What is the recommended dosage of methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)) during pregnancy?

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Last updated: June 26, 2025View editorial policy

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From the Guidelines

Methotrexate is contraindicated during pregnancy and should be discontinued at least 6 months before conception. This recommendation is based on the most recent and highest quality study, which highlights the teratogenic effects of methotrexate and the importance of discontinuing its use before attempting to conceive 1. The medication is classified as FDA Pregnancy Category X, meaning it has demonstrated fetal risk and the risks clearly outweigh any potential benefits during pregnancy. Methotrexate is a folate antagonist that can cause spontaneous abortion and severe birth defects, including craniofacial, limb, and neural tube abnormalities, by interfering with cell division and DNA synthesis, processes critical for fetal development.

Key considerations for patients taking methotrexate who are planning to conceive include:

  • Discontinuing methotrexate at least 6 months before conception to minimize the risk of teratogenicity
  • Consulting with both their rheumatologist and obstetrician to discuss alternative treatment options
  • Continuing folic acid supplementation during this period to mitigate potential folate deficiency
  • Considering alternative medications that are safer during pregnancy, such as certain TNF inhibitors or low-dose corticosteroids, to manage disease activity during pregnancy.

It is essential to prioritize the health and well-being of both the mother and the fetus, and discontinuing methotrexate before conception is crucial to minimizing the risks associated with its use during pregnancy 1.

From the Research

Methotrexate Dosage During Pregnancy

  • Methotrexate is contraindicated during pregnancy due to its teratogenic effects 2
  • The recommended dosage of methotrexate during pregnancy is not established, as it is an FDA Pregnancy Category X medication
  • However, in cases of ectopic pregnancy, methotrexate may be used at a dose of 50 mg/m2 as a single intramuscular injection 3, 4 or 60 mg/m2 orally in 2 divided doses 2 hours apart 5
  • High-dose methotrexate may be used to treat unruptured ectopic pregnancy, but it carries a risk of malformations and should only be used if the diagnosis has been confirmed 6
  • The risk of malformations is probably dose-dependent, and the low weekly doses used in rheumatology seem to have a relatively low risk of malformations 2, 6
  • It is essential to inform women of the risks to their unborn child in case of diagnostic error or treatment failure when using high-dose methotrexate 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Single dose methotrexate therapy: application to interstitial ectopic pregnancy.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 1998

Research

Oral methotrexate for treatment of ectopic pregnancy.

American journal of obstetrics and gynecology, 2002

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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