Codeine During Child Surgeries Can Cause Death, FDA Warns

At least three children given the painkiller codeine following minor surgery have died, prompting a warning from federal drug regulators that some children may have the genetic ability to transform codeine into morphine more efficiently than the rest of the population. 

On August 15, the FDA issued a codeine drug safety communication, announcing that it is reviewing reports of child deaths following tonsillectomies and adenoidectomies for obstructive sleep apnea syndrome.

At least three children have died and one suffered life-threatening respiratory depression after they were given codeine to alleviate pain following these surgeries. The children were between the ages of two and five and the FDA believes that they may have inherited a genetic trait that causes their bodies to convert codeine into morphine at a prodigious rate, causing a morphine overdose.

All codeine is transformed into morphine when it gets to the liver, due to an enzyme called cytochrome P450 2D6 (CYP2D6). However, some people have a genetic variation that makes the enzyme super-efficient, changing more of the codeine into morphine faster.

The child deaths from codeine after surgery were detailed in a case report published in the medical journal Pediatrics in April.

The high levels of morphine are quickly detectable in their blood and can cause them to suffer respiratory depression, which can be fatal. In the general population between 1% and 7% are believed to be “ultra-rapid metabolizers,” but it appears that the trait is more prevalent among children of African descent, with almost 30% of African/Ethiopians considered ultra-rapid metabolizers and 3.4% to 6.5% of African Americans carrying the trait.

The FDA investigation is trying to determine whether there are more cases of overdose or death that may have been overlooked, and whether the overdoses occur in other types of surgeries and treatments as well.

In the meantime, the agency is advising health care professionals to be aware of the risks and to use the lowest effective dose for the shortest period of time possible. The FDA also told health care professionals to prescribe the painkiller to children on an as-needed basis instead of putting them on an around-the-clock regimen.

Parents and caregivers who have children taking codeine should be vigilant for signs of morphine overdose, which can include:

• Unusual sleepiness
• Confusion
• Difficult or noisy breathing

If any of these signs becomes apparent, the child should be taken to seek medical attention immediately at an emergency room or by calling 911.