Medical Policy: 02.04.48
Original Effective Date: October 2013
Reviewed: July 2016
Revised: July 2016
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This Medical Policy document describes the status of medical technology at the time the document
was developed. Since that time, new technology may have emerged or new medical literature may
have been published. This Medical Policy will be reviewed regularly and be updated as scientific
and medical literature becomes available.
The cytochrome p450 (CYP450) family is involved in the metabolism of a significant proportion of currently administered drugs, and genetic variants in cytochrome p450 are associated with altered metabolism of many drugs. It is proposed that genetic testing for cytochrome p450 variants may assist in selecting and dosing drugs that are impacted by these genetic variants.
Drug efficacy and toxicity vary substantially between individuals. Because drugs and doses are typically adjusted to meet individual requirements as needed by using trial and error, clinical consequences may include a prolonged time to optimal therapy and serious adverse events.
Various factors may influence the variability of drug effects, including age, liver function, concomitant diseases, nutrition, smoking, and drug-drug interactions. Inherited (germline) DNA sequence variation (polymorphisms) in genes coding for drug metabolizing enzymes, drug receptors, drug transporters, and molecules involved signal transduction pathways also may have major effects on the activity of those molecules and also on the efficacy and toxicity of the drug.
Pharmacogenomics is the study of how an individual’s genetic inheritance affects the body’s response to drugs. It may be possible to predict therapeutic failures or severe adverse drug reactions in individual patients by testing for important DNA polymorphisms (genotyping) in genes related to the metabolic pathway (pharmacokinetics) or single transduction pathway (pharmacodynamics) of the drug. Potentially, test results could be used to optimize drug choice and/or dose for more effective therapy, avoid serious adverse effects and decrease medical costs.
Some CYP450 enzyme genes are highly polymorphic, resulting in some enzyme variants that have variable metabolic capacities among individuals, and some with little to no impact on activity.
Individuals with a lack of function activity in these enzymes (CYP2C19, CYP2D6, CYP2C9, etc.) can be classified according to how fast they metabolize medications:
- Poor metabolizers (PMs): lack active enzyme gene alleles, they will process a certain drug more slowly than normal because of the missing enzyme(s), the medication can build up in their system which can increase the likelihood that it will cause side effects. The individual might still be able to benefit from the medication, but at lower dosages.
- Intermediate metabolizers (IMs): have one active and one inactive enzyme gene allele, these individuals have a reduced enzyme function in processing drugs, they may not process some medications as well as a normal metabolizer would. This can increase risk of side effects and drug interactions.
- Normal metabolizers (extensive metabolizers Ems): these individuals have 2 copies (alleles) of the most common (wild type) DNA sequence of a particular CYP450 enzyme gene resulting in an active molecule and are termed extensive metabolizers. Medications are processed normally, these individuals are more likely to benefit from treatment and have fewer side effects than people who don’t process the same medication(s) as well.
- Ultra-rapid metabolizers (UMs): individuals with more than 2 alleles of an active enzyme gene, which cause the medications to leave the body too quickly and often before they have had a chance to work properly. These individuals will likely need a higher than usual dose of medications.
It is very important to realize that many drugs are metabolized to varying degrees by more than one enzyme, either within or outside of the CYP450 superfamily. In addition, interaction between different metabolizing genes, interaction of genes and environment, and interactions among different non-genetic factors also influence CYP450-specific metabolizing functions. Therefore, identification of a variant in a single gene in the metabolic pathway may be insufficient in all but a small proportion of drugs to explain inter-individual differences in metabolism and consequent efficacy or toxicity.
Genetically determined variability in drug response has been traditionally addressed using a trial and error approach to prescribing and dosing, along with therapeutic drug monitoring (TDM) for drugs with a very narrow therapeutic range and/or potential serious adverse effects outside that range. However, TDM is not available for all drugs of interest, and a cautious trial and error approach can lengthen the time to achieving an effective dose.
CYP450 enzyme phenotyping (identifying metabolizer status) can be accomplished by administering a test enzyme substrate to a patient and monitoring parent substrate and metabolite concentrations over time. However, testing and interpretation are time-consuming and inconvenient; as a result, phenotyping is seldom performed.
