Methotrexate for Rheumatoid Arthritis

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Methotrexate for Rheumatoid Arthritis


Generic NameBrand Name
methotrexateRheumatrex, 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.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.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.3

Side Effects

All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine.

Here are some important things to think about:

  • Usually the benefits of the medicine are more important than any minor side effects.
  • Side effects may go away after you take the medicine for a while.
  • If side effects still bother you and you wonder if you should keep taking the medicine, call your doctor. He or she may be able to lower your dose or change your medicine. Do not suddenly quit taking your medicine unless your doctor tells you to.

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

  • Trouble breathing.
  • Swelling of your face, lips, tongue, or throat.

Call your doctor if you have:

  • Hives.
  • Signs of an infection, such as a sore throat, fever, sneezing, or coughing.
  • Bloody vomit.
  • Signs of unusual bleeding or bruising, such as black and tarry stools or blood in the urine.
  • 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.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

These medicines can stop your immune system from fighting infection. When you are taking this medicine (and even when you have finished taking it), try not to be around people who are sick. And make sure you talk to your doctor before you get any vaccinations.

These medicines may increase your risk of getting cancer, including lymphoma.

Do not drink alcohol when you are taking these medicines. Combining alcohol with these medicines can increase your risk for liver damage.

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

Medicine is one of the many tools your doctor has to treat a health problem. Taking medicine as your doctor suggests will improve your health and may prevent future problems. If you don't take your medicines properly, you may be putting your health (and perhaps your life) at risk.

There are many reasons why people have trouble taking their medicine. But in most cases, there is something you can do. For suggestions on how to work around common problems, see the topic Taking Medicines as Prescribed.

Advice for women

Do not use this medicine if you are pregnant or planning to get pregnant. If you need to use this medicine, talk to your doctor about how you can prevent pregnancy.


Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take.

Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.



  1. Drugs for rheumatoid arthritis (2009). Treatment Guidelines From The Medical Letter, 7(81): 37–46.
  2. Walker-Bone K, Fallow S (2007). Rheumatoid arthritis, search date June 2005. Online version of BMJ Clinical Evidence. Also available online:
  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
Specialist Medical ReviewerNancy Ann Shadick, MD, MPH - Internal Medicine, Rheumatology
Last RevisedJune 5, 2012

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