近日，美国食品药品管理局（FDA）批准该公司旗下粉末/口服溶液剂Epaned（enalapril maleate）用于治疗一个月或更大年龄患者的高血压。在美国，依那普利是治疗高血压最常用的药物。
批准日期：2013年8月13日 公司：Silvergate 制药
EPANED（盐酸依那普利马来[enalapril maleate]）口服液,供口服使用
最初的美国批准：1985年
警告：胎儿毒性请查看完整的盒装警告的完整处方信息。
•检测到怀孕时，请尽快停止EPANED。
•直接作用于肾素-血管紧张素系统的药物可能导致发育中的胎儿受伤和死亡。
作用机制
依那普利在水解为依那普利拉后，抑制人类对象和动物的血管紧张素转换酶（ACE）。ACE是肽基二肽酶，其催化血管紧张素I转化为血管收缩物质血管紧张素II。血管紧张素II还刺激肾上腺皮质的醛固酮增多。依那普利在高血压和心力衰竭中的有益作用似乎主要来自抑制肾素-血管紧张素-醛固酮系统。
ACE的抑制导致血浆血管紧张素II降低，导致血管紧张素活性降低和醛固酮分泌减少。虽然后者减少，但它导致血清钾的小幅增加。在高血压患者中单独使用马来酸盐马来酸盐片剂治疗长达48周，观察到血清钾平均增加约0.2mEq/L.在使用依那普利马来酸盐片加噻嗪类利尿剂治疗的患者中，血清钾基本没有变化[见警告和注意事项]。去除血管紧张素II对肾素分泌的负反馈导致血浆肾素活性增加。
ACE与激酶相同，激酶是一种降解缓激肽的酶。是否增加血红蛋白（一种有效的血管抑制肽）的水平，在EPANED的治疗效果中发挥作用还有待阐明。
虽然EPANED降低血压的机制被认为主要是肾素-血管紧张素-醛固酮系统的抑制，但即使是低肾素高血压的患者，依那普利也是抗高血压药物。虽然依那普利马来酸盐片剂在所研究的所有种族中都是抗高血压药物，但是黑人高血压患者（通常是低肾素高血压人群）对依那普利单药治疗的平均反应比非黑人患者更小。
适应症和用法
EPANED是一种血管紧张素转换酶抑制剂，适用于：
•治疗成人和1个月以上儿童的高血压，以降低血压。降低血压可降低致命性和非致命性心血管事件（主要是中风和心肌梗塞）的风险。
•治疗症状性心力衰竭。
•治疗无症状的左心室功能不全，降低明显心力衰竭的发生率，减少心力衰竭的住院治疗。
剂量和给药
高血压
•成人：建议初始剂量为每天一次5毫克。最大剂量为每日40mg。
•儿科：建议起始剂量为每天一次0.08mg/kg（最多5mg）。
心力衰竭：每日两次，每次2.5毫克。每日两次滴定可达20毫克。
无症状性左心室功能障碍：每天两次，每次2.5毫克。
每日两次滴定至10毫克。
剂量形式和强度
EPANED口服液是一种即用型口服液：1mg/mL依那普利马来酸盐。
EPANED口服液是一种即用型解决方案，仅供口服使用。
禁忌症
•与先前使用ACEI治疗相关的超敏反应。
•遗传性或特发性血管性水肿。
•不要在糖尿病患者中共同使用阿利吉仑。
•与脑啡肽酶抑制剂联合使用。
警告和注意事项
•血管性水肿和过敏反应。
•肾功能受损：评估肾功能。
•高钾血症。
不良反应
•高血压治疗（3％）患者最常见的不良反应是疲劳。
•治疗心力衰竭（>6％）的患者最常见的不良反应是低血压和头晕。
要报告疑似不良反应，请致电1-855-379-0383联系SilvergatePharmaceuticals，或致电1-800-FDA-1088或www.fda.gov/medwatch联系FDA。
药物相互作用
•对于老年，体积消耗（如利尿剂治疗）或肾功能受损的患者，使用NSAIDs（包括选择性COX-2抑制剂）可能导致肾功能衰竭，包括肾功能衰竭。定期监测肾功能。
•肾素-血管紧张素系统的双重抑制：增加肾功能减退，低血压和高钾血症的风险。
•心力衰竭患者应避免使用钾保留剂。
•经常监测血清锂水平。
用于特定人群
•不建议新生儿和儿科患者使用EPANED
肾小球滤过率<30mL/min/1.73m。
•哺乳期：建议不要母乳喂养。
包装提供/存储和处理
EPANED是一种即用型溶液，含有1mg/mL依那普利马来酸盐。它是一种透明，无色的口服溶液，具有混合浆果风味，包装在150毫升白色圆形高密度聚乙烯瓶中，带有白色聚丙烯防儿童帽和防篡改密封。 每瓶含有150毫升。
NDC 52652-4001-1
将冷藏（2°- 8°C/36°-46°F）冷藏在密闭容器中。 患者可以存储EPANED
冷藏（2°- 8°C/36°- 46°F）或室温（20° -  25°C/68°-77°F）。如果存储在室温，60天后丢弃 避免结冰和过热。
完整说明资料附件：https://epaned.com/Epaned-Prescribing-Info.pdf
FDA-approved enalapril oral solution, is now available for ordering.  EPANED is an oral solution that enables consistent weight-based dosing for children over 1 month of age. 
EPANED reduces the potential for errors as a ready-to-use solution that does not require mixing.  EPANED is indicated for the treatment of hypertension (high blood pressure) in adult and pediatric patients older than 1 month of age, treatment of symptomatic heart failure, and treatment of asymptomatic left ventricular dysfunction。
INDICATIONS
EPANED is an angiotensin-converting enzyme (ACE) inhibitor indicated for:
treatment of hypertension in adults and children older than 1month, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
treatment of symptomatic heart failure.
treatment of asymptomatic left ventricular dysfunction, to decrease the rate of development of overt heart failure and reduce hospitalization for heart failure.
IMPORTANT SAFETY INFORMATION 
WARNING: FETAL TOXICITYWhen pregnancy is detected, discontinue EPANED as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
