• Methotrexate interferes with DNA synthesis and has more of an effect against cells that are proliferating faster than normal (these types of cells typically occur in cancer and psoriasis). It has been shown to inhibit dihydrofolate reductase (DHFR), an enzyme that participates in folic acid synthesis. Folic acid is essential in the synthesis of purines and pyrimidines, vital for protein, DNA, and RNA synthesis
• Experts are not sure how methotrexate works in rheumatoid arthritis but believe it may have multiple mechanisms including an effect on immune function.
• Methotrexate belongs to the class of medicines called antimetabolites. It may also be called a folic acid antagonist. Methotrexate is also called an immunosuppressant.

• May be used for the treatment of severe, disabling psoriasis or rheumatoid arthritis that is not responsive to other forms of treatment. May be used for its immunosuppressive or anti-inflammatory effects in psoriatic arthritis.
• May be used in the treatment of some life-threatening cancers including breast cancer, head and neck cancer, lung cancer, lymphomas, osteosarcoma, bladder cancer, hydatidiform mole, and acute lymphocytic leukemia.
• May be given to manage chronically active Crohn's disease.
• In selected patients with small, unruptured, tubal pregnancies, it may be used as an alternative to surgery for ectopic pregnancy.
• Low doses have been given for chronic progressive multiple sclerosis.
• Available orally, intravenously, and intramuscularly. May also be given intrathecally.
• Oral therapy is preferred, especially for low dosages.
• May be taken with or without food; however, food delays absorption and reduces peak concentrations.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Mouth lesions, low blood counts, poor appetite, nausea, and abdominal discomfort are the most common side effects of methotrexate. Tiredness, dizziness, skin rash, hair loss, and increased susceptibility to infection have also been reported. Diarrhea and ulcerative stomatitis that requires therapy interruption may also occur.
• May cause bone marrow, liver, lung, and kidney disease; deaths have been reported from methotrexate use. Periodic liver biopsies are recommended for people taking methotrexate long-term. Acute liver enzyme elevations have been seen.
• Regular monitoring is needed for bone marrow, lung, or kidney toxicity.
• Should only be used in life-threatening cancers or in people with psoriasis or rheumatoid arthritis with severe, disabling disease that is unresponsive to other treatments.
• Should only be prescribed by clinicians experienced at prescribing methotrexate, especially when used for the treatment of osteosarcoma which requires meticulous care. Patients need to be informed of the risks involved with therapy and the importance of seeing their healthcare provider regularly.
• Should not be prescribed on an as needed basis.
• May cause a potentially fatal and irreversible lung condition; incidence does not depend on the dosage of methotrexate or length of treatment. Dangerous pulmonary lesions may not be reversible on discontinuation and have been reported with dosages as low as 7.5mg weekly.
• Serious toxic reactions have been reported in people treated with methotrexate for cancer, psoriasis, and rheumatoid arthritis.
• The elimination of methotrexate may be compromised in people with kidney disease, ascites, or pleural effusions. Carefully monitor for toxicity and reduce dosage or discontinue if necessary.
• May not be suitable for people with anemia, poor kidney function, immunodeficiency, bone marrow disorders, gastrointestinal conditions, liver disease, fluid in the lungs, or alcoholism. Methotrexate is more likely to cause toxicity in these people. Should not be used with NSAIDs as it may cause bone marrow suppression, anemia, and damage to the stomach and intestinal lining. Methotrexate may also not be suitable for people with folate deficiency, stomach ulcers, lung disease, who are receiving radiation treatment, or with any type of infection.
• Fatal toxicity has occurred in people mistakenly administered daily, not weekly, dosages.
• May occasionally cause severe, potentially fatal skin reactions. These may occur following single or multiple doses of methotrexate.
• Interacts with many drugs, particularly those that also bind to blood proteins such as aspirin, sulfonamides, tetracyclines, and phenytoin.
• Formulations or diluents that contain preservatives should not be used for intrathecal administration or high-dose therapy.
• Methotrexate may cause several severe side effects and it should only be used if its benefits outweigh its risks. Potentially fatal opportunistic reactions, such as Pneumocystis jiroveci pneumonia have been reported.
• Has caused fetal death and birth defects when used in women who have been pregnant or become pregnant while taking methotrexate. Not recommended for women of childbearing age unless benefits outweigh risks. May affect a person's future ability to have children, whether they are a man or a woman. Women should not breastfeed while taking methotrexate.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• There are significant risks associated with the use of methotrexate and your physician should fully inform you of the risks before starting treatment. During treatment, you should be monitored regularly.
• Carefully read dosage instructions. For psoriasis and rheumatoid arthritis, methotrexate is usually prescribed WEEKLY, not daily. If your label instructs you to take it daily, double-check with your doctor that these are the correct instructions.
• Report any instance of a dry, nonproductive cough to your doctor for further investigation.
• Also report any instances of fever, unusual bleeding or bruising, loss of appetite, clay-colored stools, yellowing of the skin or eyes, swelling, diarrhea, skin reactions, vomiting, or mouth ulcers to your doctor.
• Keep up a good level of hydration while taking methotrexate. If you become dehydrated, methotrexate may need to be temporarily discontinued until you have recovered.
• Continued treatment with methotrexate may depend on the results of blood, kidney function, lung, and liver function and other tests. Keep your scheduled appointments with your doctor so that you can be adequately monitored.
• Keep up fluid levels while taking methotrexate; do not allow yourself to become dehydrated.
• May make your skin more sensitive to the sun. Cover up and wear sunblock on exposed areas of skin when outside.
• Do not take any over-the-counter NSAIDs including aspirin while you are on methotrexate unless your doctor permits this. Also, ask your doctor before taking any vitamin supplements or other medications purchased over-the-counter, or before receiving immunizations.
• You may be at an increased risk of infection while taking methotrexate so avoid crowded areas and people who are unwell if you can. Wash your hands often.
• Take good care of your mouth to help prevent mouth sores. Use a soft toothbrush and mouthwash.
• Avoid drinking alcohol or keep alcohol intake to a minimum while taking methotrexate.
• If you are a woman with child-bearing potential, you should always use a reliable form of contraception while you are taking methotrexate. Your doctor may request that you take a pregnancy test before starting methotrexate. Methotrexate may also cause changes in your menstrual cycle. Men taking methotrexate should continue to use condoms for at least three months after stopping methotrexate.
• Tell other healthcare providers that you are taking methotrexate. You should not receive any live vaccines while taking methotrexate.
• If you are caring for somebody who is taking methotrexate, wear gloves when cleaning up body fluids or handling contaminated laundry or diapers, because methotrexate can transfer into the urine, feces, and vomit. Wash any soiled items separately.

