Impacts of labelling revisions on pediatric use of codeine: interrupted time-series analysis using the Japanese nationwide claims database

Introduction The use of codeine in children aged < 12 years has been restricted in Japan since July 2017 due to safety concerns. Objective We aimed to investigate the impacts of two labelling revisions restricting codeine use in children on the trends in its prescriptions in Japan. Methods Children aged < 12 years (target group) and 12-17 years (control group) registered in the Japanese health insurance claims database between August 2015 and July 2021 were included. We analyzed the level and trend changes in monthly prescriptions of codeine and non-narcotic antitussives (reference) per 100,000 individuals using an interrupted time-series design across there period: the pre-intervention (before the first revision in July 2017), post-intervention (after the second revision in July 2019), and transitional (between the two revisions) periods. Results There was a significant reduction in codeine prescriptions of 67.5% and 36.6% in the first labelling revision in the target and control groups, respectively. In the target group, a downward trend in the level of codeine prescriptions was observed until the end of the transitional period. After the second labelling revision, the level of codeine prescriptions decreased by approximately 95% compared with the last month of the pre-intervention period. For non-narcotic antitussives, there were no significant changes in the level and trend of prescriptions until the transitional period, but the trend significantly changed to negative after the second labelling revision. Conclusion Restriction on codeine use in children by the labelling revisions could be effective for reducing codeine prescriptions in patients aged < 12 years.