• Chih-Wan Lin, Ching-Huan Wang, Wei-I Huang, Wei-Ming Ke, Pi-Hui Chao, Wen-Wen Chen, and Fei-Yuan Hsiao.
• Taiwan Drug Relief Foundation, Taipei, Taiwan.
• Drug Saf. 2017 Jul 1; 40 (7): 615-627.

IntroductionSafety concerns regarding potential life-threatening adverse events associated with codeine have resulted in policy decisions to restrict its use in pediatrics. However, whether these drug safety communications have had an immediate and strong impact on codeine use remains in question.ObjectiveWe aimed to investigate the impact of the two implemented safety-related regulations (label changes and reimbursement regulations) on the use of codeine for upper respiratory infection (URI) or cough.MethodsA quasi-experimental study was performed using Taiwan's National Health Insurance Research Database. Quarterly data of codeine prescription rates for URI/cough visits were reported, and an interrupted time series design was used to assess the impact of the safety regulations on the uses of codeine among children with URI/cough visits. Multivariable logistic regression models were used to explore patient and provider characteristics associated with the use of codeine.ResultsThe safety-related regulations were associated with a significant reduction in codeine prescription rates of -4.24% (95% confidence interval [CI] -4.78 to -3.70), and the relative reduction compared with predicted rates based on preregulation projections was 60.4, 56.6, and 53.2% in the first, second, and third year after the regulations began, respectively. In the postregulation period, physicians specializing in otolaryngology (odds ratio [OR] 1.47, 95% CI 1.45-1.49), practicing in district hospitals (OR 6.84, 95% CI 5.82-8.04) or clinics (OR 6.50, 95% CI 5.54-7.62), and practicing in the least urbanized areas (OR 1.60, 95% CI 1.55-1.64) were more likely to prescribe codeine to children than their counterparts.ConclusionsOur 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.

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