The Burden of Adverse Drug Reactions in Africa in the Context of Pharmacogenetics-Based Clinical Guidelines.

Genetic variation has a significant impact on patients' response to medicines. Variations in important pharmacogenes have been evaluated in several studies and consequently led to international guidelines from clinical pharmacogenomics consortia. However, there are limited examples of these being implemented across the African continent despite the increased evidence of how these variants contribute to adverse drug reactions (ADRs) or ineffective treatments. Considering the vast genetic diversity in Africa, there are significant gaps in understanding how much of a negative effect this might be having across healthcare across the continent. We therefore sought to establish the extent of ADRs from a subset of medicines shown to be associated with pharmacogenetic biomarkers from the last 10 years across 47 countries on the African continent. In the absence of pharmacogenetic testing on the African continent, we used international guidelines to derive a subset of definitions associated with published drug-gene-interaction associated ADRs to infer the role of pharmacogenetic variation on the prevalence of ADRs. The data showed that African countries report only 1% of ADRs in the VigiBase database, indicative of weak pharmacovigilance programs on the continent. Our analysis revealed that ADRs were mainly caused by anti-infectives such as efavirenz. The inferred pharmacogenes associated with high prevalence of ADRs were CYP2B6, CYP2D6, and CYP2C19. Using limited data, this foundational analysis may serve as the basis for stakeholders to prioritize pharmacogenetic interventions across the African continent.