Community Health Plan Washington pharmacogenetics Coverage

Coverage Criteria for Pharmacogenetic Testing

Example test listings and coding associations

This portion lists example pharmacogenetic panels, example laboratories, and example CPT/ICD associations; examples are informational only and do not guarantee coverage.

Includes lists of example pharmacogenetic panel tests and single-gene tests with associated example CPT and ICD codes and example laboratories; these are provided for claims navigation and are not comprehensive nor guarantees of coverage.

Example panels and associated example CPT codes/labs include: GeneSight Psychotropic (Assurex Health) — CPT 0345U; Psychotropic Pharmacogenomics Gene Panel (Mayo Clinic Laboratories) — CPT 81418; Psychotropic panels (examples listed under 81479).

Example common ICD codes referenced for panels and tests include: B20; C00.0–C96.9; D00.0–D49.9; F01–F99; G10; G71.14; I21.01–I22.9; I26.01–I26.99; I48.0; I60.00–I66.99; I82.210–I82.91; and others as listed in the coding examples.

Providers must reference up-to-date professional coding guidance prior to claim submission; inclusion or exclusion of codes in these lists does not guarantee coverage.

Pharmacogenetic panel tests (coverage criteria)

Pharmacogenetic panel tests (examples: 0029U, 0175U, 0345U, 0380U, 0411U, 0419U, 81418, 81479) are considered medically necessary when ALL of the following are met:

Member is age 18 years or older.

Member has a diagnosis of major depressive disorder OR generalized anxiety disorder for which a treatment medication is being considered.

Member has failed at least one medication intended to treat the diagnosed condition.

The requested test is one of the specified panels (codes listed as suggestions), for example: GeneSight (0345U), Genomind Professional PGx Express (0175U), IDgenetix (0411U), Neuropharmagen (81479), PGXPSYCH (81479), Psychotropic Pharmacogenomics Gene Panel (Mayo) (examples include 81225, 81226, 81227, 81291, 81479).

Panels investigational uses

Pharmacogenetic panels are investigational for all other indications, including the following uses:

Use of a pharmacogenetic panel as an initial screening test for medication selection is investigational.

Panels requested for indications not meeting the medical necessity criteria above are investigational.

BCHE variant analysis

BCHE variant analysis (CPT example 81479) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with mivacurium (e.g., Mivacron) OR succinylcholine (e.g., Anectine, Suxamethonium).

BCHE variant analysis is considered investigational for all other indications.

CYP2C9 variant analysis

CYP2C9 variant analysis (81227) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with any medication in the listed set (examples include: siponimod; celecoxib; dronabinol; erdafitinib; flurbiprofen; fosphenytoin; meloxicam; nateglinide; phenytoin; piroxicam; warfarin).

CYP2C9 variant analysis is investigational for all other indications.

CYP2C19 variant analysis

CYP2C19 variant analysis (81225) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with any medication in the listed set (examples include: clopidogrel; abrocitinib; belzutifan; brivaracetam; citalopram; cobazam; flibanserin; pantoprazole).

CYP2C19 variant analysis is investigational for all other indications.

CYP2D6 variant analysis

CYP2D6 variant analysis (81226 and multiple proprietary codes) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with any medication from the extensive enumerated list (examples include: eliglustat; tetrabenazine; multiple psychotropic agents such as aripiprazole, brexpiprazole, clozapine; tramadol; codeine; venlafaxine; vortioxetine; valbenazine; and others as listed in the policy).

CYP2D6 variant analysis is investigational for other indications noted in policy (for example, for managing tamoxifen in certain women).

CYP3A5 variant analysis

CYP3A5 variant analysis (81231) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with tacrolimus (examples: Envarsus, Prograf, Astagraf).

CYP3A5 variant analysis is investigational for all other indications.

CYP4F2 variant analysis

CYP4F2 variant analysis (example CPT 81479) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with warfarin (e.g., Coumadin, Jantoven).

CYP4F2 variant analysis is investigational for all other indications.

DPYD variant analysis

DPYD variant analysis (81232) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with fluorouracil OR capecitabine.

