Skip to main content
HealthPartners

Coverage criteria policies

Genetic Testing: Pharmacogenetics

These services may or may not be covered by your HealthPartners plan. Please see your plan documents for your specific coverage information. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage.

Administrative Process

Prior authorization is required for pharmacogenetic testing.

For somatic testing related to cancer, please see the Genetic Testing: Molecular Profiling for Cancer Management coverage policy.

Coverage

Indications that are covered

The following services are covered when test results will directly impact the attending healthcare professional’s ability to provide medically-appropriate treatment or care management:
  1. CFTR gene analysis prior to initiation of ivacaftor or lumacaftor/ivacaftor therapy
  2. CYP2D6 gene analysis prior to initiation of eliglustat or tetrabenazine therapy
  3. HLA-B*1502 screening prior to initiation of carbamazepine or phenytoin therapy
  4. HLA-B*5701 screening prior to initiation of abacavir therapy
  5. HLA-B*5801 screening prior to initiation of allopurinol therapy
  6. TPMT genotyping prior to initiation of 6-mercaptopurine or azathioprine therapy
  7. UGT1A1 gene analysis prior to initiation of irinotecan therapy in members with hyperbilirubinemia
  8. Single-gene pharmacogenetic testing of any other gene or for any indication other than as described above is subject to a review for medical necessity, based on current clinical literature and expert recommendations unless listed below as an indication that is not covered.

Indications that are not covered

  1. Pharmacogenetic testing is not covered and is considered not medically necessary when test results will not directly impact the treatment or management of a condition because the testing is not expected to restore or maintain the member’s health, prevent deterioration of the member’s condition, nor prevent the reasonably likely onset of a health problem or detect an incipient problem.
  2. Repeat testing of a unique gene using the identical method of gene analysis is not covered and is considered not medically necessary because it is not considered an appropriate frequency of care.
  3. Direct-to-consumer pharmacogenetic testing is not covered and is considered not medically necessary because it is not within the practice parameters of the general medical community.
  4. The following services are considered experimental/investigational because reliable evidence does not permit conclusions concerning safety, effectiveness, or effect on health outcomes:
  • A1555G genotyping prior to initiation of aminoglycoside therapy
  • Apolipoprotein E (APOE) genotyping to determine response to lipid -lowering agents
  • Cytochrome P450 (CYP450) genotyping (e.g. analysis of CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP2B6, CYP1A2, or any other gene in the cytochrome P450 families) for all other indications, including, but not limited to, prior to the initiation of therapy with antidepressants, antipsychotics, anti-arrhythmics, beta-blockers, tamoxifen, clopidogrel, warfarin, analgesics, or anti-emetics, except as described under Indications that are Covered
  • Dihidropyrimidine dehydrogenase (DPD) testing for evaluation of toxicity and/or response to fluorouracil or capecitabine therapy
  • MTHFR gene analysis for all indications
  • SLCO1B1 genotyping to guide statin therapy
  • VKORC1 genotyping to guide warfarin therapy
  • Multiple-gene panels for all pharmacogenetic indications

Definitions

Cytochrome P450 (CYP450) includes multiple genes which affect the metabolism of a variety of drug classifications.

Genotyping is the process of determining which genetic variants an individual possesses.

Pharmacogenetic tests analyze genes to identify patients who are likely to respond to a specific drug, those who may not respond, and those likely to have adverse reactions.

If available, codes for a procedure, device or diagnosis are listed below for informational purposes only, and do not guarantee member coverage or provider reimbursement. The list may not be all inclusive.

Codes

Description

G9143

Warfarin responsiveness testing by genetic technique using any method, any number of specimen(s)

0028U

CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism) gene analysis, copy number variants, common variants with reflex to targeted sequence analysis

0029U

Drug metabolism (adverse drug reactions and drug response), targeted sequence analysis (ie, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP4F2, SLCO1B1, VKORC1 and rs12777823)

0030U

Drug metabolism (warfarin drug response), targeted sequence analysis (ie, CYP2C9, CYP4F2, VKORC1, rs12777823)

0031U

CYP1A2 (cytochrome P450 family 1, subfamily A, member 2)(eg, drug metabolism) gene analysis, common variants (ie, *1F, *1K, *6, *7)

