Ann Arbor, MI—When the FDA issued a black box warning in February 2013 about significant safety risks with codeine prescribed for children undergoing a tonsillectomy or adenoidectomy, the assumption was that codeine usage in that situation would end completely.

That hasn’t happened, although prescribing has dropped, according to a report in the journal Pediatrics. The study found that about 5% of children still were receiving codeine 
after those procedures in December 2015. 

“The residual codeine prescribing is concerning since this should be a zero event,” explained lead author Kao-Ping Chua, MD, PhD, a researcher and pediatrician at University of Michigan C.S. Mott Children's Hospital who conducted the study with colleagues at the University of Chicago and Harvard Medical School. “We need to ensure children are not subjected to unnecessary potential harm when we have reasonable alternatives.”

To reach those conclusions, the researchers analyzed a national sample of claims from 362,992 privately insured children who had a tonsillectomy and/or adenoidectomy between 2010 and 2015. 

“The investigation was associated with a significant ?13.3 (95% confidence interval: -14.5 to -12.1) percentage point level change in the proportion of children with ≥1 prescription fills for codeine after tonsillectomy and/or adenoidectomy,” study authors note. “Despite this drop, 5.1% of children had ≥1 prescription fills for codeine in December 2015.”

“Though over-the-counter medications like ibuprofen are quite effective for pain after these surgeries, some children with more severe pain will require opioids like oxycodone and hydrocodone. The problem is that there are also concerns regarding the safety and abuse potential of these alternative opioids,” Chua said.

Codeine has been used for years to treat pain among children undergoing common surgical procedures, such as removal of tonsils or adenoids. As cases mounted of children with respiratory depression and death after codeine use, the FDA took action.

Most of the children with severe adverse reactions were “ultra-metabolizers” who converted codeine rapidly to morphine in the liver, resulting in dangerously high blood morphine levels. Because of the difficulty in predicting which children might react that way, the FDA initiated a safety investigation in August 2012 and ultimately issued a black box warning that specifically prohibited the use of codeine for children undergoing these surgeries.

“The problem is we don’t know how each patient metabolizes codeine. So every time a doctor prescribes codeine to a child, they are rolling the dice with the child's health,” Chua pointed out. “Our findings suggest the need to increase efforts to eliminate inappropriate codeine prescribing and encourage the use of effective non-opioid medications following tonsil and adenoid removal in children.”

“The residual inappropriate codeine prescribing is consistent with other research showing that FDA black box warnings can make substantial, but incomplete, impact on clinical practice,” added co-author Rena Conti, PhD, of University of Chicago Medicine.