Annals of Emergency Medicine
Volume 53, Issue 4 , Pages 411-417 , April 2009

Pediatric Fatalities Associated With Over the Counter (Nonprescription) Cough and Cold Medications

Presented at the XXVIII International Congress of the European Association of Poisons Centres and Clinical Toxicologists, May 2008, Seville, Spain.

  • Richard C. Dart, MD, PhD

      Affiliations

    • Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO
    • University of Colorado School of Medicine, Aurora, CO
    • Corresponding Author InformationAddress for correspondence: Richard C. Dart, MD, PhD, Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, 777 Bannock Street, Mail Code 0180, Denver, CO 80204; 303-739-1119, fax 303-739-1443
  • ,
  • Ian M. Paul, MD, MSc

      Affiliations

    • Penn State College of Medicine, Hershey, PA
  • ,
  • G. Randall Bond, MD

      Affiliations

    • Cincinnati Drug and Poison Information Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
  • ,
  • David C. Winston, MD, PhD

      Affiliations

    • Pima County Forensic Science Center, Tucson, AZ
  • ,
  • Anthony S. Manoguerra, PharmD

      Affiliations

    • Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California–San Diego, La Jolla, CA
  • ,
  • Robert B. Palmer, PhD

      Affiliations

    • Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO
  • ,
  • Ralph E. Kauffman, MD

      Affiliations

    • University of Missouri–Kansas City School of Medicine, Kansas City, MO
  • ,
  • William Banner, MD, PhD

      Affiliations

    • Oklahoma Poison Control Center, The Children's Hospital at Saint Francis, Department of Pediatrics, Oklahoma University College of Medicine, Tulsa, OK
  • ,
  • Jody L. Green, PhD

      Affiliations

    • Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO
  • ,
  • Barry H. Rumack, MD

      Affiliations

    • Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO
    • University of Colorado School of Medicine, Aurora, CO

Received 7 July 2008 ,Revised 25 August 2008 ,Accepted 16 September 2008.