DPYD variant analysis is investigational for all other indications.

HLA-A*02:01 variant analysis

HLA-A*02:01 variant analysis (81379/81380/81381) is medically necessary when ALL of the following are met:

Member is age 18 years or older.

Member has a diagnosis of metastatic or unresectable uveal melanoma.

Member has not had rapid progression of disease.

HLA-A*02:01 variant analysis is investigational for all other indications.

HLA-B*15:02 variant analysis

HLA-B*15:02 variant analysis (81381) is medically necessary when ALL of the following are met:

Patient is being considered for or currently receiving carbamazepine-containing therapy; OR

Patient is being considered for or currently receiving phenytoin; OR

Patient is being considered for or currently receiving fosphenytoin.

HLA-B*15:02 variant analysis is investigational for all other indications.

HLA-A*02:01 criteria

HLA-A*02:01 variant analysis (81379, 81380, 81381) criteria (all required):

Member is age 18 or older.

Diagnosis of metastatic or unresectable uveal melanoma.

No rapid progression of disease.

HLA-B*15:02 criteria

HLA-B*15:02 variant analysis (81381) criteria (any one qualifies):

Patient is being considered for or currently receiving carbamazepine-containing therapy.

Patient is being considered for or currently receiving phenytoin.

Patient is being considered for or currently receiving fosphenytoin.

HLA-B*57:01 criteria

HLA-B*57:01 variant analysis (81381) is medically necessary when ALL of the following are met:

Patient is being considered for or is currently receiving abacavir.

HLA-B*57:01 testing is investigational for other indications.

NAT2 criteria

NAT2 variant analysis (81479) is medically necessary when ALL of the following are met:

Patient is being considered for or is currently undergoing treatment with amifampridine/amifampridine phosphate.

NAT2 testing is investigational for all other indications.

TPMT/NUDT15 criteria

TPMT and NUDT15 variant analysis (examples: 81306, 81335, 0034U, 0169U) is medically necessary when ANY of the following are met:

Being considered for or currently undergoing treatment with azathioprine, mercaptopurine, or thioguanine.

Member is on thiopurine therapy AND has abnormal CBC results that do not respond to dose reduction.

TPMT and NUDT15 testing is investigational for all other indications.

UGT1A1 criteria

UGT1A1 variant analysis (81350) is medically necessary when ANY of the following are met:

Being considered for or receiving irinotecan.

Being considered for or receiving belinostat.

Being considered for or receiving sacituzumab govitecan.

UGT1A1 testing is investigational for all other indications.

UGT2B17 criteria

UGT2B17 variant analysis (example CPT 81479) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with belzutifan.

UGT2B17 testing is investigational for all other indications.

VKORC1 criteria

VKORC1 variant analysis (81355) is medically necessary when ALL of the following are met:

Member is being considered for or is currently undergoing treatment with warfarin.

VKORC1 testing is investigational for all other indications.

Warfarin panel criteria

Warfarin sensitivity multigene panels (examples: 81227, 81355, 0030U) are medically necessary when ALL of the following are met:

Patient is being considered for or is undergoing treatment with warfarin.

AND patient has not reached a therapeutic dose; OR is undergoing prophylaxis/treatment of venous thrombosis or pulmonary embolism; OR is undergoing prophylaxis/treatment for thromboembolic complications of atrial fibrillation and/or cardiac valve replacement; OR has a history of prior myocardial infarction.

Warfarin multigene panels are investigational for all other indications.

Investigational exclusions

Other single-gene variant analyses are considered investigational (not covered) for pharmacogenetic drug‑metabolizer determination, including but not limited to:

COMT (0032U, 81479).

CYP1A2 (0031U, 81479).

KIF6 (81479).

OPRM1 (81479).

TYMS (81479).

CYP2D6 management

CYP2D6-related drug management recommendations (selected examples from FDA Table of Pharmacogenetic Associations):

For drugs metabolized by CYP2D6 (examples include codeine, tramadol, aripiprazole, clozapine, tetrabenazine, oliceridine, pimozide, valbenazine, venlafaxine, vortioxetine), follow FDA labeling recommendations for dose adjustments, contraindications, or alternative therapy based on metabolizer status; specific recommendations vary by drug.

