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Table 2. Drug-Gene pairs with strong FDA recommendations and the commercial laboratories that offer CLIA-certified
clinical pharmacogenetic tests in the U.S.
Drug Gene(s) US FDA PGx designation Commercial labs that offer testing #
Clopidogrel CYP2C19 Boxed warning Fulgent Genetics; Sema4; Admera Health; RPRD
Diagnostics, LLC; OneOme LLC; Sanford Medical Genetics
Laboratory Sanford Imagenetics; Color; Pathway Genomics
Codeine CYP2D6 Boxed warning Fulgent Genetics; Sema4; OneOme LLC; Admera Health;
Tramadol CYP2D6 Boxed warning RPRD Diagnostics LLC; Sanford Medical Genetics
Laboratory Sanford Imagenetics; Color; Pathway Genomics
Pegloticase G6PD Boxed warning/testing required* EGL Genetic Diagnostics Eurofins Clinical Diagnostics;
Rasburicase G6PD Boxed warning/testing required* Invitae; Fulgent Genetics; Baby Genes by ArcherDX Clinical
Services; Sema4; RPRD Diagnostics, LLC
Carbamazepine HLA-B*1502 Boxed warning/testing required* OneOme, LLC; Admera Health; RPRD Diagnostics, LLC;
Oxcarbazepine HLA-B*1502 Testing required* Pathway Genomics
Abacavir HLA-B*5701 Boxed warning/testing required*
Azathioprine TPMT/NUDT15 Testing recommended RPRD Diagnostics, LLC; Admera Health; OneOme, LLC;
Mercaptopurine TPMT/NUDT15 Testing Recommended Color
Thioguanine TPMT/NUDT15 Testing recommended
Testing required means patients should be screened prior to initiation of therapy; Testing required* means genetically at-risk populations
based on ancestries should tested prior to initiation of therapy; Testing recommended means patients who experience adverse drug
#
reactions should be tested; not a comprehensive list. All commercial labs listed offers CLIA-certified, state-licensed, saliva and peripheral
(whole) blood specimen options, U.S.-based, clinical tests. Only laboratories indexed on Genetic Testing Registry (https://www.ncbi.nlm.
nih.gov/gtr/) were considered for this table; CLIA - Clinical Laboratory Improvement Amendments

enzymes responsible for the majority of drug metabolism - namely CYP2C9, CYP2C19, and CYP2D6. These
[14]
three enzymes collectively metabolize about 40% of all medications . Ultimately, the choice of the genes
to test and when to test should be based on the nature of the practice site (pre-emptive or reactive), the
clinical setting (e.g., cardiology vs. pain vs. psychiatry), and the target patient populations. In preemptive
testing, a testing panel that covers the common “pharmacogenes” may be considered so that information
resulted will be applicable to future prescribing decisions. In reactive testing, the medication prescribed
will determine the gene to be tested. Moreover, when initiating a targeted, clinical specialty-focus program
(e.g., cardiology pharmacogenetics clinic), a careful review should be conducted to use panels that target
genes implicated in the response to cardiovascular medications, have evidence of genetic association
with medication-related outcomes, and pharmacogenetic-guided therapeutic recommendation such as
clopidogrel, warfarin, and simvastatin.

Once the genes are selected for testing, a thorough review should be conducted to ensure that the test
[15]
will interrogate all the relevant and actionable variants based on evidence and target population . For
instance, if your clinic or institution serves African ancestry patients, the *5, *6, *8 and *11 variant alleles
should be included in the test for the CYP2C9 gene along with the common *2 and *3 alleles. Moreover,
clinicians should note that the designation of *1/*1 or normal metabolizer is simply the absence of the
set of interrogated variant alleles in the tested patient. Clinicians should ensure that the selected tests,
whether single-gene or panel-bases: (1) cover genes that are relevant for the medications in question; and
(2) interrogate a list of diverse variants in those genes that will inform therapeutic decisions for the target
patient population. The Association for Molecular Pathology (AMP) advises on the minimum set of variant
alleles for each gene, which is an excellent guide for those charged with selecting a pharmacogenetic test.
To date, the AMP has published guidance for CYP2C19 and CYP2C9 , and this group is planning to
[17]
[16]
publish similar guidance for CYP2D6 and other “pharmacogenes”.
The test and the laboratory
Many commercial laboratories have added pharmacogenetics to their test offerings. Traditionally, these
laboratory-developed tests have been under the supervision of the U.S. FDA; however, in August 2020,
the U.S. Department of Health and Human Services issued a statement that the FDA will not require pre-