To definitively show that pharmacogenetic testing has value in clinical practice, it is not enough to demonstrate that drug response varies by genotype. There must be an alternative treatment strategy, and proof that testing for the genotype and subsequently tailoring the treatment strategy based on genetic information are more clinically effective or cost effective (or both) than merely treating everyone in the usual manner. Use of the test to identify gene variants and affected populations must be more efficient than current practice in preventing serious adverse effects. After taking into account known non-genetic factors that cause variation in response, the remaining variability in patient response can often with appropriate monitoring, or can be reversed by withdrawal of the drug be managed by changing drugs or dosage. Adverse effects of available drugs are generally preventable.
Selection or Dosing of Clopidogrel
Clopidogrel (Plavix) and CYP2C19 Variants: Guidelines from the American Heart Association and the American College of Cardiology recommend the use of dual antiplatelet therapy with aspirin and a P2Y12 inhibitor, such as clopidogrel, prasugrel or ticagrelor, for the prevention of atherothrombotic events after acute myocardial infarction (MI). However, a substantial number of subsequent ischemic events still occur, which may be least partly due to interindividual variability in the response to clopidogrel. Clopidogrel is a prodrug which is converted by several CYP450 enzymes, CYP2C19 in particular, to an active metabolite. For this reason, genetic polymorphisms that inactive the CYP2C19 enzyme are associated with impaired pharmacodynamics response in healthy individuals.
The adverse effect of reduced function CYP2C19 alleles on the benefit from the anti-platelet agent clopidogrel (plavix) have been demonstrated in a number of studies and a meta-analysis. In March 2010, a new black box warning from the U.S. Food and Drug Administration was issued to alert clinicians that genetic testing is available to identify individuals with poor metabolizer variants of CYP2C19 who may not receive the full benefits of clopidogrel (plavix) and require dose adjustment or use of a different drug. CYP2C19 poor metabolizers (PMs) may exhibit higher cardiovascular event rates following acute coronary syndrome or percutaneous coronary intervention than patients with normal CYP2C19 function.
In 2010 ACCF/AHA collaborative document regarding clopidogrel clinical alert: approaches to the FDA “Boxed Warning” includes “Recommendations for Practice” discussion points. In summary, they indicate that more studies and trials are needed because the predictive value of genetic testing is currently very limited, and because there is insufficient evidence to recommend such testing as routine. The practice recommendations indicate that the physician should use clinical judgement to assess clinical risk and variability in patients considered to be at increased risk. Genetic testing to determine if a patient is predisposed to poor clopidogrel metabolism (poor metabolizers) may be considered before starting clopidogrel therapy in patients believed to be at moderate or high risk for poor outcomes: this includes individuals undergoing elective high risk PCI for treatment of extensive and/or very complex disease. Moreover, if a person is identified as a potentially poor metabolizer (PM), other treatments should be considered i.e. alternative dosing or use of other available agents such as prasugrel (effient), if not contraindicated for the individual.
In 2012 ACCF/AHA Focused Updated of the Guideline for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction, Class IIb recommendation suggests that a selective, limited approach to platelet genotype assessment of platelet function testing is more prudent course until better clinical evidence exists for us to provide a more scientific derived recommendation, in patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI). Also, patients who experience recurrent ACS (acute coronary syndrome) events despite ongoing therapy with clopidogrel (Plavix).
Selection or Dosing of Tetrabenazine
Tetrabenazine (Xenazine): is a monoamine depletory for oral administration, and is indicated for the treatment of chorea (abnormal involuntary movement disorder) associated with Huntington’s disease, an autosomal dominant genetic neurodegenerative disorder. The labeling for tetrabenzine states that, although the pharmacokinetics of tetrabenazine and its metabolites in subjects who do not express the drug metabolizing enzyme CYP2D6 (poor metabolizers) have not been systematically evaluated, it is likely that the exposure to beta-HTBZ would be increased compared to subjects to express the enzyme (extensive metabolizers/normal metabolizers), with an increase similar to that observed in patients taking strong CYP2D6 inhibitors. The labeling for tetrabenazine states that “patients should be genotyped for CYP2D6 prior to treatment with daily doses of tetrabenazine over 50mg, and patients who are poor metabolizers should not be given daily doses greater than 50 mg."
