More Adverse Events with Off-Label Drug Use Save

Off-label use of prescription drugs was associated with adverse drug events in a study of patients in Canada,  according to an article published online by JAMA Internal Medicine.

Off-label prescribing of drugs is common practice, especially in children, cancer, arthritis and uncommon conditions where there may be insufficient research or financial incentives for a manufacturer to pursue regulatory approval.  At issue is whether such off-label use may pose unknown risks to the patient and if this will result in more adverse drug events (ADEs).

Eguale and coauthors looked at the off-label use of prescription drugs and its effect on ADEs in 46,021 patients who received 151,305 prescribed drugs from primary care clinics in Quebec, Canada. Prescriptions dispensed from 2005 through 2009 were followed up and examined. The authors looked at off-label prescription drug use and whether or not there was strong scientific evidence to support its' use.

The authors identified 3,484 ADEs in the 46,021 study patients. The overall incidence rate of ADEs for all drugs was 13.2 per 10,000 person-months. The rate of ADEs for off-label use (19.7 per 10,000 person-months) was higher than for on-label use (12.5 per 10,000 person-months), according to the results.

Off-label use that lacked strong scientific evidence had an even higher ADE rate (21.7 per 10,000 person-months) compared with on-label use and off-label use with strong scientific evidence (13.2 per 10,000 person-months) had about the same risk for ADEs as on-label use, the study reports.

The risk for ADEs grew as the number of prescription drugs the patient used increased. For example, patients using eight or more drugs had more than a 5-fold increased risk for ADEs compared with patients who used one to two drugs.

“Off-label drug use, and particularly off-label use without strong scientific evidence, is a risk factor for ADEs. Hence, physicians and physician organizations should recognize the enormity of the problem and be active participants in the promotion of cautious prescribing of drugs for off-label uses lacking strong scientific evidence. Future EHRs should be designed to enable postmarketing surveillance of treatment indications and treatment outcomes to monitor the safety of on- and off-label uses of drugs,” the authors conclude.