FDA warns of risk of death from codeine use in postoperative children

The FDA today issued a Drug Safety Communication regarding the deaths of three children and one child who experienced a nonfatal but life-threatening case of respiratory depression after being administered codeine following tonsillectomy and/or adenoidectomy.

The children underwent surgeries to treat obstructive sleep apnea syndrome and received codeine doses that were within the typical dose range.

“The FDA is currently conducting a review of adverse event reports and other information to determine if there are additional cases of inadvertent overdose or death in children taking codeine, and if these adverse events occur during treatment of other kinds of pain, such as postoperative pain following other types of surgery or procedures,” Bob Rappaport, MD, director of the Division of Anesthesia, Analgesia and Addiction Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “The FDA will update the public when more information is available.”

According to the FDA release, one possible reason for this reaction to codeine could be ultra-rapid metabolizers, people who metabolize codeine much faster and more completely and are likely to have abnormally high levels of morphine in their blood after taking codeine. These high levels could possibly lead to overdose and death. The three children who died after receiving codeine have exhibited indications of being ultra-rapid metabolizers.

The estimated frequency of ultra-rapid metabolizers is generally 1 to 7 of every 100 people. However, among particular ethnic groups, this frequency could be as high as 28 of every 100 people.

Health care professionals and parents should be aware of the risks of administering codeine to children who have undergone tonsillectomy and/or adenoidectomy to treat obstructive sleep apnea syndrome.

When prescribing codeine-containing drugs, health care providers should use the lowest effective dose for the shortest time on an as-needed basis. If caregivers notice signs of overdose in a child — including confusion, unusual sleepiness, difficulty being aroused or awakened or noisy and difficult breathing — they should refrain from codeine and seek medical attention immediately.