Major side effects of low-dose methotrexate
- Joel M Kremer, MD
Joel M Kremer, MD
- Pfaff Family Professor and Chair in Medicine
- The Albany Medical College
- Section Editor
- Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
- Section Editor — Rheumatoid Arthritis
- Emeritus Professor of Rheumatology, Imperial College London
- Visiting Professor, Oxford University
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 of a drug that is the best therapeutic alternative for a given individual.
Potentially life-threatening hepatotoxicity, pulmonary damage, and myelosuppression are sometimes 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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- COMMON TOXICITIES
- Symptoms and findings
- POTENTIAL SEVERE ADVERSE EFFECTS
- Pulmonary toxicity
- Risk of infection
- Risk of lymphoproliferative disorders
- Pregnancy risk
- OTHER ADVERSE EFFECTS
- PREVENTION OF SIDE EFFECTS WITH FOLATE
- SUMMARY AND RECOMMENDATIONS