英文药名:Relistor(methylnaltrexone)
中文药名:溴化甲基纳曲酮皮下注射
品牌生产商:Progenics Pharmaceuticals, Inc.和Wyeth Pharmaceuticals
药品介绍
溴化甲基纳曲酮(methylnaltrexone bromide)商品名为Rdistor,由美国惠氏Wyeth制药子公司公司和 Progenics Pharmaceuticals公司联合研究开发的μ A片受体拮抗剂。2008年4月加拿大卫生部和美国 FDA分别批准溴甲纳曲酮注射剂(methylnaltrexone bromide,Relistor)上市,皮下注射,用于治疗A片类药物引起的便秘 (opioid-induced constipation,OIC)而使用轻泻药又无效的情况。 加拿大卫生部率先在全球批准了此新颖的药品。溴甲纳曲酮是在欧盟范围内获准用于A片类药物诱导便秘的第一个药物,但其禁忌用于已知或疑有机械性胃肠道阻塞患者。晚期重症患者,如癌症、由肺气肿发展所致慢性阻塞性肺病(COPD)、心衰、阿尔茨海默病和艾滋病晚期患者需要较长的一段时间中连续使用A片类药物,这类药物可通过松弛平滑肌,阻止其收缩,从而干扰正常的肠道排便功能。溴甲纳曲酮属外周作用μ-A片受体拮抗剂,它能选择性地自包括胃肠道在内的中枢神经系统外的μ-受体中替代A片类药物,阻止A片进入平滑肌细胞,同时它因自身化学结构关系难于进人中枢神经系统,故既可有效减轻 A片类药物诱导便秘、又不会影响此类药物的止痛效力。溴甲纳曲酮通过减少诸如mafei和kedaiyin等A片类药物的便秘不良反应来发挥作用而不影响它们的镇痛作用。A片类药物通过特异性地与脑和脊柱等中枢神经系统内的mu-A片类受体相互作用来镇痛或解除疼痛。然而,A片类药物也与中枢神经系统外(譬如胃肠道内)的mu-A片类受体相互作用,造成便秘。溴甲纳曲酮可选择性地替代中枢神经系统外(包括胃肠道内)的mu-受体。由于溴甲纳曲酮的化学结构特点限制其进入中枢神经系统。 溴甲纳曲酮禁用于已知或疑似患机械性胃肠道梗阻或紧急腹部外科手术患者。若治疗期间发生腹泻,应停止使用溴甲纳曲酮或向医生咨询。 溴甲纳曲酮在临床研究中的不良反应是腹痛,气胀,恶心,眩晕和腹泻。
【临床研究】 溴甲纳曲酮治疗的有效性和安全性业得到两项随机、双肓、安慰剂对照试验的证实,但其用药4个月以上及在儿童人群中的作用尚未予于适当研究。
溴甲纳曲酮先前已于2008年3月28日和4月24日分别获得加拿大和美国药政当局的批准并现均业正式上市销售。年龄中值为68岁、预期寿命少于6个月的287名受试者参加了Relistor的安全性和有效性实验。这些受试者在用药前一周的肠蠕动次数少于3次或在用药前持续2天以上无肠蠕动,而使用本品治疗后,受试者排便率明显高于安慰剂组。
美国FDA推荐,本品开始使用时,应每隔一天使用1次。本品的常见副作用包括恶心、头晕、腹痛、腹泻和多屁(排气)。
临床前以及对健康受试者试验证明,连续注射或口服Relistor都可以明显的缓解A片类药物引起的便秘,且不良反应较少;III期临床试验证明,对于使用A片类药物的老年患者皮下注射Relistor0.15 ~0.3mg•kg-1,具有理想的缓解OIC作用;采用静脉注射给药,Relistor能够减轻由A片药物诱导的尿潴留症状;Relistor 对于术后肠梗阻症状也有一定的治疗意义。
Relistor每隔一天皮下注射一次,如果需要可以缩短给药间隔,但是用药间隔不可短于24小时 。 在美国,每年大约有150万名以上的患者因为患某种晚期疾病(如癌症、晚期心肺疾病或艾滋病等)而接受阵痛治疗,多数患者是服用A片类药物进行阵痛,这些患者几乎都会出现可缓解性的便秘症状,Relistor的问世能够为服用A片类药物所引起的便秘(OIC)的晚期疾病患者极大地减轻痛苦。溴甲纳曲酮的静脉注射剂早在2008年已进入III期临床试验,用于治疗术后肠梗阻(POI)。但是据 2008年3月的报告称,其中一项临床试验味道到主要指标——缩短胃肠道功能恢复时间。
Relistor(溴化甲基纳曲酮(methylnaltrexone))皮下注射
批准日期:2008年4月25日;公司:Progenics Pharmaceuticals, Inc.和Wyeth Pharmaceuticals
一般描述: RELISTOR (溴化甲基纳曲酮)皮下注射,一种外周作用的μ-阿片受体拮抗剂,是一种消毒,透明和无色至浅黄色水溶液。溴化甲基纳曲酮的化学名是(R)-N-(cyclopropylmethyl) noroxymorphone methobromide。分子式是C21H26NO4Br,和相对分子量436.36。 适应证:
RELISTOR适用于治疗阿片诱发便秘晚期疾病接受姑息治疗的患者,当对泻药治疗反应不满意时。 尚未研究RELISTOR的使用超过4个月。
剂量和用法:
皮下注射给予RELISTOR。常用给药方案是每隔1天1次,当需要时,可比24小时期间1次更频。
禁忌证:
有已知或怀疑机械性胃肠道梗阻的患者禁忌用RELISTOR。
不良反应:
用RELISTOR报道的最常见(> 5%)不良反应是腹痛、胀气、恶心、眩晕、腹泻和多汗症。
药物相互作用:
在一项体外研究,溴化甲基纳曲酮是一种细胞色素P450(CYP)同工酶CYP2D6活性的弱抑制剂,但在一项体内研究它不显著影响CYP2D6底物美沙芬的代谢。
特殊人群中使用: 尚未确定RELISTOR在患儿中的安全性和有效性。
RELISTOR (methylnaltrexone bromide) is indicated for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. Use of RELISTOR beyond four months has not been studied.
