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Researchers Urge Caution for Off-Label Drug Use

PillsA study published in JAMA Internal Medicine took a close look at the incidence rates of adverse drug reactions in patients who were prescribed medications for approved uses versus off-label uses. The off-label use of medications is legal and is, in fact, a widely accepted and commonly performed medical practice. For example, a doctor might prescribe an anti-anxiety medication for a patient who has insomnia, even if that medication is not FDA-approved for the treatment of insomnia.

However, pharmaceutical companies are prohibited from promoting the use of their medications for off-label uses. In recent years, a slew of lawsuits have been filed against drug manufacturers, alleging in part that the defendants inappropriately marketed their drugs for the treatment of conditions for which they were not approved. Another concern is that the off-label use of drugs might possibly increase the risk of adverse drug reactions. This JAMA study sought to shed light on the latter concern.

Study results

The researchers included professionals from Harvard Medical School and McGill University. They took a look at the prescriptions of 46,021 adult patients. The drugs were dispensed between January 1, 2005 and December 30, 2009, and the data regarding adverse event reports included data from the date of the prescription issuance to the end of follow-up care.

In the study participant population, the researchers identified 3,484 adverse drug events. There was an incidence rate of 13.2 per 10,000 person-months. The total rate of adverse drug events for on-label use was 12.5 per 10,000 person-months. In contrast, the total rate of adverse drug events for off-label drug use that lacked strong scientific evidence was 21.7 per 10,000 person-months – significantly higher than on-label use. However, when off-label use was supported by strong scientific evidence, the risk of adverse events was roughly the same as for that of on-label use.

In conclusion, the researchers starkly noted that the association between off-label use and adverse drug events could not be ignored. The researchers recommended that healthcare providers exercise caution when prescribing drugs for off-label use if they do not have strong scientific evidence. They also recommended that future electronic health records (EHRs) be designed in such a manner that allows for post-market monitoring of both treatment indications and outcomes, which would further research initiatives into off-label use.

Off-label use of Risperdal and Zofran

Two groups of plaintiffs in particular may find this latest JAMA study interesting. Some plaintiffs who filed lawsuits with regard to Risperdal claim that Johnson & Johnson inappropriately marketed Risperdal for use in nursing home residents, although the drug had not been approved for the treatment of elderly dementia. Some studies have found a possible link between Risperdal use in elderly dementia patients and an increased risk of stroke and premature death. Additionally, some Risperdal lawsuits claim that the antipsychotic drug caused gynecomastia, which refers to abnormal breast growth in males.

Another drug that has stirred up controversy regarding its off-label applications is Zofran. Zofran is approved to treat nausea in patients who are undergoing chemotherapy or surgery. However, some expectant mothers were prescribed Zofran for the treatment of morning sickness during pregnancy. Some of these mothers have filed legal complaints against the manufacturer, GlaxoSmithKline (GSK), claiming that the drug caused serious birth defects such as cleft palate and heart defects.

  1. JAMA Internal Medicine, Association of Off-Label Drug Use and Adverse Drug Events in an Adult Population,

  2. Science Daily, Off-label prescription drug use and adverse drug events,