Summary of the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling
Kristen K. Reynolds, PhD
Sarah Schroer, PharmD
August 30, 2016
This is a list of medications approved by the FDA which have pharmacogenetic information in the product labeling or the drug package insert. The table includes generic drug name, the therapeutic area with which the drug is most commonly associated, the gene (biomarker) referenced in the package insert, and the section of the drug label where that information can be found.
To date (list version 8/23/16), there are 164 unique drugs listed with some having multiple entries for multi-gene information. The table is periodically updated, so the newest drugs with PGx information may not yet be listed. For example, Rexulti (brexpiprazole) was approved in July 2015 with CYP2D6 gene-dose information, but was not added to the table until almost a year later during an update.
You can follow a link to a medication’s monograph directly from the FDA biomarkers table by clicking on the drug’s generic name listed in the table. The table can be sorted by any of the column headers for ease of use. Want to know how many drugs have labels referencing CYP2D6 in some way? Just sort by biomarker.
The labeling section is a key aspect of this list. It tells you exactly where to look in the drug’s package insert to find the information. This is where it gets tricky…not all of the drugs in this table are DIRECTLY affected by the pharmacogenetic biomarker listed in the table. The type and clinical relevance of biomarker information found in these different labels varies. Read more for examples.
SPECIFIC GENOTYPE-BASED DRUG DOSING: the pharmacogenetic biomarker (gene) listed in the table has variants that affect the given drug’s safety or efficacy, and dosage.
- Example: aripiprazole CYP2D6 Poor Metabolizers should take half of the standard dose. (Abilify monograph “Dosage and Administration” section)
- Example: citalopram CYP2C19 Poor Metabolizers should not exceed 20 mg/day. (Celexa monograph“Clinical Pharmacology” section)
NON-RELEVANT GENOTYPES: some labels have a gene biomarker listed in the FDA table, but the detail shows that the gene is NOT relevant for that drug
- Example: citalopram’s second entry for CYP2D6. The“Clinical Pharmacology” section states:
Citalopram steady state levels were not significantly different in poor metabolizers and extensive metabolizers of CYP2D6.
This demonstrates that CYP2D6 has no relevance for citalopram. Thus, although there is information about CYP2D6 poor metabolizers in the citalopram package insert, and it is listed in the FDA Biomarkers Table, the citalopram-CYP2D6 drug-gene pair is not clinically meaningful.
- Example: prasugrel has four entries – CYP2C19, CYP2C9, CYP3A5, CYP2B6. The “Use in Specific Populations” section in the Effient (prasugrel) insert says:
There was no relevant effect of genetic variation in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 on the pharmacokinetics of prasugrel’s active metabolite or its inhibition of platelet aggregation.
In other words, none of the four genetic biomarkers listed for prasugrel should be used to predict prasugrel safety or efficacy.
DRUG INTERACTIONS: some labels include pharmacogenetic information that apply to drug interactions rather than the primary metabolism of the given drug.
- Example: escitalopram CYP2D6 Poor Metabolizers. The Lexapro (escitalopram) monograph “Drug Interactions” section mentions the following with regard to an escitalopram – CYP2D6 interaction:
In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers. There are…data suggesting a modest CYP2D6 inhibitory effect for escitalopram…caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.
This is an important example. Escitalopram is metabolized by CYP2C19 but has a modest inhibitory effect on CYP2D6. Thus, the FDA table listing of escitalopram and CYP2D6 indicates drug interaction potential, not a primary metabolic effect for escitalopram itself.
In summary, the FDA Pharmacogenetic Biomarkers table is an excellent resource for many drugs with pharmacogenetic relevance. Its limitations include frequency of table updates, updates being limited to drug labeling without regard for newer (post-market) clinical data, lack of consistency for the type of pharmacogenetic information included, and genetic markers listed for drugs which may not be directly affected by that gene. Package insert citations for all drug-gene pairs listed should be carefully reviewed in order to avoid accidental misinterpretation.
The PGXL PRIMER system accounts for these known pharmacogenetic markers, as well as established drug-drug interactions to provide the most comprehensive reports to guide therapeutic management decisions.
©PGXL Laboratories 2016