Summary Aims Allopurinol carries a well‐known risk of cutaneous adverse reactions (CARs). Although febuxostat, a xanthine‐oxidase inhibitor with different chemical structure, has been considered an alternative to allopurinol, post‐marketing case reports of life‐threatening febuxostat‐related CARs have been reported. We aimed to compare the risk of CARs between allopurinol and febuxostat in real‐world settings and to assess the impact of the market entry of febuxostat on allopurinol use and associated CARs. Methods A nationwide study was conducted using Taiwan's National Health Insurance Research Database. In the new‐user cohort study, patients who received their first prescriptions of allopurinol or febuxostat were included, and Poisson regression was used to estimate the incidence rate ratios (IRRs) of CARs. In the interrupted time series analysis, time series data on new users and incidence rate of CARs were divided into three periods based on the reimbursement scheme of febuxostat in Taiwan, and segmented regression models were used to estimate changes in both the level and trend in each period. Results We identified 526 cases of CARs with 487 among new users of allopurinol and 39 among new users of febuxostat (incidence rate: 15.37 vs 3.48 per 1000 person‐years). Allopurinol was associated with higher risk of CARs (adjusted IRR 5.55, 95% CI [3.97‐7.76]), mild CARs (1.86, [1.24‐2.81]), severe CARs (16.75, [8.87‐31.62]) and fatal CARs (16.18, [5.05‐51.83]) than febuxostat. The overall incidence rates of xanthine‐oxidase inhibitor‐related CARs decreased from 15.28 to 14.28 per 1000 person‐years after the initial reimbursement of febuxostat and further decreased to 9.46 after the reimbursement coverage of febuxostat expanded; however, the changes were not statistically significant. Conclusion Febuxostat can be considered an alternative for patients carrying risk factors for allopurinol‐related CARs. However, since there were fatal cases of febuxostat‐related CARs, the closely monitoring of symptoms of CARs during the initiation of febuxostat is still warranted.

Objective: After discovering the association between the HLA-B*15:02 allele and carbamazepine-related severe cutaneous adverse reactions (SCARs), particularly in Southeastern Asian populations, clinical strategies to prevent carbamazepine-related SCARs have changed. We aimed to investigate 10-year trends in carbamazepine use and carbamazepine-related SCARs and to examine the patterns and determinants of HLA-B*15:02 screening in Taiwan. Methods: A nationwide study was performed using Taiwan's National Health Insurance Research Database. In the first part of the study, new users of carbamazepine were included, and those who experienced SCAR-related admissions were further identified. In the second part of the study, recipients of HLA-B*15:02 screening (reimbursed by Taiwan's National Health Insurance since June 2010) were included and multivariate logistic regression was used to explore factors associated with the use of screening. Results: The numbers of new users of carbamazepine and SCAR cases decreasedremarkably during the 10-year period (−82.6% and −87.1%, respectively), and the incidence rates of SCARs showed a downward trend after 2011. The screening rate of the HLA-B*15:02 allele increased to 24.9% in 2014. Neurologists (odds ratio 12.33, 95% confidence interval 9.30-16.35), psychiatrists (9.97, 7.31-13.61), and neurosurgeons (3.23, 2.42-4.32) were more likely to perform screening tests than other specialties were. Physicians practicing in medical centers (6.00, 5.51-6.54) were more likely to perform screening tests than those practicing in other hospitals, whereas the screening rates in clinics remained at 0.0% throughout the study period. Significance: In recent years, the number of carbamazepine-related SCAR cases has decreased substantially in Taiwan. However, only one-fourth of new users of carbamazepine received HLA-B*15:02 screening, and there were considerable disparities in the screening rates across different physician groups. Policymakers should consider solutions to barriers to implementing screening tests in clinical practice and should not neglect the value of other safety communications and regulations to complement the limitations of pharmacogenomic testing. K E Y W O R D S antiepileptic drugs, pharmacogenomic testing, Stevens-Johnson syndrome/toxic epidermal necrolysis

Further research is required to evaluate the direct impacts of the safety announcements on clinical outcomes, treatment costs, and patient's quality of life.

Our study provides a successful example of how to effectively reduce the codeine prescriptions in children in the 'real-world' settings, and highlights areas where future effort could be made to improve the safety use of codeine. Future research is warranted to explore whether there was a simultaneous decrease in the incidence rates of codeine-related adverse events following the safety-related regulations.

Purpose: Real-world evidence has become increasingly relevant in regulatory decision making. Compared to large regulatory bodies, the national pharmacovigilance system in Taiwan is still under development, and the aim of this study is to demonstrate how a resource-limited health authority utilizes real-world evidence in decision making. Methods: We described different sources of real-world data available in Taiwan and illustrated the structural framework that integrates real-world evidence into Taiwan's national pharmacovigilance system. Additionally, we reviewed real-world studies conducted in the past 10 years and provided examples to show how these studies influenced drug safety-related decision making in Taiwan. Results: During the past 10 years, real-world evidence used when making drug safety-related regulatory decisions in Taiwan was mainly generated from nationwide claims databases, but other sources of real-world data, such as national registries and large electronic hospital databases, also became available recently. Different types of real-world evidence, including drug utilization studies, risk evaluation studies, and risk minimization measure evaluation studies, have been used to support regulatory decisions in Taiwan. Conclusions: Through collaborations between the government and academics, Taiwan has started to integrate real-world evidence into the national pharmacovigilance system. However, future efforts, including linkages between different sources of real-world data and improvements in procedural and methodological practices, are needed to generate more regulatory-quality real-world evidence.