美FDA批准静脉推注用对乙酰氨基酚制剂Ofirmev治疗疼痛和退热

2010年11月,美国FDA批准了Cadence制药有限公司开发的对乙酰氨基酚(acetaminophen)注射剂Ofirmev,用于退热以及治疗轻至中度疼痛和辅助阿片类止痛药物治疗中至重度疼痛。Ofirmev应仅以约15min经静脉内推注方式给药,且日总对乙酰氨基酚用药量不得超出最大推荐剂量值。Ofirmev是FDA迄今批准的第一种和唯一一种经静脉内给药的对乙酰氨基酚制剂,具有退热和止痛效力强、能减少阿片类药物消耗量和提高患者治疗满意度等特点。但Ofirmev禁用于有严重肝损害或严重活动性肝病患者,用于有轻至中度肝损害或活动性肝病以及酒精中毒、长期营养不良、严重血容量减少或有严重肾损害患者时也需谨慎。Ofirmev在治疗成人患者时的最常见副反应是恶心、呕吐、头痛和失眠;在治疗儿科患者时的最常见副反应为恶心、呕吐、便秘、瘙痒、激越和肺萎陷。

OFIRMEV - 对乙酰氨基酚注射液，溶液

Cadence的制药公司

最初美国批准：1951

适应症
为表示OFIRMEV（对乙酰氨基酚）注射

轻度中度疼痛的管理
管理的中度至重度疼痛与辅助阿片类镇痛药
减少发热
 
剂量和用法
OFIRMEV可作为一个单一或重复的剂量。
OFIRMEV应只有15分钟的静脉滴注给药。
重量50公斤及以上的成年人和青少年：

1000毫克每6小时或650毫克，每4个小时到最多每天4000毫克。最低给药间隔4小时。
重量在50公斤的成年人和青少年：

15毫克/公斤，每6小时或12.5毫克/公斤，每4小时最多每天75毫克/公斤。最低给药间隔4小时。
儿童：

儿童≥2至12岁：15毫克/公斤，每6小时或12.5毫克/公斤，每4小时最多每天75毫克/公斤。最低给药间隔4小时。
 
剂型和优势
注射液静脉滴注。
每100毫升玻璃瓶中含有1000毫克对乙酰氨基酚（10毫克/毫升）。
禁忌
对乙酰氨基酚是禁忌：

患者已知的过敏对乙酰氨基酚或在IV制定的任何辅料。
严重肝功能损害或严重活动性肝病患者。

注意事项：
政府在剂量超过推荐的对乙酰氨基酚可能导致肝损伤，包括严重的肝损伤和死亡的风险。
不要超过最大建议每日剂量对乙酰氨基酚。
使用时管理具备下列条件的患者对乙酰氨基酚的肝功能不全或活跃的肝脏疾病，酗酒，慢性营养不良，严重血容量不足，或严重肾功能不全的情况下，（肌酐清除率≤30毫升/分钟）。内容进行提醒
立即停止OFIRMEV，如果发生过敏或过敏症状。不要使用对乙酰氨基酚过敏的患者。
 
不良反应
的在与OFIRMEV治疗的患者最常见的不良反应是恶心，呕吐，头痛，失眠的成年患者，恶心，呕吐，便秘，皮肤瘙痒，情绪激动，在儿科患者肺不张。

药物相互作用
物质诱发或调节肝细胞色素酶CYP2E1基因可能会改变对乙酰氨基酚的代谢和增加其肝毒性的潜力。
慢性口服对乙酰氨基酚的使用剂量为4000毫克/天已经表明，有些人已在华法林钠稳定作为抗凝剂的患者增加，导致在国际标准化比值（INR）。
 
在特殊人群中使用
妊娠C类有没有孕妇静脉注射对乙酰氨基酚的研究。如果确实需要，只能使用。
哺乳母亲：管理哺乳妇女时，应谨慎行事。
儿童用药：小于2岁的婴幼儿患者治疗急性疼痛和发烧的OFIRMEV有效性尚未研究。在2岁以上的儿童患者的安全性和有效性的OFIRMEV额外的安全性和药代动力学数据为这一年龄组的成年人有足够的和很好的控制研究的证据支持。
老年用药：在安全性和有效性没有整体差异，观察之间的老人和年轻的学科。
肝功能不全：严重肝功能损害或严重活动性肝病患者的禁忌OFIRMEV，并应与肝功能不全或活动性肝病患者慎用。
肾功能不全：在严重肾功能不全，较长的给药间隔和降低总每日剂量对乙酰氨基酚的情况下可能有必要。

更新日期：11/2010

Ofirmev

Generic Name: acetaminophen
Date of Approval: November 2, 2010
Company: Cadence Pharmaceuticals, Inc.

