臺灣博碩士論文加值系統

背景與目的： Gemfibrozil為纖維鹽酸衍生物 (fibric acid derivatives) 之降血脂藥品，同時是強效CYP2C8抑制劑；repaglinide為meglitinides類的口服治療第二型糖尿病藥品，經由CYP2C8與CYP3A4代謝。目前研究顯示併用gemfibrozil與repaglinide會增加repaglinide血中濃度、延長repaglinide半衰期、增加病人嚴重低血糖風險。我國衛生福利部於2003年將repaglinide與gemfibrozil併用列為使用禁忌，然而臨床上仍有併用情形，故本研究欲探討臺灣2000-2011年間併用gemfibrozil與repaglinide之門診處方趨勢、併用處方之基本特性以及併用期間是否有低血糖事件發生。

方法： 本研究利用全民健康保險研究資料庫之2005年承保抽樣歸人檔擷取2000年至2011年間含有gemfibrozil或repaglinide之門診處方箋，利用簡單線性迴歸分析12年間併用gemfibrozil與repaglinide之門診處方趨勢，並依處方併用類型、醫事機構特性、醫師特性與病人特性進行處方分析。再利用國際疾病分類代碼觀察併用二藥期間是否有因低血糖發生入急診事件。
結果： 本研究發現2000年至2011年間共有774名病人被開立共5,499張併用gemfibrozil與repaglinide門診處方，12年來併用比率為1000/000，2003年後併用比率未有顯著的下降趨勢 (2003年1130/000至2011年1000/000，p =0.100)。併用處方主要來自同處方併用 (佔所有併用處方中78%)。依醫事機構特性分析，2003年後醫學中心併用比率有顯著的下降趨勢 (2003年1850/000至2011年590/000，p =0.011)，反觀基層院所的併用比率有顯著的上升趨勢 (2003年450/000至2011年1240/000，p =0.003)。而北臺灣、中台灣、東臺灣與外島地區的併用比率均沒有顯著的下降趨勢。依醫師特性分析，12年間以腎臟內科1720/000 最高。併用前五名的醫師科別均沒有顯著的下降趨勢。此外，藥品併用期間共有11人因低血糖而入急診就醫。

結論： 臺灣2003年至2011年間併用gemfibrozil與repgalinide門診處方比率未有顯著的下降趨勢，基層院所的併用比率仍不斷攀升，故建議衛生相關單位推廣並落實各醫事機構層級全面建置院內同處方、跨處方及跨院藥品交互作用查核攔截系統，若無自動化查核系統，建議應仔細審視健保雲端藥歷系統，此外，藥師應有責任積極向醫療人員宣導併用gemfibrozil與repaglinide屬使用禁忌以保障病人用藥安全。

Background: Gemfibrozil, a lipid lowering agent belonging to the fibric acid derivates, is a strong cytochrome P450 2C8 (CYP2C8) inhibitor. Repaglinide, an oral antidiabetic drug belonging to meglitinides category, is metabolized by CYP2C8 and CYP3A4. Recent studies indicated that concomitant use of gemfibrozil and repaglinide would markedly enhanced and prolonged the blood glucose-lowering effect of repaglinide, and might increase risk of severe hypoglycemia, a life-threatening adverse effect. Therefore, in 2003 the Ministry of Health and Welfare in Taiwan announced that the combination of gemfibrozil and repaglinide is contraindicated. However, the use of gemfibrozil-repaglinide co-medication still exists in clinical practices. This study aimed to investigate the ambulatory prescription trends of gemfibrozil-repaglinide co-medication in Taiwan during 2000-2011, explore the characteristics of co-medicated prescriptions, and observe whether the hypoglycemic events occur during the duration of concomitant of gemfibrozil and repaglinide.

Methods: In this observational study, ambulatory prescriptions including gemfibrozil or repaglinide from January 1st, 2000 to December 31th, 2011 were identified by using the Longitudinal Health Insurance Database 2005. The ambulatory prescription trends of gemfibrozil-repaglinide co-medication were analyzed by simple linear regression. Furthermore, the study investigated the co-medicated rate, co-medicated sources, characteristics of medical institutions, characteristics of physicians, and characteristics of patients. In addition, the hypoglycemic events were defined by the International Classification of Disease, 9th edition during the duration of concomitant use of gemfibrozil and repaglinide.

Results: There were 774 patients with a total of 5,499 ambulatory prescriptions of gemfibrozil and repaglinide combination. The co-medicated rate were 1000/000 during 12 years and decreased from 2003 to 2011 (1130/000 in 2003 to 1000/000 in 2011, p =0.100). Among the co-medicated prescriptions, 78% were prescribed by same prescription. The co-medicated trend in medical centers revealed a significant decrease (1850/000 in 2003 to 590/000 in 2011, p =0.011), whereas the clinics showed a significant increase (450/000 in 2003 to 1240/000 in 2011, p =0.003). Moreover, the study found that the co-medicated trend in northern Taiwan, central Taiwan, eastern Taiwan, outer islands, and the top five of physician specialties that prescribed most co-medicated prescriptions did not decreased significantly. In addition, 11 pateints had emergency vists with a hypoglycemia diagnosis during the duration of concomitant use of gemfibrozil and repaglinide.

