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Off-label drug use linked to adverse drug events

The use of off-label prescription drugs, particularly off-label drug use without strong scientific evidence, is associated with adverse drug events, according to research published in JAMA Internal Medicine.

"Off-label prescribing of drugs is common and has been identified as a potentially important contributor to preventable adverse drug events," Tewodros Eguale, MD, PhD, from the department of epidemiology, biostatistics and occupational health at McGill University in Montreal, and colleagues wrote in the study background. "Significant deleterious effects can occur with off-label use of some drugs, such as cardiac valve damage with fenfluramine and phentermine (fen-phen), status epilepticus with tiagabine hydrochloride, thrombocytopenia with quinine sulfate, and thromboembolic events with recombinant Factor VIIa."

The researchers used the Medical Office of the XXIst Century electronic health record, which includes treatment indication and treatment outcome information. The prospective study included the records of 46,021 patients aged at least 18 years and drugs prescribed between 2005 and 2009.

Eguale and colleagues reported that patients received 151,305 incident prescriptions during that time. They found that 17,847 of the prescriptions (11.8%) were for off-label use; of those, 14,431 (80.9%) lacked strong scientific evidence.

Results showed the incidence rate of adverse drug events for off-label use (19.7 per 10,000 person-months) was higher than adverse drug events for on-label use (12.5 per 10,000 person-months; adjusted HR = 1.44; 95% CI, 1.3-1.6).

The use of off-label drug use without strong scientific evidence was associated with a higher adverse drug event rate (21.7 per 10,000 person-months) compared with on-label drug use (adjusted HR = 1.54; 95% CI, 1.37-1.72).

Eguale and colleagues also found that the adverse drug event risk was higher for women (14.3 per 10,000 person-months; adjusted HR = 1.17; 95% CI, 1.06-1.28), patients who received anti-infectives (66.2 per 10,000 person-months; adjusted HR = 6.33; 95% CI, 4.58-8.76), patients who received CV drugs (15.9 per 10,000 person-months; adjusted HR = 3.3; 95% CI, 2.67-4.08), patients who received five to seven drugs (12.1 per 10,000 person-months; adjusted HR = 3.23; 95% CI, 2.66-3.92) and for drugs approved between 1981 and 1995 (14.4 per 10,000 person-months; adjusted HR = 1.62; 95% CI, 1.45-1.8).

Additionally, researchers identified a 19% increase in the rate of adverse drug events for each 1-unit increase in the continuity of care index (adjusted HR = 1.19; 95% CI, 1.12-1.26).

"Off-label drug use, and particularly off-label drug use without strong scientific evidence, is a risk factor for [adverse drug events]," Eguale and colleagues wrote. "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." – by Chelsea Frajerman Pardes

Disclosure: The researchers report no relevant financial disclosures.