Methotrexate for Rheumatoid Arthritis


Generic Name Brand Name
methotrexate Rheumatrex, Trexall

Methotrexate is given weekly either as a shot (injection) or by mouth (orally).

How It Works

Methotrexate interferes with the production and maintenance of DNA, the genetic material in the cells of your body. It is not known exactly how methotrexate works in rheumatoid arthritis, but it can reduce inflammation and slow the progression of the disease. Methotrexate is considered a disease-modifying antirheumatic drug (DMARD). DMARDs are also called immunosuppressive drugs or slow-acting antirheumatic drugs (SAARDs).

Why It Is Used

Methotrexate reduces inflammation caused by rheumatoid arthritis. It is the most common DMARD used to treat rheumatoid arthritis.footnote 1 Methotrexate may be used:

  • In the early stages of rheumatoid arthritis to prevent disease progression.
  • In combination with other medicines such as other DMARDs.

How Well It Works

Methotrexate is effective in relieving joint inflammation and pain, slowing disease progression, and preventing disability by delaying joint destruction.footnote 2 People with rheumatoid arthritis may be more likely to continue treatment with methotrexate than with other DMARDs because of favorable results and tolerable side effects.

Methotrexate is often the first DMARD prescribed for rheumatoid arthritis and usually provides relatively fast relief of at least some symptoms. If you can tolerate methotrexate, but it is not effective, your rheumatologist will recommend that you take another DMARD along with methotrexate (combination therapy). For example, methotrexate may be combined with leflunomide or with a biologic medicine.

Combination therapy may allow for lower doses of an individual drug to be used, which may reduce the risk of adverse effects that can occur with higher doses. In one large review of studies, various combinations of DMARDs plus methotrexate were more effective than either methotrexate or another DMARD alone.footnote 3

Side Effects


Here are some important things to think about:


Call 911 or other emergency services right away if you have:

  • Trouble breathing.

Call your doctor if you have:

  • Hives.
  • Bloody vomit.
  • Diarrhea.
  • Stomach pain.
  • Sores in the mouth or on the lips.

Common side effects of this medicine include:

  • Nausea, vomiting, or loss of appetite.
  • Hair loss.


What To Think About




If you are taking methotrexate, talk to your doctor before taking any other medicines, including:

  • Penicillin antibiotics.
  • Sulfa-based medicines.

While it is generally safe to take nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, with methotrexate, it is best to talk with your doctor if you plan to do so. Methotrexate is eliminated by the kidney, and NSAIDs could decrease kidney function, so it is possible that clearance of methotrexate from the body could be affected by NSAIDs.

If you have a history of liver disease, such as viral or alcoholic hepatitis, talk with your rheumatologist before taking methotrexate.

Taking medicine



Advice for women







  3. Donahue KE, et al. (2008). Systematic review: Comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Annals of Internal Medicine, 148(2): 124–134.


ByHealthwise Staff
Primary Medical ReviewerAnne C. Poinier, MD - Internal Medicine

Current as ofSeptember 9, 2014