CYP2D6, located on the minus strand of chromosome 22, encodes the Cytochrome P450 family 2 subfamily D type 6 enzyme, which mediates hepatic first-pass metabolic oxidation of numerous drugs, including the anti-arrhythmics, antidepressants, antipsychotics, beta blockers-adrenergic blocking agents, antiemetics, analgesics, and antitussives. Variants in this gene may reduce or abolish enzyme function; variations in copy number also exist, which may lead to increased function or complete deletion of the gene, resulting in phenotypes ranging from no to increased function compared to normal. The Clinical Pharmacogenetics Implementation Consortium (CPIC) released guidelines for codeine, desipramine, fluvoxamine, nortriptyline, ondansetron, paroxetine, and tropisetron treatment based on CYP2D6 metabolizer status. For example in codeine guidelines, CPIC recommends use of alternative analgesics for CYP2D6 poor metabolizers based on lack of efficacy and for ultrarapid metabolizers based of potential for toxicity. CPIC recommends use of label age- or weight-specific dosing in normal and intermediate metabolizers with an additional recommendation for intermediate metabolizers to consider alternative analgesics such as morphine or a non-opioid if there is no response. In addition, CYP2D6 genotyping may help in predicting outcomes with tamoxifen chemotherapy in breast cancer. Genotyping CYP2D6 can aid opioid treatment, antidepressant therapy, tamoxifen dosage and response, and it can prevent toxicity-related ADRs with all of these medications.
- Codeine FDA Drug Label. US Food Drug Adm. 2016. Available at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm289739.htm.
- Clinical pharmacogenetics implementation consortium (CPIC) guidelines for cytochrome P450 2D6 (CYP2D6) genotype and codeine therapy: 2014 update. Clinical Pharmacology and Therapeutics. 2014. Crews K R, et al.
- Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical Pharmacology and Therapeutics. 2017. Hicks, et al.
- Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clinical Pharmacology and Therapeutics. 2015. Hicks, et al.
- Pharmacogenetics: from bench to byte—an update of guidelines. Clinical Pharmacology and Therapeutics. 2011. Swen J J, et al.