures.

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

What has been seen in breastfed infants

Weekly methotrexate 25 mg subcutaneously begun a nursing mother on day 151 postpartum. The estimated intake of the infant at that time was 3.4 mcg/kg in the first 24 hours after administration. The mother continued to breastfeed (extent not stated) for an additional 9 months while receiving subcutaneous methotrexate 25 mg weekly. No adverse effects were noted in the infant.

Three postpartum women were erroneously dispensed methotrexate 2.5 mg daily instead of methylergonovine. They took methotrexate daily for 5, 13 and 15 days, respectively, while they were breastfeeding (extent not stated). Although all of the women developed toxicity and required hospitalization, none of their infants had clinically observable complications.

Effects on milk supply

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