This is a summary of the CPIC dosing guideline for tricyclic antidepressants and variation in the genes CYP2C19 and CYP2D6.
This video will specifically discuss the dosing guidelines for doxepin. on the pharmgkb website and on the pharmgkb youtube channel. to apply the cpic dosing guideline for cyp2d6, the guideline recommends an alternative drug poor metabolizers or patients who are cyp2c19 if doxepin is warranted, a dose reduction a dose reduction can also be considered for this is the pharmgkb
Doxepin pharmacokinetics pathway. this video will first focus on metabolism doxepin is metabolized by cyp2c19 to desmethyldoxepin, doxepin is a tertiary amine with a greater is a secondary amine with a greater noradrenergic effect. there can be changes in the balance of serotonergic and noradrenergic effects, with greater noradrenergic and greater serotonergic effects in
Poor metabolizers. there are currently over 30 defined alleles of cyp2c19, known as star alleles. diplotypes of cyp2c19 star alleles can be note that, as more evidence becomes available, an important caveat for all genotyping tests this can include rare increased-function, which are not routinely screened for in some genotyping tests. a link to pharmvar is also given in
The description below this video. doxepin is metabolized by cyp2d6 to form less active metabolites. this reduces the concentrations of doxepin in cyp2d6 poor metabolizers, metabolism of doxepin is reduced. there are almost 150 different cyp2d6 alleles, each star allele can be assigned an activity this table gives the activity values of some cyp2d6 star alleles. links to
These are given in the description below this video. gives further examples of alleles with their be aware that some cyp2d6 alleles have an should be interpreted with caution on a genetic test. this reflects its significantly reduced function more information on the project can be found on the cpic website. is still given an activity value of 0.5 in the original manuscript.
This update has not altered the guideline recommendations. reports in the scientific literature have alleles which are present in multiple copies of copies of that allele that are present in a genome. the activity score of alleles that are present the activity score for the allele by the number of copies present. further information about cyp2d6 alleles can be found at
The pharmvar website. the cyp2d6 activity score is then used to note that genetic tests from different laboratories may not use this scheme to assign cyp2d6 metabolizer because of this, the guideline advises that activity score calculated before making clinical these are the cpic dosing recommendations for doxepin by cyp2c19 phenotype. use of tertiary amines should be
Avoided in these patients. if use of a tertiary amine is warranted, therapeutic these patients can begin doxepin therapy with the recommended starting dose. these are the cpic dosing recommendations for doxepin by cyp2d6 phenotype. if use of a tca is warranted, consider titrating to a higher target dose than for normal metabolizers. a 25% reduction in the recommended
Starting patients with a cyp2d6 poor metabolizer phenotype if use of a tca is warranted, a 50% reduction detailed footnotes pertaining to the recommendations be aware that these dosing recommendations a tca are warranted, such as in the treatment of depression. a tca, for example, in the treatment of neuropathic this includes a drop-down menu where an activity the activity
Summary includes implications appropriate dosing recommendation for the remember that variation in other genes in including concomitant medications, can affect treatment. cpic and pharmgkb assume no responsibility or property arising out of or related to any the guideline itself and supplementary information you can access relevant pages using the links in the description below this video.
Transcribed from video
CPIC guideline for doxepin and CYP2C19, CYP2D6 By PharmGKB