Blog Officially Open: Safety of Off-Label Medication Use

Eguale and colleagues conducted a study to monitor and evaluate the off-label use of prescription medications and adverse drug events (ADE) in adults. The authors conducted a prospective cohort study of adult patients who visited a primary care physician in Quebec, Canada who participated in the Medical Office of the XXIst Century (MOXXI) research program and received a prescription for a medication between January 1, 2005 and December 30, 2009. The MOXXI physicians use an electronic health record (EHR) that integrates beneficiary, medical and pharmacy claims information together. The EHR requires that the physician document the indication for the medication, reasons for dose modifications and discontinuations and details related to any ADE. Indications were considered off-label if they were not approved by Health Canada (Canada’s FDA equivalent). A drug information database was used to classify the level of evidence supporting the use of the medications for the off-label indications. Strong evidence was defined as medication effective or favorable efficacy for off-label indication, medication is recommended for most patients with indication, and there are studies of efficacy, including at least one randomized controlled trial. In brief, the study included 46,021 patients who received 151,305 prescriptions of which 11.8% were prescribed off-label. The indication for use was not supported by strong evidence 80.9% of the time. The overall incidence of ADEs for all medications was 13.2 per 10,000 person-months. There was a 44% increase in risk of ADEs when medications were used off-label compared with on-label use. There were higher rates of ADE when the off-label use lacked strong evidence. The authors noted that the elderly and patients who frequent physicians may be overrepresented in their data. The authors concluded that the off-label use of medications is a risk factor for ADE.

JAMA Intern Med. 2016;176(1):55-63

Off-label use of medications is complicated. The editorial that accompanies the Eguale paper discusses some of in the issues, including the potential changes to off-label promotion of medications, the allowance of prescribers to write for off-label medication use, and the lack of surprise of the study’s results. How can EHRs in the US become more sophisticated and user friendly to allow for more clear documentation of off-label use of medications to allow for more thoughtful intervention? How can pharmacists help with the safe and effective use of medications, particularly when off-label use is being considered?

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