Selection or Dosing of Eliglustat
Gaucher disease is a rare autosomal recessive lipid storage disease in which deficiency or absence of enzyme B-glucocerebrosidase leads to lysosomal accumulation of the glycosphingolipid glycosylceramide. Untreated, this accumulation can lead to a range of effects, including anemia and thrombocytopenia, splenomegaly, bone disease, pulmonary fibrosis, and central nervous system involvement. Gaucher disease has been treated through enzyme replacement, for which 3 drugs have been FDA approval as orphan drugs (imiglucerase, velaglucerase alfa, and taliglucerase alfa) or substrate reduction therapy, for which 2 drugs have FDA approval as orphan drugs (miglustat and eliglustat tartrate). Eliglustat (cerdelga) is an orally administered selective inhibitor of glucosylceramide synthase that received FDA approval in 2014 and has been found in 3 phase 3 clinical trials to lead to improvements in hematologic metrics and organomegaly.
Eliglustat (cerdelga) is metabolized by CYP2D6 and CYP3A. FDA labeling requires that patients be selected on the basis of CYP2D6 metabolizer status as determined by genotype, with recommendations based on genotype about dosage: CYP2D6 Ems (extensive metabolizers) or IMs (intermediate metabolizers) 84 mg orally twice daily; CYP2D6 PMs (poor metabolizers) 84 mg orally once daily.
For all other medications:
Most published CYP450 pharmacogenomic studies are retrospective evaluations of CYP450 genotype association with intermediate (e.g., circulating drug concentrations) or, less often, final outcomes (e.g., adverse events or efficacy) and are largely small and underpowered or not designed to examine the clinical effects of homozygous variant poor metabolizers and of ultra-rapid metabolizers, where the strongest effects, if any, would be seen. The hazards associated with poor metabolizers are consequently difficult to interpret and decision making about how to use genotyping information is poorly defined with uncertain outcomes. As a result CYP450 genotyping is investigational. This includes, but is not limited to, CYP450 genotyping for the following indications:
- selection or dose of selective serotonin reuptake inhibitor (SSRI)
- selection and dosing of serotonin norepinephrine reuptake inhibitors (SNRIs)
- selection and dosing of tricyclic antidepressant medications
- selection or dose of antipsychotic medications
- selection or dosing of opioid analgesics
- dose of efavirenz (common component of highly active antiretroviral therapy for HIV infection)
- dose of immunosuppressant for organ transplantation
- selection or dose of beta blockers
- dosing and management of antituberculosis medications
- selection or dosing of Tamoxifen
Current evidence regarding the use of genotyping tests for the determination of drug metabolizer status indicates that while available testing methods may accurately identify genetic variations in an individual, there is insufficient data to demonstrate that such testing, and the clinical decisions made based on the testing, results in a significant impact on health outcomes. Specifically, clinical trials have not yet adequately demonstrated that such testing results in either enhanced clinical effectiveness, or in decreased short-term or long-term serious adverse events.
Practice Guidelines and Position Statements
Evaluation of Genomic Applications in Practice and Prevention (EGAPP)
CYP450 Genotyping to Predict Response to SSRIs Used to Treat Non-psychotic Depression in Adults: EGAPP™ Recommendation
Summary of Findings on Genotyping to Predict Response to SSRIs
In 2007, the independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group determined that there was not enough evidence to state whether CYP450 genotyping should or should not be used to help health care providers make decisions about beginning SSRI treatment in adults with non-psychotic depression. They discouraged use of such testing until more studies evaluating potential harms and benefits are conducted.
The EGAPP recommendation statement was based on the following key points from the evidence review:
- In studies of people undergoing SSRI treatment, the results of their CYP450 genotyping did not show a clear relationship with the actual levels of the SSRI drug in their blood.
- CYP450 genotyping results were not clearly related to how well the SSRI worked or the presence or severity of negative side effects.
- No evidence was found to indicate that the use of CYP450 genotyping improved health outcomes or helped patients or doctors make decisions about the use of SSRI drugs.
- The potential harms of CYP450 genotyping are:
- Increased health care costs without clear benefit to the patient.
- Patients may receive less effective treatment with SSRI drugs.
- Genotyping information may be used inappropriately for managing other drugs metabolized by CYP450 enzymes
American College of Cardiology Foundation (ACCF) and American Heart Assocation (AHA)
A consensus statement by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) on genetic testing for selection and dosing of clopidogrel was published in 2010.
The recommendations for practice included the following statements:
- Adherence to existing ACCF/AHA guidelines for the use of antiplatelet therapy should remain the foundation for therapy. Careful clinical judgment is required to assess the importance of the variability in response to clopidogrel for an individual patient and its associated risk to the patient.
