What Is Methotrexate?

People with severe psoriasis may have symptoms that cannot be controlled by topical medications that are applied directly to the affected skin. Healthcare providers may advise them to try a systemic treatment such as methotrexate, a medication that is taken orally and affects the entire body1.

Methotrexate is a powerful type of medicine called an antimetabolite that has been prescribed to people living with psoriasis for the past 50 years. It is available in the United States under the brand names Rheumatrex and Trexall, but may also be prescribed generically as methotrexate. It is also used to treat patients who have psoriatic arthritis that affects the joints. Methotrexate can also be used at higher doses to treat patients with cancers such as leukemia, but the doses provided to adults with psoriasis or psoriatic arthritis are much lower2.

Methotrexate for psoriasis is taken by mouth once per week in a pill or in a liquid that can be mixed with juice. Some patients take a single dose per week, while others may take three doses spread out over 24 hours3. The dose of methotrexate is usually increased slowly over several months to find the lowest possible dose that maintains symptom improvement. While injection at home is possible, methotrexate is also available for injection to be administered in a healthcare setting.

How does methotrexate work?

Methotrexate works by affecting the way a person’s immune system controls inflammation in the body. A person with psoriasis has an immune system that is overactive and produces too much inflammation. This inflammation triggers the production of an excessive amount of new skin cells, which cause older skin cells to build up on the surface of the skin as plaques. Methotrexate helps to prevent the production of new skin cells, and can also help to reduce inflammation by targeting T-cells that trigger the inflammatory process2.

Studies have shown that people with severe psoriasis treated with methotrexate typically begin to have a reduction in symptoms after 6-8 weeks of treatment. After 5 or 6 months of treatment with slowly increasing doses of methotrexate, between 50% and 70% of patients experience a reduction in symptoms of 75% or more4. Symptom reduction is frequently measured using the Psoriasis Area and Severity Index (PASI) score.

Who should not take methotrexate

Women who are pregnant, planning to become pregnant or breastfeeding can never take methotrexate because it can cause severe or fatal birth defects. Women who take methotrexate will need to use a reliable method of birth control during treatment. To make sure that a woman does not have any methotrexate in her system before becoming pregnant, she will need to stop taking methotrexate for at least four months before trying to become pregnant1. Methotrexate can also temporarily affect a man’s fertility, so men will need to stop treatment with methotrexate at least three months before trying to conceive with a partner2.

Methotrexate can also cause serious types of liver damage in a small number of people. Treatment with methotrexate is not recommended for people who have or have had any type of liver conditions, such as cirrhosis or hepatitis B and C4.

Treatment with methotrexate is also not recommended for people who have:

  • alcoholism
  • blood conditions including anemia
  • kidney problems
  • any kind of active infectious disease
  • active peptic ulcers
  • a suppressed immune system

What are the possible side effects of taking methotrexate?

Liver damage is the most serious risk linked to treatment with methotrexate. Patients at risk of liver disease may need to have liver biopsies to monitor their liver for possible damage1. Healthcare providers will advise patients about the safety of drinking alcohol while being treated with methotrexate.

Other rare but serious side effects of methotrexate include:

  • a higher risk of getting infections, such as pneumonia and shingles
  • kidney damage
  • cough or shortness of breath
  • severe anemia
  • bone marrow problems

Some of the less serious side effects that can be caused by treatment with methotrexate include:

  • nausea
  • tiredness
  • trouble sleeping
  • lightheadedness
  • increased sensitivity to sun and sunburn
  • muscle aches
  • rash
  • fever
  • chills
  • diarrhea with blood in the stool
  • easy bruising or bleeding
  • temporary mild hair loss (that reverses when the treatment is stopped)
  • burning sensation in plaques on skin

This is not an exhaustive list of side effects experienced by those who are treated with methotrexate. All patients who are treated with methotrexate will have regular blood and laboratory tests to make sure that the drug is not having a harmful effect on their bodies4.

Some of these side effects may be caused by low levels of folic acid in the body. Healthcare providers may recommend that patients take a folic acid supplement during treatment with methotrexate4.

Can methotrexate be used with other treatments or drugs?

Many other medicines interact with methotrexate in ways that can make the side effects caused by methotrexate worse1. These include:

  • certain types of oral antibiotics such as trimethoprim and sulfamethoxazole (Septra or Bactrim)
  • nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, and naproxen
  • barbiturates
  • proton pump inhibitors
  • sulfonylureas
  • colchicine
  • thiazide diuretics

It is very important to let your healthcare provider know about any and all prescription medicines, over-the-counter medicines, vitamins or supplements that you are taking to avoid any dangerous drug interactions2.

Some patients may have treatment with methotrexate rotated or used in conjunction with other treatments such as4:

In some patients, rotating the treatments can help to reduce the side effects that they can cause.

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Written by: Anna Nicholson | Last reviewed: June 2022.