More Codeine Fatalities After Tonsillectomy in North American Children

In 2009 we reported the fatal case of a toddler who had received codeine after adenotonsillectomy for obstructive sleep apnea syndrome. The child was an ultra-rapid metabolizer of cytochrome P4502D6 (CYP2D6). We now report 3 additional fatal or life-threatening cases from North America. In the 2 fatal cases, functional gene duplications encoding for CYP2D6 caused a significantly greater production of potent morphine from its parent drug, codeine. A severe case of respiratory depression in an extensive metabolizer is also noted. These cases demonstrate that analgesia with codeine or other opioids that use the CYP2D6 pathway after adenotonsillectomy may not be safe in young children with obstructive sleep apnea syndrome. Pediatrics 2012;129:e1–e5 AUTHORS: Lauren E. Kelly, MSc,abc Michael Rieder, MD, PhD,ab John van den Anker, MD,d Becky Malkin, BSc, Pharm,b Colin Ross, PhD,e Michael N. Neely, MD,f Bruce Carleton, PharmD,eg Michael R. Hayden, MD, PhD,e Parvaz Madadi, PhD,hi and Gideon Koren, MDchi aSchulich School of Medicine, and cIvey Chair in Molecular Toxicology, University of Western Ontario, London, Canada; bDepartment of Clinical Pharmacology, London Health Sciences Centre, London, Canada; dChildren’s National Medical Center, Center for Clinical and Community Research, Washington, District of Columbia; eCentre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada; fCommunication Sciences Institute, University of South California, Los Angeles, California; gChild and Family Research Institute, Vancouver, Canada; hDepartment of Clinical Pharmacology, University of Toronto, Toronto, Canada; and iDivision of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Canada