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Can Leg Cramps Be a Side Effect of Methotrexate for RA?

Medically reviewed by Ariel D. Teitel, M.D., M.B.A.
Written by Megan Cawley
Posted on July 6, 2022

Methotrexate is one of the most commonly prescribed — and most effective — drugs for treating rheumatoid arthritis (RA). As with any medication, methotrexate has a range of side effects. One possible side effect is leg cramping (also referred to as a “charley horse”).

Members of myRAteam have shared their experiences with leg cramping. One member asked if others experienced charley horses, writing, “I get them constantly, and they’re so painful.” Another member posed a similar question: “Two days ago, I experienced pain in the back of my leg. After several hours, I could hardly walk. I ended up in bed with the heating pad. The next day, I could walk but still had soreness, almost like the aftereffect of a bad charley horse.”

If you have been taking methotrexate for RA and have experienced muscle cramping, particularly in your legs, talk to your rheumatologist or another health care provider. They can determine if methotrexate may be the cause of your leg cramping and help you manage it while treating your RA.

Muscle and Leg Cramps as a Side Effect of Methotrexate

Methotrexate is often the first line of treatment for RA. It is a type of immunosuppressant known as a disease-modifying antirheumatic drug. Muscle cramps are not a common side effect of methotrexate, but muscle spasms are. Muscle spasms may lead to muscle cramps.

A muscle spasm is an involuntary (unconscious and unintended) contraction or tightening of a muscle. As of May 2020, the World Health Organization’s VigiBase system had 397 reports from people who experienced muscle spasms while taking methotrexate. Some people were taking methotrexate for RA, while others were taking it for conditions like psoriasis or psoriatic arthritis. Muscle spasms can be considered muscle cramps when they are chronic (long-lasting) and painful.

Injection Site Soreness

Methotrexate is often taken as a weekly injection. While these injections do not cause muscle cramps themselves, they may cause tenderness or soreness that may be mistaken for cramping.

Other Potential Causes of Leg Cramps

You can also experience leg cramping that’s not related to your RA treatment. Other potential causes of leg or muscle cramps include:

  • Exercising while dehydrated
  • Overworking or straining a muscle
  • Exercising with a condition that causes insufficient blood supply to the legs (such as arteriosclerosis)
  • Having compressed nerves
  • Having mineral deficiencies (particularly calcium, magnesium, or potassium deficiencies)

Managing Leg Cramps With Methotrexate

If you don’t know whether your leg cramps are caused by methotrexate or another issue, talk to your doctor. They will be able to evaluate what is causing your cramps and work with you to find a way to prevent or manage them.

The following are some recommendations your doctor may provide for managing leg cramps.

Stretching Your Muscles

If your legs cramp after exercising, gently stretch them both before and after physical activity. If your legs cramp at night, try stretching or lightly exercising before going to bed.

Staying Hydrated

Drinking plenty of fluids is one of the best ways to prevent muscle spasms and cramps. Fluids help prevent muscle irritation, hydrate the muscles’ cells, and promote muscle contraction and relaxation. It is especially important to drink plenty of liquids during and after physical activity.

Trying Heat Therapy

For immediate at-home relief of cramps or spasms, you may want to try hot packs, hot water bottles, or hot compresses. These can alleviate muscle spasms and improve blood flow, helping to reduce cramping.

Taking Pain Relievers

Your doctor may recommend taking over-the-counter pain relievers like naproxen or ibuprofen to help relieve mild to moderate pain from muscle cramping.

Managing General Side Effects

Many people who take methotrexate take a folic acid supplement to help minimize other side effects, like hair loss, mouth sores, anemia, and stomach pain. If you experience any of these side effects, talk to your doctor about how you can manage them. You may be able to take a lower dose of methotrexate or time your medication to avoid nausea or fatigue.

Find Your Team

If you or a loved one is living with rheumatoid arthritis, consider joining myRAteam today. Here, you can ask questions, offer support and advice, and connect with members from around the world who understand life with RA.

Have you experienced leg cramps while taking methotrexate? How have you managed them? Share your story or tips in the comments below or by posting on myRAteam.

Posted on July 6, 2022

A myRAteam Member

I haven't been on Methotrexate in years but I have leg cramps, especially at night. They might not have anything to do with my RA diagnosis because my mother also suffered from severe leg cramps… read more

November 25, 2023
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Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Megan Cawley is a writer at MyHealthTeam. She has written previously on health news and topics, including new preventative treatment programs. Learn more about her here.

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