Codeine-associated pediatric deaths despite using recommended dosing guidelines: Three case reports

Stefan J. Friedrichsdorf, MD; Andrea Postier Nugent, MPH; A. Quinn Strobl, MD

doi:10.5055/jom.2013.0156

Authors

Stefan J. Friedrichsdorf, MD
Andrea Postier Nugent, MPH
A. Quinn Strobl, MD

DOI:

https://doi.org/10.5055/jom.2013.0156

Keywords:

codeine, death, toxicity, child

Abstract

This report describes the deaths of three children ages 4-10 years due to codeine toxicity at home. All three children were overweight or obese; however, the codeine doses were within recommended dose ranges for adjusted lean weight. Codeine’s analgesic effect depends on its metabolic conversion to morphine in the liver via the drug-metabolizing enzyme CYP2D6. Genetic variation may result in poor analgesia, opioid toxicity, or oversedation. Caregivers must be warned about risks associated with comorbidities including obesity and polypharmacy. Codeine should no longer be prescribed to children due to its poor analgesic effect and risk of opioid toxicity and oversedation.

Author Biographies

Stefan J. Friedrichsdorf, MD

Medical Director, Department of Pain Medicine, Palliative Care, and Integrative Medicine, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota

Andrea Postier Nugent, MPH

Senior Clinical Research Coordinator, Department of Pain Medicine, Palliative Care & Integrative Medicine, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota

A. Quinn Strobl, MD

Chief Medical Examiner and Forensic Pathologist, Midwest Medical Examiner’s Office, Ramsey, Minnesota

References

Lexicomp: Morphine (systemic) in pediatric and neonatal Lexi-Drugs®. Available at http://online.lexi.com/lco/action/doc/retrieve/docid/chiminn_f/3378437. Accessed January 3, 2013.

Cascorbi I: Pharmacogenetics of cytochrome p4502D6: Genetic background and clinical implication. Eur J Clin Invest. 2003; 33 (Suppl 2): 17-22.

Williams DG, Patel A, Howard RF: Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br J Anaesth. 2002; 89(6): 839-845.

Williams DG, Hatch DJ, Howard RF: Codeine phosphate in paediatric medicine. Br J Anaesth. 2001; 86(3): 413-421.

McLellan RA, Oscarson M, Seidegard J, et al.: Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics. 1997; 7(3): 187-191.

Kelly LE, Rieder M, van den Anker J, et al.: More codeine fatalities after tonsillectomy in North American children. Pediatrics. 2012; 129(5): e1343-1347.

Ciszkowski C, Madadi P, Phillips MS, et al.: Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med. 2009; 361(8): 827-828.

Koren G, Cairns J, Chitayat D, et al.: Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006; 368(9536): 704.

US Department of Health & Human Services: Codeine use in certain children after tonsillectomy and/or adenoidectomy: Drug safety communication–Risk of rare, but life-threatening adverse events or death. US Food & Drug Administration, MedWatch Safety Information and Adverse Event Reporting Program, 2012. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm315627.htm. Accessed October 29, 2012.

Ray WA, Murray KT, Hall K, et al.: Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012; 366(20): 1881-1890.

Moore A, Collins S, Carroll D, et al.: Paracetamol with and without codeine in acute pain: A quantitative systematic review. Pain. 1997; 70(2-3): 193-201.

Moore RA, McQuay HJ: Single-patient data meta-analysis of 3453 postoperative patients: Oral tramadol versus placebo, codeine and combination analgesics. Pain. 1997; 69(3): 287-294.

Clark E, Plint AC, Correll R, et al.: A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children with musculoskeletal trauma. Pediatrics. 2007; 119(3): 460-467.

Drendel AL, Gorelick MH, Weisman SJ, et al.: A randomized clinical trial of ibuprofen versus acetaminophen with codeine for acute pediatric arm fracture pain. Ann Emerg Med. 2009; 54(4): 553-560.

Moir MS, Bair E, Shinnick P, et al.: Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope. 2000; 110(11): 1824-1827.

Morrow PL, Faris EC: Death associated with inadvertent hydrocodone overdose in a child with a respiratory tract infection. Am J Forensic Med Pathol. 1987: 8(1): 60-63.

Madadi P, Hildebrandt D, Gong IY, et al.: Fatal hydrocodone overdose in a child: Pharmacogenetics and drug interactions. Pediatrics. 2010; 126(4): e986-e989.

US Food and Drug Administration: Important information for the safe use of tussionex pennkinetic extended-release suspension–Overview. Available at http://www.fda.gov/Drugs/DrugSafety/DrugSafetyPodcasts/ucm078904.htm. Accessed January 3, 2013.