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Key Points

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  • Drug summary:

    • Pharmacogenomic information is contained in the labeling of many drugs; the type of data available determine whether the results of a test are clinically actionable or useful.

    • Pharmacogenomic tests can be used to select patients for therapy based on their ability to identify responders, predict adverse events, or guide drug dosing.

  • Most pharmacogenomic labeling has focused on drugs that

    • Have a narrow therapeutic index

    • Exhibit highly variable pharmacokinetics or responses

    • Are used to treat morbid or mortal conditions

    • Have serious toxicities

  • Several examples exist where knowledge of a patient’s genotype can significantly influence the benefit-risk profile of a drug product and aid therapeutic decision making. Some examples of this include

    • Warfarin—CYP2C9 and VKORC1 genotypes predict stable warfarin doses and risk for severe bleeding.

    • Clopidogrel—CYP2C19 genotype identifies individuals with low active metabolite exposure and diminished responses who may benefit from drugs not metabolized by CYP2C19.

    • Abacavir—HLA-B*5701 genotype identifies patients at risk for severe hypersensitivity reactions that should not receive the drug.

  • For a comprehensive list of all drugs with pharmacogenomic information appearing in their labels see http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm.

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Introduction

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In the last decade, new tools and methods to explore the human genome have tremendously accelerated discovery of genetic markers for disease susceptibility, prognosis, and drug response. Hence, many clinicians are now faced with staying abreast of the enormous amount of genomic information being generated. Numerous resources are available to keep prescribers informed of important information related to drugs, including the FDA-approved drug label. With greater ability to characterize the genetic underpinnings of drug exposure (ie, pharmacokinetics) and response, whether intended effects or toxicities, drug labels will increasingly incorporate pharmacogenomic information and serve as a key resource for genetic biomarker information. In this chapter, we highlight some of the considerations that go into labeling drugs with pharmacogenomic biomarker information, as well as some translational challenges borne out in recent years.

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General Labeling Considerations

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Prescription drug labeling is intended to provide a summary of the essential scientific information needed for the safe and effective use of a drug, so that clinicians are able to make informed prescribing decisions. The CFR§ Sec. 201.56 states that labels meet the following requirements: (1) The label must contain a summary of the essential scientific information needed for the safe and effective use of the drug. (2) The label must be informative and accurate and must be updated when new information becomes available. (3) The label must be based where possible on data derived from human experience and no claims may be made if there is inadequate evidence of safety or lack of efficacy.

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Currently, pharmacogenomic information appears in the labeling of dozens of drugs, covering nearly all therapeutic areas (Fig. 3-1; a comprehensive listing of these labels can be found on the FDA website). To date, most pharmacogenomic labeling has focused on drugs ...

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