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Pediatric Codeine Prescriptions in Outpatient and Inpatient Settings in Korea

Dajeong Kim, MS; Inmyung Song, PhD; Dongwon Yoon, PharmD; and Ju-Young Shin, PhD
Codeine was frequently prescribed for children in Korea despite the actions taken to restrict its use in that age group in Korea and other countries.
Our findings showed that in both outpatient and inpatient settings, the proportion of pediatric patients who were prescribed codeine was lower in 2013 than in 2011 and 2012, which may be attributable to a safety letter issued by the Ministry of Food and Drug Safety of Korea in 2012.13 After a slight uptick in 2014, the proportion fell back to even lower levels in 2015 and 2016, suggesting the possible impact of the label change in November 2014. Nonetheless, the extent of codeine prescriptions for children younger than 12 years remained substantial; approximately half of pediatric outpatients were treated with codeine in 2015 and 2016 after the label change. These findings highlight the need for more efforts to reduce pediatric codeine use in Korea. Similarly, since the release of the 2006 guidelines on codeine use among children by the American Academy of Pediatrics in the United States, prescribing of codeine for children and adolescents 17 years and younger did not decrease much.19 In contrast, the prescription rate of codeine decreased by approximately 60% in Italy after the issuance of a safety letter against use of codeine in infants younger than 2 years in 2007.29

The results of the logistic regression analysis showed that pediatric codeine use tends to be greater in public hospitals than in tertiary hospitals in both outpatient and inpatient settings and that outpatient codeine use is higher in clinics and in tertiary hospitals. Our findings also showed that pediatric outpatients are more likely to be treated with codeine in metropolitan areas than in nonmetropolitan areas; the reverse is true for pediatric inpatients. These findings highlight the areas of intervention for clinical practice change. Efforts to improve prescribing behaviors should be directed toward clinics where a majority of pediatric patients were treated with codeine in the outpatient setting. Furthermore, efforts should be focused on outpatient use of codeine in the metropolitan areas.

Strengths and Limitations

By using population-based insurance claims data, this study analyzed the patterns of codeine prescriptions in children younger than 12 years in Korea. All drugs containing codeine in Korea are prescription-only medications and use of these drugs is recorded in the HIRA database used for this study. This makes it possible to accurately measure children’s exposure to these drugs. Nonetheless, this study also has limitations. First, although we showed that the proportions of pediatric patients treated with codeine tended to decrease in 2015 and 2016, these findings are only descriptive. Second, it is possible that codeine may have been prescribed as a nonreimbursable drug in the ED. Furthermore, the use of codeine for which claims have not been filed to the payer would not have been captured in the HIRA database. If children younger than 12 years visit the ED more frequently than older patients, this study may have underestimated the use of codeine prescriptions for children. Third, our finding of the high proportion of pediatric patients who were prescribed codeine in the outpatient setting should be interpreted with caution due to the actual practice of patient care in Korea. All patients who receive injectable drugs are classified as inpatient, and injectable use is high in Korea.

Despite these limitations, this study generated valuable evidence that codeine has been widely prescribed for children younger than 12 years in Korea, especially in the outpatient setting, even after the 2014 label change. Our findings suggest that various efforts to further limit pediatric use of codeine should be developed and implemented. One such measure shown to be effective in the United States was a clinical intervention program including prescriber education.30 The effective use of nonopioid analgesics may significantly reduce or even eliminate the need for opioids such as codeine.15 Healthcare providers should be guided on alternative pain management in children based on recent evidence on safety and efficacy.31 Based on our findings, such efforts to restrict prescriptions of codeine among young patients should not only reach major sources of prescriptions, such as metropolitan areas, but also include general hospitals and clinics in nonmetropolitan areas in Korea. Meanwhile, informing parents of pediatric patients about the risks of pediatric codeine use may also be helpful to influence clinical practice. In addition, it is important on the nationwide level to systematically monitor codeine use and harms in the pediatric population and to develop policy measures to encourage healthcare providers to comply with contraindication of codeine in pediatric patients for analgesic and antitussive effects; an example would be limiting reimbursement for off-label use of codeine.

CONCLUSIONS

The guidelines published by many international and national organizations based on risk-benefit assessment of codeine recommend that codeine should not be prescribed for children younger than 12 years. This study showed that codeine was frequently prescribed for children younger than 12 years despite the actions taken to restrict the use of codeine in that age group in Korea as well as in many other countries. Children were more likely to be treated with codeine at clinics and public hospitals in the outpatient setting. Our findings suggest that codeine is used for its antitussive effect among children in the outpatient setting. Further efforts to limit codeine use, especially as an antitussive agent in primary care clinics in the outpatient setting, are needed to prevent the occurrence of codeine toxicity events among children younger than 12 years.

Acknowledgments

No specific funding was granted. Ms Kim and Dr Song wrote the first draft of the manuscript and are listed as co–first authors. Each author listed in the byline has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript.

Author Affiliations: School of Pharmacy, Sungkyunkwan University (DK, DY, JYS), Suwon, Gyeonggi-do, Korea; Kongju National University, College of Nursing and Health (IS), Gongju, Korea.

Source of Funding: None.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (DK, JYS); acquisition of data (DK, IS); analysis and interpretation of data (DK, IS, DY); drafting of the manuscript (DK, IS); critical revision of the manuscript for important intellectual content (DY); statistical analysis (DK, DY); administrative, technical, or logistic support (JYS); and supervision (JYS).

Address Correspondence to: Ju-Young Shin, PhD, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, South Korea. Email: shin.jy@skku.edu.
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