Conclusion: The results showed that the trend in ambulatory prescription of gemfibrozil-repaglinide co-medication from 2003 to 2011 was not significantly decreased. Moreover, elevated co-medicated rate among clinics were still observed. The study suggests that the authorites of healthcare should promote and implement the technical supports such as drug-drug interaction alert system and PharmaCloud System. Pharmacists also have responsibilities to aggressively educate the health care professionals to prevent the gemfibrozil-repaglinide co-medication and guarantee the drug safety of patients.

中文摘要 i
英文摘要 iii
目錄 vi
圖目錄 viii
表目錄 ix
縮寫表 xi
第一章 緒論 1
第一節 研究背景與動機 1
第二節 研究目的 21
第二章 文獻探討 22
第一節 藥品交互作用之國外相關研究 22
第二節 藥品交互作用之國內相關研究 24
第三章 研究方法與設計 27
第一節 研究項目與研究假設 27
第二節 研究設計與研究工具 29
第三節 統計方法 47
第四章 研究結果 48
第一節 研究族群基本特性 48
第二節 併用Gemfibrozil與Repaglinide之處方趨勢 58
第三節 不同醫事機構特性之併用處方趨勢 67
第四節 不同醫師特性之併用處方趨勢 76
第五節 併用Gemfibrozil與Repaglinide後低血糖事件 83
第五章 討論 84
第一節 研究族群基本特性之討論 84
第二節 併用Gemfibrozil與Repaglinide之處方趨勢之討論 85
第三節 依不同醫事機構特性分析併用處方趨勢之討論 88
第四節 依不同醫師特性分析併用處方趨勢之討論 90
第五節 併用Gemfibrozil與Repaglinide後低血糖事件之討論 92
第六節 研究限制 93
第六章 結論與建議 94
第一節 結論 94
第二節 建議 95
參考文獻 96

圖目錄
圖3-2-1 研究架構 29
圖3-2-2 各檔案間變項串檔之關係圖 44
圖3-2-3 研究流程圖 46
圖4-1-1 各年度含有Gemfibrozil或Repaglinide的處方張數 51
圖4-2-1 各年度併用Gemfibrozil與Repaglinide之門診處方趨勢 63
圖4-2-2 各年度Gemfibrozil與Repaglinide同處方併用、同醫療院所之跨處方併用與不同醫療院所併用之處方趨勢 66
圖4-3-1 各年度併用Gemfibrozil與Repaglinide在不同醫事機構之處方趨勢 72
圖4-3-2 各年度併用Gemfibrozil與Repaglinide在不同醫事機構地區之處方趨勢 75
圖4-4-1 各年度併用Gemfibrozil與Repaglinide在不同醫師科別之處方趨勢 82

表目錄
表1-1-1 藥品交互作用之臨床重要性分級 6
表1-2-1 口服治療糖尿病藥品與降血脂藥品之藥品交互作用 14
表3-2-1 研究資料檔名稱與擷取變項 31
表3-2-2 藥品Gemfibrozil與Repaglinide之健保藥品代碼 33
表3-2-3 研究項目之操作型定義 42
表4-1-1 各年度含有Gemfibrozil或Repaglinide的處方張數及人數 50
表4-1-2 各年度使用Gemfibrozil或Repaglinide處方醫事機構特性 52
表4-1-3 各年度使用Gemfibrozil或Repaglinide處方醫師特性 54
表4-1-4 各年度使用Gemfibrozil或Repaglinide處方之病人特性 56
表4-2-1 各年度併用Gemfibrozil與Repaglinide病人特性 59
表4-2-2 各年度併用Gemfibrozil與Repaglinide之門診處方趨勢 62
表4-2-3 各年度併用Gemfibrozil與Repaglinide在不同併用類型之處方趨勢 65
表4-3-1 各年度併用Gemfibrozil與Repaglinide處方醫事機構特性 68
表4-3-2 各年度併用Gemfibrozil與Repaglinide在不同醫事機構層級之處方趨勢 71
表4-3-3 各年度併用Gemfibrozil與Repaglinide在不同醫事機構地區之處方趨勢 74
表4-4-1 各年度併用Gemfibrozil與Repaglinide處方醫師特性 77
表4-4-2 各年度併用Gemfibrozil與Repaglinide在不同醫師科別之處方趨勢 81
表4-5-1 併用Gemfibrozil與Repaglinide期間發生低血糖之病人特性 83

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