Off-label drug prescriptions are those prescribed for a condition different from the recommended use. Some off-label drug use can be beneficial; however, it can also be harmful. A new study examined the risk of an adverse drug event with off-label drug prescriptions. The findings were published online on November 2 in the journal JAMA Internal Medicine.
The study authors note that off-label use of prescription drugs has been reported to be a major contributor to preventable adverse drug events in children. However, despite concerns regarding adverse outcomes, no systematic investigation of the effects of off-label drug use in adult populations has been conducted. Therefore, the objective of the study was to monitor and evaluate off-label use of prescription drugs and its effect on adverse drug events in an adult population.
The study group comprised 46,021 patients who received 151,305 prescribed drugs from a primary care clinics in Quebec, Canada. The investigators accessed data from the Medical Office of the XXIst Century electronic health record, which provides documentation of treatment indications and treatment outcomes. Prescriptions dispensed from January 1, 2005 through December 30, 2009 were reviewed from the date of the prescription to the date the drug use was discontinued, the end of treatment, or the end of follow-up (December 30, 2010). Data were analyzed from January 5, 2012 through to March 15, 2015.
The investigators searched for adverse drug events in off-label use with and without strong scientific evidence. The data was subjected to statistical analysis. Among the 46,021 patients, a total of 3,484 adverse drug events were found; this represented an incidence rate of 13.2 per 10,000 person-months. The rate of adverse drug events for off-label use (19.7 per 10,000 person-months) was higher than that for on-label use (12.5 per 10,000 person-months). Off-label use lacking strong scientific evidence had a higher adverse drug event rate (21.7 per 10,000 person-months) than on-label use; however, off-label use with strong scientific evidence had the same risk for adverse drug events as on-label use.
The risks for adverse drug events were higher for drugs approved from 1981 to 1995 (14.4 per 10,000 person-months) and for those used by women (14.3 per 10,000 person-months), patients receiving 5 to 7 drugs (12.1 per 10,000 person-months), patients receiving cardiovascular drugs (15.9 per 10,000 person-months) and patients receiving anti-infectives (66.2 per 10,000 person-months). Patients with a 1-unit increase in the continuity of care index had a 19% increase in adverse drug events. (The continuity of care index refers to the degree that a patient-physician relationship continues.)
The authors concluded that off-label use of prescription drugs is associated with adverse drug events. They stressed that caution should be exercised in prescribing drugs for off-label uses that lack strong scientific evidence. Future electronic health records should be designed to enable post-market surveillance of treatment indications and treatment outcomes to monitor the safety of on- and off-label uses of drugs.
The researchers are affiliated with McGill University, Montreal, Quebec, Canada; Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and Department of Social and Administrative Pharmacy, School of Pharmacy, MCPHS University, Boston, Massachusetts.
Take home message:
If you are prescribed an off-label medication, ask the physician whether its use has strong scientific evidence.