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FDA批准首个不含助溶剂的胺碘酮注射剂产品Nexterone

2018-03-08 04:14:03 作者：新特药房来源：互联网浏览次数：0 文字大小：【大】【中】【小】

简介： 近日，Prism制药公司2009年1月5日宣布，该公司首个产品――创新的不含助溶剂的盐酸胺碘酮注射剂（amiodarone HCl，Nexterone）获得FDA批准，用于治疗和预防反复发作的难治性的心室纤维颤动或不稳定型心动 ...

关键字：胺碘酮盐酸 amiodarone HCl 商标名NEXTERONE 抗心律失常药 FDA批准

近日，Prism制药公司2009年1月5日宣布，该公司首个产品――创新的不含助溶剂的盐酸胺碘酮注射剂（amiodarone HCl，Nexterone）获得FDA批准，用于治疗和预防反复发作的难治性的心室纤维颤动或不稳定型心动过速。
胺碘酮注射剂最先由惠氏公司在美上市，商品名为Cordarone。本品去除了原注射剂中的助溶剂吐温80和苯甲醇并成功地解决了胺碘酮溶解度问题。去除了这些助溶剂之后，本品就不再有诸多的有关相容性及稳定性的限制，例如，由于不含有苯甲醇，本品就不必加注“谨防新生儿致命性窒息综合症”的警告了。此外，由于相容性和稳定性的改善，使得本品首次可以制成预混即用型的注射剂产品，有效地提高了医院注射安全。
NEXTERONE (Amiodarone HCl)
Manufacturer:
Baxter
Pharmacological Class:
Class III antiarrhythmic.
Active Ingredient(s):
Amiodarone HCl 1.5mg/mL, 1.8mg/mL; premixed in dextrose; soln for IV infusion.
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.
How Supplied:
Single-dose containers (100mL, 200mL)—1
Last Updated:
12/23/2011
NEXTERONE (Amiodarone HCl) Allows For Immediate Use of Critical Antiarrhythmic Drug in Urgent Care Settings
DEERFIELD, Ill., June 13, 2011 - Baxter International Inc. (NYSE:BAX) announced today at the American Society of Health-System Pharmacists Summer Meeting and Exhibition that it has launched NEXTERONE® (amiodarone HCl) Premixed Injection, the first and only ready-to-use premixed intravenous (IV) bag version of the antiarrhythmic agent amiodarone in the United States.
In a premixed formulation, NEXTERONE does not require admixing (compounding), making it immediately available for use and also reducing the risk of medication errors associated with compounding. Amiodarone is used for ventricular tachycardia (rapid heart rate) and ventricular fibrillation (abnormal heart rhythm), and currently available vial forms of the drug must be manually admixed, even in urgent care situations.
With its premixed formulation and two-year room temperature shelf life, NEXTERONE can be stored in automated dispensing cabinets and the crash carts of emergency rooms, intensive care units or critical care units, ready for use during acute, time sensitive and life-threatening situations.
"Rapid heart rate can be life-threatening in critically ill patients and, if left untreated, can progress into a heart attack," said Tom Van Hassel, RPh, MPA, director of Pharmacy, Yuma Regional Medical Center, Yuma, Arizona. "Having a premixed treatment available will enable clinicians to treat patients at a moment's notice, by eliminating preparation steps prior to administration."
The NEXTERONE premixed IV formulations were approved by the U.S. Food and Drug Administration (FDA) in two ready-to-use dosage forms: 150 mg in a 100 mL flexible container for rapid 10-minute loading infusion and 360 mg in a 200 mL flexible container for subsequent loading and maintenance infusions.
"As an industry leader in injectable drugs offering enhanced packaging, we are pleased to introduce the first ready-to-use version of amiodarone as a complement to our already robust premix portfolio" said David Bonderud, Baxter's president of U.S. Medication Delivery.
About Ventricular Tachycardia and Ventricular Fibrillation
Ventricular tachycardia is a rapid heartbeat that may result from serious heart disease and requires prompt treatment. Ventricular fibrillation is an uncontrolled twitching of muscle fibers in the lower chambers of the heart. General symptoms for both include chest pain, feeling the heart race, shortness of breath, dizziness and fainting. If unresolved and untreated, these conditions can lead to myocardial infarction (heart attack), heart failure or sudden death.
About NEXTERONE
NEXTERONE (amiodarone HCl) Premixed Injection is indicated for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy.
The premixed formulations of NEXTERONE are the first commercially-prepared versions of ready-to-use amiodarone, produced according to FDA's Current Good Manufacturing Practices. These ready-to-use formats align with the Joint Commission Medication Management guidelines, which recommend using medications in the most ready to administer forms commercially available.1 NEXTERONE should be stored in its carton to protect it from light until it is ready-to-use.
The premixed IV bags leverage Baxter's proprietary non-PVC (polyvinyl chloride), non-DEHP (di (2-ethylhexyl) phthalate) and non-latex GALAXY container technology, which is aseptically filled. The NEXTERONE formulations do not contain polysorbate 80 or benzyl alcohol. More information can be found at www.nexterone.com .
Important Risk Information
NEXTERONE (amiodarone HCl) Premixed Injection is contraindicated in patients with known hypersensitivity to any of the components of NEXTERONE, including iodine; cardiogenic shock; marked sinus bradycardia or second- or third-degree atrio-ventricular (AV) block unless a functioning pacemaker is available.
NEXTERONE should be administered only by physicians who are experienced in the treatment of life-threatening arrhythmias, who are thoroughly familiar with the risks and benefits of amiodarone therapy, and who have access to facilities adequate for monitoring the effectiveness and side effects of treatment.
If hypotension occurs, treat hypotension initially by slowing the infusion; additional standard therapy may be needed, including: vasopressors, positive inotropic agents and volume expansion.
If bradycardia and AV block occur, treat bradycardia by slowing the infusion rate or discontinuing NEXTERONE.
The most common adverse reactions leading to discontinuation (1-2%) of intravenous amiodarone therapy are hypotension, asystole/cardiac arrest/pulseless electrical activity, VT, and cardiogenic shock.
Other important adverse reactions are torsade de pointes (TdP), congestive heart failure, liver function test abnormalities, pulmonary disorders, and thyroid abnormalities.
About Baxter International Inc.
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.