Examples: Codeine — contraindicated in children under 12 and may cause life‑threatening respiratory depression in certain metabolizer subgroups; consider alternatives. Tramadol — contraindicated in poor metabolizers and in specific pediatric settings; breastfeeding not recommended. Aripiprazole — consider lower starting dose or alternative in poor metabolizers. Refer to FDA labeling for drug‑specific dosing guidance.

CYP3A5 management

CYP3A5-related management recommendation (from FDA):

For tacrolimus, CYP3A5 intermediate or normal metabolizers may have lower systemic concentrations and lower probability of achieving target concentrations; measure trough whole blood concentrations and adjust tacrolimus dosage accordingly.

DPYD management

DPYD-related chemotherapy management (from FDA Table):

For capecitabine and fluorouracil, intermediate or poor DPYD metabolizers have higher risk of severe, life‑threatening, or fatal toxicities; withhold or discontinue therapy in the presence of early-onset or unusually severe toxicity; no safe dose established in poor metabolizers and insufficient data to recommend dosing in intermediate metabolizers.

HLA-A*02:01 eligibility

HLA-A*02:01 testing clinical applicability (from FDA and guideline sources):

Tebentafusp (KIMMTRAK) is indicated for HLA-A*02:01–positive adult patients with unresectable or metastatic uveal melanoma; testing is medically necessary for adults who meet diagnosis and disease‑course criteria to determine eligibility for therapy.

Treat HLA-A*02:01–positive eligible patients with tebentafusp until unacceptable toxicity or disease progression, consistent with FDA labeling and available guidance; rapid disease progression may limit benefit and is excluded from covered indication.

HLA-B*15:02 management

HLA-B*15:02 safety and prescribing considerations (from FDA):

Patients positive for HLA-B*15:02 are at increased risk for severe cutaneous adverse reactions (SJS/TEN) with carbamazepine, fosphenytoin, and phenytoin; avoid these drugs in allele‑positive patients when possible and consider alternatives; genotyping does not replace clinical vigilance.

TPMT/NUDT15 management

TPMT and NUDT15 recommendations for thiopurine therapy (from FDA and NCCN):

Intermediate or poor metabolizers for TPMT and/or NUDT15 have increased risk of myelosuppression with azathioprine, mercaptopurine, or thioguanine; consider alternative therapy in poor metabolizers and reduce initial dosages in poor metabolizers (often to ≤10% of recommended); intermediate metabolizers may require dose reductions based on tolerability; follow FDA labeling for specific dosing recommendations.

NCCN recommends TPMT testing in patients who develop severe neutropenia after starting 6‑MP in relevant treatment contexts.

UGT / VKORC1 management

UGT1A1, UGT2B17, and VKORC1 management recommendations (selected examples from FDA):

UGT1A1: Poor metabolizers (*28/*28) may require irinotecan dose reduction (consider reducing starting dose by at least one level) and belinostat dose reduction (to 750 mg/m2); monitor for neutropenia and other toxicities.

UGT2B17 (with CYP2C19): Poor metabolizers may have higher exposures to belzutifan; monitor for anemia and hypoxia.

VKORC1: Variant carriers (e.g., -1639G>A) have altered warfarin dose requirements; select initial dose considering genetic and clinical factors and monitor/adjust using INR.

Summary of coverage updates for pharmacogenetic testing

Summary of coverage updates for pharmacogenetic testing:

Policy updated (V2.2024) to add clinical criteria permitting coverage of small targeted warfarin sensitivity panels and to align pharmacogenetic panel testing criteria with LCD guidance for certain psychiatric indications; age ≥18 years was added to support panel coverage criteria.

