Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update.

Article Details

Citation

Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, Haidar CE, Shen DD, Callaghan JT, Sadhasivam S, Prows CA, Kharasch ED, Skaar TC

Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update.

Clin Pharmacol Ther. 2014 Apr;95(4):376-82. doi: 10.1038/clpt.2013.254. Epub 2014 Jan 23.

PubMed ID
24458010 [ View in PubMed
]
Abstract

Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine therapy.

DrugBank Data that Cites this Article

Pharmaco-genomics
DrugInteracting Gene/EnzymeAllele nameGenotypesDefining change(s)Type(s)DescriptionDetails
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*3Not AvailableEffect Directly StudiedThe presence of this polymorphism in CYP2D6 results in non-functioning enzyme variant and may be associated with reduced drug mtabolism or reduced therapeutic response when treated with codeine.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*4Not AvailableEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*5Not Available
  • Whole-gene deletion
Effect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine and lack of therapeutic response from codeine.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*6(-;-) / (-;T)Effect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with poor metabolism of codeine.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*7Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*8Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*11Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*12Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*13Not Available
  • CYP2D7/2D6 hybrid gene structure
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*14ANot AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*15Not Available
  • 137insT, 137_138insT
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*19Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*20Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*21Not Available
  • 2573insC
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*31Not Available
  • -1770G>A
  • -1584C>G
  • -1235A>G
show all 17 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*36Not Available
  • 100C>T (rs1065852)
  • -1426C>T
  • variable number of A’s in the region -1258 to -1237a
show all 9 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*38Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*40Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*42Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*44Not Available
  • 2950G>C
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*47Not Availableshow all 8 …Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*51Not Available
  • -1584C>G
  • -1235A>G
  • -740C>T
show all 9 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*56Not AvailableEffect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*57Not Available
  • 100C>T
  • 310G>T
  • 843T>G
show all 10 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*62Not Available
  • 4044C>T
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*68ANot Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 6 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*68BNot Available
  • Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*69Not Availableshow all 17 …Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*92Not Available
  • 1995delC
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*100Not Available
  • -1426C>T
  • -1235A>G
  • -1109C>T
show all 15 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*101Not Available
  • -1426C>T
  • -1235A>G
  • -1000G>A
show all 14 …
Effect InferredPoor drug metabolizer. Lack of efficacy. For individual with two non-functional alleles, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*1XNNot Available
  • Normal allele duplicated.
ADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details
CodeineCytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
CYP2D6*2XNNot AvailableADR InferredUltra-rapid drug metabolizer. Risk of toxicity, alternative drug recommended.Details