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Major side effects of low-dose methotrexate

Joel M Kremer, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


Methotrexate (MTX) use can be associated with a variety of adverse effects over a wide range of severity; the risk of most side effects is influenced by the MTX dose and treatment regimen. In rheumatoid arthritis (RA) and other disorders, MTX is administered as long-term, low-dose therapy, usually 7.5 to 25 mg weekly, unlike its use for treatment of malignant disease, where it is may be administered in a cyclic fashion in doses of 1 gram or more.

The most commonly observed side effects of MTX at doses typically used for the treatment of RA are rarely life-threatening, in contrast with the high doses used in the treatment of malignancies. Nevertheless, they may become clinically significant if they result in premature discontinuation or dose alteration of a drug that is the best therapeutic alternative for a given individual.

Potentially life-threatening hepatotoxicity, pulmonary damage, and myelosuppression may be seen with use of MTX as either high- or low-dose therapy, while nephrotoxicity is a manifestation of high-dose therapy that occurs rarely, if ever, with low-dose MTX treatment.

The major side effects of low-dose MTX are reviewed here. The use of low-dose MTX in patients with RA and other rheumatic diseases and the clinical use and adverse effects of high-dose MTX and related adverse effects are described separately. (See "Use of methotrexate in the treatment of rheumatoid arthritis" and "Therapeutic use and toxicity of high-dose methotrexate".)


Symptoms and findings — One or more of the following common toxicities associated with methotrexate (MTX) are seen in some form, at some time, in most patients:

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Literature review current through: Nov 2017. | This topic last updated: Oct 26, 2017.
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