Text

Background: Drug therapy safety is defined as the entirety of measurements aimed at ensuring an optimal medication process, with the aim of reducing medication errors and thereby minimizing preventable risks to patients during pharmacotherapy.

The admission of patients from outpatient to inpatient setting can be a critical phase in the medication process, as this transition may be particularly prone to medication-related problems (MRPs). A common source of error could be the incorrect transfer of outpatient long-term medications into the hospital electronic patient record. This presents an especially high risk with drugs that have a narrow therapeutic range, such as high-risk medication like Methotrexate (MTX).

MTX is used at high doses as a cytostatic agent functioning as an antimetabolite, inhibiting DNA synthesis. However, at lower Doses MTX, acts as an immunosuppressant and is used as a disease-modifying antirheumatic drug (DMARD).

Case reports describe potential sources of error that may lead to intoxication from overdose. In particular, incorrect dosing intervals can lead to an overdose with potentially serious adverse events. As a DMARD, MTX is typically administered once a week. However, dosing interval errors, such as multiple administrations within a single week, can cause serious adverse events, including anaemia, pancytopenia, bone marrow depression, or agranulocytosis. Even with rapid intervention and appropriate treatment, such an intoxication may be fatal.

With that in mind, EU-wide risk minimisation measures were introduced as early as 2018. Those include visual warnings on the packaging, changes to the product information and introduction of online-accessible educational materials.

As part of an ongoing project, two recent patient cases were identified in which MRPs occurred due to incorrect MTX dosing intervals. This highlights the importance of continuously raising awareness among all professionals involved in the medication use process

Materials and Methods: As part of INTERPOLAR (INTERventional POLypharmacy – drug interAction – Risks) medication analyses are carried out in various departments of the University Hospital Jena (UKJ). The aim in the ongoing project is to identify potential MRPs early and address them through interdisciplinary collaboration. The medication analyses are based on essential patient information, including medical history, diagnoses, current medications, clinical data, and laboratory results.

Results: As part of the conducted medication analyses, two recent patients in different departments of the UKJ were identified with MRPs related to incorrect MTX dosing intervals.

The first case involved a 64-year-old patient with rheumatic arthritis, who had been prescribed MTX as a DMARD. Instead of the intended weekly application on Mondays, a daily dose interval was documented in the electronic patient record.

Similarly, a 64-year-old patient with non-systemic vasculitic neuropathy, had also been treated with MTX as a DMARD in off-label-use. According to the outpatient medication plan, MTX was intended to be administered once weekly on Tuesdays. However, a twice-weekly dose interval was documented in the electronic patient record.

Both MRPs were identified in time during the chart reviews and corrected in consultation with the treating physicians. As a result those MRPs did not reach the patients.

Conclusion: Medication reviews are essential for ensuring optimal patient care and drug therapy safety. Based on the presented case reports, interdisciplinary collaboration between clinical pharmacists and physicians should be established, particularly during the transition of outpatient to inpatient care, to achieve safe and effective pharmacotherapy. Special attention should be given to high-risk patients and medications with a narrow therapeutic range, in order to identify and resolve potential MRPs before they can impact the patient.

Acknowledgement: The present work within the overarching use cases of the German Medical Informatics Initiative “INTERPOLAR_MI - Interventional POLypharmacy – drug interAction – Risks” is supported by the Federal Ministry of Research, Technology and Space (BMFTR, 01ZZ2320H).