0034U

TPMT (thiopurine S-methyltransferase), NUDT15 (nudix hydroxylase 15)(eg, thiopurine metabolism), gene analysis, common variants (ie, TPMT *2, *3A, *3B, *3C, *4, *5, *6, *8, *12; NUDT15 *3, *4, *5)

81222

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; duplication/deletion variants

81223

CFTR (cystic fibrosis transmembrane conductance regulator) (eg, cystic fibrosis) gene analysis; full gene sequence

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)

81230

CYP3A4 (cytochrome P450 family 3 subfamily A member 4) (eg, drug metabolism), gene analysis, common variant(s) (eg, *2, *22)

81231

CYP3A5 (cytochrome P450 family 3 subfamily A member 5) (eg, drug metabolism), gene analysis, common variant(s) (eg, *2A, *4, *5, *6)

81232

DPYD (dihydropyrimidine dehydrogenase) (eg, 5-fluorouracil/5-FU and capecitabine drug metabolism), gene analysis, common variant(s) (eg, *2A, *4, *5, *6)

81291

MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C)

81328

SLCO1B1 (solute carrier organic anion transporter family, member 1B1) (eg, adverse drug reaction), gene analysis, common variant(s) (eg, *5)

81335

TPMT (thiopurine S-methyltransferase) (eg, drug metabolism), gene analysis, common variant(s), (eg, *2, *3)

81350

UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide A1) (eg, irinotecan metabolism), gene analysis, common variants (eg, *28, *36, *37)

81355

VKORC1 (vitamin K epoxide reductase complex, subunit 1) (eg, warfarin metabolism), gene analysis, common variants (eg, -1639G>A, c.173+1000C>T)

81381

HLA Class I typing, high resolution (ie, alleles or allele groups); one allele or allele group (eg, B*57:01P), each

CPT Copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association

Products

This information is for most, but not all, HealthPartners plans. Please read your plan documents to see if your plan has limits or will not cover some items. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage. These coverage criteria may not apply to Medicare Products if Medicare requires different coverage. For more information regarding Medicare coverage criteria or for a copy of a Medicare coverage policy, contact Member Services at 952-883-7979 or 1-800-233-9645.

