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This has been reviewed and updated as of May 29, 2020.

Methotrexate Side Effects

If you have rheumatoid arthritis (RA) or severe psoriasis, there’s a good chance you’re taking methotrexate (MTX). This disease-modifying anti-rheumatic drug (DMARD) has a long history of effectively treating inflammatory autoimmune conditions, yet it also has the potential to raise your risk of developing certain infections.

Does being on methotrexate right now put you at high risk for contracting COVID-19?

“We don’t know how much methotrexate may contribute to being more susceptible to coronavirus,” says rheumatologist Joseph E. Huffstutter, MD, partner with Arthritis Associates in Hixson, Tennessee.

What we do know is that stopping this drug can have serious ramifications for the management of your condition: “If your disease flares you’ll have more trouble because you’ll need more medication to get a flare under control,” he explains.

Vinicius Domingues, MD, a rheumatologist in Daytona Beach, Florida, agrees that most patients should continue taking methotrexate — unless they develop symptoms of COVID-19 (more on that shortly). 

Recently published clinical guidance from the American College of Rheumatology echoes this recommendation to continue methotrexate in the absence of COVID-19 symptoms.

How Methotrexate Works in the Body

Methotrexate was originally developed as a chemotherapy drug designed to kill fast-growing cancer cells, although it is important to note that arthritis and psoriasis patients take substantially lower doses than cancer patients. (Anywhere from 100 to 300 mg is a typical chemotherapy dose; patients with inflammatory conditions like RA are usually prescribed 10 to 25 mg.)

“Methotrexate keeps cells from dividing,” says Dr. Huffstutter. “When you have active rheumatoid arthritis, the fastest-growing cells are those in the immune system. That’s how it works to suppress the immune system in someone whose immune system is overactive. We’re trying to downregulate it and make it more normal.”

More specifically, methotrexate works by blocking some of the actions of the vitamin folic acid in the body. That’s an important part of how high doses of MTX work to thwart cancer, because folic acid is required to help cells divide and replicate.

Although the most commonly reported side effects of methotrexate are fatigue, nausea, stomach pain, and loss of appetite, methotrexate might also raise your risk of some infections.

Fortunately, most arthritis patients who use this drug do not develop more infections, though if you’re also taking other DMARDs or an additional biologic agent, the risk of infections is greater.

You can read more here about methotrexate side effects.

To make sure that methotrexate hasn’t impacted your body’s production of red blood cells, platelets, and white blood cells (which help fight infections), anyone taking this drug should have a complete blood count every three months. Here is more information about how doctors monitor for methotrexate side effects.

While this blood test should give you and your doctor some indication of whether your immune system has been substantially impacted by methotrexate, it might be more difficult to get routine blood work done during the COVID-19 crisis.

If you’re due for a check, call your doctor’s office and ask whether you should get your blood test as scheduled. Patients who have been stable on methotrexate for a long time may be advised to wait an extra month, says Dr. Huffstutter.

What If You Develop Coronavirus Symptoms While on Methotrexate?

Although most patients on methotrexate should continue to take it as long as they are healthy, the guidance from the American College of Rheumatology advises that patients may temporarily stop this medication if they develop COVID-19 symptoms. Methotrexate might impair the body’s ability to combat coronavirus, says Dr. Domingues.

You should let your rheumatologist or primary care doctor know if you develop COVID-19 symptoms or have been in close contact with someone who has it. The most common symptom of COVID-19 is fever, which often goes hand-in-hand with a dry cough and shortness of breath. Here is a list of other common COVID-19 symptoms.

If you develop such symptoms, call your doctor. They may recommend temporarily stopping methotrexate to boost your odds of fighting off the virus.

Never stop taking your medications on your own without first discussing it with your health care provider. Be sure to consult your rheumatologist if you have any questions about whether to stop methotrexate and when to start it up again if you are advised to take a break from it.

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Interview with Joseph E. Huffstutter, MD, partner with Arthritis Associates in Hixson, Tennessee

Interview with Vinicius Domingues, MD, a rheumatologist in Daytona Beach, Florida

Major side effects of low-dose methotrexate. UpToDate. https://www.uptodate.com/contents/major-side-effects-of-low-dose-methotrexate.

Methotrexate. Medline Plus. U.S. National Library of Medicine. https://medlineplus.gov/druginfo/meds/a682019.html#why

Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo). American College of Rheumatology. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Methotrexate-Rheumatrex-Trexall.

Mikuls TR, et al. American College of Rheumatology Guidance for the Management of Adult Patients with Rheumatic Disease During the COVID-19 Pandemic. April 29, 2020. doi: https://doi.org/10.1002/art.41301.

Symptoms of Coronavirus. U.S. Centers for Disease Control and Prevention.

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