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Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype

Clin Pharmacol Ther. 2012 February; 91(2): 321–326.

Published online 2011 December 28. doi:  10.1038/clpt.2011.287

PMCID: PMC3289963

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Codeine Therapy in the Context of Cytochrome P450 2D6 (CYP2D6) Genotype

KR Crews,¹ A Gaedigk,² HM Dunnenberger,³ TE Klein,⁴ DD Shen,^5,6 JT Callaghan,^7,8 ED Kharasch,⁹ and TC Skaar⁷

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Abstract

Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine as an analgesic are governed by CYP2D6 polymorphisms. Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas the risk of morphine toxicity is higher in ultrarapid metabolizers. The purpose of this guideline (periodically updated at http://www.pharmgkb.org) is to provide information relating to the interpretation of CYP2D6 genotype test results to guide the dosing of codeine.

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FOCUSED LITERATURE REVIEW

A systematic literature review was conducted that focused on CYP2D6 and its relevance in codeine use (see Supplementary Data online). This guideline was developed based on interpretation of the literature by the authors and by experts in the field.