Three recent cases of fatal reactions to low-dose oral methotrexate due to interactions and dosing errors highlight the need to improve safety.
Three recent cases of fatal reactions to lowÂ-dose oral methotrexate due to interactions and dosing errors highlight the need to improve safety measures.Â Two of the cases involved patients who were taking no more than 20mg of methotrexate weekly,Â yet they died of severe methotrexate toxic effects due to other risk factors, including drugÂ interactions that increased the serum concentration of methotrexate.Â The third event was very similar to many other methotrexate errors, with patients taking theÂ medication daily instead of weekly, according to the October 2015 ISMP Community/ AmbulatoryÂ Care Medication Safety Alert. The events were originally reported in the Sept. 30 ISPMÂ Canada Safety Bulletin.Â In 2004, ISMP published a study of methotrexate errors over a fourÂ year period that resulted in 25Â deaths and 48 serious outcomes, many due to daily dosing. As a result, ISMP identified methotrexate as a highÂ alert medication in both hospital and community settings, evenÂ when used for nonÂoncologic purposes such as rheumatoid arthritis.Â ISMP’s tips for hospital, community pharmacists and nurses to avoid methotrexate errorsÂ include these 10 tips.Â Â
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Create a forcing function to ensure that every oral methotrexate prescription is reviewed with the patient or a family member when a prescription is presented or refills are processed in a community pharmacy.
If folate has not been prescribed, check with the prescriber to suggest initiation of this supplement.
Ensure that any drug interaction alerts generated during order entry and verification are communicated to and resolved with the prescriber and/or the patient.
When possible, dispense lowÂ-dose methotrexate for nonÂ-oncologic indications as a dose pack (e.g., RHEUMATREX), which helps guide patients to take the proper dose weekly.
Ensure that every patient receives education or counseling when prescribed oral methotrexate or when filling a prescription for oral methotrexate.
Double check all printed medication lists and instructions to ensure that they indicate the correct dosage regimen for oral methotrexate prior to providing them to the patient.
Ensure that the process for providing education or counseling for oral methotrexate includes clear verbal and written instructions. Ideally, EHRs and pharmacy computer systems should automatically generate this written information for patients receiving oral methotrexate.
Specifically review the dosing schedule with patients. Explain that taking extra doses is dangerous and discuss that the medication is not to be used “as needed” for symptom control. Have the patient repeat back the instructions to validate that he or she understands the dosing schedule and toxicities of the medication if taken more frequently than prescribed.