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Pediatric Codeine Prescriptions in Outpatient and Inpatient Settings in Korea
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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.
Measurements

Pediatric patients were defined as patients younger than 12 years. Pediatric codeine use was defined as the prescribing of codeine for children younger than 12 years. The proportion of pediatric patients who received a prescription for codeine was calculated by dividing the number of codeine users younger than 12 years by the number of total pediatric patients. The proportion of pediatric codeine users was calculated by patient setting (outpatient vs inpatient). The frequency and proportion of pediatric codeine use were analyzed by age group (0-2, 3-6, and 7-11 years), year, region, diagnosis, type of medical institution, and coprescribed medication.

The quarterly proportion of patients treated with codeine was plotted for inpatients and outpatients younger than 12 years. In addition, the quarterly proportion of patients treated with antibiotics was plotted to examine if it coincided with the proportion of codeine prescriptions according to seasonality. The numbers of pediatric patients and of pediatric codeine users were calculated by age group, sex, region, and clinical specialty. Pediatric patients were divided into 3 age groups (0-2, 3-6, and 7-11 years). Region was classified as metropolitan, city, or rural. Based on the classification of administrative regions provided by the government, we classified 5 megacities with surrounding satellite towns as metropolitan areas. Clinical specialties were grouped into pediatrics and nonpediatrics. The type of medical institution was divided into tertiary hospitals, general hospitals, clinics, and public hospitals.

Statistical Analysis

The Mantel-Haenszel χ2 test was performed for categorical data. Multivariate logistic regression was performed to identify characteristics associated with pediatric codeine prescriptions in each patient setting (outpatient and inpatient). Independent variables were sex, region, diagnosis, type of medical institution, and coprescribed medication. An adjusted odds ratio (OR) with 95% CI was calculated for each variable. All statistical analyses were performed using SAS version 9.3 (SAS Institute Inc; Cary, North Carolina). The study protocol was approved by the Sungkyunkwan University Institutional Review Board (IRB No. 2016-10-015).

RESULTS

A total of 929,358 and 957,746 patients younger than 12 years were treated in outpatient and inpatient settings, respectively, between 2011 and 2016 (Table 1). Of these patients, 518,895 (55.8%) and 16,337 (1.7%) patients were codeine users in those settings. The mean ages of these users were 5.5 and 4.2 years, respectively. Infants 2 years and younger comprised 22.7% and 40.3% of all pediatric codeine users in the outpatient and inpatient settings, respectively. In the outpatient setting, 51.1% of pediatric codeine users were treated in metropolitan areas. The most frequent diagnoses for pediatric codeine users were acute bronchitis (83.4% of outpatients and 91.0% of inpatients) and acute upper respiratory infection (81.0% and 88.6%, respectively). Antibiotics were coprescribed in 76.8% and 73.7% of outpatients and inpatients, respectively. In the outpatient and inpatient settings, 82.9% and 48.1% of pediatric codeine users were treated at clinics.

In both outpatient and inpatient settings, boys were as likely to be prescribed codeine as girls (Table 2). The odds of pediatric codeine prescribing in the outpatient setting were higher in nonmetropolitan areas than in metropolitan regions. Children diagnosed with acute upper respiratory infection were 1.62 to 2.22 times more likely to be prescribed codeine than those without the diagnosis. Pediatric outpatients were more likely to receive codeine at clinics (adjusted OR, 1.19; 95% CI, 1.16-1.21) and public hospitals (adjusted OR, 1.56; 95% CI, 1.28-1.91) than at tertiary hospitals; inpatients were more likely to receive codeine at public hospitals (adjusted OR, 8.38; 95% CI, 6.64-10.58) than at tertiary hospitals. The odds of pediatric codeine prescriptions were increased with coprescribing of antibiotics but were decreased with coprescribing of opioid analgesics in both settings.

The proportion of pediatric patients treated with codeine showed little change in the temporal trend (Figure). The proportion of patients prescribed antibiotics tended to fluctuate together with the proportion of pediatric outpatients prescribed codeine. There appears to be seasonality for the proportion of outpatient codeine users.

DISCUSSION

By analyzing population-based National Health Insurance claims data, we showed that 55.8% and 1.7% of patients younger than 12 years were treated with codeine in the outpatient and inpatient settings, respectively. The extent of codeine prescriptions for children appears to be remarkably higher in Korea than in other countries. Between 2000 and 2005, the prescription rate of codeine for children younger than 12 years by primary care providers in the United Kingdom was 0.11 patients per 1000 person-years, whereas the rate was 1.32 in adolescent patients aged 12 to 17 years.4 The prescription rate of codeine for children in the ED in the United States was 3.3% in patients aged 3 to 7 years and 4.5% in those aged 8 to 12 years.19 Another US study showed that although an acetaminophen–codeine combination was among the most frequently used drugs among all hospitalized patients, it was not frequently used for patients younger than 12 years.23

We showed that codeine was frequently prescribed in primary care clinics in the Korean outpatient setting. Codeine was frequently prescribed for treatment of upper respiratory infections, acute bronchitis, and asthma. Moreover, children who were prescribed antibiotics were more likely to be prescribed codeine than those who were not. Simultaneous fluctuations in the proportion of codeine users in the outpatient setting and the proportion of antibiotic users revealed that codeine was used to treat upper respiratory infections. These findings suggest that codeine was used as an antitussive agent. The prevalence of bronchitis and asthma is high among children with the common symptom of cough and, therefore, codeine is commonly used in children as an antitussive agent.24 Codeine has long been recommended as an antitussive agent that acts in the central nervous system against acute and chronic cough among children.25-27 However, evidence exists that codeine should not be used for cough due to pneumonia in infants owing to the risk of toxicity.28 Our findings and those of other studies suggest that physicians should be guided against prescribing codeine for children in the outpatient setting based on recent evidence and international guidelines.


 
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