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Codeine: Are We Prescribing the Right Opioid to Our Patients?

February 14, 2018
by Derek Decloux, Dental Anesthesia Resident at the University of Toronto’s Faculty of Dentistry


Given the epidemic of narcotic abuse in Canada, it is important we discuss choices when prescribing opiods. We should be both more pensive prior to picking up our prescription pad and more careful when prescribing opiod analgesia to our patients. It now goes without saying that we should optimize all means of non-opioid analgesia to our patients prior to taking out our prescription pad to consider a regulated medication, but that won’t stop many patients from encountering those painful situations that are not able to be managed by acetaminophen and NSAIDs alone. It is those same patients in acute discomfort that require our utmost attention lest their condition progress into a complaint more chronic.

I can recall from my days in dental school that there were essentially three prescriptions that our more senior student-colleagues urged us to memorize prior to entering our clinical rotations: amoxicillin, clindamycin (for those allergic to amoxicillin), and Tylenol #3. That’s not to say that we weren’t taught about other antibiotics and analgesics, it was simply understood that these three medications were some of the cornerstones which we would be prescribing on a regular basis. I’m not sure there was much of a push to optimize non-opioid pharmaceuticals, but there was certainly an understanding that if you were going to be completing a postoperatively painful procedure, then Tylenol #3 was likely to be distributed or prescribed.

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Yes, we were taught that codeine is a pro-drug that would be metabolized into morphine by one of the liver’s CYP systems and, yes, we were taught that some people were either hypo- or hyper-metabolizers so we should believe a patient when he/she says that Tylenol #3 does not provide adequate analgesia, but I’m not sure that I had the experience or the level of understanding then to appreciate some of the following:

  • The CYP2D6 system, which converts codeine into morphine has more than 100 allelic variants1 and varies widely in Canada’s multicultural population.2
  • Estimates that 11% of Caucasian people possess a CYP variant2 that does not convert codeine to morphine3 with the understanding that Mexican, Asian, and African American populations having some incidence (albeit less) of the same CYP variant. These patients would likely demonstrate an inadequate analgesic response to codeine.
  • In the same article by Sistonen (2007), it was noted that approximately 7% of Caucasian people possess a CYP variant, which make them ultra-rapid metabolizers of codeine. Those with the ultra-rapid metabolism of codeine are at higher risk of having more centrally-acting morphine than anticipated where effects can include associated respiratory depression as well as unnecessary and unwarranted sedation among other concerns.4 It should be noted that other ethnicities like those from Greece, Portugal, Saudi Arabia, and Ethiopia are even more likely to have this CYP variant than Caucasians.
  • There have been case reports after surgeries where patients have died due to the consequences of the side effects of over-sedation from the patients being ultra-rapid metabolizers of codeine5 and where infants have died from over-sedation from morphine in breast-milk from their ultra-rapid metabolizing mothers.6 While these are rare events, it is another reminder that the young and old are particularly susceptible to these codeine-related adverse events.

Conservatively, if we estimate that one in 20 patients receiving codeine will not be receiving as much opioid as we intend or, even worse, will be receiving more opioid than we intend, are we really doing a service to our patient prescribing that drug? I would argue that we are not. There are many equally or more efficacious drugs that will provide relief of pain after dental procedures7 without codeine’s clinical variability at a similar price point.

While we may not be far off from readily-available and inexpensive “point-of-service” analgesic susceptibility genetic testing8 (like sending off an oral swab as when we want to determine our ancestry), we are not yet there. Dental clinicians can and should be particularly attuned to the risks associated with prescribing codeine, or they can simply rid themselves of that one specific opioid from their arsenal in order to increase both the margin of safety in their practice as well as the likelihood of providing sufficient pain relief to their patients. OH

Oral Health welcomes this original article.

References:

  1. Ingelman-Sundberg M, Sim SC, Gomez A et al. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 2007: 116: 496–526.
  2. Sistonen J, Sajantila A, Lao O et al. CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenet Genomics 2007: 17: 93–101.
  3. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet 2009: 48: 689–723.
  4. Kirchheiner J, Schmidt H, Tzvetkov M et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 2007: 7 (4): 257–265.
  5. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, Ultrarapid-Metabolism Genotype, and Postoperative Death. N Engl J Med. 2009;361:827-828.
  6. Madadi P, Koren G, Cairns J et al. Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine. Can Fam Physician 2007: 53: 33–35.
  7. Au AHY, Choi SW, Cheung CW, Leung YY. The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis. PLoS ONE. 2015;10(6): e0127611.
  8. Agarwal D, Udoji MA, Trescot A. Genetic Testing for Opioid Pain Management: A Primer. Pain and Therapy. 2017;6(1):93-105.

Dr. Decloux completed his Bachelors of Science at the University of Ottawa in 2007 and his Doctor of Dental Medicine from the University of British Columbia in 2011. He practiced general dentistry for four years as a Dental Officer in the Canadian Armed Forces and is in his final year of studies at the University of Toronto to complete the combined MSc/Dental Specialty Training in Dental Anesthesia program.


RELATED ARTICLE: Barriers of Access to Deep Sedation and General Anesthesia as Identified by Ontario Dental Patients


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