What’s New in the Patient Safety World
May 2014
Pediatric Codeine Prescriptions in the ER
Our What’s New in the
Patient Safety World columns for September 2012 “FDA
Warning on Codeine Use in Children Following Tonsillectomy” and March 2013 “Further
Warning on Codeine in Children Following Tonsillectomy” described cases of
death and serious adverse effects in children treated with codeine following adenotonsillectomy for obstructive sleep apnea. Those cases
led to the FDA issuing a safety alert (FDA 2012) and
additional cases led to a subsequent black box warning for products containing codeine (FDA 2013).
The original FDA
alert was issued after reviewing reports in the literature of 3 deaths and one
near-miss case of respiratory depression in young children (ages 2-5) following
tonsillectomy and/or adenoidectomy for obstructive sleep apnea (Ciszkowski
2009, Kelly
2012). The most interesting facet
is the data presented on unusual metabolism of codeine as a root cause.
Ingested codeine is converted into morphine in the liver by cytochrome
P450 2D6 (CYP2D6). It turns out there are genetic variations that cause some
people to be “ultra-rapid metabolizers” which leads to higher concentrations of
morphine earlier. Apparently all the children in the above reports were
“ultra-rapid metabolizers”. The original FDA alert (FDA 2012)
estimates the number of “ultra-rapid metabolizers” as generally 1 to 7
per 100 people, but may be as high as 28 per 100 people in some ethnic groups
(the FDA site has a table of these rates by ethnic group).
In addition to those
rapid metabolizers who are at risk for toxicity from codeine, up to a third of
children are poor metabolizers of codeine and subsequently get little or no
benefit of codeine for pain or other conditions such as cough (Kaiser
2014). For many years the American
Academy of Pediatrics has recommended against use of codeine in children for
either analgesia or cough. The American College of Chest Physicians has
recommended against the use of codeine for cough in children since 2006. And
the World Health Organization and health ministries in Canada and Europe
likewise have recommended against use of codeine in children.
So one would anticipate that use of codeine in children would have almost stopped completely. Not so. A recent study (Kaiser 2014) has demonstrated that codeine continues to be prescribed to children in significant numbers. They analyzed emergency department visits for children between the ages of 3 and 17 from 2001 to 2010. Though the percentage of visits resulting in codeine prescriptions did drop from 3.7% to 2.9% over the study period, there was no decline in prescription rates after the 2006 guidelines recommending against use of codeine for cough or URI. For subgroups, the rate of codeine prescriptions did decrease significantly in the 3-7 year age group but not others. Overall, codeine continued to be prescribed to 500,000 to almost 900,000 children per year.
The authors note some potential interventions that might decrease the prescription of codeine in children including:
- Pocket-sized analgesic reference cards
- Removal of codeine from hospital formularies or CPOE screens
- Drug-specific prior authorization requirements
It’s pretty clear that guidelines and provider education
have been inadequate in stopping use of codeine in children. If you do
educational interventions, remember that stories
are better than statistics. Be sure to include descriptions of cases in the original literature of 3 deaths and one
near-miss case of respiratory depression (Ciszkowski 2009,
Kelly
2012). But remember that education
and training are what we consider to be weak actions. In our March 27, 2012
Patient Safety Tip of the Week “Action
Plan Strength in RCA’s” we included some slides
to help you remember which actions are strong and which are weak. Forcing
functions and constraints that make it difficult to order or
prescribe codeine for children are much more likely to be successful.
References:
FDA. FDA Drug Safety
Communication: Codeine use in certain children after tonsillectomy and/or
adenoidectomy may lead to rare, but life-threatening adverse events or death.
8/15/12
http://www.fda.gov/Drugs/DrugSafety/ucm313631.htm
FDA. FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. Update February 20, 2013
http://www.fda.gov/Drugs/DrugSafety/ucm339112.htm
Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med 2009; 361(8): 827-828
http://www.nejm.org/doi/full/10.1056/NEJMc0904266
Kelly LE, Rieder M, van den Anker J, Malkin B, Ross C, Neely MN, et al. More codeine fatalities after tonsillectomy in North American children. Pediatrics 2012; 129:5 e1343-e1347; published ahead of print April 9, 2012
Kaiser SV, Asteria-Penaloza R, Vittinghoff E, et al. National Patterns of Codeine Prescriptions for Children in the Emergency Department. Pediatrics 2014; 133(5): e1139-e1147 Published online April 21, 2014
http://pediatrics.aappublications.org/content/early/2014/04/16/peds.2013-3171.full.pdf+html
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