Reviewed by: HU Medical Review Board | Last reviewed: May 2023

Methotrexate is a disease-modifying anti-rheumatic drug (DMARD) approved for the treatment of adults with rheumatoid arthritis (RA) and other inflammatory diseases. It is also used to treat cancer.1

At a low dose, methotrexate helps control the swelling, pain, and stiffness that result from inflammation. It often is a first-line treatment for RA. Methotrexate comes in both pill and injectable forms.1-3

Methotrexate is available under both generic and brand names. Brand names and formulations include:2,3

  • Rheumatrex®
  • Trexall®
  • Otrexup®
  • Rasuvo®

What are the ingredients in methotrexate?

The active ingredient in methotrexate is methotrexate sodium.1

How does methotrexate work?

Methotrexate is a type of drug called an antimetabolite or antifolate. It blocks the metabolism of folic acid, which is necessary for the production of DNA and cell replication.1

Researchers do not understand exactly how methotrexate works against RA. They believe the drug may help dampen the overactive immune processes at work in the disease.1,2

What are the possible side effects?

Common side effects associated with methotrexate include:1-3

  • Dizziness
  • Drowsiness
  • Headache
  • Hair loss
  • Redness in eyes
  • Reduced appetite
  • Mouth sores and swelling and/or tenderness of gums
  • Sun sensitivity

In some people, methotrexate has caused serious side effects. These side effects include:1,2

  • Blurred vision or a sudden loss of vision
  • Confusion
  • Loss of consciousness
  • Seizures
  • Weakness or difficulty moving one side of the body
  • Increased risk of infection
  • Skin reactions such as fever, rash, blisters, or peeling skin

Methotrexate has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because it can cause serious side effects and problems, including anaphylaxis and death. It also causes severe fetal abnormalities (birth defects) in people who are pregnant.1-3

If you experience any of these side effects or any other unusual problems while you are taking methotrexate, call your doctor right away.

These are not all the possible side effects of methotrexate. Talk to your doctor about what to expect when taking methotrexate. You should also call your doctor if you have any changes that concern you when taking methotrexate.1

Other things to know

Before taking methotrexate, tell your doctor if you:1,2

  • Are pregnant or plan to become pregnant
  • Are breastfeeding
  • Are taking antibiotics or other medicines, including vitamins and supplements
  • Are taking non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen
  • Have kidney disease
  • Have ever had fluid around your stomach or lungs
  • Have had problems with any of your blood cells, including low blood cell counts
  • Have ever consumed alcohol heavily, since methotrexate can damage your liver
  • Have ever had lung disease, since methotrexate can damage your lungs
  • Have ever had stomach ulcers or ulcerative colitis, since methotrexate can damage the lining of your stomach, intestines, and mouth

You should not take methotrexate if you have an immune deficiency disease or liver damage. Do not take methotrexate if your body does not make enough blood cells. In addition, do not take methotrexate if you are allergic to the medicine or any of its ingredients.1-3

Certain drugs do not mix well with methotrexate. Before beginning treatment for RA, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.1

For more information, read the full prescribing information for methotrexate.

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