• Peak levels are reached within one to two hours following an oral dose. The absorption of methotrexate depends on dosage; at a higher dosage, less methotrexate is absorbed. The toxicity of methotrexate appears to depend on how fast the drug is eliminated from the body. People with poor kidney function and certain other conditions are more likely to eliminate the drug slowly. The coadministration of leucovorin may help reduce toxicity.
• Reduction in symptoms of rheumatoid arthritis such as joint swelling and tenderness may occur within 3 to 6 weeks. It also reduces inflammation and pain; however, does not cause remission of rheumatoid arthritis nor prevent long-term joint damage. Most studies have been short-term, but limited studies suggest beneficial effects on symptoms persist for up to two years with continued treatment.
• Methotrexate usually shows some benefit in psoriasis within six to eight weeks; however, full effects may not be seen for five to six months. In chronic plaque psoriasis, 50-70% report a good result.
• When given to treat cancer, the length of time for an effect depends on the type of cancer and the patient's response to methotrexate.

Medicines that interact with methotrexate may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with methotrexate. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with methotrexate include:

• adalimumab
• aminobenzoic acid
• amiodarone
• aspirin and other salicylates
• anticonvulsants, such as fosphenytoin, levetiracetam, or phenytoin
• azathioprine
• chloramphenicol
• ciprofloxacin
• cisplatin
• clozapine
• cyclosporine
• diuretics, such as furosemide
• DMARDs such as gold, hydroxychloroquine, or penicillamine
• folic acid (includes when present in multivitamins)
• infliximab
• mercaptopurine
• NSAIDs, such as ibuprofen, diclofenac, or naproxen
• other agents that have toxic effects on the liver, such as azathioprine
• penicillins, such as amoxicillin or carbenicillin
• phenytoin
• pimecrolimus or tacrolimus
• probenecid
• proton pump inhibitors, such as esomeprazole, lansoprazole, or omeprazole
• pyrimethamine
• retinoids
• theophylline derivatives
• tetracycline antibiotics
• trimethoprim or cotrimoxazole
• sulfonamides, such as sulfasalazine
• vaccinations, such as BCG or live vaccines.

Avoid drinking alcohol while taking methotrexate.

Note that this list is not all-inclusive and includes only common medications that may interact with methotrexate. You should refer to the prescribing information for methotrexate for a complete list of interactions.