OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.

ModifiedAmbetter NevadaPolicy N/A

Genetic Testing: Toxicology and Pharmacogenetics Coverage Criteria

Customize your policy alerts

Sign up for all Ambetter Nevada policy alerts

Know when Ambetter Nevada releases new policies or updates existing guidance.

Monitor payer policy activity

Receive email alerts as soon as relevant payer policies are published or updated.

This policy governs coverage criteria, coding, and clinical indications for genetic and pharmacogenetic tests used to assess drug response, toxicity, and treatment management for members of Ambetter Nevada/Centene-affiliated health plans.

Policy Summary

PayerAmbetter Nevada

PolicyGenetic Testing: Toxicology and Pharmacogenetics Coverage Criteria

Policy CodePolicy N/A

Change TypeMultiple material updates: new single-gene entries, timing language changed to 'being considered for or currently undergoing', and coding additions/removals

Effective DateN/A

Next Review DateN/A

Key ActionUse updated policy codes and documentation when requesting prior authorization and document that the member is being considered for or is currently undergoing the related therapy.

SourceLink

POLICY UPDATE CHANGES

BCHE Variant Analysis and related content were added to the Pharmacogenetic Single Gene Tests section.

Criteria language changed to apply when the member/enrollee 'is being considered' for therapies or 'is currently undergoing' therapy rather than 'beginning therapy'.

UGT2B17 and CYP3A5 variant analyses and related content were added.

VKORC1 language was changed to remove prior phrasing and to state testing is 'medically necessary when: ...' and to determine drug metabolizer status.

Added multiple single-gene variant analyses (e.g., BCHE, CYP3A5, NAT2, UGT2B17, HLA-A*02:01) and new PLA and CPT codes to the policy reference table.

Reformatted and updated clinical criteria across many gene-specific sections (e.g., Warfarin sensitivity panels, TPMT/NUDT15, CYP2C19, CYP2D6) and aligned criteria with FDA/NCCN guidance.

Removed SLCO1B1 (SLOC1B1) from non-covered gene list and deleted certain legacy CPT codes (e.g., 81346) and references.

Clarified policy language to change criteria from 'beginning therapy' to 'being considered for or currently undergoing' therapy for multiple gene tests (e.g., CYP2C9, DPYD, HLA-B*15:02, UGT1A1).

≈40billing codes referenced

severalnew gene criteria sets

multipleFDA/NCCN therapeutic recommendations referenced

4warfarin panel scenarios

4new CPT codes added

3new PLA codes added

Coverage Criteria — Gene & Panel Tests

The tests, CPT codes, and ICD codes referenced in this policy are provided for information only and are not exhaustive. Inclusion or exclusion of any code or test does not guarantee coverage; providers must reference up-to-date coding guidance and payer systems (e.g., the Concert Platform) when submitting claims.

Current evidence does not support routine pharmacogenetic testing for all clinical indications. Many pharmacogenetic tests and panels have mixed or conflicting evidence of clinical utility; as a result, testing is covered only for specific drug‑gene indications listed in this policy (see individual gene or panel sections for applicable criteria).

TYMS Single Gene - Medical Necessity

Covered when ALL of the following are met

TYMS Single Gene (Sequencing & Deletion/Duplication): The specific genetic testing (TYMS single gene sequencing and deletion/duplication) is medically necessary when the related criteria for TYMS single gene (Fulgent Genetics) are met.

Exact clinical criteria text is referenced in the policy; see test-specific section for required documentation.

BCHE Variant Analysis

Covered when ALL of the following are met for BCHE:

Policy Summary

PayerAmbetter Nevada

PolicyGenetic Testing: Toxicology and Pharmacogenetics Coverage Criteria

Policy CodePolicy N/A

Change TypeMultiple material updates: new single-gene entries, timing language changed to 'being considered for or currently undergoing', and coding additions/removals

Effective DateN/A

Next Review DateN/A

Key ActionUse updated policy codes and documentation when requesting prior authorization and document that the member is being considered for or is currently undergoing the related therapy.

