The Use of Codeine and Tramadol in the Pediatric Population-What is the Verdict Now?

J Pediatr Health Care. 2019 Jan;33(1):117-123. doi: 10.1016/j.pedhc.2018.04.016.

Abstract

Codeine and tramadol are opioid analgesics approved for the management of pain in the United States. Both agents are metabolized in the liver to active compounds via the cytochrome P450 2D6 enzyme. Case reports of pediatric patients with overactive CYP2D6 enzymes have been reported. These ultra-rapid metabolizers experience an increase in the production of active metabolites of codeine and tramadol, which can lead to oversedation, respiratory depression, and death. In 2017, the U.S. Food and Drug Administration updated their warnings regarding codeine and tramadol use in the pediatric population, making their use contraindicated in patients under the age of 12 years.

Keywords: Codeine; cytochrome P-450 CYP2D6; pediatrics; pharmacogenetics; tramadol.

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / metabolism
  • Analgesics, Opioid / pharmacokinetics*
  • Child
  • Child, Preschool
  • Codeine / adverse effects*
  • Codeine / metabolism
  • Codeine / pharmacokinetics
  • Contraindications, Drug*
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Guideline Adherence
  • Humans
  • Pain Management
  • Respiratory Insufficiency / chemically induced*
  • Tramadol / adverse effects*
  • Tramadol / metabolism
  • Tramadol / pharmacokinetics
  • United States
  • United States Food and Drug Administration

Substances

  • Analgesics, Opioid
  • Tramadol
  • Cytochrome P-450 CYP2D6
  • Codeine