The Journal of Pediatrics
Volume 160, Issue 1 , Pages 33-37.e2 , January 2012

Central Nervous System Depression of Neonates Breastfed by Mothers Receiving Oxycodone for Postpartum Analgesia

  • Jessica Lam, BSc

      Affiliations

    • Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    • Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Lauren Kelly, MSc

      Affiliations

    • Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    • Ivey Chair in Molecular Toxicology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    • ,
  • Catherine Ciszkowski, MSc

      Affiliations

    • Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    • Ivey Chair in Molecular Toxicology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    • ,
  • Marieke L.A. Landsmeer, MD

      Affiliations

    • University of Utrecht, Utrecht, The Netherlands
    • ,
  • Marieke Nauta, MD

      Affiliations

    • University of Amsterdam, Amsterdam, The Netherlands
    • ,
  • Bruce C. Carleton, PharmD

      Affiliations

    • Child and Family Research Institute, Children’s and Women’s Health Center of British Columbia, Vancouver, British Columbia, Canada
    • Pharmaceutical Outcomes Programme, Children’s and Women’s Health Center of British Columbia, Vancouver, British Columbia, Canada
    • Department of Paediatrics, Division of Translational Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Michael R. Hayden, MD, PhD

      Affiliations

    • Child and Family Research Institute, Children’s and Women’s Health Center of British Columbia, Vancouver, British Columbia, Canada
    • Department of Medical Genetics, Center for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
    • ,
  • Parvaz Madadi, PhD

      Affiliations

    • Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Gideon Koren, MD

      Affiliations

    • Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
    • Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada
    • Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    • Ivey Chair in Molecular Toxicology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
    • Corresponding Author InformationReprint requests: Gideon Koren, MD, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8.

Received 17 February 2011 ,Revised 2 June 2011 ,Accepted 29 June 2011.

References 

  1. Seaton S, Reeves M, Mclean S. Oxycodone as a component of multimodal analgesia for lactating mothers after caesarian section: relationship between maternal plasma breast milk and neonatal plasma levels. Aust N Z J Obstet Gynaecol. 2007;47:181–185
  2. Ito S. Drug therapy for breast feeding women. N Engl J Med. 2000;343:118–126
  3. Micromedex. Drugdex drug evaluation—oxycodone. Health Communication Network 2006. Available at: http://www.thomsonhc.com.myaccess.library.utoronto.ca/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/9CD1E2/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/872931/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/evidencexpert.DisplayDrugpointDocument?docId=432180&contentSetId=100&title=Oxycodone+Hydrochloride&servicesTitle=Oxycodone+Hydrochloride&topicId=mechanismOfActionPharmacokineticsSection&subtopicId=null. Accessed Dec 8, 2010.
  4. Purdue Pharma. Std. Product monograph oxycontin. Available at: www.purdue.ca/files/OXY%20IR%20Tablets%20PM%20EN.pdf. Accessed Dec 8, 2010.
  5. Poyhia R, Seppala T. Liposolubility and protein binding of oxycodone in vitro. Pharmacol Toxicol. 1994;74:23–27
  6. Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk: clinical pharmacokinetic consideration. Clin Pharmacokinet. 1998;14:217–240
  7. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder JS. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006;368:704
  8. Chen ZR, Irvine RJ, Somogyi AA, Bochner F. Mu receptor bining of some commonly used opioid and their metabolites. Life Sci. 1991;48:2165–2171
  9. Madadi P, Ross CJ, Hayden MR, Carleton BC, Gaedigk A, Leeder JS, et al. Pharmacoenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin Pharmacol Ther. 2009;85:31–35
  10. US Food and Drug Administration. Public health advisory: use of codeine by some breastfeeding mothers may lead to life-threatening side effects in nursing babies. Available at: http://www.fda.gov/cder/drug/advisory/codeine/htm(2007). Accessed Dec 10, 2010.
  11. Health Canada. Advisory: use of codeine products by nursing mothers. Available at: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2008/2008_164-eng.php. Accessed Dec 10, 2010.
  12. Willmann S, Edginton AN, Coboeken K, Ahr G, Lippert J. Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study. Clin Pharmacol Ther. 2009;86:634–643
  13. Compendium of Pharmaceuticals and Specialties: the Canadian drug reference for health professionals 2010. Ottawa, Ontario, Canada: CPS; 2010.

 Supported by a Post Market Drug Safety and Effectiveness Catalyst grant awarded by the Drug Safety and Effectiveness Network of the Canadian Institutes of Health Research. The authors declare no conflicts of interest.

PII: S0022-3476(11)00678-0

doi: 10.1016/j.jpeds.2011.06.050

The Journal of Pediatrics
Volume 160, Issue 1 , Pages 33-37.e2 , January 2012

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