How Methotrexate Works

Scientists don’t yet completely understand exactly how methotrexate works inside the body to help arthritis.

It is known that methotrexate changes how cells inside the body uses folic acid (vitamin B9), which is needed for cell growth. It is not well understood how exactly this effect, or other possible effects of methotrexate, work to help improve arthritis.

What is known is that the lower doses of methotrexate used in the treatment of arthritis can help patients by:

  • reducing the pain and swelling (inflammation) in arthritic joints
  • improving day to day function
  • preventing long-term damage caused by joint inflammation

Side Effects of Methotrexate

The most common side effect of methotrexate is nausea, feeling unwell, or feeling tired for 24 to 48 hours after taking a dose. This usually gets better over time as the body gets used to the medication. This side effect can also be reduced by lowering the dose or switching to the injected form from tablets.

Methotrexate very rarely causes a serious lung problem. Patients should call their doctor and STOP taking methotrexate if they experience:

  • New shortness of breath while resting, but don’t have a heavy cold (no runny nose or fever)
  • A new dry cough lasting weeks, especially in the absence of a cold

Patients must NOT take sulfa antibiotics, such as co-trimoxazole (Septra) or trimethoprim, while taking methotrexate. Patients should always check with their doctor or pharmacist before starting a new medication.

A doctor should review blood test results every 1-3 months to keep an eye out for any potential side effects to the liver or blood counts. It is important for patients who take methotrexate to remember to get these blood tests done.

Patients taking methotrexate should not drink alcohol.

Methotrexate may cause birth defects and result in miscarriage. Women should AVOID PREGNANCY.

The information sheets given by pharmacists do not distinguish between high and low dose Methotrexate. Arthritis treatment does not involve the high doses used in cancer treatments. The side-effects which may be seen with low-dose Methotrexate include the following:

MORE COMMON side-effects include:

  • Nausea, indigestion, and diarrhea.
  • Feeling generally unwell after taking the methotrexate.
  • Headaches & irritability.

RARE side-effects include:

  • Hair loss (rare at low doses)
  • Sensitivity to the sun (rare)
  • Liver: Methotrexate may irritate the liver. This does not usually cause symptoms but may be found on blood tests. It is uncommon and usually reversible when regularly monitored with blood tests.
  • Blood Counts: Methotrexate can cause a drop in the numbers of white blood cells (which are needed to fight infection) and platelets (which help to stop bleeding). If a patient is good at getting regular blood tests, it is unusual for this to be a serious problem.
  • Lungs: Methotrexate may irritate the lungs. If a person taking this medicine develops a cough, fever, or shortness of breath, they should STOP taking it and call their doctor immediately.
  • Infection: Any infections or fevers should be taken seriously and reviewed by a doctor.
  • Sores in the mouth.

How to minimize the side-effects of Methotrexate:

  • Take methotrexate ONCE A WEEK as prescribed by a doctor.
  • Tablets can be split up and taken at two times over a 24 hour period (i.e. take them with breakfast and dinner).
  • Taking Methotrexate before bed can sometimes help as patients may sleep through any nausea or general feelings of being unwell.
  • Taking folic acid may help to reduce the side effects of the methotrexate.
  • Some patients find switching from pills to injections helps reduce side effects.

People taking methotrexate should talk to their doctor if they are concerned about any side effects.

Who Should NOT Take Methotrexate

Patients who should NOT be taking Methotrexate include:

  • Patients taking sulfa antibiotics, such as co-trimoxazole (Septra) or trimethoprim
  • Women who are pregnant or breastfeeding
  • Women of child bearing potential who do not use reliable contraception
  • Patients with an infection. It is often best for patients who have a fever or think they have an infection to stop taking methotrexate. Phone your doctor for advice.
  • Patients who are heavy drinkers. It is best not to drink alcohol at all while taking methotrexate.

Anyone who becomes pregnant while taking Methotrexate should notify their doctor immediately.

When to Call a Doctor

People taking methotrexate should call their doctor if they feel sick and want to stop, or if they are concerned about any side effects.

Other reasons to call your doctor while taking methotrexate include:

  • Cough or difficulty breathing (especially shortness of breath)
  • Fever or possible infection
  • Developing severe mouth sores
  • Becoming pregnant or are planning on pregnancy
  • Planning to have surgery

Methotrexate Video

Watch Dr. Andy Thompson, a Canadian rheumatologist, introduce Methotrexate.