Skip to Accessibility Tools Skip to Content Skip to Footer


Methotrexate is a disease-modifying anti-rheumatic drug (DMARD) approved for the treatment of adults with RA. It has become the cornerstone of RA treatment since it was first introduced over five decades ago as an anti-cancer drug.1

Given at a low dose, methotrexate is effective in controlling the swelling, pain, and stiffness that result from inflammation. In a significant percentage of patients, it also seems to slow the progression of rheumatoid arthritis and prevent damage to joints and related structures.2,3

This medication comes in both pill and injectable forms. It has been prescribed for over half a million patients with RA and has a strong safety record when monitored appropriately.1

Methotrexate is available in generic forms. Other brand names and formulations include:

  • Rheumatrex
  • Trexall
  • Otrexup
  • Rasuvo

What are the ingredients in methotrexate?

The active ingredient in methotrexate is methotrexate sodium. In injectable formulations, methotrexate also contains small amounts of benzyl alcohol as a preservative.2

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 is not well understood how methotrexate works against RA, but researchers believe the drug helps dampen the overactive immune processes at work in the disease. It also reduces a number of the factors the body produces that cause inflammation.1

What are the possible side effects of methotrexate?

Common side effects associated with methotrexate include4:

  • Dizziness
  • Drowsiness
  • Headache
  • Hair loss
  • Redness in eyes
  • Reduced appetite
  • Swelling and/or tenderness of gums and mouth sores
  • Sun sensitivity

In some patients, methotrexate can cause serious side effects. These include blurred vision or a sudden loss of vision, confusion, loss of consciousness, seizures, and weakness or difficulty moving one side of your body. If you experience any of these side effects or any other unusual problems while you are taking methotrexate, call your doctor immediately.

This is not an exhaustive list of all potential side effects of methotrexate. For more information, consult your doctor or healthcare provider. If you notice any new or worsening side effects, contact your doctor or healthcare provider immediately.4

Things to note about methotrexate

Before taking methotrexate, tell your doctor if you:

  • 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 lung disease, since methotrexate can damage your lungs
  • Have ever had stomach ulcers or ulcerative colitis, since methotrexate can damage the lining of your stomach, intestines, and mouth4

Methotrexate can cause serious side effects and problems, and although it is rare, deaths have occurred with people being treated for RA. It also causes fetal abnormalities, even at low doses, so it should not be used if you are pregnant or breastfeeding.

You should not take methotrexate if you have an immune deficiency disease, liver damage, or your body does not make enough blood cells. Also do not take it if you are allergic to the medicine or any of its ingredients.

Certain drugs do not mix well with methotrexate, so you should tell your doctor about any other medications or supplements you are taking.4

Doctors often recommend that patients taking methotrexate also take folic acid supplements (on a different day) to reduce the medication’s side effects.3

Dosing information

Methotrexate can be taken orally (as a tablet) or by injection (subcutaneously or intramuscularly). Your doctor will determine the optimal dose of methotrexate for you based on your level of disease activity and response to the treatment.

Taken orally, methotrexate is typically started at a single dose of 7.5 mg given once weekly or in three divided doses of 2.5 mg given at 12-hour intervals. Dosing of methotrexate is adjusted gradually until optimal response is achieved. The maximum weekly dose of oral methotrexate for adults with RA usually does not exceed 25 mg.2

It may take 3 to 6 weeks of treatment before you start to experience a therapeutic response to methotrexate, then up to 12 weeks or more for the full effect to be achieved.2

Written by: Sara Finkelstein | Last reviewed: September 2019.
  1. Johnsen AK, Weinblatt M. Methotrexate: the foundation of rheumatoid arthritis therapy. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatoid Arthritis. Philadelphia, Penn: Mosby Elsevier; 2009:307-314.
  2. Prescribing Information. Methotrexate. Hospira, Inc. Revised October 2011. Accessed May 14, 2018.
  3. Carolina Negrei, Violeta Bojinca, Andra Balanescu, et al. Management of rheumatoid arthritis: Impact and risks of various therapeutic approaches. Exp Ther Med. 2016 Apr; 11(4): 1177–1183. Published online 2016 Feb 2. doi: 10.3892/etm.2016.3045 Accessed May 16, 2018.
  4. Methotrexate. MedLine Plus. National Library of Medicine. Updated April 15, 2017.
  5. Accessed May 14, 2018.