Abstract
BACKGROUND: Direct-acting antivirals (DAAs) have transformed the treatment of hepatitis C infection (HCV) globally. Exploratory studies to identify potential rare adverse drug events associated with DAAs to optimize their use are scarce. OBJECTIVE: We aimed to describe the most common serious DAA-associated adverse drug reaction (ADR) reports overall and by DAA regimen. METHODS: We conducted a cross-sectional analysis of post-market ADRs associated with DAA therapy using VigiBase, the global database of the WHO Programme for International Drug Monitoring. Reports occurring between 2013 and 2020 in which an eligible DAA brand or regimen was reported as the suspect drug were included and described. Reports of concomitant ribavirin or interferon use were excluded. The top 25 events for all reports where the outcome was indicated as 'serious' or 'life-threatening' were described overall and by drug regimen. RESULTS: We identified 56 636 global ADR reports [45% women, 38% ledipasvir/sofosbuvir use, 67% from USA/Canada, average patient age 57 (SD 13) years]. Overall, 3.8% of reports described a life-threatening event or death. Unexpected ADRs included major pulmonary (dyspnea, pneumonia, and respiratory failure) and cardiac (myocardial infarction and cardiac arrest) events. COMMENT: When examining all serious ADRs for DAAs globally, unexpected pulmonary and cardiac events were identified and may be of interest for further research on DAA safety. Future studies must examine population-level risk of ADRs for DAA therapies while accounting for confounding by indication, comorbidities, and stage of HCV disease.