Guidelines to Help Reduce the Side-Effects of Methotrexate

How to Reduce Drug Side Effects

Methotrexate (also sold under the brand names Rheumatrex and Trexall) is an immunosuppressant drug often prescribed for people with inflammatory types of arthritis.

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, discontinuation of the drug. But your dose should never be lowered - nor discontinued - without the guidance of 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 frequent blood tests, which can range from once every two weeks to once every six weeks, once your dose has been stabilized. These blood tests may include: CBC (complete blood count, especially to check your white blood cell count that indicates your risk of infection); liver chemistries; kidney function. Close follow-up of these laboratory tests is essential.

When you are started on methotrexate, ask about your doctor's practice for monitoring and follow-up. For example, some physicians will call you only if your test results are abnormal, while others call to report even normal results. Others expect you to call in to check on your labs - and may want you to stop the drug if you can't call in. That's because, occasionally, your white blood cell count can drop suddenly, leaving you at risk for infection. In such instances, continuing the drug can be dangerous but stopping it generally causes the count to return to normal.

Other side effects, both minor and serious, do cause symptoms. Following are common problems you should 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.


  • 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.

Other Symptoms

  • 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 (not common at the low doses generally used).

Your Lifestyle

Some aspects of your lifestyle may need to be changed while taking methotrexate.

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 avoid alcohol while taking methotrexate.


  • The use of methotrexate is not advisable during pregnancy.
  • If you are planning to become pregnant, or become pregnant, while taking methotrexate, report this to your physician immediately.


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

In-person and virtual
physician appointments

Urgent Ortho Care

Same-day in-person or virtual appointments

Related Content