Risk mitigations to prevent methotrexate dispensing errors in English hospitals: a mixed-methods exploratory study
Authors: Puaar S J , Scott M 
Published: April 2024

Abstract

Introduction
Oral methotrexate is indicated for paediatric cancer indications and autoimmune diseases. Unfortunately, cases of inadvertent overdose due to confusion between 2.5mg and 10mg tablet strengths are widely documented. National guidance is available to prevent such errors; indeed, the overdose of methotrexate for non-cancer treatment is a Never Event.[1] At our organisation, the main mitigations to reduce the risk of dispensing errors were to segregate tablet strengths and restrict 10mg tablets to cancer indications.[2] Adherence had not been evaluated, and alternative risk mitigations had not been explored.

Aim
We aimed to 1) determine whether methotrexate 10mg tablets were restricted to cancer indications; and 2) explore strategies to prevent errors associated with methotrexate tablet strength at a sample of hospitals.

Methods
First, an audit approach was used to determine use of 10mg tablets; standards were derived from local policy.[2] The setting was a large teaching hospital providing acute, specialist, paediatric and cancer care. Dispensing transactions of 10mg tablets on the electronic pharmacy dispensing system between April 2022 and March 2023 were included. Details of prescription, dispensed quantity, dose instructions and speciality were recorded onto the data collection tool. Data were analysed descriptively. Second, a survey was conducted with a sample of twenty English hospitals (including the study site). These comprised ten large teaching hospitals and specialist paediatric cancer centres. A relevant pharmacist was contacted by email at each trust and asked a series of open questions about local risk strategies associated with methotrexate 10mg tablets. Notes were taken and data summarised descriptively.

Results
There were 79 dispensing issues for methotrexate 10mg tablets. Of those, 65 issues were for 13 cancer patients; the other 14 were erroneous issues where 10mg were dispensed instead of 2.5mg for non-cancer indications. Whilst most errors were rectified (n=13), one patient received a weekly dose of 40mg instead of 10mg, a four-times overdose. Nineteen (95%) trusts responded to our survey. There were three broad strategies reported: to only use 2.5mg tablets (n=9); isolate dispensing of 10mg tablets to dedicated cancer or paediatric dispensaries (n=5); or reliance on local protocol and physical segregation of 2.5mg and 10mg tablets within multi-service dispensaries (n=5).

Conclusion
It was encouraging that 10mg tablets were solely intended for cancer indications. However, the incidental discovery of errors highlighted the need for improvement. Findings suggest that eliminating 10mg tablets from practice was a feasible strategy, even for organisations providing cancer services. Findings have limited generalisability due to the small sample sizes, and detail provided in survey responses was variable. Nevertheless, the audit was effective in identifying a previously unknown Never Event.
National Health Service organisations should acknowledge the risk associated with keeping 2.5mg and 10mg methotrexate tablets, particularly within dispensaries servicing multiple specialties. Dedicated cancer dispensaries are not commonplace, therefore eliminating 10mg tablets altogether should be considered. Indeed, the principle of limiting strengths is a well-established and effective medication risk management strategy. Further research should explore the potential negative implications for patients, such as increased tablet burden, if 2.5mg tablets are used exclusively for all indications. This may further inform national strategy to prevent Never Events.

References
1. Never Events List 2018. NHS Improvement. Available from: https://www.england.nhs.uk/publication/never-events/
2. High Risk Medicine Monograph: Methotrexate for non-cancer indications. Oxford University Hospitals NHS Foundation Trust. [September 2021].