Comparison of FDA Table of Pharmacogenetic Associations and Clinical Pharmacogenetics Implementation Consortium guidelines

Abstract

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Healthcare professionals need a clear understanding of information about gene-drug interactions in order to make optimal use of pharmacogenetic (PGx) testing. In this report, we compare PGx information in the US Food and Drug Administration (FDA) Table of Pharmacogenetic Associations with information presented in Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Summary Information from CPIC guidelines and the FDA Table of Pharmacogenetic Associations do not have a high level of concordance. Many drugs mentioned in CPIC guidelines are not listed in the FDA table and vice versa, and the same gene-drug association and dosing recommendation was reported for only 5 of the 126 drugs included in either source. Furthermore, classification of drugs in specific sections of the FDA table does not correlate well with CPIC-assigned or provisionally assigned clinical actionability levels. The Pharmacogenomics Knowledge Base (PharmGKB) clinical annotation levels are generally high for drugs mentioned in CPIC guidelines. PharmGKB clinical annotation levels are often unassigned or are lower level for drugs listed on the FDA table but not in CPIC guidelines. These differences may be due in part to FDA having access to PGx information that is unavailable in published literature and/or because PGx classifications are based on criteria other than clinical actionability. Conclusion There are important differences between the PGx information presented in the FDA Table of Pharmacogenetic Associations and in CPIC guidelines. FDA and CPIC have different perspectives when evaluating PGx associations and use different approaches and information resources when considering clinical validity related to specific medicines. Understanding how information sources developed by each group differ and can be used together to form a holistic view of PGx may be helpful in increasing adoption of these information sources in practice.

Precision dosing for patients on tricyclic antidepressants

“…To identify inhibitors and inducers, the authors adopted the ‘List CYP inhibitors/inducers’ from the Food and Drug Administration (FDA) website [13]. In addition, the ‘Comparison of FDA Table of Pharmacogenetic Associations and Clinical Pharmacogenetics Implementation Consortium guidelines’ [14] was also examined.…”

“…Table of Pharmacogenetic Associations and ClinicalPharmacogenetics Implementation Consortium guidelines'[14] was also examined.…”

Most patients with disorders of gut‐brain interaction receive pharmacotherapy with major or moderate drug‐gene interactions

“…First, we used the RightMed Comprehensive Test Report categories of predicted drug‐gene interactions: none, minimal, moderate, and major drug‐gene interactions. Second, we integrated the widely accepted Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 and CYP2C19 , which infer the metabolizer phenotype from allelic variants of these genes, 22 with the widely used Flockhart Table 23 that provides a list of medications that are metabolized by cytochrome P450 enzymes (Figure 1). 24 CPIC guidelines categorize CYP2D6 and CYP2C19 metabolizer phenotypes as follows: ultrarapid metabolizer (UM), normal metabolizer (NM), intermediate metabolizer (IM), and poor metabolizer (PM).…”

Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology

“…113 Previous research has highlighted discrepancies and levels of concordance among the various consortia, regulatory agencies, and drug labels. 70,71 For example, an evaluation of 54 drugs known to have an actionable gene/drug interaction by CPIC guidelines found that only half had actionable information within the drug label. 71 Furthermore, only 18% of the drugs had agreement across regulatory agencies, including FDA and European Medicines Agencies.…”