- Clinicians must be aware that genetic variability in CYP enzymes alter clopidogrel metabolism, which in turn can affect its inhibition of platelet function. Diminished responsiveness to clopidogrel has been associated with adverse patient outcomes in registry experiences and clinical trials.
- The specific impact of the individual genetic polymorphisms on clinical outcome remains to be determined.
- Information regarding the predictive value of pharmacogenomic testing is very limited at this time; resolution of this issue is the focus of multiple ongoing studies. The selection of the specific test, as well as the issue of reimbursement, is both important additional considerations.
- The evidence base is insufficient to recommend either routine genetic or platelet function testing at the present time. Clinical judgement is required to assess clinical risk and variability in patients considered to be at increased risk. Genetic testing to determine if a patient is predisposed to poor clopidogrel metabolism (poor metabolizers) may be considered before starting clopidogrel therapy in patients believed to be at moderate or high risk for poor outcomes. This might include, among others, patients undergoing elective high risk PCI procedures (e.g. treatment of extensive and/or very complex disease). If such testing identifies a potential poor metabolizer, other therapies, particularly prasurgel for coronary patients should be considered.
- There are several possible therapeutic options for patients who experience an adverse event while taking clopidogrel in the absence of any concern about medication compliance.
2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction
Since the FDA announced a “Boxed Warning” on March 12, 2010, about the diminished effectiveness of clopidogrel in patients with an impaired ability to convert the drug into its active form, there has been interest in whether clinicians should perform routine testing in patients being treated with clopidogrel. The routine testing could be for genetic variants of the CYP2C19 allele and/or for overall effectiveness for inhibition of platelet activity.
The FDA label revision does not mandate testing for CYP2C19 genotypes or overall platelet function. The revision serves to warn clinicians that certain patient subgroups may exhibit reduced clopidogrel-mediated platelet inhibition and emphasizes that clinicians should be aware of alternative treatment strategies to tailor alternative therapies when appropriate.
There are no prospective studies that demonstrate that the routine use of these tests couples with modification of antiplatelet therapy improves clinical outcomes or reduces subsequent clinical events. A recent meta-analysis demonstrated an association between the CYP2C19 genotype and clopidogrel responsiveness but no significant association of genotype and cardiovascular events. Several ongoing studies are examining whether genotype assessment with attendant alteration in antiplatelet therapy for those with loss-of-function alleles can improve clinical outcomes.
On the basis of current evidence, it is difficult to strongly recommend genotype testing routinely in patients with acute coronary syndrome (ACS), but it might be considered on a case by case basis, especially in patients who experience recurrent ACS events despite ongoing therapy with clopidogrel.
Some argue that clinicians should consider routine testing of platelet function, especially in patients undergoing high-risk PCI (percutaneous coronary interventions) to maximize efficacy while maintaining safety. Again, no completed prospective studies have examined such an approach to guide such a sweeping change in clinical management.
Our recommendations for the use of genotype testing and platelet function testing seek to strike a balance between not imposing undue burden on clinicians, insurers, and society to implement these strategies in patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) and that of acknowledging the importance of these issues to patients with UA/NSTEMI. Our recommendation that the use of either strategy may have some benefit should be taken in the context of the remarks in this update, as well as the more comprehensive analysis in the ACCF/AHA Clopidogrel Clinical Alert. The Class IIb recommendation of these strategies suggests that a selective, limited approach to platelet genotype assessment and platelet function testing is the more prudent course until better clinical evidence exists for us to provide a more scientific derived recommendation.
American Society of Clinical Oncology (ASCO)
2013 Clinical Practice Guideline for the Use of Pharmacologic Interventions for Breast Cancer Risk Reduction
Testing for CYP2D6 Allelic Variants in the Prevention Setting: Since the last guideline, additional data have been generated on the relationship between functional allele variants in cytochrome P450 2D6 gene (CYP2D6), use of CYP2D6 inhibitors including selective serotonin reuptake inhibitors, and breast cancer incidence. Data from the NSABP-P1 and STAR trials do not support the use of CYP2D6 testing to identify women not likely to benefit from tamoxifen therapy for breast cancer prevention.
Diagnostic genotyping tests for certain CYP450 enzymes are now 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 (CLIA) quality standards.
