Potentially life-threatening hepatotoxicity, pulmonary damage, and myelosuppression are sometimes seen with use of methotrexate (MTX) and can occur with either high-dose therapy as used for malignant diseases (eg, cyclic use of 1 gram or more) or with low-dose therapy (eg, weekly doses of 7.5 to 25 mg) as used in other disorders such as rheumatoid arthritis and psoriasis.
The most commonly observed side effects of MTX (at doses typically used for the treatment of rheumatoid arthritis as opposed to the high doses used in malignancy) are never life-threatening. 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. It is, therefore, important to learn the effective management of common toxicities in order to achieve optimal utilization MTX.
The major side effects of low-dose methotrexate are discussed here. The clinical use of high-dose methotrexate and related adverse effects are discussed separately. (See "Therapeutic use and toxicity of high-dose methotrexate".)
Hepatotoxicity due to MTX may result from direct damage to hepatocytes, or, in patients with concomitant viral hepatitis, MTX may enhance viral damage. Screening for hepatitis B and hepatitis C virus infection before initiating long-term MTX therapy allows for detection and a decision whether to avoid the use of MTX, to try to eradicate the viral infection before initiating therapy, or to suppress viral replication during immunosuppressive therapy. Periodic monitoring of aminotransaminase and albumin (eg, every four to eight weeks) is suggested to detect hepatotoxicity during chronic treatment with MTX [1,2]. Early studies in Scandinavian psoriatic patients on MTX indicated that alcohol ingestion was a clear risk factor for hepatotoxicity . As no one has studied the amount of alcohol which might be safe with MTX, a general recommendation would be to avoid, or minimize, alcohol intake while on the drug. (See "Hepatotoxicity associated with chronic oral methotrexate for nonmalignant disease" and "Hepatitis B virus reactivation associated with immunosuppression".)
Pulmonary toxicity of MTX is seen with both high- and low-dose treatment and may present with acute or chronic symptoms. Either symptomatic or asymptomatic radiographic lung damage may be due to inflammation, infection, or MTX-related neoplasia. We recommend that a chest radiograph be obtained prior to initiating MTX treatment . Pulmonary toxicity is discussed in detail separately. (See "Methotrexate-induced lung injury".)