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Codeine Therapy and CYP2D6 Genotype.

Authors

Dean L7.

Editors

In: Pratt V1, McLeod H2, Rubinstein W3, Dean L4, Kattman B5, Malheiro A6, editors.

Source

Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-.
2012 Sep 20 [updated 2017 Mar 16].

Author information

1
Director, Pharmacogenomics and Molecular Genetics Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Bloomington, IN 47405
2
Medical Director, The DeBartolo Family Personalized Medicine Institute, Senior Member, Division of Population Sciences, Moffitt Cancer Center, Tampa, FL 33612
3
Division Director, Clinical Data Management and Curation, CancerLinQ LLC, Alexandria, VA
4
Senior Medical Writer, Medical Genetics and Human Variation, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894
5
Chief, Medical Genetics and Human Variation, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894
6
Project Lead, Medical Genetics and Human Variation, National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, MD 20894
7
NCBI

Excerpt

Codeine is used to relieve mild to moderately severe pain, and it belongs to the drug class of opioid analgesics. The hepatic CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, including codeine. CYP2D6 converts codeine in to its active metabolite, morphine, which provides its analgesic effect. However, pain relief may be inadequate in individuals who carry two inactive copies of CYP2D6 (“poor metabolizers”), because of reduced morphine levels. In contrast, individuals who carry more than two normal function copies of the CYP2D6 gene (“ultrarapid metabolizers”) are able to metabolize codeine to morphine more rapidly and more completely. As a result, even with normal doses of codeine, these individuals may experience the symptoms of morphine overdose, which include extreme sleepiness, confusion, and shallow breathing. Nursing mothers may also produce breast milk containing higher than expected levels of morphine that can lead to severe adverse events in their infants (1). The FDA drug label for codeine states that even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose. The label also contains a boxed warning, which states that respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism (1). The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends that for a patient identified as a CYP2D6 ultrarapid metabolizer, another analgesic should be used to avoid the risk of severe toxicity with a “normal” dose of codeine. CPIC also recommends avoiding codeine in patients identified as CYP2D6 poor metabolizers due to the possibility of lack of effect (see Table 1) (2).

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