SourceLink

On This Page

BCHE variant analysis: Member is being considered for or is currently undergoing treatment with mivacurium OR succinylcholine.

Current evidence does not support BCHE variant analysis for other indications.

CYP2C9 Variant Analysis

Covered when ALL of the following are met for CYP2C9:

CYP2C9 variant analysis: Member is being considered for or is currently undergoing treatment with any listed CYP2C9-metabolized medication (e.g., siponimod, celecoxib, dronabinol, erdafitinib, flurbiprofen, fosphenytoin, meloxicam, nateglinide, phenytoin, piroxicam, warfarin).

Current evidence does not support CYP2C9 variant analysis for other indications.

CYP2C19 Variant Analysis

Covered when ALL of the following are met for CYP2C19:

CYP2C19 variant analysis: Member is being considered for or is currently undergoing treatment with any listed CYP2C19-metabolized medication (e.g., clopidogrel, abrocitinib, belzutifan, brivaracetam, citalopram, clobazam, flibanserin, pantoprazole).

Current evidence does not support CYP2C19 variant analysis for other indications.

CYP2D6 Variant Analysis

Covered when ALL of the following are met for CYP2D6:

CYP2D6 variant analysis: Member is being considered for or is currently undergoing treatment with any listed CYP2D6-metabolized medication (including eliglustat, tetrabenazine, amphetamine, aripiprazole, atomoxetine, brexpiprazole, clozapine, deutetrabenazine, gefitinib, iloperidone, lofexidine, meclizine, metoclopramide, oliceridine, pimozide, pitolisant, propafenone, thioridazine, tramadol, valbenazine, venlafaxine, vortioxetine, codeine).

Current evidence does not support CYP2D6 variant analysis for other indications (explicitly excludes use for tamoxifen management).

CYP3A5 Variant Analysis

Covered when ALL of the following are met for CYP3A5:

CYP3A5 variant analysis: Member is being considered for or is currently undergoing treatment with tacrolimus.

Current evidence does not support CYP3A5 variant analysis for other indications.

CYP4F2 Variant Analysis

Covered when ALL of the following are met for CYP4F2:

CYP4F2 variant analysis: Member is being considered for or is currently undergoing treatment with warfarin.

Current evidence does not support CYP4F2 variant analysis for other indications.

DPYD Variant Analysis

Covered when ALL of the following are met for DPYD:

DPYD variant analysis: Member is being considered for or is currently undergoing treatment with fluorouracil OR capecitabine.

Current evidence does not support DPYD variant analysis for other indications.

HLA-A*02:01 Variant Analysis

Covered when ALL of the following are met for HLA-A*02:01:

HLA-A*02:01 variant analysis: Member is age 18 or older AND has metastatic or unresectable uveal melanoma.

Testing intended to identify eligibility for tebentafusp (KIMMTRAK); not supported for other indications.

HLA-B*15:02 Variant Analysis

Covered when ALL of the following are met for HLA-B*15:02:

HLA-B*15:02 variant analysis: Member is being considered for or is currently undergoing treatment with carbamazepine-containing therapy OR phenytoin OR fosphenytoin.

Current evidence does not support HLA-B*15:02 variant analysis for other indications.

HLA-B*57:01 Variant Analysis

Covered when ALL of the following are met for HLA-B*57:01:

HLA-B*57:01 variant analysis: Member is being considered for or is currently undergoing treatment with abacavir.

Current evidence does not support HLA-B*57:01 variant analysis for other indications.

NAT2 Variant Analysis

Covered when ALL of the following are met for NAT2:

NAT2 variant analysis: Member is being considered for or is currently undergoing treatment with amifampridine (amifampridine phosphate).

Current evidence does not support NAT2 variant analysis for other indications.

TPMT and NUDT15 Variant Analysis

Covered when ANY of the following are met for TPMT and NUDT15 (either pathway A or B):

TPMT and NUDT15 variant analysis: A: Member is being considered for or is currently undergoing treatment with azathioprine OR mercaptopurine OR thioguanine; OR B: Member is on thiopurine therapy AND has had abnormal complete blood count results.