Opioid-induced constipation is a challenge in palliative care More than 1.5 million Americans have an advanced illness.1 Many patients receive opioid analgesics to palliate moderate-to-severe pain, which can often lead to constipation.2 While laxatives may provide constipation relief for some patients, this treatment may be insufficient.
Target the underlying cause of OIC with RELISTOR RELISTOR is the first opioid-induced constipation treatment that targets the underlying cause of OIC without impacting opioid-mediated analgesic effects on the central nervous system.2,3 RELISTOR delivers constipation relief for patients with advanced illness receiving palliative care by displacing opioid binding in tissues in the gastrointestinal tract.3
RELISTOR delivers rapid constipation relief In 2 clinical studies, 62% and 48% of patients treated with RELISTOR had a bowel movement within 4 hours of the first injection.3 In each study, 50% of those who responded in 4 hours did so within 30 minutes.3
Dosage and administration for RELISTOR
RELISTOR is administered as a subcutaneous injection. Administer as needed but do not exceed 1 dose per 24-hour period.
Recommended Dose by Weight
Patient Weight in Pounds |
Patient Weight in Kilograms |
Injection Volume |
Dose |
84 to less than 136 |
38 to less than 62 |
0.4 mL |
8 mg |
136 to 251 |
62 to 114 |
0.6 mL |
12 mg |
Patients whose weight falls outside of these ranges should be dosed at 0.15 mg/kg. The injection volume for these patients should be calculated using one of the following:
Multiply the patient weight in pounds by 0.0034 and round the volume up to the nearest 0.1 mL Multiply the patient weight in kilograms by 0.0075 and round the volume up to the nearest 0.1 mL In patients with severe renal impairment (creatinine clearance less than 30 mL/min) dose reductions of Relistor by one half is recommended.
RELISTOR
Generic Name for RELISTOR
Methylnaltrexone bromide 8mg/0.4mL, 12mg/0.6mL; soln for SC inj.
Legal Classification:
Rx
Pharmacological Class for RELISTOR
Opioid antagonist (peripheral).
Manufacturer of RELISTOR
Salix Pharmaceuticals, Inc.
Indications for RELISTOR
Opioid-induced constipation.
Adult dose for RELISTOR
Give by SC inj in upper arm, abdomen, or thigh once every other day as needed (max 1 dose/24hrs); rotate inj sites. <38kg or >114kg: 0.15mg/kg. 38–<62kg: 8mg. 62–114kg: 12mg. Severe renal impairment (CrCl<30mL/min): reduce dose by ½. Prefilled syringes: use only for 8mg or 12mg fixed doses.
Children's dosing for RELISTOR
Not recommended.
Contraindications for RELISTOR
Mechanical GI obstruction (known or suspected).
Warnings/Precautions for RELISTOR
Discontinue if severe or persistent diarrhea occurs. GI tract lesions (known or suspected); discontinue if symptoms occur. Peritoneal catheterization. Bowel movement may occur within 30min of dosing. Pregnancy (Cat.B). Nursing mothers.
Adverse Reactions for RELISTOR
Abdominal pain, flatulence, nausea, dizziness, diarrhea, hyperhidrosis; rare: GI perforation.
How is RELISTOR supplied?
Single-use vial (12mg/0.6mL)—1; Kit (w. 7 vials [12mg/0.6mL], syringes, needles, supplies)—1; Prefilled syringes (8mg/0.4mL, 12mg/0.6mL)—7
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