Navigating CPT Coding for Pharmacogenetic (PGx) Testing Reimbursement
Many drugs are now FDA-approved with pharmacogenetic biomarkers, requiring or recommending genetic testing to guide treatment decisions. The rise of precision medicine has also led healthcare systems to explore integrating PGx testing into clinical care to optimize medication therapy.
However, broader adoption of pharmacogenomics faces reimbursement challenges. Much of PGx testing occurs as laboratory services sent out to specialized labs for analysis. Correct CPT coding is essential for labs to secure payer coverage and reimbursement.
We offer an in-depth overview of current CPT codes used for billing various pharmacogenetic lab tests.
Core CPT Codes for PGx Genotyping Assays
Targeted genotyping panels analyzing key drug metabolism genes make up some of the most common pharmacogenetic lab tests. Here are the main CPT codes used for billing core PGx gene panels:
CYP2D6 Gene Analysis (81227)
The CYP2D6 enzyme metabolizes over 25% of commonly used drugs. Testing variants in this gene predicts metabolism rates of medications like antidepressants, antipsychotics, opioids, and beta-blockers. 81227 specifically reports CYP2D6 genotype testing and is billed for identifying an individual’s metabolizer phenotype (e.g. poor, intermediate, normal, or ultra-rapid metabolizer).
Example: CYP2D6 genotyping to determine if a patient has an abnormal metabolizer phenotype that could lead to adverse events when prescribed standard doses of tricyclic antidepressants.
CYP2C19 Gene Analysis (81226)
CYP2C19 genotypes help predict metabolizer status for anticonvulsants, proton pump inhibitors, and antiplatelet therapy. 81226 identifies a patient’s CYP2C19 metabolizer phenotype based on variants like *2, *3, and *17.
Example: CYP2C19 testing to determine if a patient will have reduced efficacy on standard clopidogrel antiplatelet therapy due to abnormal CYP2C19 metabolism.
CYP2C9 and VKORC1 Testing (81227, 81355)
Combination testing of CYP2C9 and VKORC1 variants helps predict warfarin sensitivity and optimize anticoagulation dosing. 81227 covers testing of relevant CYP2C9 variants, while 81355 reports VKORC1 genotype. These codes are stacked when performed together for warfarin PGx testing.
Example: Using both CYP2C9 and VKORC1 genotyping to identify optimal initial warfarin dose for a patient beginning anticoagulation therapy.
Factor V and Factor II Thrombophilia Testing (81240, 81241)
Testing for Factor V Leiden (FVL) and prothrombin Factor II (FII) G20210A mutations helps determine thromboembolism risk and guide anticoagulant therapy. CPT codes 81240 and 81241 identify the presence or absence of these thrombophilia variants.
Example: Checking for Factor V and Factor II mutations in a patient with recurrent pulmonary emboli to guide anticoagulation therapy selection and dosage.
It is critical to select the right CPT code specifically describing the PGx gene or variant analyzed and ensure codes are stacked properly when multiple genes are tested as part of a pharmacogenetic panel.
CPT Codes for Expanded PGx Sequencing
In addition to targeted assays of specific medication metabolism genes, labs can also perform more extensive PGx sequencing:
Expanded Pharmacogenetic Gene Panels (81120, 81121, 81161, 81162)
Larger panels analyzing between 10-30 pharmacogenes important for drug response may be reported using stacked codes:
- 81120 x1: Pharmacogenomic testing, 10-30 genes
- 81121 x2: Pharmacogenomic testing, 31-60 genes
- 81162 x3: Pharmacogenomic testing, 61-90 genes
- 81163 x4: Pharmacogenomic testing, 91 or more genes
These codes are used for PGx sequencing of pre-specified lists of drug metabolism, transportation and receptor genes beyond the common cytochrome P450 genes.
Example: A 45 gene PGx panel assessing cytochromes, HLA alleles, and other pharmacogenes related to immunosuppressant metabolism and response.
Whole Exome and Whole Genome Sequencing (81415, 81416, 81415)
When an expanded pharmacogenomic exome (all protein-coding exons) or genome analysis is performed, different codes apply:
- 81435: Exome sequence analysis – reports sequencing of all known exons in the genome.
- 81436: Exome re-evaluation – covers subsequent exon analysis of the same sample.
- 81425: Genome sequence analysis – reports whole genome sequencing of patient germline DNA.
These codes can be used if pharmacogenomic findings are derived from a whole exome or genome sequence vs a targeted PGx panel.
Example: Incidental finding of a TPMT gene variant affecting thiopurine drug toxicity risk identified on a whole exome sequence performed for an unrelated condition.
Proper CPT code selection is important even when PGx testing occurs in the context of large scale genomic sequencing.
Additional CPT Codes for Pharmacogenetic (PGx) Testing
- 81225: CYP1A2 (cytochrome P450 family 1, subfamily A, member 2)(eg, drug metabolism) gene analysis, common variants (eg, *1C, *1F, *1K)
- 81231: CYP3A4 (cytochrome P450 family 3 subfamily A member 4) (eg, drug metabolism) gene analysis, common variants (eg, *2, *22)
- 0119U: Drug metabolism (adverse drug reactions and drug response), targeted sequence analysis (ie, CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP4F2, SLCO1B1, VKORC1 and rs12777823)
- 0142U: Drug metabolism (warfarin drug response), targeted sequence analysis (ie, CYP2C9, CYP4F2, VKORC1, rs12777823)
Billing and Reimbursement Considerations
Despite growing recognition of PGx testing benefits, coverage and payment for pharmacogenetic analysis faces multiple obstacles:
Payer Coverage Limitations
Many payers limit PGx testing coverage only to instances where specific drugs have PGx biomarker labels or established guidelines like warfarin. Billing for broad “pre-emptive” PGx panel testing before drugs are prescribed often results in denials. Clear documentation of medication links is necessary.
Unlisted Codes for New Tests
Emerging pharmacogenetic tests don’t immediately have dedicated CPT codes until years of utilization data are available. Labs must initially use miscellaneous unlisted codes which have lower reimbursement until specific codes are established.
Out-of-State Billing Issues
As PGx testing is often sent to large specialized labs like Mayo Medical Labs or Quest Diagnostics, the ordering provider and performing lab may be in different states leading to billing complications. Smaller practices may lack out-of-state billing expertise.
High Patient Responsibility
Due to limited coverage policies, pharmacogenetic testing often has high out-of-pocket costs for patients. This surprises patients and reduces willingness to consent to testing their provider recommends.
To overcome reimbursement difficulties, PGx testing labs leverage prior authorization, peer-to-peer consults, test bundling and patient counseling to aid payment success.
Emerging Issues and Updates in PGx CPT Coding
Labs should be aware of evolving considerations around PGx test coding:
Code Stacking Clarity
Clear payer policies are still emerging on how PGx panels can be coded – stacking multiple CPTs vs one bundled panel code to avoid rejected claims. Open communication with payers is important.
Advances in Testing
As PGx technical capabilities advance with next generation sequencing, new types of tests will continually emerge requiring new CPT codes to be established by the AMA.
ICD-10 Links
Links between PGx tests and correlated ICD-10 diagnosis codes are still developing. Savvy test-diagnosis coding maximizes payer acceptance.
Increased Scrutiny
As PGx becomes more prominent, payers are tightening policies on coverage criteria and documentation requirements for pharmacogenetic testing reimbursement.
By staying abreast of evolving payer expectations, coverage determinations and coding specifics, labs can improve their pharmacogenomic test reimbursement success.
Conclusion
Pharmacogenetic testing adoption in clinical care is hampered by reimbursement difficulties related to coding complexity, coverage limitations and outdated payer medical policies. By learning the specific CPT codes for billing PGx gene panels, sequencing and custom tests, labs can increase transparency with payers and providers to aid reimbursement.
However, given rapid advances in PGx testing, ongoing payer education by both labs and the ordering clinicians is essential to align coverage policies with emerging clinical practice. With time, coverage is likely to expand as evidence supporting PGx testing’s ability to improve outcomes and lower costs continues accumulating. But for now, meticulous documentation, persistence, and coding savvy remain necessary to unlocking the benefits of pharmacogenomics for patients.
Keep in mind, at Medwave we provide Pharmacogenetic (PGx) Testing billing.
