Cytochrome p450 Genotyping
Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
DESCRIPTION
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. Several testing kits for CYP450 genotyping have been cleared by FDA. Test kits specific for the CTP2D6 include the AmpliChip® (33 CYP2D6 alleles) and the xTAG® CYP2D6 kit.
Test kits for CYP2C19 include the INFINITI™ CYP2C19 Assay, the Verigene CYP2C19 Nucleic Acid Test, and the Spartan RX® CYP2C19 testing system. Several manufacturers market diagnostic panel tests for genotyping that include multiple CYP450 genes, such as the You Script Panel (CYP2D6, CYP2C19, CYP2C9, VKORC1,CYP3A4, and CYP3A5). Other panel tests include both CYP450 and other non-CYP450 genes involved in drug metabolism, such as the Persona Gene Genetic Panels.
POLICY
Cytochrome P450 (CYP2D6) and (CYP2C9) genotyping to determine drug metabolizer status is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Cytochrome P450 (CYP450) genotyping for the purpose of aiding in the choice of drug or dose to increase efficacy and/or avoid toxicity for the following drugs is considered investigational:
Selection or dosing of clopidogrel
Selection or dosing of selective serotonin reuptake inhibitors (SSRIs)
Selection or dosing of selective norepinephrine reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors
Selection or dosing of tricyclic antidepressants
Selection or dosing of antipsychotic drugs
Selection or dosing of codeine
Dosing of efavirenz and other antiretroviral therapies for HIV (human immunodeficiency virus) infection
Dosing of immunosuppressants for organ transplantation
Selection or dosing of beta blockers
Dosing and management of anti-tuberculosis medications
Selection or dosing of tamoxifen
Cytochrome P450 (CYP2C19) genotyping to determine drug metabolizer status in the treatment of Helicobacter pylori is considered investigational.
The use of genetic testing panels that include multiple CYP450 mutations is considered investigational.
MEDICAL APPROPRIATENESS
Genotyping of Cytochrome P450 (CYP2D6) or (CYP2C9) to determine drug metabolizer status is considered medically appropriate if ANY ONE of the following are met:
CYP2D6 genotyping and ANY ONE of the following:
Individual with Gaucher disease being considered for treatment with eliglustat
Individual with Huntington’s disease being considered for treatment with tetrabenazine in a dosage greater than 50 mg per day
CYP2C9 genotyping for relapsing forms of multiple sclerosis (i.e., clinically isolated syndrome, relapsing – remitting disease, active secondary progressive disease) being considered for treatment with siponimod
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g., statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
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.
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/American Heart Association. (2012). 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.
Association for Molecular Pathology. (2019). Recommendations for clinical CYP2C9 genotyping allele selection A joint recommendation of the association for molecular pathology and college of american pathologists. Retrieved August 16, 2022 from https://www.jmdjournal.org.
BlueCross BlueShield Association. Evidence Positioning System. (8:2023). Genotype-guided tamoxifen treatment (2.04.51). Retrieved September 22, 2023 from http://www.evidencepositioningsystem.com. (62 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Evidence Positioning System. (7:2023). Cytochrome p450 genotype-guided treatment strategy (2.04.38). Retrieved September 22, 2023 from http://www.evidencepositioningsystem.com. (23 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Evidence Positioning System. (8:2023). Genetic testing for diagnosis and management of mental health conditions. (2.04.110). Retrieved September 22, 2023 from http://www.evidencepositioningsystem.com. (34 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.
Drögemöller, B., Wright, G.E.B., Shih, J., Monzon, J.G., Gelmon, K.A., Ross, C.J.D., et al. (2019). Breast Cancer Research and Treatment, 173 (3), 521-532. Abstract retrieved October 8, 2019 from PubMed database.
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. (2023, March). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer. V 4.2023. Retrieved September 23, 2023 from the National Comprehensive Cancer Network.
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. (2019, March). Center For Drug Evaluation and Research. Approval decision for 505(b) of the federal food, drug, and cosmetic act (FDCA) for Mayzent (siponimod) tablets. Retrieved August 16, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000Approv.pdf.
U.S. Food and Drug Administration. (2019, March). Center For Drug Evaluation and Research. Drug label for Mayzent (siponimod) tablets. Retrieved August 16, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/209884Orig1s000Approv.pdf
Xi, Z., Fang, F., Wang, J., AlHelal, J., Zhou, Y., & Liu, W. (2019). CYP2C19 genotype and adverse cardiovascular outcomes after stent implantation in clopidogrel-treated Asian populations: a systematic review and meta-analysis. Platelets, 30 (2), 229-240. Abstract retrieved October 8, 2019 from PubMed database.
ORIGINAL EFFECTIVE DATE: 11/12/2005
MOST RECENT REVIEW DATE: 11/9/2023
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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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