Purpose: This study aims to investigate the potential causal relationship between the use of indapamide and rhabdomyolysis. Previous research and pharmacovigilance monitoring activities have suggested a potential association between indapamide use and rhabdomyolysis. However, limited information is available on this association. Methods: A case-control study conducted using EHR data, between July 1,2016, and December 31,2022. Patients who have rhabdomyolysis event (cases) were matched to four controls bases on age, gender and date. We examined the odds for indapamide exposure through three risk periods: current use, recent use, and former. The study outcome was ascertained through the presence of CK level over 1,000 U/L (i.e. rhabdomyolysis event). Subsequently, a multivariable conditional logistic regression analysis was utilized to assess the causal impact of indapamide exposure on the likelihood of developing rhabdomyolysis, while accounting for potential confounding variables. Results: The study population consisted of 2,965 cases and 11,860 controls. The results of the conditional logistic regression analysis indicated a lack of association between exposure to indapamide for the current users the OR was 0.7 (95% CI: 0.49 - 0.92) and the AOR was 0.6 (95% CI: 0.39 - 1.05). The recent users showed OR of 0.9 (95% CI: 0.56 - 1.50) and AOR of 0.2 (95% CI: 0.14 - 0.47). Lastly, the former users demonstrated an OR of 0.8 (95% CI: 0.47 - 1.26), and AOR of 0.1 (95% CI: 0.07 - 0.23). Conclusions: In this study, we did not find association between indapamide use and rhabdomyolysis regardless timing of exposure.

Aim: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. Methods: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. Results: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). The majority of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 x 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n=21 [41.2%]). Conclusion: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials, and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.