Dangerous overdosing of a common prescription drug used to treat rheumatoid arthritis, psoriasis and inflammatory bowel disease has been linked to avoidable deaths as researchers warn of a worrying rise in dosing errors.
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Of the 22 deaths associated with methotrexate since 2000, eight people died after taking the oral medication daily instead weekly, found the study of national data by the NSW Poisons Information Centre (NSW PIC).
A total of 91 cases of serious incorrect dosing - where patients took the drug three days in a row - were also identified after researchers analysed coronial and Therapeutics Goods Administration data, as well as cases reported to the Australian Poisons Information Centres.
"Every case is a potentially life threatening error," said Dr Rose Cairns, lead researcher and senior poisons specialist at NSW PIC.
Methotrexate is often dispensed in packs of 50 tablets, a year's supply of the drug that can be mistaken for daily prescription medications.
"It's so easy to take too much. Patients confuse their weekly dose of methotrexate with their daily medications, and it only take three days for the effect to be lethal," Dr Cairns said.
Mistaking the drug for folic acid, often prescribed alongside methotrexate, or prednisone were common reasons of accidental overdosing, as well as packaging errors at pharmacies, or patients misunderstanding instructions by a doctor or pharmacists, the study found.
"We don't see this dosing error effect with any other prescription drug," she said.
Daily dosing can suppress a patient's bone marrow, reducing their immunity, leaving them susceptible to sepsis, gastrointestinal mucosal ulceration and death.
"It would be an extremely uncomfortable way to die, very nasty," Dr Cairns said. "But the thing is these are avoidable deaths. If methotrexate is used a prescribed it's considered safe."
The data published in the Medical Journal of Australia on Monday revealed "a worrying increase in methotrexate medication errors" between 2014 and 2015, the researchers wrote.
While it was unclear what caused the sudden rise, Dr Cairns warned the risk of accidental overdosing would continue to increase with the ageing population.
The age of patients who died after taking incorrect doses ranged from 66 to 87, while the average age of those documented with serious incorrect dosing was 65.
Roughly 260,000 methotrexate tablet scripts were dispensed on the PBS in 2015, but the cheapness of the medication means many more doses are dispensed on private scripts.
While methotrexate-related deaths were rare, older people were at increased risk because they were prone to confusion, memory problems, age-related cognitive decline and poor eyesight, the researchers said.
The researchers recommended current pack sizes be reduced to contain just one month's supply of the drug, or four tablets.
They also suggested packaging the drug with folic acid, which is taken daily and often co-prescribed, in a way that mimics the packaging of the oral contraceptive pill, with sugar tablets used in place of methotrexate six out of seven days a week.
"This would make it nearly impossible to make these kinds of errors," Dr Cairns said.
Clear warning on the pack as well as formulating distinctive coloured tablets, and prescriber alerts in dispensing software were also recommended.