References 

  1. Consumer Healthcare Product Association. OTC Sales by Category—2003-2006. Washington, DC: Consumer Healthcare Products Association; 2007;
  2. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287:337–344[methods described in unpublished data analysis provided to McNeil Consumer Healthcare by D. Kaufman]
  3. Dart RC. Review of national poison center data and fatality root cause analysis. Testimony before Advisory Committee to the Food and Drug Administration (October 18, 2007). Washington, DC.
  4. Srinivasan A, Budnitz D, Shehab N. Infant deaths associated with cough and cold medications—two states, 2005. MMWR Morb Mortal Wkly Rep. 2007;56:1–4
  5. Aubrey A. Poll: parents still trust cold meds for kids. http://www.npr.org/templates/story/story.php?storyId=17184769Accessed December 26, 2007.
  6. Dockets Management. Joint meeting of the Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee, October 18-19, 2007 (Briefing information). http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4323b1-00-index.htmAccessed November 19, 2007
  7. Davis JH, Hunt HH. Accidental Benadryl poisoning: report of a fatal case. J Pediatr. 1949;34:358–361
  8. Wyngaarden JB, Seevers MH. The toxic effects of antihistaminic drugs. JAMA. 1951;145:277–282
  9. Aaron FE. A case of acute diphenhydramine hydrochloride poisoning. Br Med J. 1953;2:24
  10. Timpermann J, Verbauwhede W. Toxic epidermal necrolysis (Lyell syndrome) and its medico-legal implications. Z Rechtsmed. 1972;71:139–144
  11. Bayley M, Walsh FM, Valaske MJ. Fatal overdose from Bendectin. Clin Pediatr (Phila). 1975;14:507–509514
  12. Vycudilik W, Pollak ST. Determination of diphenhydramine in autolyzed brain tissue in the course of cerebral death syndrome caused by intoxication. Zeitschrift Rechtsmedizin. 1985;95:129–135
  13. Knight KM, Doucet HJ. Gastric rupture and death caused by ipecac syrup. South Med J. 1987;80:786–787
  14. Goetz CM, Lopez G, Dean BS, et al. Accidental childhood death from diphenhydramine overdosage. Am J Emerg Med. 1990;8:321–322
  15. Maswoswe JJ, Egbunike I, Stewart KR, et al. Suspected fatal diphenhydramine toxicity by application to the skin of an infant with varicella. Hosp Pharm. 1994;29:26;28-30
  16. Hanzlick R. National Association of Medical Examiners Pediatric Toxicology (PedTox) Registry Report 3 (Case submission summary and data for acetaminophen, benzene, carboxyhemoglobin, dextromethorphan, ethanol, phenobarbital, and pseudoephedrine). Am J Forensic Med Pathol. 1995;16:270–277
  17. Lindsay CA, Williams GD, Levin DL. Fatal adult respiratory distress syndrome after diphenhydramine toxicity in a child: a case report. Crit Care Med. 1995;23:777–781
  18. Hanzlick R. National Association of Medical Examiner's Pediatric Toxicology (PedTox) Registry. Toxicology. 1996;107:153–158
  19. Jumbelic MI, Hanzlick R, Cohle S. Alkylamine antihistamine toxicity and review of Pediatric Toxicology Registry of the National Association of Medical Examiners (Report 4: alkylamines). Am J Forensic Med Pathol. 1997;18:65–69
  20. Magnani B, Evans R. Codeine intoxication in the neonate. Pediatrics. 1999;104:e75
  21. Bailey B, Daneman R, Daneman N, et al. Discrepancy between CYP2D6 phenotype and genotype derived from post-mortem dextromethorphan blood level. Forensic Sci Int. 2000;110:61–70
  22. Groudine SB, Hollinger I, Jones J, et al. New York State guidelines on the topical use of phenylephrine in the operating room (The Phenylephrine Advisory Committee). Anesthesiology. 2000;92:859–864
  23. Gunn VL, Taha SH, Liebelt EL, et al. Toxicity of over the counter cough and cold medications. Pediatrics. 2001;108:E52
  24. Baker AM, Johnson DG, Levisky JA, et al. Fatal diphenhydramine intoxication in infants. J Forensic Sci. 2003;48:425–428
  25. Boland DM, Rein J, Lew EO, et al. Fatal cold medication intoxication in an infant. J Anal Toxicol. 2003;27:523–526
  26. Marinetti L, Lehman L, Casto B, et al. Over the counter cold medications-postmortem findings in infants and the relationship to cause of death. J Anal Toxicol. 2005;29:738–743
  27. Sharfstein JM. The Baltimore Statement on the Use of Over the Counter Cough and Cold Medications by Children Five and Under. Baltimore, MD: City of Baltimore Health Department; 2006;
  28. Pragst F, Herre S, Bakdash A. Poisonings with diphenhydramine—a survey of 68 clinical and 55 death cases. Forensic Sci Int. 2006;161:189–197
  29. Wingert WE, Mundy LA, Collins GL, et al. Possible role of pseudoephedrine and other over the counter cold medications in the deaths of very young children. J Forensic Sci. 2007;52:487–490
  30. Consumer Healthcare Products Association. Makers of OTC cough and cold medicines announce voluntary withdrawal of oral infant medicines. http://www.chpa-info.org/ChpaPortal/PressRoom/NewsReleases/2007/10_11_07_CCMedicines.htmAccessed November 19, 2007.
  31. Sorenson SB, Shen H, Kraus JF. Coroner-reviewed infant and toddler deaths. Eval Rev. 1997;1997:58–76
  32. Herman-Giddens ME, Brown G, Verbiest S, et al. Underascertainment of child abuse mortality in the United States. JAMA. 1999;282:463–467
  33. Webster RA, Schnitzer PG, Jenny C, et al. Child death review: the state of the nation. Am J Prev Med. 2003;25:58–64
  34. Rimsza ME, Newberry S. Unexpected infant deaths associated with use of cough and cold medications. Pediatrics. 2008;122:e318–e322
  35. Schaefer MK, Shehab N, Cohen AL, et al. Adverse events from cough and cold medications in children. Pediatrics. 2008;121:1–5
  36. Chang MY. Regulatory history of pediatric cough/cold products (Joint meeting of Nonprescription Drug Advisory Committee (NDAC) and the Pediatric Advisory Committee (PAC), Silver Spring, Maryland). http://www.fda.gov/ohrms/dockets/AC/07/slides/2007-4323s1-02-FDA-chang.pptAccessed August 6, 2008.

 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.

PII: S0196-0644(08)01779-4

doi: 10.1016/j.annemergmed.2008.09.015

Annals of Emergency Medicine
Volume 53, Issue 4 , Pages 411-417 , April 2009