May 29, 2023

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 cyp2d6, this video will specifically discuss the recommendations for tramadol and cyp2d6. videos discussing the recommendations for codeine and hydrocodone can be found on the pharmgkb website and on the pharmgkb youtube channel. due to the potential for toxicity in cyp2d6 ultrarapid metabolizers

And the greatly reduced efficacy of tramadol in cyp2d6 poor metabolizers, the guideline recommends that tramadol is the guideline also recommends that cyp2d6 intermediate metabolizers are monitored to this image is adapted from the pharmgkb tramadol pathway. tramadol is metabolized in the liver to form a number of metabolites. central to this guideline is the metabolism

Of tramadol by cyp2d6 to o-desmethyltramadol. o-desmethyltramadol is the most active metabolite of tramadol and provides the analgesic effect of tramadol. in cyp2d6 ultrarapid metabolizers, the formation of o-desmethyltramadol from tramadol is increased. this puts the patient at an increased risk of experiencing toxicity. in cyp2d6 poor metabolizers, the formation of

O-desmethyltramadol from tramadol is greatly reduced. as a result, patients who are cyp2d6 poor metabolizers do not get sufficient pain relief from tramadol due to the low levels of o-desmethyltramadol formed. 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 this table gives the activity values of some cyp2d6 star alleles. it is based on the cyp2d6 allele functionality table, which is available on the pharmgkb 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 be aware that some cyp2d6 alleles have an unknown or uncertain functional status and should be interpreted with caution on a genetic test. in addition, an important caveat for all genotyping tests is that any alleles which are not detected 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. reports in the scientific literature have 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 for example, a patient with the genotype *2×3/*4 has three copies of

The *2 allele and one 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 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 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 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 tramadol, as shown in table 3 of the guideline. patients with a cyp2d6 ultrarapid metabolizer phenotype will have increased formation of o-desmethyltramadol following administration of tramadol, which increases the risk of toxicity.

If opioid use is warranted, consider using a non-codeine opioid. patients with a cyp2d6 normal metabolizer phenotype will have these patients can be given tramadol using the age- or weight-specific dosing recommendations patients with a cyp2d6 intermediate metabolizer phenotype will have if the patient does not respond to tramadol and opioid use is warranted, patients

With a cyp2d6 poor metabolizer phenotype will have greatly reduced o-desmethyltramadol 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 for specific combinations the activity summary includes implications for

The patient’s response to tramadol, the appropriate dosing recommendation for the specific metabolizer phenotype and the strength 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 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 the guideline itself and supplementary information are freely available at the pharmgkb and cpic websites. in the description below this video.

Transcribed from video
CPIC guideline for tramadol and CYP2D6 By PharmGKB