Beware of erroneous daily oral methotrexate
From the April 3, 2002 issue
PROBLEM: The perils of low-dose oral methotrexate are
clearly evident in the dozens of fatalities reported in patients
who have been prescribed this cytotoxic agent for alternative
conditions. While methotrexate has a well-established role in
oncology, increasingly it's being used in low doses for immunomodulation
in rheumatoid arthritis, asthma, psoriasis, inflammatory bowel
disease, myasthenia gravis, and inflammatory myositis. Used
for these purposes, it's administered as a weekly dose. But
mistakes have been all too frequent because relatively few medications
are dosed in this manner and clinicians and patients are much
more familiar with daily dosing of medications. For example,
one patient died after he misunderstand the directions for use
and took methotrexate 2.5 mg every 12 hours for six consecutive
days, instead of 2.5 mg every 12 hours for three doses each
week. Another patient died after he misread the directions on
a prescription bottle and took 10 mg every "morning"
instead of every "Monday." Errors also have been reported
with hospitalized patients. In one case, the physician had properly
recorded that the patient had been taking methotrexate 7.5 mg
weekly as an outpatient. But when he prescribed three 2.5 mg
tablets weekly, it was transcribed incorrectly as three times
daily. Upon transfer to another unit, the dose was transcribed
incorrectly as three times a week. In each case the errors did
not reach the patient because they were detected during pharmacy
review of the order. Similar errors have been reported overseas.
For example, in Australia, one patient took extra doses of methotrexate
as needed to relieve arthritic symptoms. Three elderly patients
took the medication daily despite clearly written instructions
to take it weekly. Two cases involved incorrect transcription
of the dosing schedule with hospitalized patients. Three of
the six patients died as a result of the errors.
SAFE PRACTICE RECOMMENDATION: Because of the number of
fatalities from errors with oral methotrexate, clinicians should
consider it a high alert medication. As such, there are several
measures that can help reduce the risk of an error when oral
methotrexate is prescribed:
- Build alerts in electronic prescribing systems and pharmacy
computers to warn clinicians whenever doses of oral methotrexate
have been entered (and to remind staff to check the indication
with the patient in a retail setting). Configure the systems
to avoid defaulting to a daily dosing schedule.
- Have a pharmacist conduct a prospective drug utilization
review before dispensing oral methotrexate to determine
its indication for use, verify proper dosing, confirm the
correct dosing schedule on medication administration records
and prescription labels, ensure staff and patient education,
and promote appropriate monitoring of the patient.
- Establish a system that ensures that outpatients receive
counseling when picking up new prescriptions and refills
(e.g., mark the bag with a red flag to alert clerical staff
that counseling is required, not optional).
- Provide patients with clear written instructions that
name a specific day of the week for taking the tablet(s).
When possible avoid choosing Monday since it could be misread
as "morning." Prepare instructions in big print
to assist elderly patients with poor eyesight.
- Advise patients to contact their physician if they miss
taking a dose. Tell them that a flare-up of the disease
is unlikely with one missed dose.
- Ensure that written drug information leaflets are given
to patients and that they contain clear advice about the weekly dosage schedule, not a daily dosing
- Explain to patients that taking extra doses is dangerous.
Encourage feedback to ensure that the patient understands
the weekly dosing schedule and that the medication should
not be used "as needed" for symptom control.
- Solicit help from a responsible caregiver if the patient
appears to have cognitive or severe sensory difficulties.
- Prescribe the drug as a dose pack (e.g., RHEUMATREX
by Lederle), which helps to reinforce the weekly dosing