Nationwide patterns of long-term ranitidine use and its associated factors in Korea

초록

Background: Ranitidine, a histamine H2-receptor antagonist, has recently been recalled due to contamination with N-nitrosodimethylamine. Because ranitidine is used for both for treatment of gastrointestinal disorders and for gastroprotection in long-term NSAIDs use in some chronic diseases, it is necessary to identify the nationwide patterns of long-term use. Objectives: To assess patterns of long-term ranitidine use and factors affecting the long-term prescribing in the Korean population. Methods: We analyzed prescribing patterns of ranitidine and characteristics of long-term users using Korea Health Insurance Review and Assessment database between 2007 and 2018. We calculated the annual number of patients who received ranitidine, and each patient's total prescription days and doses for 12 years. Long-term prescription was defined as prescription for more than 365 days considering the distribution of total prescription days in study population. We identified patient's comorbid status including upper gastrointestinal (UGI) disease (ICD-10, K20-K31), rheumatic diseases (M05.x, M06.x, M31.5, M32.x-M34.x, M35.1, M35.3, M36.0), or musculoskeletal diseases (M07-M99 except for the codes included in rheumatic diseases). We categorized patients' type of insurance as medical insurance, medical aid, and veterans. We applied multivariable logistic regression model to examine factors associated with long-term prescription of ranitidine. Results: A total of 42,311,376 patients received ranitidine prescription between 2007 and 2018 in Korea (51.8% female; mean age 41.7 (±19.1) years), which accounting for approximately 82% of the Korean population. The number of patients has increased steadily from 5,466,816 in 2007 to 19,571,060 in 2018. Of these, 2,300,403 (5.4%) were long-term users. In the multivariable analysis, increased age (OR=1.822; 95% CI 1.820-1.824, 10-year increments), comorbid rheumatic disease (OR=4.37; 95% CI 4.34-4.40), UGI disease (OR=3.54; 95% CI 3.53-3.56), musculoskeletal diseases (OR=2.85; 95% CI 2.84-2.86), medical aid (OR=2.79; 95% CI 2.78-2.81), and veterans (OR=4.45; 95% CI 4.28-4.61) were associated with long-term prescription of ranitidine. Conclusions: Long-term prescription of ranitidine was associated with increased age, socioeconomic status, and specific comorbidities of patients. Patient characteristics associated with the long-term prescription of ranitidine could aid identifying at-risk patients, and provide information for designing further research assessing cancer risk associated with chronic exposure to ranitidine.