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.