Codeine: Time to Say “No”
RESEARCH REVIEW
Dan Murphy
Pediatrics
Vol. 138, No. 4; October 2016; e2 0162396
The official journal of the American Academy of Pediatrics
Joseph D. Tobias, MD, Thomas P. Green, MD, Charles J. Cote, MD
Various organizations and regulatory bodies, including the World Health Organization, the US Food and Drug Administration, and the European Medicines Agency, have promulgated stern warnings regarding the occurrence of adverse effects of codeine in children. These and other groups have or are considering a declaration of a contraindication for the use of codeine for children as either an analgesic or an antitussive.”
KEY POINTS FROM THIS ARTICLE:
1.The chemical name for codeine is 3-methylmorphine.
[morphine]
2.Codeine has seen widespread clinical use for more than 50 years as an analgesic and an antitussive agent.
[Codeine is an opioid drug]
3.Codeine has been prescribed to pediatric patients for many decades as both an analgesic and an antitussive agent.
4.“Published reports and clinical evidence have shown the potential dangers of codeine as an analgesic or as an antitussive.”
5.Codeine’s analgesic effects occur after it is metabolized in the liver into morphine. The efficiency of this conversion is genetic and varies greatly—from no effect to high sensitivity.
6.Children who are ultra-rapid metabolizers of codeine
^Children who are ultra-rapid metabolizers of codeine into morphine often suffer respiratory depression and death. 5 5
into morphine often suffer respiratory depression and death. Ultra-rapid metabolizers produce large amounts of morphine that can cause respiratory depression or apnea.
7. Poor metabolizers of codeine show a lack of effect from these drugs. “Even before these reports of adverse events, many physicians had concerns regarding the efficacy of codeine, mostly related to its lack of effect in a significant proportion of the population (poor metabolizers).”
8. Patients with the greatest adverse risk from taking codeine are those with obstructive sleep apnea.
9. Despite concerns and hazards of codeine, it continues to be widely available from many pharmacies and inpatient hospital formularies for use in outpatient pediatric settings and is commonly prescribed to pediatric patients.
10. A study horn 2011 reported that codeine was prescribed to more than 800,000 patients younger than 11, more
than any other opioid in the study.
11. The providers most likely to prescribe codeine are:
• Otolaryngologists
• Dentists
• Pediatricians
• General practice/family physicians
12. In the past five years, various organizations and regulatory bodies have promulgated warnings regarding adverse responses associated with codeine:
• March 2011: The World Health Organization deleted codeine from its list of essential medications for children because of concerns that its “efficacy and safety were questionable in an unpredictable portion of the pediatric population.”
• August 2012: The US Food and Drug Administration (FDA) issued a safety alert regarding the use of codeine in children after tonsillectomy, adenoidectomy, or adenotonsillectomy.
• February 2013: An update from the FDA added a “black box warning” to the drug label of codeine and codeine-containing preparations. The warning advises healthcare professionals “to prescribe an alternative analgesic [to codeine] for postoperative pain control
■ ^February 2013: An update from the FDA added a “black box warning” to the drug label of codeine and codeine-containing preparations. J J
in children undergoing tonsillectomy and/or adenoidectomy.”
• June 2013: The European Medicines Agency issued a report recommending the restriction of codeine for the treatment of pain to children older than 12, as well as a contraindication to its use in children younger than 18 undergoing tonsillectomy and/or adenoidectomy. In addition, it recommended against codeine use in breastfeeding women.
• June 2013: Health Canada announced that it had reviewed the safety of prescription pain and cough medications containing codeine, and recommended against their use in children younger than 12.
• March 2015: The European Medicines Agency completed a review of the use of codeine for cough and cold and recommended against its use in children younger than 12, as well as children and adolescents between the ages of 12 and 18 who have problems with breathing.
13.“The evidence linking the use of codeine with lifethreatening or fatal respiratory depression is based on a series of case reports that have appealed in the literature regularly since 2004.”
■ "Neither the value of suppressing cough nor the effectiveness of codeine in children with acute illnesses has been shown. J J
14. Other opiate drugs show similar toxicity as codeine, including hydrocodone, oxycodone, and tramadol.
15. “Codeine is also prescribed as an antitussive agent and is still available in over-the-counter cough and cold formulations without a prescription from outpatient pharmacies in 28 US states and the District of Columbia.”
• “Neither the value of suppressing cough nor the effectiveness of codeine in children with acute illnesses has been shown.”
• In April 2015, the European Medicines Agency announced that codeine must not be used to treat cough and cold in children younger than 12, and further cautioned that codeine is not recommended in children and adolescents between the ages of 12 and 18 with compromised respiratory function, including those with asthma and other chronic breathing problems.
• On July 1, 2015, the FDA issued a drug safety communication stating that it is investigating the
possible risks of using codeine-containing medicines to treat coughs and colds in children younger than 18 because of the potential for serious adverse effects, including slowed or difficult breathing.
• An FDA advisory panel met in December 2015 and, by an overwhelming majority vote, recommended that the use of codeine in the treatment of cough in all children up to 18 years of age should be contraindicated.
16.“Although these concerns have been emphasized by the FDA, the European Medicines Agency, Health Canada, and the American Academy of Pediatrics, regular codeine administration to children continues.”
"" A drug, codeine, used in children primarily for pain control and for cough suppression for more than 50 years, carries serious effectiveness problems and serious side effects, including death. JJ
COMMENTS FROM DAN MURPHY
This article highlights a major problem with a pharmacological healthcare delivery system. A drug, codeine, used in children primarily for pain control and for cough suppression for more than 50 years, carries serious effectiveness problems and serious side effects, including death. Despite the call by international regulatory agencies worldwide to curtail or eliminate the use of this drug in children, it is still commonly prescribed by a wide variety of providers.
Dan Murphy graduated magna cum laude from Western States Chiropractic College in 1978, and has more than 39 years of practice experience. He received his Diplomat in Chiropractic Orthopedics in 1986. Since 1982, Dan Murphy has served as part-time undergraduate faculty at Life Chiropractic College West, where he is currently teaching classes to seniors in the Management of Spinal Disorders and Spinal Pathology Neurology. Dan Murphy reviews articles regarding alternative health issues, which can be accessed through his website at www. danmurphydc. com.
