Incorrect drug dosage linked to numerous deaths


People have been taking it daily rather than weekly as prescribed

A drug used to treat rheumatoid arthritis, psoriasis and inflammatory bowel disease has been linked to numerous deaths since 2000, say the authors of research published in the Medical Journal of Australia.

Methotrexate, a synthetic folic acid analogue with immunomodulating properties, is indicated at a low dose of 7.5-25mg to be administered weekly.

However, a retrospective review following up methotrexate-related deaths since 2000 has revealed a variety of ways the drug has been transformed from safe to potentially lethal.

Researchers found 22 recorded instances in coronial reports where methotrexate was listed as a cause of death. Of these, seven cases recorded dosing errors.

The Therapeutic Goods Administration received 16 reports of methotrexate-related adverse events, including five deaths. Unintended daily dosage was documented in ten cases, including two deaths.

Data from Australian Poison Information Centres (PIC) revealed 92 cases of methotrexate-related medication error.

There was little overlap in the cases drawn from these three datasets.

Where documented, reasons for errors in the PIC dataset from most to least common were:

  1. Mistaking methotrexate for another medication, often folic acid or prednisone;
  2. Carer or nursing home errors;
  3. Methotrexate being newly prescribed for the patient;
  4. Dosette packing errors by the pharmacy;
  5. Misunderstanding instructions given by the doctor or pharmacist;
  6. Patient believing it would improve efficacy;
  7. Prescribing errors; and
  8. Dispensing or labelling errors.

Older people may be at increased risk of error due to age-related decline in visual acuity, confusion and memory difficulties, the authors note.

“Methotrexate use is likely to continue increasing as Australia’s population ages, so additional measures are needed to prevent these errors,” the authors conclude.

Their recommendations to decrease the level of methotrexate-related adverse events include:

  • Reducing the pack size, as current Australian pack sizes for methotrexate can exceed a year’s supply
  • Formulating methotrexate as a distinctively coloured tablet to reduce the risk of medication error
  • Clearer labelling added to packs with a reminder that the medication should be taken weekly, not daily
  • Packaging folate alongside methotrexate, in a manner similar to oral contraceptives and sugar pills, since the two are often co-prescribed and the tablets can be confused
  • Use of prescribing software to include alerts when methotrexate is prescribe daily or dispensed too frequently

MJA 2016; online 6 June

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