- 學位論文
Atorvastatin的使用適當性及安全性評估
Evaluation of Appropriateness and Safety of Atorvastatin Use
摘要
研究背景： Atorvastatin為高單價藥物，廣泛用於治療高血脂症，減少心血管疾病發生。在臺灣，使用atorvastatin需依照中央健保局規定，在服藥後三至六個月檢驗血脂濃度以評估療效並監測副作用的產生。Atorvastatin易與其他CYP 3A4抑制劑產生藥物交互作用提高不良反應的風險。此外，民眾不當的就醫行為更增加發生不良反應的機會。因此atorvastatin的用藥評估十分必要。 研究方法： 本研究分別以2010年3月份高雄醫學大學附設中和紀念醫院及2008年3月份“全民健康保險研究資料庫─2005年承保抽樣歸人檔”進行門急診使用atorvastatin之高血脂症病患進行用藥評估。兩者均分別記錄為期十個月內病人所有相關就醫資訊。依照中央健保局藥品使用規範進行藥品使用適當性評估，藥品不適當使用的定義為半年內未檢測血脂濃度與肝功能指標；藥品處方安全性則依Micromedex®與Lexi-Interact™ Online交互作用資料庫進行評估；atorvastatin引起的肝毒性與肌肉副作用則分別依照CIOMS與醫學文獻定義statin肌肉副作用進行評估；最後了解民眾就醫情形影響處方藥品間的交互作用。 結果： Atorvastatin主要是由醫學中心處方，主要使用於心臟內科及新陳代謝科。監測期十個月內未曾檢測任一血脂濃度者，在單一醫學中心及2005年承保抽樣歸人檔中分別為7.2%及8.1%；未曾檢測任一肝功能者分別為20.2%及20.8%；未曾檢測CPK者分別為93.4%及84.5%。若以「服用藥品半年內未檢測完整血脂數據與任一肝功能」判定藥品不適當使用，單一醫學中心及2005年承保抽樣歸人檔不適當使用比率分別為42.5%及63.3%；若依「服用藥品半年內未曾檢測過任一血脂數據與任一肝功能」判定藥品不適當使用，則不適當使用比率皆約23%。研究期間出現肝功能異常並經CIOMS評估可能（possible）為atorvastatin引起者為0.4%。 不論在單一醫學中心或2005年承保抽樣歸人檔用藥評估中，約10.5%病人接受具潛在交互作用的處方，增加橫紋肌溶解症的風險，處方藥物以diltiazem、fenofibrate、amiodarone、colchicine、verapamil和gemfibrozil為主；8位病人在同一時間服用兩種以上的statins。本次研究並未發現atorvastatin引起的橫紋肌溶解症。 使用atorvastatin病人的年平均就診次數、平均處方品項、年平均藥費均高於整體平均值；使用atorvastatin的病人中接受具藥品交互作用處方者該月份平均門診就診次數、平均處方品項、平均藥費均高於未接受藥品交互作用處方者。不同的民眾就醫行為並未增加處方中藥品交互作用的風險。 研究結論與建議： Atorvastatin使用安全性高，副作用小，然而在測量血脂濃度確認藥品的療效與處方安全性方面，仍有改善空間。
並列摘要
Background: Atorvastatin is of high price and is commonly prescribed to manage dyslipidemia to prevent cardiovascular disease. In Taiwan, prescription of atovastatin should follow the regulation of Bureau of National Health Insurance to monitor its effect and side effects. There are several common CYP 3A4 inhibitors that may interact with atorvastatin. Furthermore, inadequate health-seeking behavior of patients may easily precipitate the drug-drug interaction to cause severe adverse reactions. Therefore, medication-use evaluation（MUE）of atovastatin is highly appreciated. Methods: Hyperlipidemia patients taking atorvastatin in Kaohsiung Medical University Chung-Ho Memorial Hospital（KMUH）in March 2010 and Longitudinal Health Insurance Database 2005（LHID 2005）in March 2008, respectively, were included for MUE. Related data in LHID 2005 were collected and complete review of medical records of KMUH patients was done. The appropriateness of MUE of atovastatin use was evaluated by the regulation of Bureau of National Health Insurance. The safety issue regarding the severity of drug-drug interactions（DDIs）between co-prescribing medications was examined according to the database of Micromedex® and Lexi-Interact™ Online. The drug-induced liver injury（DILI）and myopathy caused by atorvastatin was evaluated by CIOMS and clinical definitions published before. Health-seeking behavior of patients was examined to determine its association with DDIs of co-prescribing medications. Results: Atorvastatin was mostly prescribed from medical center by the departments of cardiology and endocrinology. Physicians who prescribed atorvastatin without examination of any lipid profile within 10-month interval were 7.2% and 8.1%, without any liver function tests were 20.2% and 20.8%, and without CPK were 93.4% and 84.5% in KMUH and LHID 2005, respectively. Under the MUE criteria that prescription of atorvastatin needs to evaluate complete lipid profile, i.e. total cholesterol, triglyceride, HDL, and LDL, and either AST or ALT, the inappropriateness of prescription was 42.5% in KMUH and 63.3% in LHID 2005. If the MUE criteria were changed into prescription of atorvastatin needs to evaluate any lipid profile and either AST or ALT, the inappropriateness of prescription was 23% in both KMUH and LHID 2005. Among the patients evaluated, the rate of atovastastin-associated liver injury assessed by CIOMS was 0.4%. 10.5% patients had co-medications with potential DDIs which will increase the risk of rhabdomyolysis. The common co-medications at risk were diltiazem、fenofibrate、amiodarone、colchicine、verapamil and gemfibrozil. However, no rhabdomyolysis was found under various health-seeking behaviors. Conclusion: Atorvastatin is safe, but the appropriateness and safety of prescriptions need to be improved.