Help prevent methotrexate toxicity from unintentional dosing errors

Methotrexate, a folate analog that inhibits RNA and DNA synthesis, is prescribed for malignancies, organ transplantation and autoimmune diseases. For rheumatoid arthritis, it is one of the recommended starting medications and is dosed once weekly. Methotrexate side effects range in severity from mild (e.g., stomatitis, nausea, vomiting, liver enzyme elevation) to severe (e.g., bone marrow suppression, hepatotoxicity, multi-organ toxicity resulting in death).1 Taking methotrexate more frequently than prescribed can be a fatal dosing error. The Oregon Poison Center recently described methotrexate ingestions reported to them over a 10-year period (2009-2019). The report identified 111 human-related ingestions; 79 patients (71%) were female and most were older than 40 years of age.1 Read: Antihistamines improve response to immunotherapy in cancer patients Eighty-eight ingestions (79%) were unintentional. Taking a single additional dose was the most frequent error. In many of these situations, the patient forgot that they had already taken a dose earlier. Despite only taking a single extra dose, some patients still required hospitalization, treatment and lab monitoring.1 Two patients died, one from a six-fold dosing error because of a prescription incorrectly written by a physician. The second death resulted from a nurse administering methotrexate 15 mg daily (instead of weekly as it was prescribed) for six days.1 Forty-one (36%) patients were hospitalized after the ingestion, and 31 (75.6%) of hospitalized patients received leucovorin to treat the methotrexate toxicity. The largest number of unintentional ingestions were the result of ingesting a single extra dose. Although healthcare professional errors were rare, they did result in two deaths reported to the Oregon poison centre. It is important for healthcare professionals to adopt safety mechanisms to ensure proper methotrexate dosing. An interdisciplinary approach may be ideal, with efforts focused on patient education, frequent physician or pharmacist monitoring, particularly in the medication initiation phase, improved devices for methotrexate dispensing (e.g., prescription bottle timer caps) and weekly drug dispensing or limiting the quantity dispensed.1 Read: Short-term fasting reduces tumour growth Several strategies have been suggested for pharmacists to help prevent dosing errors with methotrexate: Before dispensing, ensure that the dose, strength, route, frequency and directions for administration are correct. Implement automated alerts (e.g., in pharmacy information systems) that will prompt a review of the indication and dosing frequency whenever methotrexate is entered. Provide patient counselling for any patient receiving a new or modified methotrexate prescription. Use patient counselling sessions as opportunities to double-check methotrexate prescriptions for accurate dose, strength, route, frequency and directions. Ensure that patients understand how many tablets to take and when and how to take them. Ensure that patients are aware of the signs and symptoms of methotrexate toxicity and the importance of laboratory monitoring and follow-up care with the prescriber. Provide written patient information to supplement verbal counselling. For patients taking methotrexate for autoimmune disorders (e.g., rheumatoid arthritis), ensure that patient handouts contain only information applicable to autoimmune disorders and the weekly dosing schedule. In consultation with the patient, choose a specific day of the week for methotrexate dosing (avoiding Monday, which has been misinterpreted as “morning”). Include explicit dosing instructions for methotrexate (e.g., specific day of the week) on pharmacy-generated prescription labels. Give the patient a calendar suitable for recording doses of medication administered. Limit dispensed quantities of oral methotrexate to no more than a one-month supply whenever possible. Share with pharmacy staff examples of errors that have occurred with methotrexate. Highlight the significant patient harm that can occur if this medication is incorrectly prescribed, dispensed, administered, or taken daily instead of weekly.2 References 1. Thompson JA, Love JS, Hendrickson RG. Methotrexate toxicity from unintentional dosing errors: calls to a poison center and death descriptions. J Am Board Fam Med 2021;34(6):1246-8. https://www.jabfm.org/content/jabfp/34/6/1246.full.pdf (accessed December 13, 2021). 2. Blinova E, Volling J, Koczmara C, et al. Oral methotrexate: preventing inadvertent daily administration. Can J Hosp Pharm 2008;61:275-7. (accessed December 13, 2021).

Help prevent methotrexate toxicity from unintentional dosing errors

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