References

  1. Altar, C. A., Carhart, J., Allen, J. D., Hall-Flavin, D., Winner, J., & Dechairo, B. (2015). Clinical utility of combinatorial pharmacogenomics-guided antidepressant therapy: Evidence from three clinical studies. Molecular Neuropsychiatry, 1, 145-155.
  2. Becker, M. A. (2016). Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi. In: H. R. Schumacher & P. L. Romain (Eds.). UpToDate. Waltham, MA: UpToDate.
  3. Bird, S. J. (2016). Chronic immunomodulating therapies for myasthenia gravis. In: J. M. Shefner, I. N. Targoff, & J. F. Dashe (Eds.). UpToDate. Waltham, MA: UpToDate.
  4. Birdwell, K. A., Decker, B., Barbarino, J. M., Peterson, J. F., Stein, C. M., Sadee, W., . . . MacPhee, I. A. (2015). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosage. Clinical Pharmacology and Therapeutics, 98, 19-24.
  5. Brennan, F. X., Gardner, K. R., Lombard, J., Perlis, R. H., Fava, M., Harris, H. W., & Scott, R. (2015). A naturalistic study of the effectiveness of pharmacogenetic testing to guide treatment in psychiatric patients with mood and anxiety disorders. The Primary Care Companion for CNS Disorders, 17, doi: 10.4088/PCC.14m0171
  6. Canestaro, W. J., Austin, M. A., & Thummel, K. E. (2014). Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genetics in Medicine, 16, 810-819.
  7. Caudle, K. E., Rettie, A. E., Whirl-Carrillo, M., Smith, L. H., Mintzer, S. E., Lee, M. T. M., . . . Clinical Pharmacogenetics Implementation Consortium. (2014). Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clinical Pharmacology and Therapeutics, 96, 542-548.
  8. Caudle, K. E., Thorn, C. F., Klein, T. E., Swen, J. J., McLeod, H. L., Diasio, R. B., & Schwab, M. (2013). Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clinical Pharmacology and Therapeutics, 94, 640-645.
  9. Clancy, J. P., Johnson, S. G., Yee, S. W., McDonagh, E. M., Caudle, K. E., Klein, T. E., . . . Clinical Pharmacogenetics Implementation Consortium. (2014). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clinical Pharmacology and Therapeutics, 95, 592-597.
  10. Crews, K. R., Gaedigk, A., Dunnenberger, H. M., Leeder, J. S., Klein, T. E., Caudle, K. E., . . . Clinical Pharmacogenetics Implementation Consortium. (2014). Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clinical Pharmacology and Therapeutics, 95, 376-382.
  11. Dai, R., Feng, J., Wang, Y., Yang, Y., Deng, C., Tang, X., . . . Zhang, F. (2015). Association between SLCO1B1 521 T>C and 388 A>G polymorphisms and statins effectiveness: A meta-analysis. Journal of Atherosclerosis and Thrombosis, 22, 796-815.
  12. Dou, Y., Zhu, X., Wang, Q., Tian, X., Cheng, J., & Zhang, E. (2015). Meta-analysis of the SLCO1B1 c.521T>C variant reveals slight influence on the lipid-lowering efficacy of statins. Annals of Laboratory Medicine, 35, 329-335.
  13. ECRI Institute. (2015a). GeneSight Psychotropic Pharmacogenetic Testing (Assurex Health, Inc.) for guiding medication selection for patients with neuropsychiatric disorders. Plymouth Meeting, PA: ECRI Institute.
  14. ECRI Institute. (2015b). Pharmacogenetic testing to guide treatment of behavioral and mental health disorders. Plymouth Meeting, PA: ECRI Institute.
  15. ECRI Institute. (2016a). Pharmacogenetic testing to guide treatment of chronic pain. Plymouth Meeting, PA: ECRI Institute.
  16. ECRI Institute. (2016b). Proove Opioid Response (Proove Biosciences, Inc.) for predicting clinical response and optimal dosing of opioid medications. Plymouth Meeting, PA: ECRI Institute.
  17. ECRI Institute. (2016c). Proove Opioid Risk (Proove Biosciences, Inc.) for assessing risk of opioid misuse. Plymouth Meeting, PA: ECRI Institute.
  18. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. (2009). Recommendations from the EGAPP Working Group: Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genetics in Medicine, 11, 15-20.
  19. Flockhart, D A., O’Kane, D., Williams, M. S., Watson, M. S., Flockhart, D. A., Gage, B., . . . ACMG Working Group on Pharmacogenetic Testing of CYP2C9, VKORC1 Alleles for Warfarin Use. (2008). Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genetics in Medicine, 10, 139-150.