Current evidence does not support TPMT/NUDT15 testing for indications other than those listed; FDA guidance provides dosing and monitoring recommendations for affected subgroups.

UGT1A1 Variant Analysis

Covered when ALL of the following are met for UGT1A1:

UGT1A1 variant analysis: Member is being considered for or is currently undergoing treatment with irinotecan OR belinostat.

Current evidence does not support UGT1A1 variant analysis for other indications; FDA labeling includes dose-reduction guidance for affected genotypes.

UGT2B17 Variant Analysis

Covered when ALL of the following are met for UGT2B17:

UGT2B17 variant analysis: Member is being considered for or is currently undergoing treatment with belzutifan.

Testing is medically necessary only for belzutifan-associated metabolizer assessment; not supported for other indications.

Warfarin Sensitivity Analysis Panels

Covered when ALL of the following are met for warfarin multigene panels:

Warfarin multigene panel: Member is being considered for or is undergoing treatment with warfarin AND the member has not reached a therapeutic dose.

Alternatively covered when the member is undergoing prophylaxis/treatment for venous thrombosis/PE, prophylaxis/treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement, OR has history of previous myocardial infarction. FDA guidance supports using CYP2C9, CYP4F2, and VKORC1 for initial dosing considerations.

UGT2B17 variant analysis (medically necessary condition)

UGT2B17 variant analysis is covered when ALL of the following are met

UGT2B17 for belzutifan: Member is being considered for or is currently undergoing treatment with belzutifan.

UGT2B17 testing is limited to assessing metabolizer status relevant to belzutifan therapy.

Warfarin sensitivity multigene panel (medically necessary conditions)

Multigene warfarin sensitivity panel is covered when ALL of the following are met

Warfarin panel coverage: Member is being considered for or is undergoing treatment with warfarin, AND the member has not reached a therapeutic dose, AND the member is undergoing prophylaxis/treatment for venous thrombosis or pulmonary embolism OR undergoing prophylaxis/treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement OR has a history of previous myocardial infarction.

Panel coverage is limited to these clinical scenarios per policy.

Non-covered/Not supported single-gene analyses

Other single-gene pharmacogenetic variant analyses are not supported when ANY of the following apply:

Other single-gene tests not supported: Variant analysis of other genes (including but not limited to COMT, CYP1A2, KIF6, OPRM1, TYMS) is not supported by current evidence for determining drug metabolizer status.

Explicit non-support statement in the policy reference table.

General single-gene pharmacogenetic testing criteria

Covered when gene-specific criteria are met (policy language was updated to 'being considered for' or 'currently undergoing' specified therapies).

General gene-specific criteria: Testing for single-gene pharmacogenetic analyses is addressed when the member is being considered for or is currently undergoing therapies where a known gene-drug interaction affects dosing or risk of severe toxicity.

Policy language updated to replace 'beginning therapy' with 'being considered for or currently undergoing' therapy; see individual gene sections for drug-specific lists and documentation requirements.

Warfarin sensitivity analysis panels

Warfarin sensitivity panel coverage logic.

Warfarin-related gene testing: Testing for CYP2C9, CYP4F2, and VKORC1 may be used to select initial warfarin dosing, taking into account clinical and genetic factors; monitor and adjust dosages based on INR per FDA therapeutic management recommendations.

Policy permits small targeted panels for warfarin sensitivity in specified clinical scenarios.

General timing and indication updates

Multiple gene-specific coverage criteria were updated; coverage generally permitted when the member is being considered for or is currently undergoing therapy with drugs relevant to the gene-drug interaction, per FDA/NCCN guidance.

Updated timing language: For many gene tests (e.g., CYP2C9, DPYD, HLA-B*15:02, UGT1A1, CYP2D6, TPMT/NUDT15) criteria were changed from 'beginning therapy' to 'being considered for or currently undergoing' therapy.

See individual gene sections in the full policy for drug-specific lists and evidence references.

Warfarin sensitivity analysis panels

Warfarin sensitivity and related small targeted panels:

Warfarin sensitivity panels: Clinical criteria reformatted to allow coverage of small targeted panels for warfarin sensitivity when policy conditions are met.

Includes allowance for small targeted panels where previously only larger panels were specified.

HLA-A*02:01 Variant Analysis

New HLA-A*02:01 criteria:

HLA-A*02:01 Variant Analysis: New criteria set created to identify adults with metastatic or unresectable uveal melanoma who are HLA-A*02:01 positive for consideration of tebentafusp therapy.

Policy removed prior rapid-progression restriction; testing is limited to this indication per FDA labeling.

Variant analysis of additional pharmacogenes — including but not limited to COMT, CYP1A2, KIF6, OPRM1, and TYMS — is not supported by current evidence to determine drug metabolizer status for therapeutic management and therefore is not presented as a supported clinical use in this policy.

Certain genes that are not listed in the FDA Table of Pharmacogenetic Associations Section 1 are not presented here as having FDA‑supported therapeutic management recommendations. Tests for such genes are therefore not described as supporting FDA‑endorsed medication management in this policy.

For each named gene included in this policy (for example CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, DPYD, TPMT/NUDT15, UGT1A1, UGT2B17 and others), the policy states that variant analysis is not supported to determine drug metabolizer status for indications other than the specific drug‑ or indication‑linked uses listed under that gene. See the individual gene sections for the covered drug lists and the related clinical criteria.

Pharmacogenetic panel testing intended for routine, across‑the‑board use is not supported because the literature shows variable designs and conflicting results and the FDA does not provide general recommendations for panels. Therefore, panel testing is only considered medically necessary when the specific panel and clinical scenario meet the policy’s listed criteria.

Single‑gene variant analyses for genes that are not supported by FDA Section 1 therapeutic management recommendations (e.g., COMT, CYP1A2, KIF6, OPRM1, TYMS) are not presented as supporting therapeutic management and are not considered clinically supported uses in this policy.

Policy language was updated in several sections to replace prior wording that labeled tests as 'Investigational' with clearer statements that current evidence does not support certain uses of pharmacogenetic testing. The substantive coverage logic — i.e., which gene‑drug indications are addressed — remains anchored in the listed gene‑specific criteria.

Covered Indications by Gene or Panel

Coding — CPT/PLA/ICD Reference

Pharmacogenetic Panel Tests - Covered/Referenced codesmixed

81418	Pharmacogenetic Panel common billing code
0029U	Focused Pharmacogenomics Panel - example code
0033U	Serotonin Receptor Genotype (HTR2A/HTR2C) - example code
0173U	Psych HealthPGx Panel - example code
0175U	Genomind Professional PGX - example code
0286U	CNT Genotyping Panel - example code
0345U	GeneSight Psychotropic - example code

Pharmacogenetic Single Gene and Variant Analysis Codesmixed

0070U	CYP2D6 Common Variants and Copy Number - example code
0071U	CYP2D6 Full Gene Sequencing - example code
81225	CYP2C19 variant analysis - listed
81226	CYP2D6 variant analysis - listed
81227	CYP2C9 variant analysis - listed
81231	CYP3A5 variant analysis - listed
81232	DPYD Genotyping - example code
81306	TPMT genotyping - example code
81335	NUDT15 genotyping - example code
81350	UGT1A1 variant analysis - example code

1–10 of 11

1/2

Diagnosis Codes referenced in policy tablesICD-10

B20	Diagnosis code referenced in policy table
C00.0-C96.9	Range of neoplasm diagnosis codes referenced
F01-F99	Range of mental/neurologic diagnosis codes referenced
Z13.71-Z13.79	Encounter for genetic counseling/testing codes referenced

Examples of single-gene CPT/PLA codes citedCPT

0032U	COMT - example PLA/CPT code listed
0031U	CYP1A2 - example PLA/CPT code listed
81479	Unlisted molecular pathology procedure (used in document alongside several genes)

Updated molecular pathology CPT referencedCPT

81479

Unlisted molecular pathology procedure (replacement referenced for 81381)

Example ICD-10 codes added to gene-specific sectionsICD-10

E78.00	Hypercholesterolemia, unspecified (example addition)
E78.1	Pure hyperglyceridemia (example addition)
C64	Malignant neoplasm of kidney, except renal pelvis (example addition)
F32	Major depressive disorder, single episode (example addition)
K21.9	Gastro-esophageal reflux disease without esophagitis (example addition)
L20	Atopic dermatitis (example addition)
Q85.83	Genetic susceptibility to disease (example addition)
R56.9	Unspecified convulsions (example addition)
R68.82	Postviral fatigue syndrome (example addition)
C50.11 - C50.929	Range of breast cancer site codes (example addition)

1–10 of 12

1/2

Pharmacogenetic CPT codes addedCPT

0423U	CPT code added to policy reference table
0434U	CPT code added to policy reference table
0437U	CPT code added to policy reference table
0438U	CPT code added to policy reference table

PLA codes addedCPT

0476U	PLA code added to policy reference table
0477U	PLA code added to policy reference table
0516U	PLA code added to policy reference table

Removed CPT codesCPTNot Covered

81346

Removed from Other Single Gene Variant Analysis (legacy code)

Dose reduction / management examples

Belinostat (UGT1A1)For UGT1A1 *28/*28 (poor metabolizers) reduce starting dose of belinostat to 750 mg/m2.

Irinotecan (UGT1A1)In UGT1A1 poor metabolizers consider reducing the starting dose by at least one level and monitor closely for neutropenia and diarrhea; modify dosing based on tolerance per FDA labeling.

Sacituzumab Govitecan-hziy (UGT1A1)For UGT1A1 *28/*28 (poor metabolizers) monitor for neutropenia and consider tolerance to treatment per FDA labeling.

Thioguanine (TPMT/NUDT15)In poor TPMT or NUDT15 metabolizers substantially reduce thioguanine dose (examples reference reductions to ~10% of usual dosing) and monitor for myelosuppression.

Provider Actions — Authorization, Billing, Documentation

Prior Authorization

Prior authorization and CPT code information

CPT codes in the policy are provided for informational purposes only; providers must use the Concert Platform for additional registered tests and to follow the payer’s prior authorization process.

Codes listed are not comprehensive and do not guarantee coverage.
Refer to Concert Platform for registered tests and prior authorization submission.

Prior Authorization

Prior authorization required for warfarin sensitivity panels

Multigene warfarin sensitivity panels are considered medically necessary only when the member is being considered for or is undergoing warfarin and meets the policy’s specified clinical conditions.

Must be ordered when member is being considered for or is undergoing warfarin and has not reached a therapeutic dose, or for specified scenarios: prophylaxis/treatment of venous thrombosis/PE; thromboembolic prophylaxis/treatment with atrial fibrillation and/or cardiac valve replacement; or history of myocardial infarction.

Prior Authorization

Prior authorization for UGT2B17 and warfarin panels

Prior authorization is required when ordering UGT2B17 variant analysis for the specific indication of assessing metabolizer status for belzutifan, and for multigene warfarin panels under their medically necessary conditions.

UGT2B17 testing only medically necessary when member is being considered for or currently undergoing belzutifan.
Warfarin panels require the member to meet the warfarin-related clinical criteria in the policy.

Prior Authorization

Use updated CPT 81479 for some single-gene authorizations

Use the updated miscellaneous molecular pathology CPT 81479 (replacement referenced for prior code) when requesting authorization for certain single-gene variant tests; confirm the correct CPT when submitting prior authorization requests.

Policy notes replacement of prior code (e.g., 81381) with 81479; verify current CPT coding before authorization submission.
Codes in the policy are informational—confirm with Concert Platform and current coding guidance.

Prior Authorization

Updated coding added to policy reference table — impacts prior authorization

New PLA and CPT codes were added to the policy reference table; providers must follow updated prior authorization requirements and bill using the codes listed in the policy reference table.

Added CPT codes (e.g., 0423U, 0434U, 0437U, 0438U) and PLA codes (0476U, 0477U, 0516U) to the reference table.
Prior authorization and coverage determinations apply per the updated policy criteria.

Note

General provider action — follow payer processes and coding guidance

(No specific action text provided in source excerpts.)

If ordering or billing tests, follow the Concert Platform and current coding guidance referenced in the policy.

Step Therapy

Step therapy not defined

No explicit step therapy sequences are defined in the policy excerpts; there are no mandated sequential therapy requirements described.

Providers should not assume step therapy pathways are specified for these genetic tests based on this policy text.
Coverage determinations follow the listed medical necessity criteria rather than step sequences.

Step Therapy

Consider prior therapy history before TPMT testing

For TPMT testing, document prior treatment history—testing is recommended per NCCN for patients who develop severe myelosuppression after starting 6‑MP; consider prior adverse drug reaction when ordering TPMT/NUDT15 tests.

NCCN recommends TPMT testing for patients who develop severe myelosuppression after starting 6‑MP.
Order TPMT/NUDT15 testing when clinical history (e.g., abnormal CBC on thiopurine therapy or severe myelosuppression) aligns with policy criteria.

Documentation Required

Link medical necessity determination to the specific gene/panel criteria

Medical necessity determinations must reference the specific gene test and meet the gene- or panel-specific criteria listed in the policy to support coverage.

Coverage requires that the ordered test match the gene-specific medical necessity criteria in the policy.
Document how the member meets the listed criteria for the specific gene or panel.

Documentation Required

Document warfarin-related clinical status and dosing

When ordering a warfarin multigene panel, document that the member is being considered for or is undergoing warfarin and either has not reached a therapeutic dose or meets one of the specified clinical scenarios in the policy.

Document if member has not reached therapeutic dose on warfarin.
Alternatively document prophylaxis/treatment for venous thrombosis/PE, thromboembolic complications with AF or cardiac valve replacement, or history of MI.

Documentation Required

Document belzutifan treatment status for UGT2B17 testing

When ordering UGT2B17 variant analysis, document that the member is being considered for or is currently receiving belzutifan to meet the policy’s indication for testing.

UGT2B17 testing is medically necessary only for members being considered for or currently treated with belzutifan.
Include clinical documentation linking the test order to belzutifan therapy.

Documentation Required

Document clinical indication for TPMT testing (per NCCN)

Document the clinical indication when ordering TPMT testing—per NCCN guidance, include notes such as development of severe myelosuppression after initiating 6‑MP to support medical necessity.

NCCN recommends TPMT testing for patients with severe myelosuppression after starting 6‑MP.
Include clinical details (e.g., abnormal CBC, timing relative to therapy) in the documentation.

Billing Rule

Use updated policy reference table codes when billing

Bill using the codes listed in the updated policy reference table and follow the updated clinical criteria for coverage; the policy was updated with new PLA and CPT codes that must be used per the reference table.

Policy reference table now includes new PLA and CPT codes—providers must use the listed codes when billing.
Codes in the policy are informational; verify current coding guidance prior to claim submission.

Denial Risk

Coding listed does not guarantee coverage — verify before claim submission

Inclusion or exclusion of a code in the policy does not guarantee coverage; providers should confirm up-to-date coding guidance before submitting claims to avoid denials.

The policy states that inclusion/exclusion of codes does not represent a guarantee of coverage.
Providers should reference current CPT/professional coding guidance prior to claim submission.

Note

Not Covered — Unsupported Tests & Uses

Pharmacogenetic testing is not supported for all indications. Panels and specific gene tests are covered only when the clinical scenario meets the explicit criteria listed in this policy; routine or broad testing outside those criteria is not supported.

Variant analysis of other pharmacogenes such as COMT, CYP1A2, KIF6, OPRM1, and TYMS is not supported by current evidence for determining drug metabolizer status and is therefore not covered for therapeutic‑management uses.

General pharmacogenetic panel testing for indications beyond those explicitly listed in this policy is not supported due to inconsistent and low‑certainty evidence of clinical benefit; as a result, broad or routine panel use across unlisted indications is not covered.

Tests for genes that are not represented in FDA Section 1 of the Table of Pharmacogenetic Associations are not presented in this policy as having FDA‑supported therapeutic management recommendations and therefore are not supported for therapeutic‑management testing.

SLCO1B1 (SLOC1B1) testing has been removed from the policy’s coverage list to align with local coverage determinations and the policy reference table; legacy CPT codes associated with removed tests (for example, 81346) have been deleted from the table.

Definitions and Background

Pharmacogenetic and toxicology tests are used to assess genetic or biochemical factors that affect drug response, risk of toxicity, and treatment selection. Test methods may include targeted variant analysis, sequencing, copy‑number assessment, and panels; sample types and analytic approaches vary by test and clinical question. The policy provides gene‑specific criteria to guide when variant or panel testing is considered medically necessary to inform medication selection, dosing, or monitoring.

Pharmacogenetic testing

DefinitionPharmacogenetic testing: tests used to assess genetic variants that affect drug metabolism, efficacy, or toxicity.

PurposeTo identify gene variants that impact drug response and guide medication selection, dosing, or monitoring.

Test typesIncludes single-gene variant analyses and multigene pharmacogenetic panels.

Pharmacogenetic panel (general)

Panel definition (concise)A pharmacogenetic panel is a genetic test analyzing more than one gene used to determine drug metabolizer status and pharmacogenetic risk.

Distinct from single-genePanels analyze multiple pharmacogenes simultaneously and are considered separate from single-gene variant analyses.

Policy noteThe FDA does not address pharmacogenetic panels generally; clinical utility evidence for panels is variable.

Pharmacogenetic panel (policy context)

IntentMultigene testing intended to determine a patient's drug metabolizer status across multiple pharmacogenes.

FDA stanceFDA does not provide general guidance for pharmacogenetic panels; FDA describes clinical utility for specific single-gene tests rather than panels.

Evidence variabilityPrimary literature shows mixed and sometimes conflicting results about clinical utility of panels, with low certainty in effect sizes for some indications (e.g., major depression).

FDA Section 1 pharmacogenetic association

FDA Section 1 meaningPharmacogenetic Association (Section 1) = gene-drug interactions for which data support therapeutic management recommendations.

Examples - DPYDDPYD with capecitabine or fluorouracil: intermediate/poor metabolizers have higher risk of severe toxicity; withhold or discontinue in early/unusually severe toxicity; no safe dose established for poor metabolizers.

Examples - TPMT/NUDT15TPMT and/or NUDT15 with azathioprine/mercaptopurine/thioguanine: intermediate/poor metabolizers require dosage reductions or alternative therapy; monitor for myelosuppression.

Examples - VKORC1/CYP2C9/CYP4F2Warfarin: genetic variants (e.g., VKORC1 -1639G>A) alter initial dosage selection; monitor and adjust dosing based on INR per FDA guidance.

Pharmacogenetic testing (general)

ScopePharmacogenetic testing includes single-gene and multigene panel testing to inform medication selection, dosing, or toxicity monitoring.

Coverage considerationCoverage is gene- and indication-specific; many tests are only supported for listed drug-specific uses and not for routine panel screening.

Evidence basisFDA tables and select guideline/primary literature inform recommendations; evidence for panels is variable and indication-dependent.

TYMS single-gene testing (policy link)

Test listedTYMS single gene testing (sequencing and deletion/duplication) is included in the policy reference table (example: Fulgent Genetics).

Coverage linkageTYMS testing is described as medically necessary when meeting the related gene-specific criteria in the policy.

Not broadly supportedVariant analysis of TYMS and several other genes is noted as not supported by current evidence for determining drug metabolizer status unless specifically listed with criteria.