Methotrexate - What You Must Know Before Taking the Drug

Considered the "Gold Standard" DMARD

Looking at methotrexate directions on bottle.
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Drug Class

Methotrexate belongs to the drug class known as ​DMARDs (disease-modifying anti-rheumatic drugs). DMARDs slow the progression of rheumatoid arthritis and other rheumatic diseases, and help prevent joint damage.

Methotrexate was developed as a leukemia drug in the 1940s. The drug was considered experimental in the 1970s. It was approved by the Food and Drug Administration to treat rheumatoid arthritis in 1988.

There are other DMARDs which were approved by the FDA to treat rheumatoid arthritis and certain other rheumatic conditions:

  • Arava (leflunomide)
  • Azulfidine (sulfasalazine)
  • Plaquenil (hydroxychloroquine)
  • CellCept (mycophenolate)
  • Neoral (cyclosporine)
  • Cytoxan (cyclophosphamide)
  • Imuran (azathioprine)
  • Leukeran (chlorambucil)
  • Minocin (minocycline)
  • Myochrysine (gold shots)
  • Auranofin (oral gold)
  • Penicillamine (cuprimine)

Dosing Information

Methotrexate is available in 2.5 mg tablets. The usual adult starting dose for methotrexate is 7.5 mg to 10 mg (3 or 4 pills) taken together one day a week. The dose may be increased as needed up to 20-25 mg/week.

  • The Rheumatrex Dose Pack contains blister cards containing the exact number of pills for a patient's weekly dose.
  • Trexall (a brand name) is available in 5 mg, 7.5 mg, 10 mg, and 15 mg tablets.
  • Methotrexate is also available as an injectible formulation.

Conditions Treated by Methotrexate

Methotrexate was first used as chemotherapy.

In low doses, methotrexate taken weekly is an effective treatment for rheumatoid arthritis, psoriatic arthritis, juvenile chronic arthritis, vasculitis, and lupus. With ankylosing spondylitis, methotrexate may benefit peripheral joint disease, but has little effect on the spine.

How Long Before Noticeable Improvement?

According to the American College of Rheumatology, noticeable improvement in arthritis and other rheumatic diseases is usually seen about 3 to 6 weeks after treatment with methotrexate.

It may take 12 weeks for some people to realize the full benefit of methotrexate treatment.

How Does Methotrexate Work?

Methotrexate interferes with enzymes active in the immune system. By blocking the enzyme, dihydrofolate reductase, methotrexate interferes with production of a form of folic acid important for growing cells of the blood, skin, gastrointestinal tissues and immune system. How methotrexate decreases arthritis activity is not clear.

Common Side Effects

The most common side effects associated with methotrexate include:

Who Should Not Take Methotrexate?

Methotrexate is contraindicated in pregnant women or those who plan to become pregnant because of the risk of birth defects. It is contraindicated in people who have abnormal kidney or liver function.

People who are having surgery need to ask their doctor about temporarily stopping methotrexate.

Your doctor will advise you.

People should not drink alcohol while taking methotrexate because of an increased risk of liver damage. Some doctors allow up to 2 alcoholic drinks per month.

More Essential Facts

  • Patients taking methotrexate should also take folic acid supplements (or folinic acid).
  • Your doctor will use blood tests to monitor your liver and kidney function on a regular basis.
  • If you want to become pregnant, talk to your doctor. Methotrexate can cause birth defects and birth complications. You may be advised to use contraception until at least 3 months after you stop methotrexate.


Trexall/Methotrexate. Indications. RXList.

Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo). Cannon M.D., Michael. March 2015. American College of Rheumatology.

Arthritis Without Pain. Zashin M.D., Scott J.. Dallas, Texas: Sarah Allison Publishing Company, 2004.

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