Risks associated with prescribing oral methotrexate

NPS is reminding health professionals to be alert to the risks associated with prescribing oral methotrexate.   Methotrexate has been used for many years in the treatment of some cancers. 

Increasingly low dose methotrexate is being used in the treatment of autoimmune or inflammatory disorders such as rheumatoid arthritis and severe psoriasis where it is usually prescribed as a weekly dose.  This can present difficulties for some people in making sure they take the correct dose on the correct day.  If the weekly dose is exceeded this may result in a high rate of adverse events, sometimes resulting in fatal toxicity.  

NPS CEO Dr Lynn Weekes says it is important for prescribers and other health professionals to be aware of the risks and to take practical measures to reduce the chance of adverse effects due to errors.  

“Methotrexate is taken either as a single dose once a week or as a divided dose at 12 hourly intervals over two days, once a week, and this dosage can translate poorly into instructions for patients,” says Dr Weekes.  

 “We know that prescribing, dispensing and administration errors, a lack of regular monitoring and poor patient awareness are all contributing factors to the possible development of methotrexate toxicity.  

“A range of common sense measures can be implemented by doctors prescribing methotrexate to help reduce adverse events around this medicine,” says Dr Weekes.   When prescribing or dispensing methotrexate to patients or carers, prescribers should:  

  • stress the importance of taking methotrexate only as prescribed
  • provide clear written and verbal instructions to ensure the dosage regimen is understood (for example, the Methoblastin consumer medicine information leaflet contains instructions about safe use and may be a useful counselling aid)
  • for weekly regimens, agree on a specific day of the week for taking methotrexate (preferably one of significance for the individual) and make sure once-weekly dosing is not confused with once-daily dosing
  • explain that extra or irregular doses are dangerous
  • advise not to take a catch up dose if one dose is missed; the flare-up of disease is unlikely
  • emphasise the importance of regular monitoring (blood tests)
  • warn about possible signs and symptoms of toxicity and explain what to do if these develop.  
Nurses looking after patients in different care settings should also be vigilant when monitoring patients taking methotrexate. By being aware of the correct dosage and frequency, nurses can help identify potential errors and ensure the safety of patients being treated with methotrexate.  

For more information about methotrexate, see the Australian Prescriber article or read the NPS RADAR article. consumers can read the Methoblastin consumer medicine information (CMI) leaflet here.  


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