Article

Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism

Divisions of Surgical and Medical Intensive Care, Geneva University Hospital, Switzerland.
New England Journal of Medicine (Impact Factor: 54.42). 01/2005; 351(27):2827-31. DOI: 10.1056/NEJMoa041888
Source: PubMed

ABSTRACT Life-threatening opioid intoxication developed in a patient after he was given small doses of codeine for the treatment of a cough associated with bilateral pneumonia. Codeine is bioactivated by CYP2D6 into morphine, which then undergoes further glucuronidation. CYP2D6 genotyping showed that the patient had three or more functional alleles, a finding consistent with ultrarapid metabolism of codeine. We attribute the toxicity to this genotype, in combination with inhibition of CYP3A4 activity by other medications and a transient reduction in renal function.

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Available from: Jules Desmeules, Aug 21, 2015
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    • "Codeine is a commonly used medicine for symptoms such as pain and cough. Despite its uncertain therapeutic effect and the potential for life-threatening adverse reactions, codeine is easily available and affordable as a combination product or as a stand-alone opioid (Gasche et al., 2004; Chung, 2008). Codeine exhibits an affinity to micro-opioid receptors 200 times lower than morphine, with the capability of producing opiate intoxication, dependence, and withdrawal (Prommer , 2011). "
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    • "Severe respiratory depression is observed after morphine overdose or in the case of extremely high metabolizing rates of codeine to morphine [6] [7]. Amplification of the CYP2D6 gene was assumed to be the cause of some cases of death from respiratory depression after codeine administration [8] [9] [10] [11] [12] [13]. Therefore, genotyping of CYP2D6 prior to codeine administration has been recommended and a warning is issued in the official FDA drug label [14] [15]. "
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    • "For instance, codeine is metabolized by CYP2D6 to morphine. In such cases, enhanced CYP2D6 activity (i.e., in CYP2D6 ultra-rapid metabolizers) predisposes one to opioid intoxication (Gasche et al. 2004). • CYP 2C19 (S-mephenytoin hydroxylase) acts on weakly or strongly basic drugs containing one hydrogen bond donor, or if there are functional groups containing carbon or sulfur double bonded to oxygen present in the substrate. "
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