If the FDA has included a particular gene-drug interaction does that mean the FDA advocates using a pharmacogenetic test before a doctor prescribes a medication?

The fact that the FDA has included a particular gene-drug interaction in the table does not necessarily mean the FDA advocates using a pharmacogenetic test before prescribing the corresponding medication unless the test is a companion diagnostic. Tests that are essential for the safe and effective use of a therapeutic product, including those that identify patients for which the drug is contraindicated, are companion diagnostics.

Specific information regarding therapeutic management is provided for some pharmacogenetic associations listed in the table, but most of the associations listed have not been evaluated in terms of the impact of genetic testing on clinical outcomes, such as improved therapeutic effectiveness or increased risk of specific adverse events. In addition, clinical studies, if available, may only have linked genetic variation to a drug’s pharmacokinetics (such as the way in which the drug is metabolized), and differences in drug efficacy or safety across different genotype subgroups may not be known. If no statements related to efficacy or toxicity are provided, the scientific evidence the FDA reviewed was considered insufficient to support such associations.

What is the FDA’s position on different sources and strengths of evidence in doctor’s prescribing medications based on genetics?

The FDA recognizes that practitioners will consider different sources and strengths of evidence and will make prescribing decisions based on their judgment about which treatments are appropriate for individual patients. In particular, each patient’s genetic makeup is only one of many factors that may impact drug concentrations and response, highlighting the fact that information provided in this table is limited to certain pharmacogenetic associations only and does not provide comprehensive information needed for safe and effective use of a drug. Accordingly, health care providers should refer to FDA-approved labeling for prescribing information, including monitoring instructions and information on other factors that may affect drug concentrations, benefits, and risks.

Is the FDA table complete?

The FDA recognizes that various other pharmacogenetic associations exist that are not listed here, and this table will be updated periodically with additional pharmacogenetic associations supported by sufficient scientific evidence.

Are there medications with pharmacogenetic associations which may have a potential impact on Safety or Response?

Pharmacogenetic Associations for which the Data Indicate a Potential Impact on Safety or Response

DrugGeneAffected Subgroups+Description of Gene-Drug Interaction
AllopurinolHLA-B*58:01 allele positiveResults in higher adverse reaction risk (severe skin reactions).
CarbamazepineHLA-A*31:01 allele positiveResults in higher adverse reaction risk (severe skin reactions). Consider risk and benefit of carbamazepine use in patients positive for HLA-A*31:01. Genotyping is not a substitute for clinical vigilance.
CarvedilolCYP2D6poor metabolizersResults in higher systemic concentrations and higher adverse reaction risk (dizziness).
CevimelineCYP2D6poor metabolizersMay result in higher adverse reaction risk. Use with caution.
CodeineCYP2D6poor metabolizersResults in lower systemic active metabolite concentrations and may result in reduced efficacy.
EfavirenzCYP2B6poor metabolizersResults in higher systemic concentrations and higher adverse reaction risk (QT prolongation).
IsoniazidNonspecific (NAT)poor metabolizersMay result in higher systemic concentrations and adverse reaction risk.
LapatinibHLA-DRB1*07:01 allele positiveResults in higher adverse reaction risk (hepatotoxicity). Monitor liver function tests regardless of genotype.
LapatinibHLA-DQA1*02:01 allele positiveResults in higher adverse reaction risk (hepatotoxicity). Monitor liver function tests regardless of genotype.
NilotinibUGT1A1*28/*28 (poor metabolizers)Results in higher adverse reaction risk (hyperbilirubinemia).
OxcarbazepineHLA-B*15:02 allele positiveResults in higher adverse reaction risk (severe skin reactions). Patients positive for HLA-B*15:02 may be at increased risk of severe skin reactions with other drugs that are associated with a risk of Stevens Johnson Syndrome/Toxic Epidermal necrolysis (SJS/TEN). Genotyping is not a substitute for clinical vigilance.
PazopanibHLA-B*57:01 allele positiveMay result in higher adverse reaction risk (liver enzyme elevations). Monitor liver function tests regardless of genotype.
PazopanibUGT1A1*28/*28 (poor metabolizers)Results in higher adverse reaction risk (hyperbilirubinemia).
PerphenazineCYP2D6poor metabolizersResults in higher systemic concentrations and higher adverse reaction risk.
ProcainamideNonspecific (NAT)poor metabolizersAlters systemic parent drug and metabolite concentrations. May result in higher adverse reaction risk.
SimvastatinSLCO1B1521 TC or 521 CC (intermediate or poor function transporters)Results in higher systemic concentrations and higher adverse reaction risk (myopathy). The risk of adverse reaction (myopathy) is higher for patients on 80 mg than for those on lower doses.
Sulfamethoxazole and TrimethoprimNonspecific (NAT)poor metabolizersMay result in higher adverse reaction risk.
SulfasalazineNonspecific (NAT)poor metabolizersResults in higher systemic metabolite concentrations and higher adverse reaction risk.
TolterodineCYP2D6poor metabolizersResults in higher systemic concentrations and higher adverse reaction risk (QT prolongation).
VoriconazoleCYP2C19intermediate or poor metabolizersResults in higher systemic concentrations and may result in higher adverse reaction risk.

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