Codeine Intoxication Associated with Ultrarapid CYP2D6 Metabolism

2004/12/30 by Yvan Gasche, Youssef Daali, Marc Fathi +4 · 7 citations
Pharmacology, Toxicology and Pharmaceutics · Chemistry · #Pharmacogenetics and Drug Metabolism #Alkaloids: synthesis and pharmacology #Chemical synthesis and alkaloids

paper · pdf · doi:10.1056/nejmoa041888

openalex publication_date 2004/12/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

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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• Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety
• Codeine: Time to Say “No”
• Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update
• Genes and the Response to Drugs
• Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice
• Concentrations of Scheduled Prescription Drugs in Blood of Impaired Drivers: Considerations for Interpreting the Results
• Codeine [wikipedia]
• Oxycodone [wikipedia]