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Patient Guidelines to Help Reduce the Side Effects of Methotrexate

Methotrexate (also sold under the brand names Rheumatrex and Rasuvo) is an immunosuppressant drug often prescribed for people with inflammatory types of arthritis. It is especially commonly used in patients with rheumatoid arthritis. The medication is taken once a week (sometimes taken as two doses 12 hours apart once a week).

Yellow pill tablets.

Many patients on methotrexate have few or no side effects. Among those who do have problems, most side effects resolve by lowering the dose or, if needed, discontinuing the drug. But your dose should never be lowered or discontinued without guidance from your physician. Sudden discontinuation of the drug may put you at risk for a flare of your disease, so your doctor will want to monitor you appropriately.

However, it is important for you to be aware of any symptoms of possible side effects so that you can report them to your doctor promptly − and appropriate action can be taken if necessary.

Some serious side effects can occur without causing any symptoms you would immediately notice. That's why your physician will want to monitor you with blood tests more frequently early on in treatment. These blood tests may include: CBC (complete blood count, especially to check your white blood cell count,) liver chemistries and kidney function. Close follow-up of these laboratory tests is essential, since methotrexate can, at times, cause a drop in white blood cell count, for example. It can also at times cause an elevation of liver chemistries. These are generally reversible when dose is decreased or medication stopped, but it’s good to pick them up earlier than later.

When you are started on methotrexate, ask about your doctor's practice for monitoring and follow-up. For example, some physicians will contact you only if your test results are abnormal, while others will contact you about all results, even if normal.

Other side effects, both minor and serious, do cause symptoms.

What are common side effects to be aware of while taking methotrexate?

Stomach upset

  • Take methotrexate after meals, which may reduce the risk of stomach upset.
  • If you develop nausea or vomiting, report it promptly because another medication may be prescribed to control these symptoms.
  • Some people feel some nausea and fatigue the day after taking methotrexate. One strategy sometimes used by doctors to improve this is by giving dextromethorphan with the MTX dose and again 8 to 12 hours later. We usually prescribe this as a tablet (Mucinex DM).


  • Signs of infection include: fever over 101 degrees, production of colored sputum, pain on passing your urine, or development of a boil on the skin.
  • Such symptoms should be reported to your doctor immediately.
  • If the infection is severe, you will probably need to have your blood count checked, since a low white blood cell count could be making the problem worse.


  • Abnormal bleeding, such as from the gums or in the urine, should be promptly evaluated.
  • Purple spots on the legs could be a sign of slight bleeding into the skin.
  • Again, such symptoms require that your platelet count checked as soon as possible, since methotrexate can sometimes lower the platelet count.

What other symptoms can taking methotrexate cause?

  • If any of the following occur, they should be brought to your physician's attention within 24 hours: black stools, difficulty breathing, yellow eyes or skin, marked fatigue, dizziness, or skin rash.
  • If any of the following occur, they should be reported to your physician at your next appointment: mouth sores or hair loss (both of which can be dose-related, and appear to happen less when you take folic acid, which is routinely advised along with methotrexate).
  • Methotrexate can cause sun-sensitivity, and getting a sunburn much more quickly than you might have in the past. After starting methotrexate, be especially careful the first time in the sun, perhaps staying no more than five minutes, just to be sure you haven’t developed sun-sensitivity. Most people don’t develop this, but it’s best to find out in a more gentle way if this is the case for you.

Liver function

  • As discussed above, your doctor will check your liver function regularly since methotrexate can sometimes cause toxic effects on the liver.
  • Since alcohol can also have toxic effects on the liver, it is advisable to significantly limit alcohol while taking methotrexate. If you think you are not able to limit your alcohol intake, be sure to discuss this with your doctor, since at times the doctor might choose to avoid methotrexate if you aren’t going to limit alcohol.


  • The use of methotrexate is not advisable during pregnancy. If you are planning to try to become pregnant in the near future, methotrexate is not a good choice of medication for you.
  • Data has recently shown that a man taking methotrexate does not appear to be a problem if his partner is planning or has become pregnant.
  • If you unexpectedly become pregnant while taking methotrexate, stop this medication immediately and report this to your physician.
  • has a good resource on methotrexate in pregnancy, useful for both women and men.

Do I have to adjust my lifestyle when taking methotrexate?

Some aspects of your lifestyle may need to be changed while taking methotrexate. This can include reducing alcohol intake, reducing or switching other medications, and, in some people, reducing exposure to sunlight.


  • Most people can take methotrexate without discomfort, and it is an important and, often, effective medication.
  • There are ways to help prevent and minimize many of the side effects of methotrexate, and close monitoring can allow an early detection of most other side effects.


Theodore R. Fields, MD, FACP
Attending Physician, Hospital for Special Surgery
Professor of Clinical Medicine, Weill Cornell Medical College

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