Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol: Nested Case-Control and Case-Time-Control Studies

Abstract

Purpose: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea re-quested a post-marketing surveillance study to investigate its safety profile. Materials and Methods: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens–Johnson syndrome (SJS), using the claims database of South Korea, 2010–2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respec-tively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. Results: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small num-ber of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71–3.62). In the CTC de-sign, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09–3.47). Conclusion: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphy-laxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.