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A decade of Australian methotrexate dosing errors

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Methotrexate is a synthetic folic acid analogue used for its antineoplastic and immunomodulating properties. It competitively inhibits folic acid reductase, decreasing tetrahydrofolic acid production and inhibiting DNA synthesis. Low dose methotrexate (administered weekly in doses of 7.5–25 mg) is indicated for rheumatoid arthritis, psoriasis and inflammatory bowel disease.1

The unusual dosing schedule of low dose methotrexate is associated with a risk that it will be prescribed, dispensed or administered daily instead of weekly. Used appropriately, methotrexate is considered safe and efficacious; accidental daily dosing, however, can potentially be lethal. Higher or more frequent doses can result in gastro-intestinal mucosal ulceration, hepatotoxicity, myelosuppression, sepsis and death.2 Indeed, there are several literature reports of serious morbidity and mortality linked with methotrexate medication errors.37 A study of medication errors reported to the United States Food and Drug Administration over 4 years identified more than 100 methotrexate dosing errors (25 deaths), of which 37% were attributed to the prescriber, 20% to the patient, 19% to dispensing, and 18% to administration by a health care professional.8,