High-Alert Medications

Methotrexate (Rheumatrex, Trexal)

Safety Sheet

Oral methotrexate (to treat other conditions other than cancer)

Extra care is needed because methotrexate is a high-alert medicine.

High-alert medicines have been proven to be safe and effective. But these medicines can cause serious injury if a mistake happens while taking them. This means that it is very important for you to know about this medicine and take it exactly as directed.

Top 10 List of Safety Tips for Methotrexate

When receiving a prescription

  1. Look for the reason. Ask your doctor to put the reason for your medicine on all prescriptions. You might take a medicine like methotrexate daily for a week at a time if you have cancer, but just once or twice a week if you have arthritis or psoriasis (or certain other conditions). If the pharmacist knows your condition, he or she will make sure the directions for taking your medicine are correct.
  2. Ask for special packaging. Ask your doctor if the medicine comes in a special package designed for weekly use. For example, Rheumatrex, one brand of methotrexate, comes in a weekly dose pack. Never leave the doctor’s office unless you clearly understand how to take your medicine.
  3. Disclose all medicines. Tell your doctor about all prescription, nonprescription, and herbal products you take, particularly ibuprofen (Motrin, Advil), aspirin, echinacea, and vitamins.
  4. Avoid during pregnancy or breastfeeding. Tell your doctor if you are pregnant or trying to get pregnant. Methotrexate may cause birth defects or death of the unborn fetus if taken during pregnancy. Avoid pregnancy for at least 3 months following treatment with methotrexate. Do not take this medicine while breastfeeding, as it may reduce your infant's ability to fight infections.
  5. Pick a day(s). Pick the day(s) of the week that you’ll be taking your medicine, and ask your pharmacist to include that in the instructions.
  6. Ask for education. Ask the pharmacist to go over the directions for taking the medicine. Be sure it agrees with what the doctor told you.
  7. Take weekly, not daily. Never take the medicine daily for more than 1 consecutive week.
  8. Never take extra doses. Do not take extra doses for symptom relief. Relief of symptoms is gradual and begins in 3 to 6 weeks after starting the medicine. Continued improvement occurs during the first 12 weeks of taking the medicine.
  9. Avoid direct sunlight. Methotrexate causes an abnormal skin reaction if you are exposed to sunlight. You could develop severe redness, pain, and peeling of the skin. If you are in the sun, use sunscreen on your skin and wear eye protection and a hat.
  10. Report side effects. Let your doctor know about any side effects you experience, particularly a rash, fever, chills, trouble breathing, cough, racing heartbeat, bleeding, and changes in how often you urinate.

Methotrexate is a cancer medicine. However, it is also used to treat other conditions like rheumatoid arthritis and psoriasis. It works well for these conditions if you take the medicine just once or twice a week, and in smaller doses. But if you take the medicine every day by accident, you could be harmed. Sadly, some people have even died.

In several instances, this happened because people misread the directions on the prescription bottle.

In one case, a man with arthritis mistakenly took one tablet each morning, but the directions said to take one tablet each Monday. In another case, the prescription label said to take the medicine every 12 hours for just three doses. But a woman took the medicine every 12 hours for 6 days in a row. Another man took many extra doses to help relieve arthritis pain—something that should never be done.

Harmful mistakes may happen because you, your doctor, and your pharmacist are more familiar with medicines that are taken daily. Serious harm, even death, could occur if you take methotrexate daily for conditions other than cancer.

See the Top 10 List of Safety Tips to help you avoid mistakes when taking methotrexate less often than daily.

 Topics Fast Facts
Generic name
  • methotrexate (pronounced meth o TREKS ate)
Common brand names
  • Rheumatrex and Trexall
Generic available
  • Yes
Common uses
  • Cancer, psoriasis, rheumatoid arthritis
Other uses
  • Crohn's disease, ectopic (tubal) pregnancy
Safe dose limits
  • No more than three tablets (each taken 12 hours apart), or a total dose of 20 to 25 mg each week for treatment of psoriasis and arthritis
  • Higher doses are used only if treating cancer
Special instructions and precautions
  • Typically taken once or twice each week
  • Do not take daily for more than 1 consecutive week
  • Avoid alcohol
  • Do not take any new medicine unless approved by your doctor
  • Causes sun sensitivity, so use sunscreen and protective eyewear and clothing
  • Do not take with milk-rich foods
Safety during pregnancy/breastfeeding
  • Do not take during pregnancy; may cause birth defects
  • Do not take while breastfeeding
  • Avoid pregnancy for at least 3 months following treatment
This medicine should not be taken if you have:
  • Liver or kidney disease, AIDS, certain blood or bone marrow disorders
Also tell your doctor if you have:
  • Peptic ulcer disease or ulcerative colitis
Storage and disposal
  • Store at room temperature and protect from light
  • Avoid touching the tablets with your hands as much as possible
  • Dispose of the medicine securely in the trash
Side effects
  • Minimal side effects occur with low doses to treat psoriasis or rheumatoid arthritis
  • Possible side effects include: nausea, vomiting, drowsiness
  • Low-dose methotrexate has been associated with the rare development of cancerous lymphomas (tumors in lymph nodes)
Side effects to report to your doctor immediately (usually seen when taking high doses)
  • Rash, excessive fatigue, mental confusion, fever, chills, mouth sores, shortness of breath, dry cough, rapid heartbeat or palpitations, unusual bleeding or bruising, black stools, persistent stomach disturbances, change in how often you urinate
Nonprescription medicines/herbals/vitamins to avoid when taking methotrexate
  • Nonsteroidal anti-inflammatory agents (e.g., ibuprofen [Motrin, Advil]) or aspirin
  • Vitamins that contain folate, echinacea
Prescription medicines that should not be taken with methotrexate
  • Check with your doctor; some of the medicines that may be a problem include: acitretin, cyclosporine, sulfonamides, trimethoprim, vaccines, clozapine, carbamazepine
Special tests your doctor may prescribe
  • Blood tests may be prescribed every 1 to 4 months to make sure your kidneys and liver are functioning well and your body is making enough blood cells

This information does not replace the need to follow your doctor's instructions and read the drug information leaflet provided with your prescription.

This project was supported by grant number R18HS017910 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not represent the official views of the Agency for Healthcare Research and Quality.