某區域教學醫院Spironolactone潛在藥物交互作用處方型態分析

【研究背景】藥物與藥物交互作用(Drug-Drug Interactions，DDI)是臨床上造成治療失敗及藥物不良反應發生的原因之一，隨著人口的老化，病人多重疾病及多重用藥越來越普遍，藥物使用越多發生藥物交互作用的機率就越大，尤其在心血管疾病的處方發生潛在藥物交互作用的風險很高。根據國外研究文獻發現，藥物交互作用的發生率在心臟內科的比率最多，Spironolactone是醛類脂醇(Aldosterone)的競爭性抑制劑，它能抑制醛固酮通過競爭在遠端腎小管細胞醛固酮依賴性鈉 - 鉀交換場地的影響，這增加了水和鈉的分泌，同時降低鉀的排泄，可用於治療高血壓、心衰竭及改善水腫情況，臨床上常與其他心血管藥物併用，但目前針對Spironolactone藥物進行潛在藥物交互作用之探討與分析尚不多見。【研究目的】探討某區域教學醫院門診處方Spironolactone發生潛在藥物交互作用的比例、嚴重度、類型、影響與處置及其潛在交互作用之處方型態，分析可能發生交互作用之病人性別、年齡、科別、藥物劑量及處方藥品筆數，探討Spironolactone處方常見之藥物交互作用組合，藥物交互作用處方之合理性，擬藉由本次研究結果提供臨床Spironolactone用藥安全性評估參考，並希望能節省醫療成本及幫助醫師在面對交互作用時，可降低治療風險，作更好的臨床決策及照護參考。【研究方法】本研究為回溯性研究，收集某區域教學醫院自2013年1月1日至2013年6月30日之門診處方，藥品交互作用資料分析依據Drug Interaction Facts 2013版，利用資料庫篩選門診患者開立Spironolactone且發生潛在藥物交互作用處方，確認病患的基本資料、用藥記錄、潛在藥品交互作用的類型。使用SPSS 17.0 for Windows 套裝軟體進行分析，統計方法以百分比、平均數及標準差等進行描述性統計，及以Chi-Square、ANOVA分析方法進行推論性統計。【研究結果】在2013年1月至2013年6月與Spironolactone發生潛在藥物交互作用的門診處方共1001張，為門診總處方之0.49%，納入分析具臨床意義且影響程度較大之一級至三級藥物交互作用處方共860張，分析結果顯示一級藥物交互作用處方比例最高434張(50.47%)，二級藥物交互作用處方173張(20.11%)，三級藥物交互作用處方253張(29.42%)，性別分析結果男性467人(54.30%)，女性393人(45.70%)，以男性居多; 平均年齡為70.08 ± 14.67歲，平均處方藥品筆數為5.87 ± 1.64筆，使用平均給藥天數為26.67 ± 4.57天，平均每日劑量為26.99 ± 14.01mg，就醫科別以心臟內科發生率最高為88.14%。與Spironolactone發生具臨床意義之一到三級潛在藥物交互作用門診處方，發生年齡以老年人居多，65歲以上人口佔63.02%，處方藥品筆數分析顯示67.90%的病人同時併用5-7種藥物，交叉分析各年齡層之處方藥品筆數是否有差異，分析結果顯示，85歲以上之患者平均處方藥品筆數最多(6.52±1.52筆) 統計上具顯著差異。發生一級潛在藥物交互作用之前三名藥物依序為CO-DiovanR 190張(43.78%)、DiovanR 68張(15.67%)、VastrilR 39張(8.99%)。【結論】本研究結果顯示，與Spironolactone產生潛在一級交互作用之處方型態，藥理分類以血管張力素II受體阻斷劑(Angiotensin II receptor blockers, ARB)或血管張力素轉化酶抑制劑(Angiotensin converting enzyme inhibitors, ACEI) 之併用最為常見。儘管臨床上常見Spironolactone與血管張力素II受體阻斷劑或血管張力素轉化酶抑制劑併用於心衰竭患者的治療，然而如此併用可能會造成病患血鉀升高，導致心律不整，尤其併用於腎功能不全病人、糖尿病人與老年患者時，需謹慎監控血鉀濃度，避免藥物不良反應之發生，進而提高病患的用藥安全及確保療效。研究發現處方藥品筆數及每日劑量會影響藥物交互作用等級，在統計上具顯著差異(p＜0.05)。若能適當評估病人的用藥必要性，減少門診病人不必要的多重用藥，盡量精簡患者的用藥筆數，尤其是年齡較大的病人，以降低病人發生可能的藥物交互作用風險與多重用藥造成的身體健康負擔，可減少不必要的醫療浪費，希望此研究在臨床上可以幫助醫師面對藥物交互作用時，做更好的臨床決策進而提升醫療品質。

