[4] Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth.

It is effective for the treatment of several cancers, including solid tumours of breast, head and neck, lung, bladder, as well as acute lymphocytic leukemias, non-Hodgkin's lymphoma, osteosarcoma, and choriocarcinoma and other trophoblastic neoplasms.

[22][19][23][24] Use of low doses of methotrexate together with NSAIDs such as aspirin or analgesics such as paracetamol is relatively safe in people being treated for rheumatoid arthritis, with appropriate monitoring.

[26] Studies and reviews have found that most rheumatoid arthritis patients treated with methotrexate for up to one year had less pain, functioned better, had fewer swollen and tender joints, and had less disease activity overall as reported by themselves and their doctors.

[27] Those individuals with rheumatoid arthritis treated with methotrexate have been found to have a lower risk of cardiovascular events such as myocardial infarctions and strokes.

[16][29] Likewise, a 2016 study found the use of methotrexate, in combination with anti-TNF agents, is effective for the treatment of ulcerative colitis.

[4] Routine monitoring of the complete blood count, liver function tests, and creatinine are recommended.

[21] The most common adverse effects include hepatotoxicity, stomatitis, blood abnormalities (leukopenia, anaemia and thrombocytopenia), increased risk of infection, hair loss, nausea, reduced appetite, abdominal pain, diarrhea, fatigue, fever, dizziness, drowsiness, headache, acute pneumonitis and renal impairment.

[38] Methotrexate pneumonitis is a rare complication of therapy and appears to be reducing in frequency in most recent rheumatoid arthritis treatment trials.

[39] In the context of rheumatoid arthritis interstitial lung disease, methotrexate treatment may be associated with a lower incidence of ILD over time.

[41] Central nervous system reactions to methotrexate have been reported, especially when given via the intrathecal route (directly into the cerebrospinal fluid), which include myelopathies and leukoencephalopathies.

[44] Proton-pump inhibitors such as omeprazole and the anticonvulsant valproate have been found to increase the plasma concentrations of methotrexate, as have nephrotoxic agents such as cisplatin, the GI drug colestyramine, and dantrolene.

Not taking the medicine for two weeks might result in a minor increase of inflammatory disease flares in some people.

For cancer, methotrexate competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis.

In 1947, a team of researchers led by Sidney Farber showed aminopterin, a chemical analogue of folic acid developed by Yellapragada Subbarao of Lederle, could induce remission in children with acute lymphoblastic leukemia.

[citation needed] In 1951, Jane C. Wright demonstrated the use of methotrexate in solid tumors, showing remission in breast cancer.

[58] Wright's group was the first to demonstrate use of the drug in solid tumors, as opposed to leukemias, which are a cancer of the marrow.