A Guide to Methotrexate Medication

A Commonly Prescribed Drug for Rheumatoid Arthritis and Other Rheumatic Diseases

In This Article

Methotrexate (brand names Rheumatrex, Trexall, Otrexup, Rasuvo) is commonly prescribed to treat rheumatoid arthritis and certain other rheumatic conditions. Methotrexate was approved by the FDA in 1988 for the treatment of rheumatoid arthritis. Prior to its approval for rheumatoid arthritis, methotrexate had been used to treat psoriasis and cancer. It was originally developed as a leukemia drug in the 1940s.

Aside from rheumatoid arthritis, methotrexate may be prescribed for:

Methotrexate Is a Slow-Acting DMARD

Methotrexate is classified as a DMARD (disease-modifying anti-rheumatic drug). The drug is used to reduce pain and swelling associated with rheumatoid arthritis, prevent joint damage, and lower the risk of disability by slowing disease progression. Improvement from methotrexate may be seen as soon as three to six weeks, but it may require 12 weeks or possibly even up to six months of treatment for full benefit to be realized.

Mechanism of Action

Methotrexate interferes with certain enzymes which play a role in immune system function. Methotrexate blocks the enzyme dihydrofolate reductase. By doing so, it affects the production of a form of folic acid which is needed for actively growing cells. It remains unclear exactly how methotrexate decreases arthritis activity.


Oral methotrexate is taken one day a week for rheumatoid arthritis. It is not taken daily like most pills. Methotrexate is available in 2.5-milligram tablets. The starting dose for most adults with rheumatoid arthritis is 7.5 to 10 milligrams (i.e., three or four pills). The three or four pills are taken together once a week (on the same day each week). If needed, the total dose of methotrexate can be increased to 20 or 25 milligrams each week.

The brand name Rheumatrex dose pack contains blister cards containing the exact number of pills to take each week. The brand name Trexall is available in 5, 7.5, 10, and 15-milligram tablets. Methotrexate is also available in an injectable form, which most patients are able to self-inject.

Side Effects

Methotrexate can cause abnormal liver function. It's important to routinely have your blood tested for liver function so your doctor can monitor you for unwanted side effects. Other than abnormalities with liver function, the most common side effects associated with methotrexate are nausea and vomiting.

The side effects already mentioned—nausea, vomiting, and liver function—may be dose-dependent. If you have any of these side effects, adjusting the dose may eliminate the problem. Many people experience no significant side effects while taking methotrexate.

Other possible side effects (some serious) include:

  • mouth sores
  • rashes or severe skin reactions
  • diarrhea
  • blood count abnormalities
  • liver damage/cirrhosis of the liver (rare)
  • kidney damage
  • lung disease
  • lymphoma
  • opportunistic infections
  • persistent cough
  • unexplained shortness of breath
  • hair loss (gradual)
  • sun sensitivity


  • The increased risk of liver damage with methotrexate is significant for people who drink alcohol. Ideally, you should not drink alcohol if you take methotrexate. At most, with your doctor's permission, you should have no more than two drinks per month.
  • Methotrexate should not be taken by people with known chronic liver or kidney disease. A rheumatologist may decide to prescribe methotrexate to people with mild liver or mild kidney disease—but with vigilance and an abundance of caution.
  • Methotrexate may need to be stopped prior to a surgical procedure, temporarily, while you are healing. This is due to a possible effect on the immune system and potential increased risk of infection with its use.
  • Anyone treated with methotrexate should take a folic acid supplement. Since methotrexate is a folic acid antagonist, replenishing folic acid by taking a supplement helps to minimize certain side effects associated with the drug.
  • Methotrexate should not be taken if you are pregnant or plan to become pregnant. Methotrexate can cause serious birth defects as well as pregnancy complications. You should be using some form of contraception while taking methotrexate and for three months after you stop taking methotrexate. It is important to note that although a woman should not take methotrexate during pregnancy, taking the drug does not decrease the chance of future pregnancies.
  • You should not take methotrexate if you are breastfeeding.
  • You should not take methotrexate if you have severe anemia, low white blood cell counts, or low platelet counts.
  • Methotrexate should be used with caution if you have a condition that weakens your immune system.
  • It is important to remind your doctor of all the medications you take (prescription and over-the-counter). Some medications and natural remedies may increase methotrexate toxicity. Drugs known to increase methotrexate toxicity include the antibiotic Trimethoprim (Bactrim). NSAIDs (nonsteroidal anti-inflammatory drugs), though often prescribed together with methotrexate, can affect the level of methotrexate. Your doctor and pharmacist will be aware of unsafe drug interactions.
  • The American College of Rheumatology recommends avoiding caffeine (coffee, tea, cola) near the time you plan to take methotrexate, as it may affect absorption of the drug.

A Word From Verywell

Methotrexate is among the most commonly prescribed drugs used to treat rheumatoid arthritis. In some cases, it is taken alone. In other cases, methotrexate is prescribed as part of combination therapy, where it is taken along with another DMARD or biologic drug.

It is imperative that you take methotrexate exactly as directed. It is also essential that you be aware of potential side effects and report anything unusual to your doctor immediately. Methotrexate can be a safe and effective medication when used properly.

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  2. Bedoui Y, Guillot X, Sélambarom J, et al. Methotrexate an old drug with new tricks. Int J Mol Sci. 2019;20(20). doi:10.3390/ijms20205023

  3. Conway R, Carey JJ. Risk of liver disease in methotrexate treated patients. World J Hepatol. 2017;9(26):1092-1100. doi:10.4254/wjh.v9.i26.1092

  4. Humphreys JH, Warner A, Costello R, Lunt M, Verstappen SMM, Dixon WG. Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate. Ann Rheum Dis. 2017;76(9):1509-1514. doi:10.1136/annrheumdis-2016-210629

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