Pediatrics/original researchPediatric Fatalities Associated With Over the Counter (Nonprescription) Cough and Cold Medications
Introduction
The increasing use of nonprescription (over the counter) cough and cold medicines is a worldwide phenomenon. Sales of these products is approximately $3.5 billion annually in the United States.1 Approximately 4 million children younger than 12 years are treated with nonprescription cough and cold products each week in the United States.2
Cough and cold products have been sporadically associated with severe toxicity and death in children. The American Association of Poison Control Centers reported a total of 64,658 exposures to cough and cold products in children younger than 2 years in 2005; of these, 28 (0.04%) were associated with a major adverse effect or death.3 Recent reports of death associated with these products have brought this issue to the attention of regulatory bodies.4
The Food and Drug Administration (FDA) convened an external advisory committee to evaluate the efficacy and safety of nonprescription cough and cold products. On October 19, 2007, the committee recommended that the use of these medications be prohibited in children younger than 6 years. Despite the advisory committee's recommendations, a poll performed by National Public Radio, the Kaiser Family Foundation, and the Harvard School of Public Health after the recommendation reported that 20% of parents with children younger than 2 years and 30% of parents with children aged 2 to younger than 6 years plan to use cough and cold medicines for their children.5
A risk evaluation of the use of cough and cold products in children is needed but has been difficult because the information publicly available consists of a small number of case reports and retrospective case series. To evaluate the role of nonprescription cough and cold medications associated with fatal cases, an expert panel was convened to compile all available pediatric fatalities associated with cough and cold medications, assess the causal relationship to the medications involved, estimate the dose involved, and identify factors contributing to the poisoning.
Section snippets
Materials and Methods
The panel assessed all reported pediatric fatalities that could be gathered from 5 sources (Figure 1): the National Poison Database System of the American Association of Poison Control Centers (January 1983 through June 30, 2007), adverse event reports submitted to the major manufacturers of nonprescription cough and cold products (1980 to 2007), the FDA briefing materials for its advisory committee meeting on October 18 to 19, 2007,6 a Citizen Petition to the FDA submitted March 1, 2007,6 and
Results
A total of 189 US deaths in children younger than 12 years were identified by the search strategy.4, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 The panel excluded 11 cases (Figure 1). Of the remaining 178 cases, 41 were judged “unlikely related” or “definitely not related,” and there were 19 cases in which the causal relationship could not be assessed. The net result was 118 cases in which the panel concluded that a relationship between the cough and
Limitations
The primary limitation of our analysis is the use of databases containing spontaneously reported information. It is likely that other cases with some association to cough and cold medications have occurred but have not been reported. We addressed this concern with extensive attempts to find cases, including sources not always available such as manufacturer's adverse event databases. The true total number of cases is unknown and likely to be higher than reported herein. Like all retrospective
Discussion
Our results provide the most comprehensive evaluation available of pediatric fatalities associated with nonprescription cough and cold medications. Our search strategy discovered many fatalities not previously considered in the evaluation of these medications. The expert panel concluded that 103 cases involved a plausible relationship between a nonprescription cough and cold ingredient and death. In cases in which the dosage could be assessed, the panel concluded that evidence of an overdose
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Supervising editors: Michael W. Shannon, MD; Michael L. Callaham, MD
Dr. Shannon and Dr. Callaham were the supervising editors on this article. Dr. Dart did not participate in the editorial review or decision to publish this article.
Author contributions: RCD and JLG conceived the study, designed the process, and obtained research funding. RCD and JLG supervised the conduct of the trial and data collection. RCD and JLG recruited panel members and managed the data, including quality control. RCD drafted the article, and all authors group contributed substantially to its revision. RCD takes responsibility for the paper as a whole.
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. This research was supported by an investigator-initiated grant from McNeil Consumer Healthcare to Denver Health and Hospital Authority. The panel members received a stipend from Denver Health and Hospital for their participation. The project was proposed and designed by Dr. Dart. The cases in the category of “manufacturer’s adverse events” were identified by each manufacturer individually and supplied to Denver Health. None of the researchers received consultation fees or any other compensation from the manufacturer. McNeil Consumer Products had no input into the design, definitions of causality, panel proceedings, analysis of results or drafting of the article.
Publication dates: Available online December 19, 2008.
Reprints not available from the authors.