Last reviewed 2026-04-22 · How we verify

methotrexate + misoprostol

Methotrexate inhibits dihydrofolate reductase to suppress cell proliferation, while misoprostol protects the gastrointestinal mucosa from methotrexate-induced damage.

Methotrexate inhibits dihydrofolate reductase to suppress cell proliferation, while misoprostol protects the gastrointestinal mucosa from methotrexate-induced damage. Used for Medical abortion (methotrexate-misoprostol combination), Ectopic pregnancy, Rheumatoid arthritis (methotrexate with gastroprotection).

At a glance

Mechanism of action

Methotrexate is an antimetabolite that blocks folate metabolism, leading to inhibition of DNA synthesis and cell division. Misoprostol is a prostaglandin analog that enhances gastric and intestinal mucosal protection by increasing mucus production and bicarbonate secretion, thereby reducing the risk of methotrexate-induced gastrointestinal toxicity and ulceration.

Approved indications

• Medical abortion (methotrexate-misoprostol combination)
• Ectopic pregnancy
• Rheumatoid arthritis (methotrexate with gastroprotection)

Common side effects

• Gastrointestinal cramping and diarrhea
• Bone marrow suppression
• Hepatotoxicity
• Nephrotoxicity
• Mucositis
• Vaginal bleeding (in abortion context)

Key clinical trials

• Is More Than One Dose of Misoprostol Needed to Expedite Vaginal Delivery in a Patient With an Unripe Cervix? (PHASE2)
• Comparing Methotrexate Followed by Misoprostol to Misoprostol Alone for Early Abortion (PHASE4)
• Comparison of Telephone Follow-up With In-person Follow-up After Medical Abortion (NA)

Primary sources

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