This is a summary of the CPIC guideline for opioids and variation in the genes CYP2D6, OPRM1 and COMT.
This is a summary of the cpic guideline for opioids and variation in the genes videos discussing the recommendations for codeine and tramadol can be found on the pharmgkb website and on the pharmgkb youtube channel. this guideline was last updated in december 2020. patients with decreased cyp2d6 function may have reduced formation of
Hydromorphone, as a result, the guideline recommends that patients who are cyp2d6 intermediate or poor metabolizers are monitored to determine their response to hydrocodone. the guideline gives no recommendation for cyp2d6 ultrarapid metabolizers. this is due to a lack of evidence. this image is adapted from the pharmgkb hydrocodone
Pathway. a link to the original pathway is provided in the description below this video. hydrocodone is extensively metabolized in the liver. central to this guideline is the metabolism of hydrocodone by cyp2d6 to hydromorphone. hydromorphone is the most active metabolite of hydrocodone in cyp2d6 intermediate or poor metabolizers, the formation of
Hydromorphone from hydrocodone there are almost 150 different cyp2d6 alleles, which are designated as star alleles. each star allele can be assigned an activity value based on its activity level compared to the *1 allele. the *1 allele has an activity value of 1. this table gives the activity values of some cyp2d6 star alleles. it is based
On the cyp2d6 allele functionality table, which is available links are given in the description below this video. it is strongly recommended that you consult the full allele functionality table, as it gives further examples of alleles with their activity values as well as extensive footnotes and caveats that should be considered.
Be aware that some cyp2d6 alleles have an unknown or uncertain functional status and should be in addition, an important caveat for all genotyping tests is that any alleles which are not detected in the assay are designated as *1. this can include rare increased-function, reduced-function and non-functional alleles which are not routinely screened for
In some genotyping tests. it is also important to note that patients can carry multiple copies of cyp2d6. described cases where up to 13 copies of cyp2d6 alleles which are present in multiple copies are given the suffix xn, where n is the number of copies of that allele that are present in a genome. for example, a patient with
The genotype *2×3/*4 has three copies of the *2 allele and one copy of the *4 allele. the activity score of alleles that are present in multiple copies is calculated by multiplying the activity score for the allele by the number of copies present. in this case, the activity score of *2×3 is 1 multiplied by 3, which equals 3. further information about
Cyp2d6 alleles can be found at the pharmvar website at www.pharmvar.org. a link to pharmvar is also given in the description below this video. the activity values of a patient’s cyp2d6 alleles can be added together to give a total cyp2d6 activity score for the patient. the cyp2d6 activity score is then used to assign a cyp2d6 note that genetic
Tests from different laboratories may not use this scheme to assign cyp2d6 metabolizer phenotypes. because of this, the guideline advises that a patient’s cyp2d6 diplotype is noted and activity score calculated before making clinical decisions based on this guideline. these are the cpic dosing recommendations for hydrocodone, as shown in table 4
Of the guideline. no recommendation is given for patients with a cyp2d6 ultrarapid metabolizer phenotype. this is because there is only minimal evidence linking this phenotype with a change in the pharmacokinetic or clinical effect of hydrocodone. patients with a cyp2d6 normal metabolizer phenotype will have normal hydromorphone formation.
These patients can be given hydrocodone using the age- or weight-specific dosing with a change in the pharmacokinetic or clinical effect of hydrocodone. the guideline recommends that these patients be given hydrocodone using the age- or weight-specific dosing recommendations given on the label. if the patient does not respond to hydrocodone
And opioid use is warranted, consider a non-codeine or non-tramadol opioid. patients with a cyp2d6 poor metabolizer phenotype will have decreased metabolism of hydrocodone to hydromorphone. however, there is insufficient evidence to determine if this affects analgesia or side effects. the guideline recommends that these patients be given
Hydrocodone using the age- or weight-specific dosing recommendations given on the label. if the patient does not respond no recommendation is given for patients with the cyp2d6 indeterminate phenotype. this guideline has been annotated on the pharmgkb website. this includes a drop-down menu where an activity summary can be
Given the activity summary includes implications for the patient’s response to hydrocodone, the appropriate dosing recommendation for the specific metabolizer phenotype and the strength of that recommendation. remember that variation in other genes in addition to demographic and clinical factors, including concomitant medications, can affect
Treatment. it remains the responsibility of the clinician to determine the best course of treatment for a patient. cpic and pharmgkb assume no responsibility for any injury to persons or damage to persons or property arising out of or related to any use of cpic’s guideline, or for any errors or omissions. the guideline itself and supplementary
Information are freely available at the pharmgkb and cpic websites. the links in the description below this video.
Transcribed from video
CPIC guideline for hydrocodone and CYP2D6 By PharmGKB