Methotrexate is a folic acid antagonist. It competes with dihydrofolate for binding to dihydrofolate reductase (DHFR), an enzyme that catalyses the conversion of dihydrofolate to tetrahydrofolate, the active form of folic acid. Although the graphic shows methotrexate's mechanism of action (see also the oncology section and the section on inflammatory bowel disease), it is unknown how it acts in rheumatoid arthritis. Methotrexate is believed

to have anti-inflammatory, antiproliferative, and immunomodulatory properties. Methotrexate is prescribed orally or subcutaneously in doses of 7.5-30 mg once a week.

Myelosuppression (pancytopenia) and hepatitis are most common potentially serious side effects of methotrexate. Therefore, blood counts and liver enzymes should be monitored. Other adverse effects include nausea, hair loss and acute pneumonitis. Patients on methotrexate are in general provided with folic acid to prevent some of the side effects. Patients with rheumatoid arthritis with alcoholism, alcoholic liver disease, infectious hepatitis or other chronic liver disease should not receive methotrexate.


Methotrexate has the following significant adverse effects, EXCEPT: