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: 55.87). 01/2005; 351(27):2827-31. DOI: 10.1056/NEJMoa041888
Source: PubMed


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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