Codeine is no longer recommended for use in children. After years of debate, the American Academy of Pediatrics (AAP) has issued a Clinical Report recommending against the use of codeine for cough or pain in children, regardless of age. The recommendation from the AAP’s Section on Anesthesiology and Pain Medicine, Committee on Drugs, notes that codeine is a prodrug of morphine, and the conversion occurs in the liver. There is substantial genetic variability in the activity of the responsible hepatic enzyme leading to significant individual variation in the effect of codeine. Some children experience no effect at all, while others are ultrarapid metabolizers, which may result in high serum morphine levels. The FDA has received multiple reports of respiratory depression and death after receiving codeine in children, many of whom were subsequently found to be rapid metabolizers. Children with sleep apnea seem to be at particularly high risk. The FDA and the World Health Organization are considering similar warnings. Despite these concerns, codeine continues to be commonly prescribed, with more than 800,000 prescriptions for children < 11 years of age in 2011. Unfortunately, other opioids have similar safety concerns, precluding their use as an alternative, leaving nonsteroidal anti-inflammatory drugs and acetaminophen as options (Pediatrics Sep 2016, e20151648; doi: 10.1542/peds.2016-2396). An FDA advisory panel met last December and by an overwhelming majority recommended that the use of codeine is contraindicated for the treatment of cough in children ≤ 18 years of age; however, the FDA has not yet acted on the recommendation.
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