關鍵字

藥物交互作用； Spironolactone

並列摘要

【Background】 Drug-drug interactions is one of the reasons caused clinical treatment failure and adverse drug reactions. Polypharmacy is common in the elderly. Drug-Drug Interactions (DDI) will enable pharmacotherapeutic failure, and be associated with morbidity and mortality. Cardiological prescriptions are with high risk of potential drug-drug interactions. Spironolactone is a renal competitive aldosterone antagonist. It inhibits the effect of aldosterone by competing for the aldosterone-dependent sodium-potassium exchange site in the distal tubule cells. This increases the secretion of water and sodium, while decreasing the excretion of potassium. Spironolactone is used primarily to treat hypertension, heart failure, edematous conditions; it can also be combined with other cardiovascular drugs to increase efficacy. 【Objective】 The objective of this study is to analyze the patterns of potential drug interactions among spironolactone in a regional teaching hospital. We attempted to evaluate incidence, severity, classification, influence and management for potential drug interactions. Thus, we conduct this research to aim at exploring the drug interaction possibilities and related factors of spironolactone. And through the understanding of drug interaction mechanism and severity. We will make it a reminder for doctors to follow while treating patients, then providing better medical services for patients. 【Methods】 This is a retrospective study about the drugs we prescribed to outpatients in our hospital from January 2013 to June 2013. We screened for the pattern of potential drug interaction including severity, documentation and onset. These data of potential drug interactions are defined according to Drug Interaction Facts 2013. The data are processed and analyzed by SPSS 17.0 for Windows and explained with descriptive statistics of percentage, mean value, median value and standard deviation, as well as inferential statistics of Chi-Square test and ANOVA analysis. 【Results】 There were 1001 outpatient prescriptions of potential drug interactions among spironolactone from January 2013 to June 2013. It is about 0.49% of the total outpatient prescriptions. In this study, 860 potential drug interactions were identified (1st grade~3rd grade). Of these 860 potential DDIs prescriptions, the severity of the potential adverse effect was rated as 1st grade in 50.47%, 2nd grade in 20.11%, and 3rd grade in 29.42%. The mean age of the patients with potential drug interactions was 70.08 ± 14.67 years. And 54.30% among them were male, 45.70% were female and the mean kinds of prescribed drug were 5.87 ± 1.64, for 26.67±4.57 days, and the mean daily dose was 26.99 ± 14.01 mg. The highest rate (88.14%) of potential drug interaction was prescribed by the cardiologist among all medical specialties. Patients whose age over 65 y/o were the major population of potential DDIs (63.02%). We found that 67.90% used at least 5-7 prescription medications concurrently. The results showed that patients whose age over 85 y/o have the biggest average prescription items 6.52 ± 1.52, with a statistically significant difference. The 1st grade potential drug interactions of the top three drugs are CO-DiovanR 43.78%, DiovanR 15.67%, VastrilR 8.99%. 【Conclusions】 This study showed that Spironolactone and Angiotensin II receptor blockers (ARB) or Angiotensin converting enzyme inhibitors (ACEI) were the most common combination involving potential drug-drug interactions. Though Spironolactone combined with Angiotensin II receptor blockers (ARB) or Angiotensin converting enzyme inhibitors (ACEI) to treat CHF were commonly prescribed clinically. These combinations do caused the elevation of plasma potassium level, which may yield to severe arrhythmia. So the potential monitoring indicators of this drug-drug interaction is potassium level, especially in patients with renal insufficiency, diabetes, older age. The more drugs a patient takes, the greater the risk of adverse reactions and drug interactions. And among elder patients, polypharmacy is a common problem. The principles of pharmacotherapy in patients are to keep the number of drugs in lowest items. Optimizing prescribing by reducing polypharmacy and avoiding inappropriate medications is a highly individualized process for outpatient. We hope this paper will help medical practitioners predict and manage effects of drug interactions and will improve the quality and safety of medical treatment.

並列關鍵字

Drug Interaction ； Spironolactone

參考文獻

1.Leape LL, Brennan TA, Laird NM, Lawthers AG, Localio AR, Barnes BA, Hebert L, Newhouse JP, Weiler PC, Hiatt H. Nature of adverse events in hospitalized patients: results of the Harvard Medical Practice II. N Engl J Med 1991; 324:377-84.

Google Scholar

2.Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, et al. Incidence of adverse drug events and potential adverse drug events. JAMA 1995; 274(1):29-34.