BALTIMORE – The vast majority of reported U.S. episodes of cough and cold medication serious adverse event episodes in young children occurred by an accidental, self-administration overdose, according to a review of all pediatric episodes collected by the designated national surveillance system during 2008-2014.

This pattern highlights the continued need for diligent education of families about the potential danger posed by these largely OTC products as well as a possible additional need for further improvement in protective packaging, Dr. G. Sam Wang said at the annual meeting of the Pediatric Academic Societies.

Although the manufacturers of these products voluntarily changed their labeling in 2007 to say “do not use” in children younger than 4 years old, the continued vulnerability of very young children and the high rate of self-administration suggests that labeling restrictions alone are “unlikely to have a significant impact” on the problem, he said. “What could be better is storage and [packaging] engineering controls to prevent the accidental ingestions that seem to represent the majority of cases,” Dr. Wang said in an interview.

The good news was that the 4,250 reported U.S. cases during 2008-2014 in children younger than age 12 years and judged by an expert review panel to be at least potentially related to cold and cough medications represents a significant decline, compared with earlier periods, and is also “quite low” when compared with the millions of units in annual U.S. sales.

“The overall adverse event rate compared with the volume sold is in the single digits per million of products sold, and the rate has been declining,” said Dr. Wang, a pediatric toxicologist at the University of Colorado in Denver and a consultant to the Rocky Mountain Poison & Drug Center, also in Denver, the group that maintains and reviews this registry, begun in January 2008. “I think we’re making progress,” but diligent education by physicians and other health care providers about the dangers posed by these drugs must continue, he said.

The analysis also identified that two drugs were by far the top culprits in causing pediatric adverse reactions to cough and cold medications, diphenhydramine and dextromethorphan. Diphenhydramine played a role in 53% of the 4,224 nonfatal adverse reaction cases and 54% of the 26 fatal cases identified by the registry panel as at least potentially related to a cough and cold medication, while dextromethorphan was responsible for 41% of the nonfatal and 19% of the fatal cases. In a majority of cases, these drugs were in products with a single active ingredient, although products with combined ingredients also played a role for some cases. Most often these drugs were in OTC formulations and in pediatric formulations.

Dr. Wang called it unlikely that manufacturers would formulate cold and cough medications without diphenhydramine or dextromethorphan because these drugs have the antitussive and sedative properties that consumers seek from cough and cold medications. He also noted that the addition of bittering agents to formulations have not had a history of reducing accidental self-administrations by children, but added “a good taste doesn’t help.”

During 2008-2014 U.S. surveillance by the registry review panel identified a total of 5,342 unique case reports of serious adverse events in children less than 12 years old and believed related to any of eight drugs commonly found in cold and cough medications. The reports came from any of five sources: the National Poison Data System, the Food and Drug Administration’s adverse event reporting system, safety reports to manufacturers, and through surveillance of the medical literature, and the news media. The panel winnowed these down to 4,250 cases at least potentially related to these drugs.

Among the 26 fatal cases, 16 (62%) occurred in children less than 2 years old and an additional four (15%) were in children aged 2 years to less than 4 years. Nine of these cases (35%) involved parental administration, with only two cases (8%) involving self-administration. An additional nine cases (35%) had no reported source of administration, and the remaining six (23%) cases involved other sources of administration. Seven of the 26 fatalities involved confirmed overdoses, with the dose unknown for the remaining 19 cases, Dr. Wang reported.

Among the 4,224 nonfatal cases, 15% occurred in children less than 2 years, 46% in children ages 2 years to less than 4 years, 19% in children 4 years to less than 6 years and 20% in children 6 years to less than 12 years. These cases involved a confirmed overdose in 73% of cases, a therapeutic range dose in 7%, with the remainder involving a dose of unknown size. Self-administration occurred 75% of the time.

mzoler@frontlinemedcom.com

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Pediatric self-administration drives cough and cold drug mishaps