FDA Approves Ofirmev
The U.S. Food and Drug Administration (FDA) has granted marketing approval for Ofirmev (acetaminophen) injection, the first and only intravenous (IV) formulation of acetaminophen to be approved in the United States. Ofirmev is indicated for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, and the reduction of fever.

Highlights of Ofirmev Prescribing Information
These highlights do not include all the information needed to use Ofirmev safely and effectively. See full prescribing information for Ofirmev.

Indications and Usage
Ofirmev (acetaminophen) injection is indicated for the
•Management of mild to moderate pain
•Management of moderate to severe pain with adjunctive opioid analgesics
•Reduction of fever

Dosage and Administration
•Ofirmev may be given as a single or repeated dose.
•Ofirmev should be administered only as a 15-minute intravenous infusion.

Adults and Adolescents Weighing 50 kg and Over:
•1000 mg every 6 hours or 650 mg every 4 hours to a maximum of 4000 mg per day. Minimum dosing interval of 4 hours.

Adults and Adolescents Weighing Under 50 kg:
•15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours to a maximum of 75 mg/kg per day. Minimum dosing interval of 4 hours.

Children:
•Children ≥ 2 to 12 years old: 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours to a maximum of 75 mg/kg per day. Minimum dosing interval of 4 hours.

Dosage Forms and Strengths
•Injection for intravenous infusion.
•Each 100 mL glass vial contains 1000 mg acetaminophen (10 mg/mL).

Contraindications
Acetaminophen is contraindicated:
•In patients with known hypersensitivity to acetaminophen or to any of the excipients in the IV formulation.
•In patients with severe hepatic impairment or severe active liver disease.

Warnings and Precautions
•Administration of acetaminophen in doses higher than recommended may result in hepatic injury, including the risk of severe hepatotoxicity and death.
•Do not exceed the maximum recommended daily dose of acetaminophen.
•Use caution when administering acetaminophen in patients with the following conditions: hepatic impairment or active hepatic disease, in cases of alcoholism, chronic malnutrition, severe hypovolemia, or severe renal impairment (creatinine clearance = 30 mL/min).
•Discontinue Ofirmev immediately if symptoms associated with allergy or hypersensitivity occur. Do not use in patients with acetaminophen allergy.

Ofirmev side effects
Adverse Reactions
The most common adverse reactions in patients treated with Ofirmev were nausea, vomiting, headache, and insomnia in adult patients and nausea, vomiting, constipation, pruritus, agitation, and atelectasis in pediatric patients.

Drug Interactions
•Substances that induce or regulate hepatic cytochrome enzyme CYP2E1 may alter the metabolism of acetaminophen and increase its hepatotoxic potential.
•Chronic oral acetaminophen use at a dose of 4000 mg/day has been shown to cause an increase in international normalized ratio (INR) in some patients who have been stabilized on sodium warfarin as an anticoagulant.

Use In Specific Populations
•Pregnancy: Category C. There are no studies of intravenous acetaminophen in pregnant women. Use only if clearly needed.
•Nursing Mothers: Caution should be exercised when administered to a nursing woman.
•Pediatric Use: The effectiveness of Ofirmev for the treatment of acute pain and fever has not been studied in pediatric patients less than 2 years of age. The safety and effectiveness of Ofirmev in pediatric patients older than 2 years is supported by evidence from adequate and well controlled studies in adults with additional safety and pharmacokinetic data for this age group.
•Geriatric Use: No overall differences in safety or effectiveness were observed between geriatric and younger subjects.
•Hepatic Impairment: Ofirmev is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease.
•Renal Impairment: In cases of severe renal impairment, longer dosing intervals and a reduced total daily dose of acetaminophen may be warranted.
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生产厂家中文参考译名:
CADENCE PHARMS
生产厂家英文名:
CADENCE PHARMS
原产地英文商品名:
OFIRMEV 1000MG/100ML/VIAL
原产地英文药品名:
ACETAMINOPHEN
中文参考商品译名:
OFIRMEV 1000毫克/100毫升/瓶
中文参考药品译名:
对乙酰氨基酚