Pat Anson, Editor

A drug that’s long been used to treat rheumatoid arthritis and other autoimmune diseases has been linked to dozens of deaths in the U.S. and Australia, mainly because patients have taken it daily rather than the recommended weekly dose, according to a new study published in the Medical Journal of Australia.

Methotrexate was originally developed and is still used for chemotherapy because of its ability to stop the growth and spread of tumors. Because it is also effective as an immune system inhibitor, low doses of methotrexate became a front line therapy for rheumatoid arthritis in the 1950’s. It is also used to treat psoriasis, lupus, sarcoidosis, and inflammatory bowel diseases such as Crohn’s.

Researchers say methotrexate is safe when taken once or twice a week, but the drug is so potent that accidental daily dosing can be lethal.

“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,” said lead author Rose Cairns, PhD, of the NSW Poisons Information Centre in Australia.

“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.”

In a review of medication errors in Australia from 2004 to 2014, researchers linked methotrexate to 22 deaths, including seven cases in which erroneous daily dosing was documented. One patient took methotrexate for 10 consecutive days. Reasons for the errors included patient misunderstanding and incorrect packaging of the drug by pharmacists.

A similar study of medication errors in the U.S. over a 4 year period identified over 100 methotrexate dosing errors that resulted in 25 deaths. Over a third (37%) of the errors were attributed to the prescriber, 20% to the patient, 19% to pharmacists, and 18% to administration by a health care professional.

The researchers also found a “worrying increase” in the number of medication errors just in the past year.

“It is difficult to explain this increase, but the risk of methotrexate medication error may be increasing as the population ages. Older people may be at increased risk because of a range of problems that includes confusion, memory difficulties, and age-related decline in visual acuity,” said Cairns.

Cairns and her colleagues say more needs to be done by drug makers and health professionals to reduce the risk of methotrexate overdosing, such as clearer labeling, smaller sized packages, and distinctly colored tablets.

"Methotrexate use is likely to continue increasing as Australia's population ages, so that additional measures are needed to prevent these errors," the authors concluded.