Adverse drug events cause hundreds of infant deaths annually

By Doug Payne

WASHINGTON, D.C. – After a review of more than 500,000 adverse events over three years, researchers concluded that an average of 243 infant deaths occur yearly from prescription drugs, biological products and other therapeutic chemicals.

The research, "Reported Adverse Drug Events in Infants and Children Under 2 Years of Age," published in the November issue of Pediatrics, is the first broad review of such incidents. It's based on reports received by the U.S. Food and Drug Administration from November 1997 through December 2000.

Of the half-million adverse events reviewed, the authors—from the George Washington University school of public health and health services and the University of Maryland—identified 7,111 reports about infants and children younger than age two.

After analysis for health outcome (i.e., death, hospitalization, congenital anomaly), principal suspect drug, and whether the route of drug exposure was direct administration or through the mother in the perinatal period, the authors identified 1,902 different therapeutic drugs, non-therapeutic chemicals, biological products, vaccines, over-the-counter medications, vitamins, minerals, dietary supplements, blood products and illegal substances. But they found that "only 17 drugs or biological products were a suspect in 54% of all serious and fatal adverse events in drugs administered directly."

A single biological product, palivizumab, a monoclonal antibody indicated for prevention of severe respiratory syncytial virus disease in high-risk pediatric patients, accounted for 28% of all such adverse events.

Although 183 different drugs were identified as principal suspect drug on at least one adverse report with an outcome of death, only four drugs accounted for 38% of the reported deaths. The drugs were palivizumab (15%), nitric oxide (11%), indomethacin (10%) and cisapride (3%).

Cisapride was not FDA-approved for use in infants, but was nevertheless widely used to treat infants with gastroesophageal reflux. It was withdrawn from the U.S. market in 2000 because of adverse event reports linking cisapride with cardiac arrhythmia and sudden death.

In 24% of the reported adverse event cases of all levels of severity, exposure to the drug was from the mother during pregnancy, delivery or lactation. One quarter of those were drugs typically used to prevent HIV transmission.

The authors found that 31% of the deaths occurred during the first month of life and another 50% from day two to the 12th month. The potential for adverse drug reactions in young children "is greater than in adults, because young children have immature detoxification mechanisms and because doses must be individually adjusted for a much wider range of body size and weight," the authors said.

Given the limited clinical testing in the infant population, spontaneous adverse event reports become a primary source of information to the risks of drug therapy in the youngest children.

The researchers cautioned that when a report is filed about an apparent adverse drug effect, it does not necessarily mean the medicine was at fault. But "these results," they concluded, "underscore the need for additional drug testing in the youngest pediatric patients and for carefully weighing the risks versus benefits of medication."

The publication of the study came just two weeks after a U.S. federal court said the FDA does not have the power to require drug makers to test adult medicines in children.