药品信息: 近日，Prism制药公司宣布，美国食品药品管理局(FDA)已批准Nexterone，即抗心律失常药胺碘酮的一种预混静脉注射(IV)剂。Nexterone适合作为采用其他方法治疗无效的频繁复发性心室颤动(VF)和室性心动过速(VT)的初步治疗和预防用药。
导致停止静脉注射胺碘酮治疗的最常见的不良反应是低血压、心脏停搏/心脏骤停/无脉性电活动、VT和心源性休克。其他严重的不良反应包括尖端扭转型室性心动过速、充血性心力衰竭、肺病和肝功检测结果异常。
指示（S）：
开始经常重复的心室颤动（VF）和其他治疗难治性患者血流动力学不稳定的室性心动过速（VT）或口头形式是行不通的治疗和预防。
药理：
胺碘酮通常被认为是一个Ⅲ类抗心律失常药物，但它拥有所有四个Vaughan ·威廉斯类的电生理特征。
我的药物，胺碘酮在快速起搏频率块中的钠离子通道，如II类药物，胺碘酮施加一个非竞争性的antisympathetic行动，如类。在长时间的管理，其主要作用之一，是延长心肌动作电位，第三类的效果。胺碘酮负变时，在节点组织的影响是类似的IV类药物的效果。此外阻断钠通道，胺碘酮块心肌钾离子通道，从而有助于减慢传导和延长耐火度。 antisympathetic行动，钙和钾离子通道的块负责的负面dromotropic影响窦房结和减慢传导和延长房室结耐火度。它舒张血管作用，可以减少心脏负荷，因此心肌耗氧量。
临床试验：
两个随机，平行，剂量 - 反应的研究评估在抑制经常性VF或血流动力学不稳定的VT四胺碘酮急性成效。在这些研究中，至少有两个情节VF或血流动力学不稳定的VT在过去的24小时内的患者被随机分配接收的第一个24小时，约125mg或1000mg的剂量。患者接受初始的快速装输液，较慢的6个小时的装载输液，然后18小时维修输液，这是持续达48小时。更频繁地给予额外的10分钟输注150毫克IV胺碘酮“突破”的VT / VF 125mg剂量组。主要的结果，平均每小时的VT / VF发作率，患者接受高剂量和患者接受低剂量0.07 0.02，对应约0.5与1.7，每天发作（P = 0.07，双面，在这两项研究）。在一项研究中，第一集的VT / VF的时间显着延长（约10小时的患者接受患者接受高剂量，低剂量和14小时）。在这两项研究中，显著较少的补充输注给予高剂量组的患者。
有两个其他研究显示抗心律失常的作用desethylamiodarone显著水平之前，可能已经积累了胺碘酮。一个四胺碘酮安慰剂对照研究后冠状动脉搭桥术患者室上性和2 - 3连续击败室性心律失常，表现出从12小时减少心律失常。一个与复发性，难治的VT / VF患者的基线控制的研究表明，抗心律失常活性起病急，与基线相比，胺碘酮治疗的VT发作减少85％。
法律分类：
接收
成人：
个性化。第一个24小时：加载输液：150毫克（15mg/min）在第10分钟快速静脉滴注，然后在未来的6个小时，缓慢静脉滴注（1mg/min）360mg，维护输液：在剩下的18小时540mg（0.5mg/min ）缓慢静脉滴注。第一个24小时后：继续通过直接输注0.5mg/min（每24小时720mg）的维修输液速度。切换到口服胺碘酮：见文献。
儿童：
不推荐。
禁忌（S）：
心源性休克。标志着窦性心动过缓。第二或第三度房室传导阻滞，除非节奏。
警告/注意事项：
有经验的处方此药前，危及生命的心律失常的治疗和监测。在使用之前，正确的钾和镁的不足。手术。在治疗过程中监测QTc延长。治疗前评估甲状腺功能，并在此后定期。监测肺和肝毒性，减少剂量或停止，如果任一情况。定期做眼科检查。提款谨慎。怀孕（Cat.D）。哺乳的母亲：不推荐。
相互作用（S）：
相互作用可能会持续个月后停止。 Potentiates抗心律失常药物（如奎尼丁，普鲁卡因胺;⅓减少其剂量），环孢素，地高辛（半高辛剂量减少或停止），华法林抗凝血剂（⅓抗凝血剂剂量减少到半和监视PT），苯妥英钠，利多卡因。由CYP3A4代谢的他汀类药物的肌病。由蛋白酶抑制剂，氯雷他定，西咪替丁，曲唑酮，柚子汁Potentiated。抗心律失常心律失常的发作。添加剂心动过缓，房室传导阻滞β-受体阻滞剂，钙通道阻滞剂，芬太尼。 QTc延长与喹诺酮类，大环内酯类抗生素，唑类抗真菌药，丙吡胺。拮抗利福平，圣约翰草，胆。与氯吡格雷抑制血小板聚集可能无效。可能会影响甲状腺功能检查。见文献。
不良反应（S）：
低血压，心跳停止/ /无脉搏电活动的心脏骤停，心源性休克，瑞士法郎，心动过缓，肝功能试验异常，房室传导阻滞，室速，尖端扭转型室性心动过速，甲状腺功能紊乱。
Nexterone - Nexterone is an antiarrhythmic medication that affects the rhythm of heartbeats. Nexterone is used to help keep the heart beating normally in people with life-threatening heart rhythm disorders of the ventricles (the lower chambers of the heart that allow blood to flow out of the heart).
