AAP: Stop Giving Codeine to Children

Troy Brown, RN

September 19, 2016

Healthcare providers and parents should stop giving codeine to children, according to a new clinical report from the American Academy of Pediatrics, published online September 19 in Pediatrics. The authors also call for formal restriction of its use in children.

Despite a growing body of evidence that codeine can cause a life-threatening or fatal breathing reaction in children, the authors note that the drug is still available in over-the-counter cough formulas in 28 states and the District of Columbia, as well as by prescription in all states. One recent study, cited in the report, found that more than 800,000 children younger than 11 years received prescriptions for the medication between 2007 and 2011.

The clinical report describes potential alternatives to codeine for pain relief in children, including oxycodone, hydrocodone, oral morphine, and tramadol, but none of them are without risks. Researchers and clinicians are also reevaluating the use of acetaminophen and nonsteroidal anti-inflammatory medications including ibuprofen and ketorolac.

"The answer may not lie in using more medication or different medications but merely using more effectively other options that are currently available," write Joseph D. Tobias, MD, and colleagues.

"The evolving information about the genetic variability in drug metabolism will yield important insights to guide physicians in the safe and effective treatment of their patients. Additional clinical research must extend the understanding of the risks and benefits of both opioid and nonopioid alternatives for orally administered, effective agents for acute pain," they conclude.

The World Health Organization deleted codeine from its list of essential medications because of concerns about its safety and efficacy in March 2011, and the US Food and Drug Administration (FDA) issued a safety alert about codeine in August 2012. The FDA added a "black box warning" to its codeine label in February 2013, and since then, the European Medicines Agency and Health Canada have both recommended restrictions on the drug's use in children. In July 2015, the FDA cautioned against the use of cough medications containing codeine in children younger than 18 years.

An FDA advisory committee recommended against the use of codeine for treatment of cough in children in December 2015, but final recommendations from the agency are still pending.

Codeine is a prodrug that is converted to morphine by the hepatic enzyme CYP2D6. However, genetic variability causes some patients to metabolize it too slowly, and others to metabolize it too quickly. Some patients, particularly children and individuals with obstructive sleep apnea, are "ultrarapid metabolizers," who experience sometimes fatal respiratory depression after taking therapeutic doses of the medication.

"Although CYP2D6 genotyping that could identify patients at higher risk is available (although currently expensive), patients with normal metabolism are also at theoretical risk of high morphine levels. Therefore, further investigation is required to determine the value of such testing, which will depend on the population in whom it is applied," the authors write.

Physicians have also expressed concern about some patients who experienced inadequate pain relief from codeine.

The authors note that many of the life-threatening events and deaths share clinical features, including young patient age, a postoperative regimen of acetaminophen and codeine, and adenotonsillectomy for sleep-disordered breathing. However, they caution that clinicians cannot be sure serious adverse events will not occur in other clinical settings, especially as obesity increases the likelihood of undiagnosed sleep-disordered breathing, which would extend the risk.

"Additional measures are needed to prevent future problems with the use of codeine in the pediatric population. Improved education of parents and more formal restrictions regarding its use in children, regardless of age, are necessary," the authors conclude. "Additional clinical research must extend the understanding of the risks and benefits of both opioid and nonopioid alternatives for orally administered, effective agents for acute pain."

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online September 19, 2016. Full text

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