近日，美国食品和药物管理局（FDA）批准Qbrelis（Lisinopril）口服液，是第一个也是唯一一个FDA批准的赖诺普利口服液。 Qbrelis™适用于治疗成人患者和6岁及以上儿童患者的高血压（高血压），心力衰竭的辅助治疗以及成人急性心肌梗死的治疗.
Qbrelis提供了赖诺普利（ACE抑制剂）的可靠功效，其有效性已在临床试验中得到很好的证实.作为口服溶液的独特配方，Qbrelis除了质量外，还在每种剂量中提供一致的效力和稳定性根据FDA法规和要求生产的产品。
批准日期：2016年7月29日 公司：SILVERGATE PHARMACEUTICALS INC
QBRELIS（赖诺普利[lisinopril]）溶液供，口服使用
美国最初批准：1988年
警告：胎儿毒性请参阅完整的BOXED警告的完整预定信息。
•检测到怀孕时，请尽快停止QBRELIS。
•直接作用于肾素 - 血管紧张素系统的药物可能会对发育中的胎儿造成伤害和死亡。
作用机制
赖诺普利抑制人受试者和动物中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向血管收缩物质血管紧张素II的转化。血管紧张素II还刺激肾上腺皮质分泌醛固酮。赖诺普利在高血压和心力衰竭中的有益作用似乎主要是由于肾素-血管紧张素-醛固酮系统的抑制。ACE的抑制导致血浆血管紧张素II降低，这导致血管加压活性降低和醛固酮分泌减少。后者的减少可能导致血清钾的少量增加。单用赖诺普利治疗肾功能正常的高血压患者长达24周，血清钾平均升高约0.1 mEq/L;然而，大约15％的患者增加大于0.5mEq/L，大约6％的患者减少大于0.5mEq/L.在同一项研究中，接受赖诺普利和氢氯噻嗪治疗长达24周的患者血清钾平均降低0.1mEq/L;大约4％的患者增加大于0.5mEq/L，大约12％的患者减少大于0.5 mEq/L[见临床研究]。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。是否增加缓激肽水平，一种有效的血管抑制肽，在QBRELIS的治疗效果中发挥作用仍有待阐明。
虽然QBRELIS降低血压的机制被认为主要是抑制肾素-血管紧张素-醛固酮系统，但QBRELIS即使在低肾素高血压患者中也具有抗高血压作用。虽然赖诺普利在所有研究的种族中均具有抗高血压作用，但黑人高血压患者（通常是低肾素高血压患者）对单药治疗的平均反应要小于非黑人患者。
同时给予赖诺普利和氢氯噻嗪可进一步降低黑人和非黑人患者的血压，血压反应的任何种族差异都不再明显。
适应症和用法
QBRELIS是一种血管紧张素转换酶（ACE）抑制剂，适用于：
•治疗6岁及以上的成人和儿科患者的高血压。
•心力衰竭的辅助治疗。
•急性心肌梗死的治疗。
剂量和给药
•高血压：初始成人剂量为每天一次10毫克。根据血压反应每天滴定高达40毫克。以每天一次5毫克的利尿剂开始患者。
•肾小球滤过率> 30mL/min/1.73m 2的儿科患者：6岁及以上患者的初始剂量为每天0.07mg/kg（总计高达5mg）。
•心力衰竭：每日一次，每次5毫克。增加剂量，每日耐受40毫克。
•急性心肌梗死（MI）：MI后24小时内给予5mg，24小时后给予5 mg，然后每天10mg。
•肾功能损害：对于肌酐清除率≥10mL/min且≤30mL/min的患者，通常的初始剂量减半。对于肌酐清除率<10mL/min或血液透析的患者，推荐的初始剂量为2.5mg。
剂量形式和强度
口服溶液：1mg/mL。
禁忌症
•血管性水肿或遗传性或特发性血管性水肿的病史。
•过敏者禁用。
•阿利吉仑与QBRELIS联合用于糖尿病患者。
•与脑啡肽酶抑制剂联合使用。
警告和注意事项
•血管性水肿：停止使用QBRELIS;提供适当的治疗和监测直至解决。
•肾功能损害：定期监测肾功能。
•低血压：患有其他心脏病或肾病的患者风险增加，开始后监测血压。
•高钾血症：定期监测血清钾。
•胆汁淤积性黄疸和肝功能衰竭：监测黄疸或肝功能衰竭的迹象。
不良反应
使用时常见的不良反应（事件比安慰剂高2％）：
•高血压：头痛，头晕和咳嗽。
•心力衰竭：低血压和胸痛。
•急性心肌梗塞：低血压。
要报告疑似不良反应，请致电1-855-379-0383联系Silvergate制药公司，或致电1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH联系FDA。
药物相互作用
•利尿剂：血压过度下降。
•NSAIDS：肾功能损害的风险增加和抗高血压疗效丧失。
•肾素 - 血管紧张素系统的双重抑制：肾功能损害，低血压和高钾血症的风险增加。
•锂：锂毒性的症状。
•金：已报道亚硝酸盐反应。
用于特定人群
•哺乳期：建议不要母乳喂养。
•种族：黑人的抗高血压作用低于非黑人。
包装提供/存储和处理
QBRELIS（赖诺普利），1毫克/毫升，以150毫升透明至微乳白色，无色水性口服液的形式提供，在含有儿童防护帽的150毫升高密度聚乙烯（HDPE）瓶中具有甜味（ NDC 52652-3001-1）。
在控制室温20°C-25°C（68°F-77°F）[见USP]的密闭容器中保存。防止结冰和过热。
完整说明资料附件：
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f6e4e57-a489-4b36-b093-b93865d3717c
QBRELIS(lisinopril) oral solution
IMPORTANT SAFETY INFORMATION
WARNING: FETAL TOXICITY
See full Prescribing Information for complete boxed warning.
When pregnancy is detected, discontinue QBRELIS as soon as possible.
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
INDICATIONS
QBRELIS is an angiotensin-converting enzyme (ACE) inhibitor indicated for:
treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure (BP). Lowering BP decreases the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (MI).
reduction of signs and symptoms of systolic heart failure.
reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute MI. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and beta-blockers.
ADDITIONAL IMPORTANT SAFETY INFORMATION
Qbrelis is contraindicated in patients who are hypersensitive to lisinopril or any component of Qbrelis, or in patients with a history of hypersensitivity related to previous ACE inhibitor treatment.
Qbrelis is contraindicated in patients with hereditary or idiopathic angioedema and should not be co-administered with aliskiren in patients with diabetes.
Qbrelis is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Qbrelis within 36 hours of switching to or from sacubitril/valsartan.
Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx, including some fatal reactions, have occurred in patients treated with ACE inhibitors, including Qbrelis, at any time during treatment. Patients with a history of angioedema unrelated to ACE inhibitor therapy 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 non-Black patients.
Intestinal angioedema has been reported with ACE inhibitors. Discontinue Qbrelis and obtain appropriate therapy.
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. Symptoms have not been relieved by antihistamines in these situations. 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 and in patients undergoing desensitizing treatment with hymenoptera venom.
Impaired Renal Function: Monitor renal function in patients treated with Qbrelis. Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the renin-angiotensin system (RAS). Patients whose renal function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-MI or volume depletion) may be at particular risk of developing acute renal failure on Qbrelis. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Qbrelis.
Hypotension: Qbrelis can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. Qbrelis should be started under close medical supervision and followed closely for the first 2 weeks of treatment and whenever the dose of Qbrelis and/or a diuretic is increased. Avoid the use of Qbrelis in hemodynamically unstable patients after acute MI.
Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Qbrelis may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and it is considered to be due to this mechanism, it can be corrected by volume expansion.
Hepatic Failure: ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death. If jaundice or marked elevations of hepatic enzymes develop, discontinue the ACE inhibitor and receive appropriate medical follow-up.
Hyperkalemia: Serum potassium should be monitored in patients receiving Qbrelis. 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 lisinopril exceeds the rate on placebo by at least 2%) occurring in greater than 1% of patients with:
Hypertension: headache, dizziness, and cough.
Systolic heart failure: hypotension and chest pain.
Acute MI: hypotension and renal dysfunction.
See full Prescribing Information for further information, including other Adverse Reactions.
Initiation of Qbrelis in patients on diuretics may result in excessive reduction of blood pressure. This can be minimized by either decreasing or discontinuing the diuretic or increasing salt intake prior to initiating Qbrelis treatment.
Qbrelis attenuates potassium loss caused by thiazide-type diuretics. If concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently.
Concomitant administration of Qbrelis and antidiabetic medicines may cause an increased blood-glucose-lowering effect.
In patients who are elderly, volume-depleted (as on diuretic therapy), or with compromised renal function, use of non-steroidal anti-inflammatory agents (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, with ACE inhibitors, including lisinopril, may result in deterioration of renal function, including renal failure. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy.
Dual Inhibition of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure), compared to monotherapy. Closely monitor BP, renal function and electrolytes in patients receiving Qbrelis and agents that effect the RAS.
Avoid use of aliskiren with Qbrelis in patients with renal impairment.
Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs that cause elimination of sodium, including ACE inhibitors. It is usually reversible upon discontinuation of lithium and the ACE inhibitor. Monitor serum lithium levels during concurrent use.
Nitritoid reactions have been reported rarely in patients with injectable gold (sodium aurothiomalate) and concomitant lisinopril therapy.
mTOR or neprilysin inhibitors: Patients receiving coadministratoin of an ACE inhibitor and a mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (e.g., sacubitril) may be at increased risk for angioedema.
Because of the potential for severe adverse reactions in the breastfed infant, advise women not to breastfeed while taking Qbrelis.
Qbrelis is not recommended in children under the age of 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2.