A new boxed warning, the strongest warning used by the Food and Drug Administration (FDA), has been added to the labeling of the narcotic codeine, related to its use after tonsillectomy or adenoidectomy in children with obstructive sleep apnea. The FDA reviewed all reported cases of death or serious adverse events in children who took codeine. Most of the cases occurred after adenotonsillectomy, although a few occurred in the presence of respiratory tract infections.

The FDA's database contained reports of 10 pediatric deaths and three overdoses from codeine between 1969 and 2012 (through May 1). (Seven of these cases had been reported in the literature.) The children ranged from 21 months to nine years of age. In most cases the amount of codeine prescribed was appropriate. Many of the children involved-although not all-were found to be more rapid metabolizers of codeine than would normally be expected. Codeine is metabolized to morphine in the liver through the cytochrome P-450 isoenzyme system. Rapid metabolism increases the circulating level of morphine, leading to narcotic overdose.

Although children with obstructive sleep apnea may be more susceptible to respiratory depression from narcotics than children without sleep apnea, the label revision indicates that codeine use is now contraindicated in all children who undergo tonsillectomy or adenoidectomy. Genotype testing to determine whether a child is a rapid metabolizer isn't recommended because some children with normal results may convert codeine to morphine at the same rate ultrarapid metabolizers do. If children are treated with codeine for other types of pain, the dose should be as low as possible and the duration of use as short as possible.

Nurses should closely monitor children receiving codeine for pain for signs of respiratory distress. They should instruct parents to give only the recommended dose of codeine to their child and administer it only when needed.

The FDA Drug Safety Communication can be found at http://1.usa.gov/YcZ9to.