FDA releases tables on the use of pharmacogenetic testing for specific medications

CPIC and PharmGKB applaud the release of additional guidance from the FDA on the use of pharmacogenetic testing for specific medications. Numerous members of the pharmacogenetics implementation community have asked CPIC and PharmGKB for our views on the FDA release and we identify some similarities and differences below.

There are substantial areas of overlap in those gene/drug pairs that CPIC/PharmGKB and FDA consider clinically actionable. There are also a few discordances between FDA’s table and CPIC guidelines and CPIC’s classification of gene/drug pairs as level A or B (i.e. clinically actionable). For example, CPIC recommends avoiding phenytoin for phenytoin-naïve patients with HLA-B*15:02, while phenytoin is not listed yet on the FDA tables. There are also instances in which the FDA’s table states “Refer to FDA labeling for specific dosing recommendations,” but the FDA label doesn’t include specific guidance on how much to reduce dosage or provide explicit dosing recommendations (e.g. azathioprine), information which CPIC guidelines often provide.

PharmGKB clinical annotations are based on the evaluation of published literature.  CPIC guidelines are based on evidence which is referenced in detail as part of each guideline, with expert evaluation of published literature that supports (or refutes) prescribing recommendations. At this time, it is not clear what evidence has been used by FDA to construct their tables of recommendations. It would be informative to include citations to evidence supporting these FDA tables of associations for use by others in the community.

CPIC and PharmGKB are evaluating the recent tables provided by the FDA to identify the differences between these tables and the content of the PharmGKB clinical annotations, PharmGKB annotations of the labels on the FDA Biomarker table, and CPIC guidelines.  

CPIC and PharmGKB look forward to continuing to work with the FDA and the scientific community to provide evidence-based pharmacogenetic prescribing guidelines.