10 ways to avoid fatal methotrexate errors

Three recent cases of fatal reactions to low-dose oral methotrexate due to interactions and dosing errors highlight the need to improve safety measures.

Two of the cases involved patients who were taking no more than 20 mg of methotrexate weekly, yet they died of severe methotrexate toxic effects due to other risk factors, including drug interactions that increased the serum concentration of methotrexate.

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The third event was very similar to many other methotrexate errors, with patients taking the medication daily instead of weekly, according to the October, 2015, ISMP Community/ Ambulatory Care Medication Safety Alert! The events were originally reported in the September 30, 2015, ISPM Canada Safety Bulletin.

In 2004, ISMP published a study of methotrexate errors over a four-year period that resulted in 25 deaths and 48 serious outcomes, many due to daily dosing. As a result, the organization has identified methotrexate as a high-alert medication in both hospital and community settings, even when used for non-oncologic purposes such as RA.

ISMP’s tips for hospital and community pharmacists and nurses to avoid methotrexate errors include:

1. 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.

2. If folate has not been prescribed, check with the prescriber to suggest initiation of this supplement.

 3. Ensure that any drug interaction alerts generated during order entry and verification are communicated to and resolved with the prescriber and/or the patient.

4. When possible, dispense only a four-week supply of methotrexate at a time.

5. When possible, dispense low-dose methotrexate for non-oncologic indications as a dose pack (e.g., RHEUMATREX), which helps guide patients to take the proper dose weekly.

Next: Recommendations 6-10

6. Ensure that every patient receives education or counseling when prescribed oral methotrexate or when filling a prescription for oral methotrexate.

7. 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.

8. 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.

9. 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.

10. Ask the patient or caregivers about the use of specific prescription and over-the-counter medications that may interact with methotrexate.