Weekly Article: Death and ultrarapid metabolism of codeine after T&A

by Shilpa Patel
Children's National

Many of you are aware of the black box warning on the use of codeine specifically after adenotonsillectomy issued by the FDA in August of 2012. For those of you on the Holy Cross email list, you may have seen this recently discussed there. It has also been circulating on various other web forums and this week the NEJM did a nice perspective piece summarizing the issue. Here are the highlights: 

Codeine is converted to morphine by CYP2D6. Genetic variations in CYP2D6 affect the amount of codeine that is converted to morphine.

Ultrarapid metabolizers can convert codeine into large amounts of morphine.

The prevalence of ultrarapid metabolizers is variable and universal testing for this genotype is not recommended.

Less than 1% of Chinese and Japanese patients. Higher than 15% among Middle Eastern and North African patients. A case series published in April 2012 of Pediatrics of 3 patients who died after T&A (indication was OSA) prompted an FDA investigation.

The investigation revealed a total of 13 cases (10 deaths and 3 life threatening cases of respiratory depression) including those reported in April 2012, ages 21 months to 9 years. Though many of the patients were, not all of these patients were ultrarapid metabolizers and none of them were given excessive doses.

In 2011-2012 otolaryngologists were also becoming concerned about this issue and surveyed all ENTs to learn more about these events. They shared their findings with the FDA.

The author states that “currently available evidence suggests that the risk is most substantial in child after they have undergone tonsillectomy, adenoidectomy, or both. Many such children have sleep-disordered breathing and [they] are known to be more sensitive to opioids.”

Official FDA Warning: “Health care professionals should prescribe an alternate analgesic for post-operative pain control in children who are undergoing tonsillectomy and/or adenoidectomy. Codeine should not be used for pain in children following these procedures. For management of other types of pain in children, codeine should only be used if the benefits are anticipated to outweigh the risks.” http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm