Methotrexate error outcomes ‘frequently catastrophic’

detective with magnifying glass

Pharmacists need to ensure their own practices are as safe as possible, finds a new report into methotrexate which noted seven deaths and 28 notifications

The Pharmacy Board of Australia has published a summary report of an analysis of notifications involving oral methotrexate.

The Board had commissioned Ahpra’s research unit to undertake the analysis, following recommendations from the Coroner’s Court of Victoria, which asked it to improve public safety regarding the issue.

The recommendations stemmed from a 2018 inquest into a death caused by oral methotrexate poisoning.

In this instance, the pharmacist had identified an error with the dose and frequency of a script for a patient with psoriatic arthritis.

The pharmacist contacted the prescribing doctor, but in the end felt compelled to dispense the script, even though they felt it was inappropriate. The report considered this patient’s death to have been preventable.

The report found that since 2010, there have been 28 notifications involving pharmacists and methotrexate.

These included seven deaths (30% of the notifications) and nine incidents (39%) where patients had to go to or stay in hospital.

“Dosage administration aids (DAAs) being packed with once-daily dosing in error for weekly dosing (54%) as well as problems with labelling (29%) featured prominently,” the report found.

“Failing to resolve prescribing MTX errors, dispensing MTX in error and inadequate counselling all featured as underlying issues.

“Many of the labelling errors involved no label on the primary bottle containing MTX, or no directions or wrong direction being provided.”

Labelling issues included: where there were no directions on an old bottle of the medicine that the patient decided to resume after a long break; where the bottle was labelled “as directed” – taken daily, not weekly; and where the box said, “Take 10 tabs a week” when the script was for one 10mg tab a week.

More issues include where the box was labelled for the wrong patient, though the methotrexate bottle was labelled correctly; wrong patient name and address; labelling on the box, not the bottle; and wrong labels.

The report noted that when dosed and administered appropriately, methotrexate is considered safe and effective.

“In reviewing these cases, half of all errors involved a failure in packing or checking of DAAs,” the report notes.

“Pharmacists, including proprietors of pharmacies must ask themselves, what quality control provisions are in place to avoid once-weekly MTX being inadvertently packed once-daily?

“Oral cytotoxic medicines, including methotrexate, must be packed separately to a patient’s other medicines.”

The report notes that consideration has to be given to the solutions which could mitigate error in this hazardous process.

“Labelling is a core professional and legal requirement performed by pharmacists when dispensing medicines,” it states.

“Appropriate labelling of medicines is always important and is even more so for medicines such as MTX with a narrow therapeutic index, which have the possibility to cause lethal toxicity if directions for the patient are absent, ambiguous or incorrect on the primary container.

“A cytotoxic medication, such as MTX, also requires an ancillary label.

“Failure to ‘gatekeep’ prescription errors was the root cause for two incidents that each led to a Coronial investigation. In both cases, the patient was prescribed and dispensed MTX daily instead of weekly.

“Pharmacist scope of practice includes denial of supply, if their professional judgment is that the medicine or prescribed dose or frequency is unsafe for the patient, irrespective of instruction from the prescriber to dispense.”

The report also found that the number of notifications about the medicine is unlikely to reflect the true extent of errors, which is likely to be “considerably” higher.

It highlighted that while all notifications it considered were about pharmacists working in community pharmacy, this does not mean errors with oral MTX have not occurred in hospital pharmacies during this period.

“As hospitals have governance systems for errors and complaints, it is possible complaints would be made to the hospital rather than Ahpra or other jurisdictional regulators and thus not captured in these data,” it suggested.

“Noteworthy, is that it is commonplace in Australian hospital pharmacies for oral MTX to be stored in a dedicated cytotoxic location of the dispensary, reducing inappropriate drug selection, and also requiring two signing pharmacists to endorse patient supply, to further limit human error.

“It is possible such measures contributed to the absence of notifications involving hospital pharmacies and may provide insights to limit oral MTX errors in community practice.”

In conclusion, the report stated that while the number of notifications around oral methotrexate was relatively low, “the outcomes were frequently catastrophic”.

“Pharmacists need to ensure their own processes and those of the pharmacy where they are practising support them to exercise their professional responsibilities in the safest way possible.”

The Board says it will continue to engage with key stakeholders about the risk of errors involving methotrexate, and “share the details of any developments to ensure that these risks remain in the forefront of the minds of all pharmacists and their support staff”.

“To date, changes have been made to methotrexate packaging and product information, however, the available proprietary packs of methotrexate tablets include more than one month’s supply and therefore, extra care must be taken to ensure that the correct quantity, directions and counselling are provided when supplying this medication to patients.

“The Board will also consider any necessary changes to its guidelines for pharmacists when it begins a review this year and will undertake wide-ranging public consultation on any revised proposals,” it says.

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  1. Tamer Ahmed

    The only change that is needed is to involve the medical professionals legally when they blatantly refuse to listen to a pharmacist advice.

  2. Russell Smith

    Sometimes, after the “refuse to listen” one just has to endorse the Rx with a “declined to dispense” and send the patient back to the doctor – ensuring no defamatory comments – oh – and keep a photocopy, diarise the discussion and wait for the result

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