Table 1. FDA drug labels that include genetic and genomic prescribing information.

Shown are selected drugs that contain pharmacogenomic information in label sections Boxed Warning, Warnings and Precautions, Indications and Usage, or Dosage and Administration. A full list of pharmacogenomic biomarkers in drug labels is available at the FDA Web site (www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm). Three different types of pharmacogenomics study approaches were used to identify genetic variations associated with drug-response phenotypes in study populations: (i) GWA studies are based on an agnostic approach in which more than 100,000 genetic variants that scan the entire genome are each tested for a significant association with a phenotypic trait such as an adverse drug reaction in a study cohort; (ii) candidate gene studies are based on a priori knowledge that is used to select a limited number of genetic variants and associate them with a phenotypic trait such as drug response in a study cohort; and (iii) in prospective clinical trials, patients are randomly assigned to one of several treatment groups; the treatments are initiated, and the results from the different treatments groups are compared at a predetermined end point.

Drugs	Label sections	Genetic test (germline variants; recommendation in drug label)	Types of reactions	Types of pharmacogenomics research (GWA studies/candidate gene studies/clinical trial)	Clinical guidelines
Abacavir	Boxed Warning, Warnings and Precautions	HLA-B*5701; screening for the HLA-B*5701 allele is recommended.	HLA-B-*5701 allele; high risk of hypersensitivity to abacavir.	Prospective clinical trial (43)	FDA-approved drug label (33)
Aripiprazole	Dosage and Administration	CYP2D6 activity; the Dosage and Administration section of the label says that “dosing for CYP2D6 poor-metabolizers should initially be reduced to one-half of the usual dose and then adjusted to achieve a favorable clinical response.”	CYP2D6 poor-metabolizers have 80% increase blood aripiprazole concentrations relative to controls. Elderly poor-metabolizers have increased risk of death. Patients with major depressive disorders may experience worsening of their depression or suicidal ideation and behavior.	None of the above	(33); variants in CYP2D6 could be found in (44, 45).
Azathioprine 6-mercaptopurinethioguanine	Dosage and Administration, Warnings and Precautions	Thiopurine methyltransferase (TPMT) genomic variants (TPMT*2, TPMT*3A, and TPMT*3C) and TPMT activity; genetic and phenotypic testing of TPMT can be used to identify patients with absent or reduced TPMT activity but cannot replace complete blood count monitoring in patients.	Myelosuppression (low activity of the bone marrow resulting in low red blood cells, white blood cells, and platelets) in patients with an inherited deficiency of TPMT. Lower dose is recommended in patients with reduced TPMT activity.	Candidate gene study (46–48)	(32, 33)
Carbamezepine	Carbamezepine Boxed Warning, Warnings and Precautions	HLA-B*1502; FDA recommends that patients of Chinese ancestry be genotyped for this variant prior to initiating treatment.	HLA-B*1502 allele; risk of developing Stevens-Johnson syndrome (inflammatory eruption of the skin and mucous membranes) or toxic epidermal necrolysis.	Candidate gene study (20)	FDA-approved drug label
Clopidogrel	Boxed Warning, Warnings and Precautions, Dosage and Administration	CYP2C19 variants; Boxed Warning drug label section says that “a test is available to identify the CYP2C19 genotype and can be used as an aid in determining therapeutic strategy.”	CYP2C19*2 and CYP2C19*3 alleles yield poor-metabolizers who display lower active metabolite exposure, lower inhibition of platelet aggregation, and higher cardiovascular event rates after acute coronary syndrome or percutaneous coronary intervention, relative to normal metabolizers.	Candidate gene and GWA studies (3, 49)	(33, 50)
Irinotecan	Irinotecan Dosage and Administration, Warnings and Precautions	UGT1A1*28 allele; Warnings and Precautions section of the drug label section says that patients with this allele are at greater risk for neutropenia.	UGT1A1*28 allele results in reduced UGT1A1 enzyme activity and increased risk for neutropenia.	Candidate gene study (51)	(33)
Ivacaftor	Indications and Usage	cystic fibrosis transmembrane conductance regulator gene (CFTR); this drug is approved for cystic fibrosis patients (>6 years old) with the G551D mutation in CFTR (occurs in 4 to 5% of patients with cystic fibrosis) (2, 52).	Patients who are homozygous for the CFTR F508del mutation will not respond to this drug.	Prospective clinical trial (2)	FDA-approved drug label
Tetrabenazine	Tetrabenazine Dosage and Administration, Warnings and Precautions	CYP2D6 activity; the Dosage and Administration section of the label says that “before prescribing a daily dose of tetrabenazine that is greater than 50 mg per day, it is necessary to determine whether patients are poor, extensive, or intermediate metabolizers.”	May increase the risk of depression and suicidal thoughts and behavior. Other Warnings and Precautions are QTc prolongation, sedation, fatigue, and akathisia.	None of the above	FDA-approved drug label; CYP2D6 variants can be found in (44, 45).
Warfarin	Dosage and Administration, Warnings and Precautions	CYP2C9 (CYP2C9*2 or CYP2C9*3) and VKORC1 variants (−1639G>A); FDA recommends that genotype information can assist in selection of the starting dose	CYP2C9*2 or CYP2C9*3 alleles are associated with increased risk of bleeding. The VKORC (−1639G>A) variant is associated with lower warfarin dose requirements	Candidate gene and GWA studies (23, 29, 53)	(24); warfarin algorithm*

^*Warfarin algorithms: 1, www.warfarindosing.org/Source/Home.aspx; 2, (25); and 3, (23).