Annotation of CPIC Guideline for hydrocodone and CYP2D6

December 2020

The authors of the CPIC® guideline for opioids and CYP2D6, OPRM1 and COMT evaluated the available evidence for therapeutic dose recommendations for hydrocodone and CYP2D6 metabolizer phenotypes.

• These guidelines are applicable to:

  • adult patients
  • pediatric patients

• Excerpts from the guideline:

  • " For CYP2D6 ultrarapid metabolizers, there is insufficient evidence and confidence to provide a recommendation to guide clinical practice at this time (no recommendation, CPIC level C)."
  • "For CYP2D6 intermediate and poor metabolizers, there is some evidence to support decreased metabolism of hydrocodone to the more active metabolite hydromorphone, but there is insufficient evidence to determine if these effects on pharmacokinetics translate into decreased analgesia or adverse events. Because of this, the use of hydrocodone label recommended age- or weight-specific dosing is recommended. However, if there is no response to hydrocodone in a CYP2D6 intermediate or poor metabolizer, the use of an alternative analgesic (non-opioid or opioid not affected by CYP2D6 phenotype) should be considered (optional recommendation, CPIC level B)."
  • "It is not known if increasing the dose of hydrocodone would affect analgesia response in intermediate or poor metabolizers."

• Download and read:

  • CPIC® Guideline for Opioids and CYP2D6, OPRM1 and COMT
  • 2020 supplement
  • CYP2D6 Gene-Specific Information Tables
  • Hydrocodone Drug Resource Mappings
  • Hydrocodone Pre and Post Test Alerts
  • Hydrocodone Clinical Decision Support Flow Chart

Table 1: Hydrocodone therapy recommendations based on CYP2D6 phenotype

Adapted from Tables 1 and 4 of the guideline.

^a See the CYP2D6 Frequency Table on the CYP2D6 Gene-Specific Information Tables page for biogeographical group-specific allele and phenotype frequencies.
^b Assignment of allele function and allele activity values including citations for allele function can be found in the CYP2D6 Allele Definition Table and CYP2D6 Allele Functionality Table. For a complete list of CYP2D6 diplotypes and resulting phenotypes, see the CYP2D6 Genotype to Phenotype Table. All of these tables can be accessed on the CYP2D6 Gene-Specific Information Tables page.
^c Where xN represents the number of CYP2D6 gene copies. For individuals with CYP2D6 duplications or multiplications, see supplemental data for additional information on how to translate diplotypes into phenotypes.
^d Rating scheme described in the Strength of Recommendations section in the guideline supplement