Pain Medicines and Immunomodulators Top List of Drugs With Adverse Events

HUNTINGDON VALLEY, Pa., Sept. 10 -- Reports of drug-related injury, disability, and death sent to the FDA nearly tripled during an eight-year period beginning in 1998, according to an analysis of agency data.

A minority of drugs-usually painkillers and immune modulators-- accounted for a majority of adverse events reports, according to a study in the Sept. 10 issue of Archives of Internal Medicine, but only a modest number were related to drugs such as rofecoxib (Vioxx), which were withdrawn because of safety concerns.

Thomas J. Moore, A.B. of the Institute for Save Medication Practices here, and colleagues at Wake Forest analyzed all serious adverse drug events and medication errors reported to the FDA from 1998 through 2005. During that time the reports of serious adverse events increase from 34,966 to 89,842 and reports of fatal events increased form 5,519 to 15,107.

Among the most frequently reported drugs there was a disproportionate contribution of pain medications and drugs that modify the immune system, they reported.

For example, oxycodone was suspected in 5,548 deaths, ranking it number one of 15 drugs linked to mortality. By contrast, rofecoxib was suspect in 932 deaths and ranked number 14.

Estrogen, which was linked to 11,514 reports of serious injury or disability, earned the number one rank in that category followed by insulin with 9,597 reported adverse events. Inflixmab (8,754 events), interferon beta (8,320), and paroxitine (8,095) were ranked third, fourth, and fifth followed in sixth place by rofecoxib, which was linked to 7,766 events.

The authors sought to limit the impact of well-publicized drug withdrawals by excluding adverse event reports received more that 14 days after events such as the withdrawal of rofecoxib in September 2004.

But even if the authors had included those reports, they would have accounted for fewer than 10% of all reported events and the number of reports associated with recalled drugs declined since 1999, they wrote.

The rate of increase in reports of adverse events and deaths actually outstripped the growth in prescriptions-growing at a rate that was four times faster than the growth in prescriptions, Moore and colleagues wrote.

Among the findings:

• A minority of reports, 19.1% were made directly to the FDA, while 67.2% came to the FDA via the drug makers.
• Doctors and other health professionals filed more than 70% of all adverse event reports and 82% of the fatal event reports.
• 17.3% of reports involved a death outcome, 7% indicated permanent disability or birth defect and 75.7% represented serious outcomes.
• Most of the reports involved women (55.5%) and 33.6% of reports involved adults ages 65 or older.
• A total of 1,489 drug products were named in adverse event reports, but 298 drugs accounted for 87.1% of reported events.
• The number of serious adverse events associated with anti-tumor necrosis factor, interferon alpha, and interferon beta products rose 15.8 -fold from 1998 through 2005.

The study was limited by its reliance on the Adverse Event Reporting System, which is a collection of voluntary reports. Moreover, the submission of a report "does not establish causality," the authors cautioned.

Additionally, the authors "focused on only the primary suspect drug even though a median of two drugs per case were names and one quarter of the cases identified five or more drugs."

The authors concluded that rapid increase in the number of reports of drug-related adverse events "shows that the existing system is not adequately protecting patients and underscores the importance of recent reports urging far-reaching legislative, policy, and institutional changes."