Pharmacogenomics in clinical practice: Biomarker information in Brazilian drug labels

This review examines the PGx annotations in package inserts (bulas in Brazilian Portuguese) approved by ANVISA, the Brazilian Health Regulatory Agency, for 19 gene-drug pairs with strong or moderate recommendations for initial dosing alteration in the CPIC (Clinical Pharmacogenetic Implementation Consortion) guidelines and PGx testing required or recommended by health regulatory agencies listed in the PharmGKB Drug Label Annotations table. It is assumed that drug-gene pairs with these two features should be prioritized for adoption by the Brazilian Public Health System (SUS). PGx annotations were distributed across seven of the ten sections of the bulas and classified as PGx testing required (n = 5), PGx testing recommended (n = 5), actionable PGx (n = 4) and no PGx clinical information (n = 4). Pairwise comparison of assigned PGx levels in ANVISA bulas vs. the selected regulatory agencies revealed poor concordance (Cohen's kappa coefficient κ < 0.20 for all pairs); however, discordance among these agencies is also considerable (Fleiss's kappa coefficient κ = 0.08). The frequency of the examined PGx risk biomarkers in representative Brazilian cohorts range from <0.1% to 10.8%. Importantly, Native Americans (0.4% of the current Brazilian population), display wide PGx diversity, both interethnically and in relation to non-Indigenous Brazilians. The author suggests that addition of a PGx section to the ANVISA bulas would avoid dispersion of clinically relevant PGx information across sections, assure integration of this information with SUS determinations and prevent discrepancies across sections, as observed in the bulas for thiopurines.