A drug used to treat rheumatoid arthritis, psoriasis and inflammatory bowel disease has been linked to numerous deaths since 2000, partly because people have taken it daily rather than weekly, as prescribed, according to the authors of research published in the Medical Journal of Australia.

Dr Rose Cairns, of the NSW Poisons Information Centre, and colleagues say that changes can be made to avert such accidental overdoses.

Methotrexate is a synthetic folic acid analogue used for its ability to inhibit the growth and spread of tumours or malignant cells. It is also an immunomodulator. It is quite safe if used appropriately, but accidental daily dosing can be lethal.

"Higher or more frequent doses [than prescribed] can result in gastro-intestinal mucosal ulceration, hepatotoxicity, myelosuppression, sepsis and death," the authors wrote.

Accidental overdosing can result from the patient mistaking methotrexate for another medication, from other patient or carer error, or from incorrect packaging of dosette packs by pharmacists, among other reasons.

"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," the authors noted.

The authors' recommendations include:

  • The pack size could be reduced, as current Australian pack sizes can exceed a year's supply.
  • Methotrexate could be formulated as a distinctively coloured tablet to reduce the risk of medication error.
  • Clear labelling could be added to packs with a statement saying: "Warning: this medication is usually taken weekly. It could be harmful if taken daily."
  • As folate is often co-prescribed with methotrexate and the tablets can be confused, the products could be packaged together, in a manner similar to that of oral contraceptives and sugar pills.
  • Prescribing software could include warnings when methotrexate is prescribed daily and dispensing software could include alerts if it is being dispensed too frequently.

"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.

Article: A decade of Australian methotrexate dosing errors, Rose Cairns, et al., Medical Journal of Australia, doi: 10.5694/mja15.01242, published 6 June 2016.