Several test kits for CYP450 genotyping have been cleared for marketing by the FDA (FDA product code: NTI). These include:
- The AmpliChip® (Roche Molecular Systems, Inc.) is an FDA-cleared test for CYP450 genotyping. The AmpliChip® is a microarray consisting of many DNA sequences complementary to 2 CYP450 genes and applied in microscopic quantities at ordered locations on a solid surface (chip). The AmpliChip® tests the DNA from a patient’s white blood cells collected in a standard anticoagulated blood sample for 29 polymorphisms and mutations for the CYP2D6 gene and 2 polymorphisms for the CYP2C19 gene. CYP2D6 metabolizes approximately 25% of all clinically used medications (e.g., dextromethorphan, beta-blockers, antiarrhythmics, antidepressants, and morphine derivatives), including many of the most prescribed drugs. CYP2C19 metabolizes several important types of drugs, including proton-pump inhibitors, diazepam, propranolol, imipramine, and amitriptyline. FDA cleared the test “based on results of a study conducted by the manufacturers of hundreds of DNA samples as well as on a broad range of supporting peer-reviewed literature.” According to FDA labeling, “Information about CYP2D6 genotype may be used as an aid to clinicians in determining therapeutic strategy and treatment doses for therapeutics that are metabolized by the CYP2D6 product.”
- The xTAG® CYP2D6 Kit (Luminex Molecular Diagnostics, Toronto, ON) was cleared for marketing in August 2010 based on substantial equivalence to the AmpliChip CYP450 test. It is designed to identify a panel of nucleotide variants within the polymorphic CYP2D6 gene on chromosome 22.
- The INFINITI CYP2C19 Assay (AutoGenomics Inc., Vista, CA) was cleared for marketing in October 2010 based on substantial equivalence to the AmpliChip CYP450 test. It is designed to identify variants within the CYP2C19 gene (*2, *3, and *17).
- Verigene CYP2C19 Nucleic Acid Test (Nanosphere Inc., Northbrook, IL) , designed to identify variants within the CYP2C19 gene, was cleared for marketing in November 2013 based on substantial equivalence to the INFINITI CYP2C19 Assay.
- The Spartan RX CYP2C19 Test System Spartan Bioscience, Redwood Shores, CA), designed to identify variants in the CYP2C19 gene (*2, *3, and *17 alleles), was cleared for marketing in August 2013 based on substantial equivalence to the INFINITI CYP2C19 Assay.
- The xTAG® CYP2C19 Kit v3 (Luminex Molecular Diagnostics, Toronto, ON), designed to identify variants in the CYP2C19 gene (*2, *3, and *17 alleles) was cleared for marketing in September 2013 based on substantial equivalence to the INFINITI CYP2C19 Assay.
FDA approval 2008 Tetrabenazine (xanazine): Patients requiring doses above 50 mg per day should be genotyped for the drug metabolizing enzyme CYP2D6 to determine if the patient is a poor metabolizer (PM) or an extensive metabolizer (EM). Maximum daily dose in PMs: 50 mg with a maximum single dose of 25 mg; Maximum daily dose in Ems and intermediate metabolizers (IMs): 100 mg with a maximum single dose of 37.5 mg.
FDA Approval 2014 Cerdelga (eliglustat): Select patients using an FDA cleared test for determining CYP2D6 genotype: CYP2D6 Ems or IMs: 84 mg orally twice daily. CYP2D6 PMs: 84 mg orally once daily.
See also related medical policies:
- 02.01.33 Genetic Testing for Warfarin Sensitivity
- 02.04.54 Genetic Testing for Mental Health Conditions
CYP450 genotyping (CYP2C19) for the purpose of aiding in the choice of clopidogrel (plavix) versus alternative antiplatelet agents or in decisions on the optimal dosing for clopidogrel (plavix), may be considered medically necessary for any one of the following indications:
Patient with unstable angina; or
Patient with non-ST-elevation myocardial infarction; or
Patient who experiences recurrent acute coronary syndromes (unstable angina/myocardial infarction) despite ongoing therapy with clopidogrel.; or
Patients undergoing high risk percutaneous coronary interventions (PCI) with extensive and/or very complex disease.
Note: Per American Heart Association: Acute Coronary Syndrome is defined as those situations where the blood supplied to the heart muscle is suddenly blocked.
