BlueCross BlueShield of Tennessee Medical Policy Manual

Cytochrome p450 Genotyping

DESCRIPTION

Drug efficacy and toxicity vary substantially by individual.  Because drugs and doses are typically adjusted, if needed, by trial and error, clinical consequences may include a prolonged time to optimal therapy.  Pharmacogenomics is the study of how an individual’s genetic inheritance affects the body's response to drugs. It has been investigated as a tool in predicting therapeutic failures or severe adverse drug reactions.  Pharmacogenetics tests for DNA sequence variations in drug metabolizing enzymes, drug receptors, and drug transporters. Potentially the identification of significant polymorphisms could be used to improve efficacy and safety of drug choice and /or dosage.

The cytochrome P450 (CYP450) family is a major subset of all drug-metabolizing enzymes.  Several CYP450 enzymes are involved in the metabolism of a significant proportion of currently administered drugs.  CYP2D6 metabolizes approximately 25% of all clinically used medications (e.g., dextromethorphan, beta blockers, antiarrhythmics, antidepressants and morphine derivatives).  CYP450 enzyme genes can have distinct variations which can affect individual capability to metabolize specific drugs. CYP450 genotyping has been proposed as a way to direct early selection of the most effective drug or dose to avoid significant adverse events and speed the process of achieving a therapeutic dose.

Diagnostic genotyping tests for certain CYP450 enzymes are available.  Some tests are offered as in-house laboratory-developed test services, which do not require U.S. Food and Drug Administration (FDA) approval but which must meet Clinical Laboratory Improvement Act (CLIA) quality standards for high-complexity testing.  Several testing kits for CYP450 genotyping have been cleared by FDA.  These include the AmpliChip® (Roche Molecular Systems, Inc.), the xTAG® CYP2D6 kit (Luminex Molecular Diagnostics), the INFINITI CYP2C19 Assay (AutoGenomics Inc.), Verigene CYP2C19 Nucleic Acid Test (Nanosphere Inc.), the Spartan RX CYP2C19 test system (Spartan Bioscience), and the xTAG®CYP2C19 kit v3 (Luminex Molecular Diagnostics).

POLICY

See also:  Genetic Testing for Warfarin Dose

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION

Individuals with genetic variants of cytochrome P450 have a decreased ability to metabolize clopidogrel, but the impact on clinically meaningful outcomes is uncertain.  While genotyping appears in some studies to be helpful in identifying individuals at higher risk of treatment failure and may be useful in selected individuals, more information is needed to refine optimal use of testing and to better understand the relative merit of management options.

The evidence for cytochrome P450 genotyping in individuals with various clinical conditions undergoing or being considered for treatment with a drug metabolized by CYP450 enzymes is insufficient to determine the effects of the technology on health outcomes.

SOURCES 

Ahern, T., Hertz, D., Damkier, P., Eilertsen, B., Hamilton-Dutoit, S., Rae, J., et al. (2017). Cytochrome P-450 2D6 (CYP2D6) genotype and breast cancer recurrence in tamoxifen-treated patients: evaluating the importance of loss of heterozygosity. American Journal of Epidemiology, 185 (2), 75-85. Abstract retrieved November 20, 2017 from PubMed database.

American College of Cardiology Foundation. (December, 2011). 2011 ACCF/AHA/SCAI guideline for percutaneous coronary artery intervention. Retrieved August 7, 2015 from the National Guideline Clearinghouse (NGC: 008816).

American College of Cardiology Foundation/American Heart Association. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Retrieved February 2, 2016 from http://content.onlinejacc.org.

American College of Cardiology Foundation/American Heart Association. (2010). ACCF/AHA clopidogrel clinical alert: approaches to the FDA “boxed warning”. Retrieved September 27, 2012 from http://circ.ahajournals.org/content/122/5/537.

BlueCross BlueShield Association.  Medical Policy Reference Manual. (6:2017). Genetic testing for tamoxifen treatment (2.04.51). Retrieved November 17, 2017 from BlueWeb. (80 articles and/or guidelines reviewed)

BlueCross BlueShield Association. Medical Policy Reference Manual. (6:2017). Cytochrome p450 genotyping (2.04.38). Retrieved November 17, 2017 from BlueWeb. (116 articles and/or guidelines reviewed)

Bykov, K., Schneeweiss, S., Glynn, R., Mittleman, M., Bates, D., & Gagne, J. (2017). Updating the evidence of the interaction between clopidogrel and CYP2C19-inhibiting selective serotonin reuptake inhibitors: a cohort study and meta-analysis. Drug Safety, 40 (10), 923-932. Abstract retrieved November 20, 2017 from PubMed database.

Cahaba Government Benefit Administrators, LLC. (2016, January). LCD for pathology and laboratory: CYP2C19, CYP2D6, CYP2C9, and VKORC1 Genetic Testing (L35660). Retrieved November 17, 2017 from https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35660&ver=8&Date=&DocID=L35660&bc=iAAAABAAAAAAAA%3d%3d.

Huang, B., Cui, D., & Zhao, X. (2017). Effect of cytochrome P450 2C19*17 allelic variant on cardiovascular and cerebrovascular outcomes in clopidogrel-treated patients: a systematic review and meta-analysis. Journal of Research in Medical Sciences, 22, 109. (Level 1 evidence)

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer. Retrieved November 17, 2017 from the National Comprehensive Cancer Network.

National Institute for Health and Care Excellence. (2017). Eliglustat for treating type 1 Gaucher disease. Retrieved November 17, 2017 from www.nice.org.uk/guidance/hst5.

Ormeci, A., Emrence, Z., Baran, B., Soyer, O., Gokturk, S., Evirgen, S., et al. (2016). Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism? European Review for Medical and Pharmacological Sciences, 20, 1795-1797. (Level 5 evidence)

Prapitpaiboon, H., Mahachai, V., & Vilaichone, R. (2015). High efficacy of levofloxacin-dexlansoprazole-based quadruple therapy as a first line treatment for helicobacter pylori eradication in Thailand. Asian Pacific Journal Cancer of Cancer Prevention, 16 (10), 4353-4356. Abstract retrieved March 16, 2016 from PubMed database.

U. S. Food and Drug Administration. (2005, January). Center for Devices and Radiological Health. Medical devices. AmpliChip CYP450 Test for CYP2C19 510(k) Summary. Retrieved December 12, 2015 from https://www.accessdata.fda.gov/cdrh_docs/pdf4/K043576.pdf.

U.S. Food and Drug Administration. (2014, August). Center for Drug Evaluation and Research. Cerdelga(eliglustat). Retrieved February 2, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205494Orig1s000lbl.pdf.

U.S. Food and Drug Administration. (2015, June). Center for Drug Evaluation and Research. Xenazine® (tetrabenazine). Retrieved February 2, 2016 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021894s010lbl.pdf.

ORIGINAL EFFECTIVE DATE:  11/12/2005

MOST RECENT REVIEW DATE:  12/14/2017

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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