Annotation of DPWG Guideline for codeine and CYP2D6

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Summary

The Pharmacogenetics Working Group Guideline for codeine includes individual recommendations for cough or pain for CYP2D6 poor, intermediate, and ultrarapid metabolizer. In addition, for ultrarapid metabolizer, higher or lower doses and additional risk factors are taken into consideration.

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Important information about alleles in DPWG guidelines.

Annotation

Note that the FDA released a safety announcement on 4/20/2017 stating that codeine and tramadol should not be used in children under 12 years.

Read more about how PharmGKB curates DPWG guidelines using extra information provided by DPWG to enable the interactive genotype tool above.

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2D6 and opioids (codeine, tramadol and oxycodone). European journal of human genetics (2021)

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group published a paper with the guidelines as per the November 2018 update including more details and scoring the clinical implementation [Article:34267337]

November 2018 update

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for codeine based on CYP2D6 genotype. The guideline includes individual recommendations for cough or pain for CYP2D6 poor, intermediate, and ultrarapid metabolizer. In addition, for ultrarapid metabolizer the recommendations consider higher or lower doses and additional risk factors.

Wording in table taken from the Dutch guidelines November 2018 update

Read for more information about this recommendation, Read about gene information from DPWG

Preemptive genotyping

Excerpts from the DPWG risk analysis document for codeine and CYP2D6:

The Dutch Pharmacogenetics Working Group considers genotyping before starting codeine in doses higher than 20 mg every 6 hours for adults and 10 mg every 6 hours for children aged 12 years or older, and in patients with additional risk factors, such as co-medication with CYP3A4 inhibitors and/or impaired renal function, to be beneficial for drug safety. It is advised to genotype these patients before (or directly after) drug therapy has been initiated to guide drug and dose selection.

Read more about how DPWG assigns their recommendations for preemptive genotyping.

2011 Guideline

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for codeine based on CYP2D6 genotypes [Article:21412232]. They recommend alternative analgesics for patients carrying the poor metabolizer (PM) alleles, intermediate metabolizer (IM) alleles or ultrarapid metabolizer (UM) allleles.

  • *See Methods or [Article:18253145] for definition of "good" and "moderate" quality.
  • S: statistically significant difference.
  • Please see attached PDF for detailed information about the evaluated studies: Codeine CYP2D6

PharmGKB ID

PA166104970