CYP450 genotyping (CYP2D6) to determine drug metabolizer status may be considered medically necessary for individuals with the following:
Repeat CYP450 genotype testing (CYP2C19, CYP2D6) for the above medically necessary indications have no proven value and is considered investigational
Genotyping to determine cytochrome P450 (CYP2C19, CYP2D6, CYP2C9, etc.) for the purpose of aiding in the choice of drug or dose to increase efficacy an/or avoid toxicity for all other drugs is considered investigational. This includes, but is not limited to the following:
Selection or dosing of selective serotonin reuptake inhibitors (SSRI)
Selection or dosing of antipsychotic drugs
Selection or dosing of opioid analgesics
Selection and dosing of selective norepinephrine reuptake inhibitors (SNRIs)
Selection and dosing of tricyclic antidepressants
Dosing of efavirenz (common component of highly active antiretroviral therapy for HIV)
Dosing of immunosuppressants for organ transplantation
Selection or dose of beta blockers
Dosing and management of antituberculosis medications
Selection or dosing of Tamoxifen
Selection or dosing of Clopidogrel (Plavix) except as indicated above
Dosing of Tetrabenzine (Xenazine) except as indicated above
Dosing of Eliglustat (Cerdelga) except as indicated above
Current evidence regarding the use of genotyping tests for the determination of drug metabolizer status indicates that while available testing methods may accurately identify genetic variations in an individual, decision making regarding dose or medication selection changes in response to CYP450 metabolizer status is poorly defined, and outcome changes are uncertain. Specifically, clinical trials have not yet adequately demonstrated that such testing results in either enhanced clinical effectiveness, or in decreased short-term or long-term serious adverse events. The evidence is insufficient to determine the effects of this technology on health outcomes. Therefore, this testing is considered investigational.
Procedure Codes and Billing Guidelines:
- To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
- 81225 CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) (eg, drug metabolism), gene analysis common variants (eg *2, *3, *4, *8, *17)
- 81226 CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg. drug metabolism), gene analysis common variants (eg *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN)
- 81227 CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3, *5, *6)
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- UpToDate External SiteClopidogrel Resistance and Clopidogrel Treatment Failure, Udaya S. Tantry, PhD, Charles H. Hennekens, M.D., DrPH, James L. Zehnder, M.D., Paul A. Gurbel, M.D. August 6, 2013
- JAMA, December 28, 2011-Vol 306, No24. Michael V. Holmes, MBBS, Msc, Pablo Perel, PhD, Tina Shah, PhD, Aroon D. Hingorani, PhD, Juan P. Casas, PhD. CYP2C19 Genotype, Clopidogrel Metabolism, Platelet Function, and Cardiovascular Events. A Systemic Review and Meta-Analysis
- American Heart Association. Circulation Cardiovascular Interventions. Guillaume Pare and John W. Eikelboom. 2011; 4:514-521. CYP2C19 Genetic Testing Should not be Done in all Patients Treated with Clopidogrel who are Undergoing Percutaneous Coronary Intervention
- Chest. Chest/141/2/February 2012 Supplement. John W. Eikelboom, MBBS; Jack Hirsh, M.D., FCCP; Frederick A. Spencer, M.D.; Trevor P. Baglin, MBChB, PhD; and Jeffrey I. Weitz, M.D., FCCP. Antiplatelet Drugs. Antithrombotic Therapy and Preventions of Thromobosis, 9th ed: Amerincan College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
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- 2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction. Journal of the American College of Cardiology External Site
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- ECRI External SiteHotline Response. Pharmacogenomic Testing to Guide Treatment of Behavioral Disorders. March 2014.
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- Medscape External SiteJaekyu Shin, Pharm.D., Julie A. Johnson, Pharm.D. Pharmacogenetics of Beta Blockers. Phamacotherapy. 2007;27(6):874-887.
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- Y-Shin Huang, Recent Progress in Genetic Variation and Risk of Antituberculosis Drug Induced Liver Injury. ScienceDirect External SiteOctober 14, 2013.
- UpToDate External Site. Huntington Disease. Management. Oksana Suchowersky, M.D., FRCPC, FCCMG. Topic Last Updated September 28, 2015.
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- FDA Center for Drug Evaluation and Research. Summary Review for Regulatory Action: Cerdelga/eliglustat tartrate External Site 2014; FDA Drugs
- FDA. Highlights of Prescribing Information: Xenazine (tetrabenazine) External Site 2015; FDA Drugs
- Update External SiteGaucher Disease: Treatment. Derralynn Hughes, M.D., Topic last updated July 13, 2015.
- Cerdelga External Site(eliglustat).
- July 2016 - Annual Review, Policy Revised
- August 2015 - Annual Review, Policy Revised
- September 2014 - Annual Review, Policy Revised
- October 2013 - New Policy
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