——FDA批准镇痛药Exparel用于控制术后疼痛

2011年10月31日,美国食品药品管理局(FDA)已批准Exparel(布比卡因脂质体注射用混悬液)1.3%用于控制术后手术部位的疼痛。Exparel是将布比卡因与储库泡沫(DepoFoam)技术相结合的一种非阿片类局部镇痛药，该给药技术可在所需的时间范围内给药。Pacira宣称单剂Exparel可产生长达72 h的镇痛效果，并可减少这段时间内对阿片类药物的需求。

在一项比较Exparel与安慰剂的关键性痔切除术试验中，疼痛控制不充分的所有患者均接受阿片类药物缓解疼痛，而接受Exparel用药的患者在累积疼痛评分方面显著降低，同时伴有阿片类药物用量的减少，镇痛效果长达72 h。

Exparel的安全性已在21项临床试验中得到评价，安全性数据库中涵盖逾1300名受试者的资料。有10项随机、双盲的临床试验对Exparel局部用于手术部位的效果进行了评估，共涉及823例行各种外科手术的患者。对患者所使用的Exparel剂量范围介于66 mg~532 mg之间。

研究中使用Exparel后最常见的不良反应(发生率>10%)为恶心、便秘和呕吐。

Exparel禁用于产科宫颈旁阻滞麻醉。

给予Exparel后的96 h内不宜使用布比卡因的其他制剂。

Manufacturer:
Pacira Pharmaceuticals

Pharmacological Class:
Local anesthetic (amide-type).

Active Ingredient(s):
Bupivacaine 13.3mg/mL; liposome injectable suspension; preservative-free.

Indication(s):
For administration into the surgical site to produce postsurgical analgesia.

Pharmacology:
Exparel is an aqueous suspension of multivesicular liposomes containing bupivacaine. After injection of Exparel into soft tissue, bupivacaine is released from the multivesicular liposomes over a period of time.

Bupivacaine is related chemically and pharmacologically to the amide-type local anesthetics. Local anesthetics block the generation and the conduction of nerve impulses presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential.

Clinical Trials:
A multicenter, randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of Exparel 106mg in 193 patients undergoing bunionectomy. Study medication was administered directly into the wound at the conclusion of the surgery, prior to wound closure. Pain intensity was rated by the patients on a 0 to 10 numeric rating scale (NRS) out to 72 hours. The primary outcome measure was the area under the curve (AUC) of the NRS pain intensity scores (cumulative pain scores) collected over the first 24 hour period. There was a significant treatment effect for Exparel compared to placebo. In this clinical study, Exparel demonstrated a significant reduction in pain intensity compared to placebo for up to 24 hours. The difference in mean pain intensity between treatment groups occurred only during the first 24 hours following study drug administration. Between 24 and 72 hours after study drug administration, there was minimal to no difference between Exparel and placebo treatments on mean pain intensity.

A multicenter, randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of Exparel 266mg in 189 patients undergoing hemorrhoidectomy. Study medication was administered directly into the wound (greater than or equal to 3 cm) at the conclusion of the surgery. Pain intensity was rated by the patients on a 0 to 10 NRS at multiple time points up to 72 hours. The primary outcome measure was the AUC of the NRS pain intensity scores (cumulative pain scores) collected over the first 72 hour period. There was a significant treatment effect for Exparel compared to placebo. In this clinical study, Exparel demonstrated a significant reduction in pain intensity compared to placebo for up to 24 hours. The difference in mean pain intensity between treatment groups occurred only during the first 24 hours following study drug administration. Between 24 and 72 hours after study drug administration, there was minimal to no difference between Exparel and placebo treatments on mean pain intensity; however, there was an attendant decrease in opioid consumption, the clinical benefit of which was not demonstrated.

Exparel has not been demonstrated to be safe and effective in other procedures.

Legal Classification:
Rx

Adults:
For single-dose administration only. Base dose on surgical site and volume required to cover area. Inject slowly into soft tissue via infiltration. Bunionectomy: 106mg (volume: 8mL). Hemorrhoidectomy: 266mg (volume: 20mL). See literature for administration.

Children:
<18yrs: not recommended.

Contraindication(s):
Obstetrical paracervical block.

Warnings/Precautions:
Not interchangeable with other forms of bupivacaine. Avoid intravascular inj. To be administered under the supervision of experienced clinicians. Cardiovascular disease. Hepatic or renal impairment. Monitor cardiovascular and respiratory vital signs. Pregnancy (Cat.C), nursing mothers: not recommended.

Interaction(s):
Do not dilute with water or hypotonic agents (may result in disruption of liposomal particles). Do not mix with lidocaine or other non-bupivacaine-based local anesthetics. Do not administer other forms of bupivacaine within 96hrs following administration of Exparel. May administer after at least 20 minutes following local administration of lidocaine.

Adverse Reaction(s):
Nausea, constipation, vomiting, pyrexia, dizziness, edema peripheral, anemia, hypotension, pruritus, tachycardia, headache, insomnia, anemia postoperative, muscle spasms, hemorrhagic anemia, back pain, somnolence, and procedural pain; CNS effects (eg, excitation, depression, restlessness, anxiety, dizziness, tremors), cardiovascular effects (eg, myocardium depression, decreased cardiac output, heart block, hypotension, bradycardia, ventricular arrhythmias, cardiac arrest), allergic-type reactions, neurologic effects (eg, spinal block, urinary retention, paresthesia, weakness, headache, paralysis of lower extremities).

How Supplied:
Single-use vial (10mL, 20mL)—10

Last Updated:
4/23/2012

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