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Codeine use in children

January 4, 2017

In September 2016, the American Academy of Pediatrics issued a clinical report against the use of codeine-containing products in children under 18 years of age.1 With cough and cold season upon us, this is a perfect opportunity to review these recommendations.

Codeine is an opioid agonist with limited affinity for the mu receptor and no analgesic effects. The analgesic effects of codeine are the result of hepatic metabolism via the cytochrome P450 2D6 (CYP2D6), which converts codeine to morphine. Since the activity of CYP2D6 varies among individuals, the rate of conversion from codeine to morphine also varies. Lack of effect is noted in those that are slow metabolizers, while adverse effects are noted in those that are rapid metabolizers.1

Over the last several years, surveillance revealed life-threatening and fatal respiratory depression in children receiving codeine. Many of these children were deemed ultra-rapid metabolizers, who convert codeine to morphine at the fastest rate. Additionally, children with documented or suspected obstructive sleep apnea appear to be at very high risk for adverse events.1-6

Several agencies and regulatory bodies have issued warnings related to the adverse events of codeine in children. Timeline of Events

For the treatment of pain in children, several other options exist including oxycodone, acetaminophen, and non-steroidal anti-inflammatory drugs. For the treatment of cough in children with acute illness, the value of suppressing the cough is not clear. Additionally, some over-the-counter cough and cold products carry warnings related to use in small children. In all circumstances, when considering alternatives to codeine, patient and family needs must be individualized.1

1Tobias JD, Green TP, Cote CJ. "Codeine: Time to Say ?No.?? Pediatrics. September 19, 2016; 138 (4):e1-e7. DOI: 10.1542/peds.2016-2396. Accessed on November 21, 2016.
2?FDA Drug Safety Communication: FDA evaluating the potential risks of using codeine cough-and-cold medicines in children." U.S. FDA. July 1, 2015. Accessed on November 21, 2016.
3?FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy.? U.S. FDA. February 20, 2013. Accessed on November 21, 2016.
4?FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death.? U.S. FDA. August 15, 2012. Accessed November 21, 2016.
5Firth S. ?FDA Panel Urges Stronger Regulation of Codeine.? MedPageToday. December 10, 2015. Accessed November 21, 2016.
6?FDA Gets Even Tougher on Codeine in Kids.? January 2016. Patient Safety Solutions. Accessed November 21, 2016.


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