Nexterone is used to treat or prevent ventricular tachycardia or ventricular fibrillation. Nexterone may also be used for other purposes not listed in this medication guide.
Active ingredients: Amiodarone
Indication(s):
Initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) in patients refractory to other therapy or when oral form is not feasible.
Pharmacology:
Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes.
Like class I drugs, amiodarone blocks sodium channels at rapid pacing frequencies, and like class II drugs, amiodarone exerts a noncompetitive antisympathetic action. In prolonged administration, one of its main effects, is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. The antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular node. Its vasodilatory action can decrease cardiac workload and consequently myocardial oxygen consumption.
Clinical Trials:
Two randomized, parallel, dose-responsive studies assessed the acute effectiveness of IV amiodarone in suppressing recurrent VF or hemodynamically unstable VT. In these studies, patients with at least two episodes of VF or hemodynamically unstable VT in the preceding 24 hours were randomly assigned to receive doses of approximately 125mg or 1000mg over the first 24 hours. Patients received an initial rapid loading infusion, followed by a slower 6-hour loading infusion and then an 18-hour maintenance infusion, which was continued up to hour 48. Additional 10-minute infusions of 150mg IV amiodarone for “breakthrough” VT/VF were given more frequently to the 125mg dose group. The primary outcome, the median rate of VT/VF episodes per hour, was 0.02 in patients receiving the high dose and 0.07 for patients receiving the low dose, corresponding to approximately 0.5 versus 1.7 episodes per day (p=0.07, 2-sided, in both studies). In one study, the time to first episode of VT/VF was significantly prolonged (approximately 10 hours in patients receiving the low dose and 14 hours in patients receiving the high dose). In both studies, significantly fewer supplemental infusions were given to patients in the high-dose group.
There were two other studies of amiodarone showing an antiarrhythmic effect before significant levels of desethylamiodarone could have accumulated. A placebo-controlled study of IV amiodarone in post-CABG patients with supraventricular and 2- to 3-consecutive-beat ventricular arrhythmias showed a reduction in arrhythmias from 12 hours on. A baseline-controlled study in patients with recurrent, refractory VT/VF showed rapid onset of antiarrhythmic activity; amiodarone therapy reduced episodes of VT by 85% compared to baseline.
Legal Classification:
Rx
Adults:
Individualize. First 24hrs: loading infusions: 150mg over the first 10min (15mg/min) by rapid IV infusion, then 360mg over the next 6hrs (1mg/min) by slow IV infusion; maintenance infusion: 540mg over the remaining 18hrs (0.5mg/min) by slow IV infusion. After the first 24hrs: continue the maintenance infusion rate of 0.5mg/min (720mg per 24hrs) by direct infusion. Switching to oral amiodarone: see literature.
Children:
Not recommended.
Contraindication(s):
Cardiogenic shock. Marked sinus bradycardia. 2nd- or 3rd-degree AV block unless paced.
Warnings/Precautions:
Be experienced with the treatment and monitoring of life-threatening arrhythmias before prescribing this medication. Before use, correct potassium and magnesium deficiencies. Surgery. Monitor for QTc prolongation during treatment. Evaluate thyroid function before therapy and periodically thereafter. Monitor for pulmonary and liver toxicity; reduce dose or discontinue if either occurs. Do regular ophthalmic exams. Withdraw cautiously. Pregnancy (Cat.D). Nursing mothers: not recommended.
Interaction(s):
Interactions may persist months after discontinuing. Potentiates antiarrhythmics (eg, quinidine, procainamide; reduce their doses by ⅓), cyclosporine, digoxin (reduce digoxin dose by ½ or discontinue), warfarin-type anticoagulants (reduce anticoagulant dose by ⅓ to ½ and monitor PT), phenytoin, lidocaine. Myopathy with statins metabolized by CYP3A4. Potentiated by protease inhibitors, loratadine, cimetidine, trazodone, grapefruit juice. Exacerbation of arrhythmias with antiarrhythmics. Additive bradycardia, AV block with β-blockers, calcium channel blockers, fentanyl. QTc prolongation with quinolones, macrolides, azole antifungals, disopyramide. Antagonized by rifampin, St. John’s wort, cholestyramine. Possible ineffective inhibition of platelet aggregation with clopidogrel. May affect thyroid function tests. See literature.
Adverse Reaction(s):
Hypotension, asystole/cardiac arrest/pulseless electrical activity, cardiogenic shock, CHF, bradycardia, liver function test abnormalities, VT, AV block; torsade de pointes, thyroid disorders.
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