Opioids in the Brazilian Healthcare Landscape: Crucial Analysis through Anvisa VigiMed Data and Pharmacogenetic Aspects

Abstract

Adverse Drug Reactions (ADRs) present a significant challenge to healthcare systems, contributing substantially to hospital admissions. Opioid analgesics are widely used in the pharmacological treatment of various types of pain; however, ADRs represent a major limitation to their use. This study aims to investigate the profile of ADRs reported in Vigimed (the official Brazilian ADR reporting system) following the implementation of active surveillance through pharmacovigilance trackers. Additionally, it evaluates pharmacogenetic evidence to identify genes potentially involved in opioid-related ADRs. This retrospective cross-sectional study analyzed ADR cases reported to Vigimed from January 2018 to April 2023. Data were extracted from Vigimed, tabulated, and subjected to statistical analysis, using the reporting odds ratio (ROR) to assess the strength of associations between opioids and ADRs. During the study period, there were 238,363 ADR reports, of which 6,001 were related to opioid treatment. The distribution among opioids was as follows: 36.7% morphine, 32.4% tramadol, 21.6% fentanyl, 5.4% methadone, 3.7% codeine, and 0.2% oxycodone. The most frequent adverse events associated with opioids were cardiac disorders (ROR 1.70), skin and subcutaneous tissue disorders (ROR 2.18), gastrointestinal disorders (ROR 2.88), and nervous system disorders (ROR 1.19). Furthermore, pharmacogenetic evidence indicates that the CYP2D6 gene has a Level 1 association for codeine and tramadol and a Level 2 association for oxycodone. These findings highlight significant associations between specific opioids and ADRs, emphasizing the influence of genetic variations on adverse reactions and the need for personalized medicine in pain management.