  20. Franchini, M., Mengoli, C., Cruciani, M., Bonfanti, C., & Mannucci, P. M. (2014). Effects on bleeding complications of pharmacogenetic testing for initial dosing of vitamin K antagonists: A systematic review and meta-analysis. Journal of Thrombosis and Haemostasis, 12, 1480-1487.
  21. Gautier-Veyret, E., Fonrose, X., Tonini, J., Thiebaut-Bertrand, A., Bartoli, M., Quesada, J. L., . . . Stanke-Labesque, F. (2015). Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell transplantation: Impact of cytochrome p450 polymorphisms and comedications on initial and subsequent trough levels. Antimicrobial Agents and Chemotherapy, 59, 2305-2314.
  22. Guilloux, J. P., Bassi, S., Ding, Y., Walsh, C., Turecki, G., Tseng, G., . . . Sibille, E. (2015). Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression. Neuropsychopharmacology, 40, 701-710.
  23. Hayes, Inc. (2014). HLA-B testing for guidance of treatment with anticonvulsant drugs. Philadelphia, PA: Hayes, Inc.
  24. Hayes, Inc. (2015a). Comprehensive Personalized Medicine Panel. Philadelphia, PA: Hayes, Inc.
  25. Hayes, Inc. (2015b). CYP3A4 Genotyping for ivacaftor metabolism and toxicity. Philadelphia, PA: Hayes, Inc.
  26. Hayes, Inc. (2015c). Cytochrome P450 (CYP450) genotyping to predict responses to antidepressant and antipsychotic medications. Philadelphia, PA: Hayes, Inc.
  27. Hayes, Inc. (2015d). Cytochrome P450 genotyping to predict response to opioid pain medication. Philadelphia, PA: Hayes, Inc.
  28. Hayes, Inc. (2015e). STA2R SureGene Test for antipsychotic and antidepressant response. Philadelphia, PA: Hayes, Inc.
  29. Hayes, Inc. (2016). SLCO1B1 Pharmacogenomic genotyping for statin dosing or selection. Philadelphia, PA: Hayes, Inc.
  30. Hicks, J. K., Bishop, J. R., Sangkuhl, K., Muller, D. J., Ji, Y., Leckband, S. G., . . . Clinical Pharmacogenetics Implementation Consortium. (2015). Clinical Pharmacology and Therapeutics, 98, 127-134.
  31. Hicks, J. K., Crews, K. R., Flynn, P., Haidar, C. E., Daniels, C. C., Yang, W., . . . Relling, M. V. (2014). Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes. Pharmacogenomics, 15, 1065-1078.
  32. Hicks, J. K., Swen, J. J., Thorn, C. F., Sangkuhl, K., Kharasch, E. D., Ellingrod, V. L., . . . Clinical Pharmacogenetics Implementation Consortium. (2013). Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosage of tricyclic antidepressants. Clinical Pharmacology and Therapeutics, 93, 402-408.
  33. Hirata, K., Nagata, N., Kato, T., Okuyama, Y., Andoh, H., Takahashi, K., . . . Mishima, H. (2014). Prospective phase II trial of second-line FOLFIRI in patients with advanced colorectal cancer including analysis of UGT1A1 polymorphisms: FLIGHT 2 study. Anticancer Research, 34, 195-201.
  34. Hodgson, K., Tansey, K., Dernovsek, M. Z., Hauser, J., Henigsberg, N., Maier, W., . . . McGuffin, P. (2014a). Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. Journal of Psychopharmacology, 28, 133-141.
  35. Hodgson, K., Uher, R., Crawford, A. A., Lewis, G., O’Donovan, M. C., Keers, R., . . . McGuffin, P. (2014). Genetic predictors of antidepressant side effects: A grouped candidate gene approach in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study. Journal of Psychopharmacology, 28, 142-150.
  36. Kato, M., Serretti, A., Nonen, S., Takekita, Y., Wakeno, M., Azuma, J., & Kinoshita, T. (2015). Genetic variants in combination with early partial improvement as a clinical utility predictor of treatment outcome in major depressive disorder. Translational Psychiatry, 5, e513.
  37. Leckband, S. G., Kelsoe, J. R., Dunnenberger, H. M., George, Jr., A. L., Tran, E., Berger, R., . . . Clinical Pharmacogenetics Implementation Consortium. (2013). Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clinical Pharmacology and Therapeutics, 94, 324-328.
  38. MacDermott, R. P. (2015). 6-mercaptopurine (6-MP) metabolite monitoring and TPMT testing in the treatment of inflammatory bowel disease with 6-MP or azathioprine. In: P. Rutgeerts & S. Grover (Eds.). UpToDate. Waltham, MA: UpToDate.
  39. Miura, I., Zhang, J. P., Nitta, M., Lencz, T., Kane, J. M., Malhotra, A. K., . . . Correll, C. U. (2014). BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: A meta-analysis. Schizophrenia Research, 152, 365-372.
