Methotrexate Toxicity from Unintentional Dosing Errors: Calls to a Poison Center and Death Descriptions

Methotrexate is a folate analog prescribed for varying disease with weekly administration as opposed to daily. Dosing errors can prove clinically significant and sometimes fatal.

We performed a retrospective poison center review of methotrexate calls between 2009 and 2019.

Of 111 human-related poison center calls, most patients taking methotrexate were women ages 41 to 80 years old and were prescribed methotrexate for rheumatoid arthritis. Eighty-eight (79%), and 41 (36%) were admitted to the hospital. Thirty-one (75%) of hospitalized patients received leukovorin treatment for their exposure. Two patients died from methotrexate dosing errors.

Most methotrexate accidental ingestions reported to poison centers result from dose frequency errors. However, we note a higher incidence of unintentional therapeutic errors (79% vs 13.7%) than reported in the National Poison Data System in 2019. Patients are often hospitalized for lab monitoring, and many receive leucovorin.

Most methotrexate calls to our poison center resulted from taking the drug more often than prescribed. Efforts may focus on patient education, physician or pharmacist monitoring during initiation, improved dispensing devices, or weekly drug dispensing.