Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1)    Pharmacogenetics is the study of variability in drug response due to genetic factors.

2)    Many pharmacogenetics test are considered experimental and investigational because their clinical utility has not been proven.

3)    All pharmacogenetics testing requires prior authorization.

QualChoice follows MCG guidelines on Pharmacogenetics Testing. Please refer to appropriate MCG guidelines or DNA Direct for details.

1)    The following tests are considered experimental and investigational due to inconclusive or non-supportive evidence, and therefore are not covered:

a)    Cytochrome P450 – 3A4/3A5 Genotyping; MCG ACG: A-0775 (AC) Hepatic cytochrome P450 enzymes play a significant role in drug metabolism. Cytochrome P450 3A4 (CYP3A4) and cytochrome P450 3A5 (CYP3A5) are responsible for the metabolism of many endogenous substrates of the many commonly used medications, including immunosuppressives (e.g., tacrolimus), opioid analgesics (e.g., fentanyl, methadone),antibiotics (e.g., erythromycin, clarithromycin), psychotropics (e.g., clozapine, quetiapine), statins (e.g., simvastatin), and tyrosine kinase inhibitors (e.g., sunitinib);

b)    Psychotropic Medication Pharmacogenetics – CYP450 Polymorphisms and AmpliChip Panel; MCG ACG: A-0692 (AC). Cytochrome P450 enzymes, primarily CYP2D6 (11) and CYP2C19, (12) are involved in the metabolism of tricyclic antidepressants, SSRIs, and antipsychotics; more than one CYP450 enzyme may be involved in the metabolism of a given psychotropic medication;

c)    Psychotropic Medication Pharmacogenetics – ABCB1, BDNF, COMT, DRD, FKBP5, HTR, MC4R, SLC6A4, SPTA1, and TPH1 Genes; MCG ACG: A-0859 (AC);

d)    Psychotropic Medication Pharmacogenetics – Gene Panels; MCG ACG: A-0861 (AC);

e)    Psychotropic Medication Pharmacogenetics – HLA Typing; MCG ACG: A-0862 (AC);

f)     GeneSight panel or any other pharmacogenomics testing panel for Major Depressive Disorder (CPT 81599, 81479 and 84999)-- DNA Direct.

g)    Azathioprine and 6-Mercaptopurine Pharmacogenetics – TPMT Gene; MCG ACG: A-0628 (AC);

h)   Clopidogrel Pharmacogenetics – CYP2C19 Gene; MCG ACG: A-0631 (AC);

i)     Irinotecan Pharmacogenetics – UGT1A1 Gene; MCG ACG: A-0624 (AC);

j)      Tamoxifen Pharmacogenetics – CYP2D6 Gene; MCG ACG: A-0647 (AC) (NCCN and DNA Direct also do not support this);

k)    Carbamazepine Pharmacogenetics – HLA Testing; MCG ACG: A-0649 (AC);

l)     Hepatitis C Medication Pharmacogenetics – IFNL3 and IFNL4 Genes; MCG: A-0783 (AC);

m)  Citalopram Pharmacogenetics – GRIK4 Gene; MCG ACG: A-0820 (AC);

n)   Naltrexone Pharmacogenetics – OPRM1 Gene; MCG ACG: A-0845 (AC);

o)    ADHD Medication Pharmacogenetics – ADRA2A, COMT, CYP2B6, and CYP2D6 Genes for Atomoxetine (Strattera); MCG ACG: A-0764 (AC).

2)    The following pharmacogenetics tests require prior-authorization:

a)    Warfarin Pharmacogenetics – CYP2C9, CYP4F2, and VKORC1 Gene testing may be indicated for members who meet the following criteria:

                          i.    Age 18 years and older;

                         ii.    Venous thromboembolism prophylaxis with warfarin planned for elective hip or knee arthroplasty;

                       iii.    No history of bleeding disorder or thrombophilia.

b)    5-Fluorouracil Pharmacogenetics – DPYD, MTHFR, and TYMS Gene testing requires that the member is considering or is currently on therapy with any 5-FU containing drug including:

                          i.    i5-fluorouracil (Fluorouracil®, Adrucil®);

                         ii.    Capecitabine (Xeloda®);

                       iii.    Fluorouracil topical formulations (Carac®, Efudex®, Fluoroplex®).

Codes Used in This BI:

G9143    Warfarin responsiveness testing by genetic tech using any method, any # of specimen(s)

S0265    Genetic counseling, under physician supv, ea 15 mn

81225    CYP2C19, gene analysis, common variants

81226    CYP2D6, gene analysis, common variants

81227    CYP2C9, gene analysis, common variants

81230    CYP3A4, gene analysis, common variants

81231    CYP3A5, gene analysis, common variants

81232    DPYD, gene analysis, common variant(s)

81283    IFNL3, gene analysis, rs12979860 variant

81291    MTHFR gene analysis, common variants

81335    TPMT, gene analysis, common variants

81346    TYMS, gene analysis, common variant(s)

81350    UGT1A1, gene analysis, gene analysis, common variants

81355    VKORC1, gene analysis, common variant(s)

81373    HLA Class I typing, low resolution; one locus, ea

81376    HLA Class II typing, low resolution; one locus, ea

81380    HLA Class I typing, high resolution; one locus, ea

81381    HLA Class I typing, high resolution; one allele or allele group, ea

81382    HLA Class II typing, high resolution; one locus, ea

81479    Unlisted molecular pathology procedure

96040    Medical genetics & genetic counseling services, ea 30 mn face-to-face w/patient/family

0028U   CYP2D6, gene analy, copy # variants, common variants w/reflex to targeted seq anal  

              (code deleted 1/1/19)             

0030U   Drug metabolism, targeted seq anal

0033U   HTR2A, HTR2C gene analysis, common variants

0034U   TPMT, NUDT15 gene analysis, common variants

Any pharmacogenetic test that meets the above prior-authorization criteria is covered once per member’s life time.

1.     Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA. Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmacogenomics and Personalized Medicine 2016; 9:97-106. DOI: 10.2147/PGPM.S86013.

2.     Wang D, Sadee W. The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy. Journal of personalized medicine 2012; 2(4):175-91.

3.     Booth RA, et al. Assessment of thiopurine s-methyltransferase activity in patients prescribed thiopurines: a systematic review. Annals of Internal Medicine 2011; 154(12):814-23.

4.     Moon W, Loftus EV. Review article: recent advances in pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in inflammatory bowel disease. Alimentary Pharmacology and Therapeutics 2016; 43(8):863-83.

5.     Mega JL, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. New England Journal of Medicine 2009; 360(4):354-62.

6.     Sorich MJ, Polasek TM, Wiese MD. Challenges and limitations in the interpretation of systematic reviews: making sense of clopidogrel and CYP2C19 pharmacogenetics. Clinical Pharmacology and Therapeutics 2013; 94(3):376-82.

7.     Kohli A, Shaffer A, Sherman A, Kottilil S. Treatment of hepatitis C: a systematic review. Journal of the American Medical Association 2014; 312(6):631-40.

8.     Indolfi G, Azzari C, Resti M. Polymorphisms in the IFNL3/IL28B gene and hepatitis C: from adults to children. World Journal of Gastroenterology 2014; 20(28):9245-52.