  40. National Comprehensive Cancer Network. (2017a). Colon cancer (version 1). Fort Washington, PA: National Comprehensive Cancer Network.
  41. National Comprehensive Cancer Network. (2017b). Rectal cancer (version 2). Fort Washington, PA: National Comprehensive Cancer Network.
  42. Peters-Golden, M. (2015). Agents affecting the 5-lipooxygenase pathway in the treatment of asthma. In: R. A. Wood, B. S., Bochner, & H. Hollingsworth (Eds.). UpToDate. Waltham, MA: UpToDate.
  43. Phillips, E. J., & Mallal, S. A. (2015). Abacavir hypersensitivity reaction. In: J. G. Bartlett & J. MItty (Eds.). UpToDate. Waltham, MA: UpToDate.
  44. Press, R. D., Bauer, K. A., Kujovich, J. L., & Heit, J. A. (2002). Clinical utility of factor V Leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders. Archives of Pathology and Laboratory Medicine, 126, 1304-1318.
  45. Prows, C. A., Zhang, X., Huth, M. M., Zhang, K., Saldana, S. N., Daraiseh, N. M., . . . Sadhasivam, S. (2014). Codeine-related adverse drug reactions in children following tonsillectomy: A prospective study. Laryngoscope, 124, 1242-1250.
  46. Ramsey, L. B., Johnson, S. G., Caudle, K. E., Haidar, C. E., Voora, D., Wilke, R. A., . . . Niemi, M. (2014). The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical Pharmacology and Therapeutics, 96, 423-428.
  47. Ramsey, T. L., Liu, Q., & Brennan, M. D. (2014). Replication of SULT4A1-1 as a pharmacogenetic marker of olanzapine response and evidence of lower weight gain in the high response group. Pharmacogenomics, 15, 933-939.
  48. Relling, M. V., Gardner, E. E., Sandborn, W. J., Schmiegelow, K., Pui, C. H., Yee, S. W., . . . Clinical Pharmacogenetics Implementation Consortium. (2011). Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical Pharmacology and Therapeutics, 89, 387-391.
  49. Schachter, S. C. (2016). Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects. In: P. Garcia & A. F. Eichler (Eds.). UpToDate. Waltham, MA: UpToDate.
  50. Sicras-Mainar, A., Guijarro, P., Armada, B., Blanca-Tamayo, M., & Navarro-Artieda, R. (2014). Influence of the CYP2D6 isoenzyme in patients treated with venlafaxine for major depressive disorder: Clinical and economic consequences. PLoS One, 9, e90453.
  51. Simon, R. H. (2016). Cystic fibrosis: Overview of the treatment of lung disease. In: G. B. Mallory & A. G. Hoppin (Eds.). UpToDate. Waltham, MA: UpToDate.
  52. Stein, M. B., Keshaviah, A., Haddad, S. A., Van Ameringen, M., Simon, N. M., Pollack, M. H., & Smoller, J. W. (2014). Influence of RGS2 on sertraline treatment for social anxiety disorder. Neuropsychopharmacology, 39, 1340-1346.
  53. Tantry, U. S., Hennekens, C. H., Zehnder, J. L., & Gurbel, P. A. (2016). Clopidogrel resistance and clopidogrel treatment failure. In: L. L. K. Leung, D. Cutlip, & G. M. Saperia (Eds.). UpToDate. Waltham, MA: UpToDate.
  54. Van der Weide, K., & van der Weide, J. (2014). The influence of the CYP3A4*22 polymorphism on serum concentration of quetiapine in psychiatric patients. Journal of Clinical Psychopharmacology, 34, 256-260.
  55. Van der Weide, K., & van der Weide, J. (2015). The influence of the CYP3A4*22 and CYP2D6 polymorphisms on serum concentrations of aripiprazole, haloperidol, pimozide, and risperidone in psychiatric patients. Journal of Clinical Psychopharmacology, 35, 228-236.
  56. Wang, B., Canestaro, W. J., & Choudhry, N. K. (2014). Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels. JAMA Internal Medicine, 174, 1938-1944.
  57. Wang, Y., Zhao, X., Lin, J., Li, H., Johnston, S. C., Lin, Y., . . . CHANCE Investigators. (2016). Association between CYP2C19 loss-of-function allele status and efficacy of clopidogrel for risk reduction among patients with minor stroke or transient ischemic attack. JAMA, 316, 70-78.
  58. Zonios, D., Yamazaki, H., Murayama, N., Natarajan, V., Palmore, T., Childs, R., . . . Bennett, J. E. (2014). Voriconazole metabolism, toxicity, and the effect of cytochrome P450 2C19 genotype. Journal of Infectious Disease, 209, 1941-1948.

Go to

Policy activity

  • 10/18/2010 - Date of origin
  • 05/01/2017 - Effective date
Review date
  • 02/2017
Revision date
  • 02/01/2017

Related content