March 2, 2015

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What side effects are possible with Methotrexate?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is used in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who uses this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people using this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • dizziness
  • hair loss
  • loss of appetite
  • nausea or vomiting
  • upset stomach

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • black, tarry stools
  • blurred vision
  • chest pain
  • confusion
  • cough or hoarseness
  • dark urine
  • diarrhea
  • drowsiness
  • fever or chills
  • lower back or side pain
  • mood changes
  • mouth sores
  • painful or difficult urination
  • pinpoint-sized red spots on skin
  • ringing in the ears
  • sensitivity to sunlight
  • shortness of breath
  • skin rash
  • sore eyes
  • stomach pain
  • unusual bleeding (e.g., vomiting blood, coughing up blood, blood in urine or stools) or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • convulsions (seizures)
  • severe skin reaction (e.g., blistering or peeling skin)
  • symptoms of a severe allergic reaction (e.g., hives, difficulty breathing, swelling of the face, mouth, tongue, or throat)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for Methotrexate?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.


October 19, 2012

Health Canada has issued new restrictions concerning the use of methotrexate. To read the full Health Canada Advisory, visit Health Canada's web site at

Blood counts: Methotrexate can cause a decrease in the number of white blood cells, red blood cells, and platelets in your blood, especially when higher doses are used to treat cancer. This may increase your risk of bleeding or infections. Your doctor will monitor your blood counts with regular blood tests.

If you are using this medication to treat cancer and already have a blood disorder such as anemia, reduced white blood cell counts, or reduced platelet counts, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

To help prevent infections, avoid contact with people with contagious infections, wash your hands frequently, and do not touch your eyes or the inside of your nose unless you have just washed your hands. Tell your doctor if you begin to notice signs of an infection, such as fever or chills.

Also, tell your doctor about any signs that your blood is not clotting as quickly. Such symptoms may include black and tarry stools, blood in the urine, pin-point red spots on your skin, easy bruising, or cuts that won't stop bleeding. Be careful when you are flossing or brushing your teeth and check with your doctor before having dental work. Take care not to cut yourself when using sharp objects such as a knife, scissors, or a razor.

Cancer: This medication may cause lymphoma (cancer of the immune cells) that may resolve when the medication is stopped. Your doctor will monitor for this.

Dizziness/fatigue: This medication may cause dizziness and fatigue. Do not drive or operate machinery until you are certain that taking this medication does not impair your ability to safely perform these tasks.

Infection: If you are using this medication to treat rheumatoid arthritis and have an infection, talk to your doctor about whether you need to temporarily stop this medication until the infection resolves. If you are using this medication to treat cancer, refer to the information above under "blood counts".

Kidney function: If you have reduced kidney function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you are using this medication to treat cancer, your doctor may want you to drink extra fluids to help prevent kidney problems.

Liver problems: Methotrexate can cause liver problems. Your doctor will check your liver function with blood tests before starting this medication and regularly during treatment. If you have liver problems or reduced liver function discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Do not drink alcohol while you are taking this medication as this can increase the chance of liver problems.

Lung problems: Methotrexate may cause lung problems. If you experience symptoms of lung problems (e.g., dry, non-productive cough, fever, shortness of breath), contact your doctor immediately.

Stomach and intestinal problems: If you have stomach or intestinal ulcers or ulcerative colitis, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Sun sensitivity: You may be more sensitive to the sun while using this medication. Avoid excessive sun exposure and do not use sunlamps or sun beds until you know how this medication affects your skin.

Vaccines: Vaccines may be ineffective if given during treatment with methotrexate. Live virus vaccines (e.g., smallpox, measles, mumps, rubella, chickenpox, shingles) are not recommended during treatment with methotrexate.

Pregnancy: There is a possibility of birth defects if either partner is using methotrexate at the time of conception. If it is used during pregnancy, methotrexate may also cause birth defects or harm the baby.

Effective birth control should be practiced if either partner is using this medication, including for a period of time after the medication is stopped. Talk to your doctor about how long you should wait to become pregnant after you or your partner stop taking methotrexate. If you become pregnant while taking this medication, contact your doctor immediately.

If you have rheumatoid arthritis or psoriasis, you should not use this medication if you are pregnant. If you might be pregnant, do not start methotrexate until you know for sure that you are not pregnant.

Breast-feeding: Women who are using methotrexate should not breast-feed.

Children: Methotrexate has been used to treat cancer in children. Methotrexate has also been used under close supervision of a doctor to treat other conditions in children.

Seniors: If you are a senior, you may be more at risk of experiencing side effects (including serious ones) and your doctor will monitor you very closely while you are using this medication.

What other drugs could interact with Methotrexate?

There may be an interaction between methotrexate and any of the following:

  • acitretin
  • alcohol
  • aminoglycosides (e.g., tobramycin)
  • amphotericin B
  • azathioprine
  • chloramphenicol
  • cyclosporine
  • echinacea
  • eltrombopag
  • folic acid
  • leflunomide
  • live vaccines (e.g., BCG, yellow fever, measles, mumps, rubella)
  • mercaptopurine
  • natalizumab
  • neomycin
  • nitrous oxide
  • nonsteroidal anti-inflammatory medications (NSAIDs; e.g., ibuprofen, naproxen)
  • penicillins (e.g., amoxicillin, ampicillin, penicillin, cloxacillin)
  • phenytoin
  • pimecrolimus
  • polymyxin B
  • probenecid
  • retinoids (e.g., tretinoin, retinol)
  • roflumilast
  • salicylates (e.g., ASA, salsalate)
  • sulfonamides (e.g., sulfasalazine, sulfamethoxazole, sulfadiazine)
  • tacrolimus
  • tetracyclines (e.g., doxycycline, tetracycline)
  • theophylline
  • trimethoprim
  • vancomycin

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

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