A new safety review shows that products that contain codeine should not be used for pain relief following tonsillectomy or adenoidectomy in children, due to a possible risk of serious adverse events.
The warning, issued by the US Food and Drug Administration (FDA; Silver Spring, MD, USA), is based on reports of three deaths and one life-threatening case of respiratory depression published in the medical literature following the use of codeine in children with obstructive sleep apnea (OSA) who underwent tonsillectomy or adenoidectomy. The children were determined to be ultra-rapid metabolizers, genetically susceptible to converting normal doses of codeine into dangerous levels of morphine in the body.
Following the reports, a review of the FDA's Adverse Event Reporting System from 1969 to May 1, 2012, and a physician survey conducted by the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS; Alexandria, VA, USA) uncovered a total of 12 deaths and three overdoses associated with codeine use in patients ranging in age from 21 months to 9 years. Eight of the cases involved codeine use after adenotonsillectomy, and three involved a respiratory tract infection. The codeine doses were appropriate in most cases.
“Since these children already had underlying breathing problems, they may have been particularly sensitive to the breathing difficulties that can result when codeine is converted in the body to high levels of morphine,” concluded the FDA advisory. “However, [the new] contraindication applies to all children undergoing tonsillectomy and/or adenoidectomy because it is not easy to determine which children might be ultra-rapid metabolizers of codeine.”
A boxed warning regarding the contraindication will be added to the labels of all codeine-containing products in the United States. The contraindication to codeine use does not apply to other types of pain management in children, although the FDA recommends that codeine should only be used if the benefits are anticipated to outweigh the risks.
Codeine (3-methylmorphine), a natural isomer of methylated morphine, is an opiate used for its analgesic, antitussive, antidiarrheal, antihypertensive, antianxiety, sedative, and hypnotic properties. It is used to suppress premature labor contractions, myocardial infarction (MI), cough suppression, as well as many other uses. Common adverse effects associated with the use of codeine include drowsiness, constipation, euphoria, itching, nausea, vomiting, and others. Rare adverse effects include anaphylaxis, seizure, and respiratory depression.
US Food and Drug Administration
American Academy of Otolaryngology-Head and Neck Surgery