Methotrexate is a slow-acting anti-rheumatic drug (SAARD) that has traditionally been used to control inflammation in people with chronic inflammatory conditions like ankylosing spondylitis (AS), psoriatic arthritis, and rheumatoid arthritis. It may also be referred to as a traditional disease-modifying anti-rheumatic drug (DMARD).1 It is also used to treat certain types of cancer and the skin condition psoriasis.2

Treatment recommendations for AS recommend against using methotrexate to manage AS, as there is little to no evidence for its effectiveness in treating AS. However, in some cases, methotrexate may be used in combination with other treatments, such as a TNF (tumor necrosis factor) inhibitor.3

Methotrexate is available in generic forms. Brand names for methotrexate are also available and include Rheumatrex®, Trexall®, Otrexup®, and Rasuvo®.

What is the active ingredient in methotrexate?

The active ingredient in methotrexate is methotrexate sodium. In injectable formulations, methotrexate also contains small amounts of benzyl alcohol as a preservative.4

How does methotrexate work?

Methotrexate is a type of drug called an antimetabolite or antifolate. It inhibits the metabolism of folic acid, which is necessary in the production of DNA and in cell replication. It also reduces a number of the factors the body produces that cause inflammation. Several studies have found that methotrexate has benefits in treating rheumatoid arthritis, but the research has not found a similar effectiveness in people with AS.1,4

What are the possible side effects of methotrexate?

Common side effects of methotrexate include dizziness, drowsiness, headache, hair loss, redness in the eyes, reduced appetite, swelling or tenderness of the gums, and mouth sores.2,4 Folic acid is prescribed to be taken along with methotrexate which usually prevents many of these side effects.

In some patients, methotrexate can cause serious, life-threatening side effects. These include liver damage, lung problems, severe anemia, severe skin reactions, serious opportunistic infections, or damage to the lining of the mouth, stomach, or intestines. Methotrexate may increase a person’s risk of developing lymphoma, a type of blood cancer (this type of lymphoma usually resolves with stopping the methotrexate).2

This is not an exhaustive list of all potential side effects of methotrexate. Any new or worsening side effects should be reported to a doctor or healthcare provider immediately.

Things to know about methotrexate

Before taking methotrexate, patients should talk to their doctor about all their health conditions and medications, including if they4:

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

Women should take methotrexate while pregnant or breastfeeding, as it may cause harm to the baby.2

People taking methotrexate should avoid unnecessary or prolonged sun exposure and should avoid using tanning beds or sunlamps, as methotrexate can make the skin more sensitive.2

People receiving treatment with methotrexate should talk to their doctor before having any vaccinations.2

If surgery, including dental surgery, is needed, patients should tell their surgeon they are taking methotrexate.2

Dosing information

Methotrexate is available as a tablet and as an injection. Patients should talk to their doctor about any questions on their dosing regimen.

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Written by: Emily Downward | Last reviewed: February 2019