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Impact of Safety-Related Regulations on Codeine Use in Children: A Quasi-Experimental Study Using Taiwan’s National Health Insurance Research Database

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Abstract

Introduction

Safety 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.

Objective

We 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.

Methods

A 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.

Results

The 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.

Conclusions

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.

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Acknowledgements

The authors thank the NHIA and NHRI for making available the databases for this study; however, the content of this article in no way represents any official position of the NHIA or NHRI.

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Authors and Affiliations

  1. Taiwan Drug Relief Foundation, Taipei, Taiwan

    Chih-Wan Lin, Ching-Huan Wang, Wei-I Huang, Wei-Ming Ke, Pi-Hui Chao & Wen-Wen Chen

  2. Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Room 220, 33, Linsen S. Rd, Taipei, 10050, Taiwan

    Fei-Yuan Hsiao

  3. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

    Fei-Yuan Hsiao

  4. Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan

    Fei-Yuan Hsiao

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  1. Chih-Wan Lin
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  2. Ching-Huan Wang
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Correspondence to Fei-Yuan Hsiao.

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Funding

This work was supported by a research grant from the Food and Drug Administration, Ministry of Health and Welfare (MOHW), Taiwan (MOHW 105-FDA-D-113-000411). The funding source had no role in the design and conduct of the study; collection, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Conflict of interest

Chih-Wan Lin, Ching-Huan Wang, Wei-I Huang, Wei-Ming Ke, Pi-Hui Chao, Wen-Wen Chen, and Fei-Yuan Hsiao have no conflicts of interest that are directly relevant to the content of this study.

Ethical approval

This study was approved by the Institutional Review Board of the National Taiwan University Hospital (201601018RIND). Informed consent was waived since the identification information in Taiwan’s National Health Insurance Research Database is encrypted to ensure privacy.

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Lin, CW., Wang, CH., Huang, WI. et al. Impact of Safety-Related Regulations on Codeine Use in Children: A Quasi-Experimental Study Using Taiwan’s National Health Insurance Research Database. Drug Saf 40, 615–627 (2017). https://doi.org/10.1007/s40264-017-0524-3

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