Coding and Billing References

Example panel CPT Codes (informational)CPT

0345U

Example common CPT code for GeneSight Psychotropic panel (example)

Common single-gene CPT Codes (examples)CPT

81227	CYP2C9 variant analysis (example)
81225	CYP2C19 single gene (example)
81226	CYP2D6 variant analysis (example)

HLA-related CPT CodesCPT

81381	HLA-B15:02 / HLA-B57:01 variant analyses (examples)
81379	HLA-A*02:01 variant analysis (example)
81380	HLA-A*02:01 variant analysis (example)

Consolidated examples of covered or mentioned codesCPTCovered

81381	HLA-B*15:02 variant analysis
81335	TPMT and NUDT15 variant analysis (listed in coding implications)
81479	Other pharmacogenetic single gene / panel variant analysis
81227	CYP2C9 variant analysis
81225	CYP2C19 variant analysis
81226	CYP2D6 variant analysis
81231	CYP3A5 variant analysis
81232	DPYD variant analysis
81379	HLA-A*02:01 variant analysis

Referenced CPT/HCPCS codes in this sectionmixed

81379	HLA-A*02:01 variant analysis (one or more CPTs referenced)
81380	HLA-A*02:01 variant analysis
81381	HLA HLA-B related variant analyses (used for HLA-B15:02, HLA-B57:01)
81479	Unlisted molecular pathology procedure/single gene variant analysis (used for NAT2, UGT2B17, others)
81306	TPMT variant analysis
81335	NUDT15 variant analysis
0034U	TPMT related molecular test (HCPCS/PLA)
0169U	NUDT15 related molecular test (HCPCS/PLA)
81350	UGT1A1 variant analysis
81355	VKORC1 variant analysis

1–10 of 12

1/2

FDA pharmacogenetic associations (CYP2D6 examples)mixed

81226

CYP2D6 variant analysis (FDA-listed gene-drug management examples referenced)

New/additional CPT codes for pharmacogenetic panel testsCPT

0423U	CPT - new pharmacogenetic panel code (added to policy coding reference table)
0434U	CPT - new pharmacogenetic panel code (added to policy coding reference table)
0437U	CPT - new pharmacogenetic panel code (added to policy coding reference table)
0438U	CPT - new pharmacogenetic panel code (added to policy coding reference table)

Coding applicability note

ApplicabilityCodes listed in this policy are examples for informational purposes only; inclusion or exclusion of any code does not guarantee coverage.

Provider actionProviders should reference the most up-to-date professional coding guidance prior to claim submission.

ScopeExample tests, associated laboratories, CPT and ICD codes in the document are not comprehensive and are provided to aid claims navigation only.

Coverage implicationListing a code in this policy is not a determination of coverage or non-coverage.

Minimum age for PGx panels

Provider Action Items and Prior Authorization

Note

Coding Implications

This clinical policy references Current Procedural Terminology (CPT®). CPT is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2023, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. The tests, associated laboratories, CPT codes, and ICD codes contained within this document serve only as examples to help users navigate claims and corresponding criteria; as such, they are not comprehensive and are not a guarantee of coverage or non-coverage. Please see the Concert Platform for a comprehensive list of registered tests.

Prior Authorization

Warfarin pharmacogenetic panel prior authorization / coverage condition

Multigene warfarin sensitivity panels require prior authorization/coverage conditions. Small targeted warfarin panels (e.g., tests including CYP2C9, VKORC1, and/or CYP4F2) are considered medically necessary when ALL of the following are met:

Definitions and Reference Resources

Pharmacogenetic test — definition

DefinitionA pharmacogenetic test is a germline genetic test developed to aid in assessing an individual's response to a drug treatment or to predict risk of toxicity from a specific drug treatment.

TimingTesting may be performed prior to initiation of treatment or during treatment to assess adverse reactions or treatment response.

MethodologiesIncludes gene sequencing, deletion/duplication analysis, and single nucleotide variant testing.

Pharmacogenetic panel tests (definition)

DefinitionPharmacogenetic panel tests are multi-gene assays used to guide medication selection (examples listed in policy include GeneSight, Genomind, IDgenetix, Neuropharmagen, PGXPSYCH, and psychotropic panels).

Coverage note

OpenPayer

CONCERT GENETIC TESTING: PHARMACOGENETICS (VERSION B)

Coverage Criteria for Pharmacogenetic Testing

Coding and Billing References

Provider Action Items and Prior Authorization

Definitions and Reference Resources