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Practice Guideline
. 2017 Jul;102(1):37-44.
doi: 10.1002/cpt.597. Epub 2017 Feb 13.

Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update

J K Hicks  1 , K Sangkuhl  2 , J J Swen  3 , V L Ellingrod  4 , D J Müller  5 , K Shimoda  6 , J R Bishop  7 , E D Kharasch  8 , T C Skaar  9 , A Gaedigk  10 , H M Dunnenberger  11 , T E Klein  2 , K E Caudle  12 , J C Stingl  13
Affiliations
Practice Guideline

Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update

J K Hicks et al. Clin Pharmacol Ther. 2017 Jul.

Abstract

CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, clomipramine, doxepin, imipramine, and trimipramine). Evidence is presented for CYP2D6 and CYP2C19 genotype-directed dosing of TCAs. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants.

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Conflict of interest statement

CONFLICT OF INTEREST

A.G. is a paid consultant of Millennium Laboratories. T.E.K is a paid scientific advisor to the Rxight™ Pharmacogenetic Program. K.S. has received research support from Shionogi & Co., Ltd., Eli Lilly Japan, K.K., Yoshitomi Pharmaceutical Industries, Ltd., Meiji Seika Pharma Co., Ltd., Eisai Co., Ltd., Pfizer Inc., GlaxoSmithKlein K.K., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., and Takeda Pharmaceutical Co., Ltd. and honoraria from Kowa Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Meiji Seika Pharma Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., GlaxoSmithKlein K.K., and Eisai Co., Ltd

All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Major metabolic pathway of the tertiary amine amitriptyline and the secondary amine nortriptyline. For the structural representation the following 2D-images from the National Center for Biotechnology Information PubChem Compound Database are used: amitriptyline - CID=2160 (https://pubchem.ncbi.nlm.nih.gov/compound/2160); nortriptyline - CID=4543 (https://pubchem.ncbi.nlm.nih.gov/compound/4543); 10-hydroxyamitriptyline - CID=6420900 (https://pubchem.ncbi.nlm.nih.gov/compound/6420900); 10-hydroxynortriptyline - CID=6420504 (https://pubchem.ncbi.nlm.nih.gov/compound/6420504) (37). All entries were accessed Nov. 8, 2016.
See this image and copyright information in PMC

References

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    1. [Accessed September 16 2016];PGx Gene-specific Information Tables for CYP2C19. < https://www.pharmgkb.org/page/cyp2c19RefMaterials>.
    1. Scott SA, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clinical pharmacology and therapeutics. 2011;90:328–32. - PMC - PubMed

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