ADDITIONAL IMPORTANT SAFETY INFORMATION
When pregnancy is detected, discontinue EPANED as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
ADDITIONAL IMPORTANT SAFETY INFORMATION
Epaned is contraindicated in patients who are hypersensitive to enalapril or any component of Epaned.
Epaned is contraindicated in patients with a history of hypersensitivity related to previous treatment with an ACE inhibitor.
Epaned is contraindicated in patients with hereditary or idiopathic angioedema.
Do not co-administer aliskiren with Epaned in patients with diabetes.
Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx, including some fatal reactions, have been reported in patients treated with ACE inhibitors, including Epaned, at any time during treatment. Epaned should be promptly discontinued and appropriate therapy and monitoring provided until complete and sustained resolution of signs and symptoms of angioedema has occurred. Patients with a history of angioedema may be at increased risk of angioedema while receiving an ACE inhibitor. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients.
Intestinal Angioedema has been reported in patients treated with ACE inhibitors.
Anaphylactoid Reactions: Sudden and potentially life-threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. Life-threatening anaphylactoid reactions have been reported with concomitant ACE inhibitor and desensitizing treatment with hymenoptera venom.
Hypotension: Epaned can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high-dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology. These patients should be started under close medical supervision and closely followed for the first 2 weeks of treatment with Epaned and whenever the dose of Epaned and/or a diuretic is increased. Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy.
Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Epaned may block angiotensin II formation secondary to compensatory renin release.
Hepatic Failure: Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. Patients who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
Impaired Renal Function: Monitor renal function in patients treated with Epaned. Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the renin-angiotensin system. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Epaned.
Hyperkalemia: Serum potassium should be monitored in patients receiving Epaned. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.
Adverse Reactions (where rate on enalapril exceeds the rate on placebo by at least 0.2%) occurring in greater than 1% of patients with hypertension treated with enalapril in controlled trials include: fatigue, orthostatic effects, asthenia, cough, and rash. Adverse reactions reported in clinical trials of heart failure were similar to those seen in clinical trials for hypertension. In patients treated for heart failure, there was an increased incidence of hypotension and dizziness.