近日，美国食品和药物管理局(FDA)批准MOVANTIK，为成人慢性非癌痛患者治疗阿片类药物所致便秘(OIC)的首个每日口服外周作用mu-阿片类受体拮抗剂(PAMORA)。 批准日期：2014年9月16日 公司：阿斯利康 MOVANTIK(纳洛西格[naloxegol])片，供口服使用 美国初步批准:2014年 最近的重大变化 适应症和用法:08/2017 作用机制 MOVANTIK是阿片类药物在阿片类受体上结合的拮抗剂。当以推荐剂量水平给药时，纳洛西格尔在胃肠道等组织中作为外周作用的阿片受体拮抗剂，从而减少阿片类药物对便秘的影响。 MOVANTIK是纳洛酮的聚乙二醇衍生物，是p -糖蛋白转运蛋白(P-gp)的底物。此外，与纳洛酮相比，纳洛酮中聚乙二醇部分的存在降低了它的被动渗透率。由于naloxegol通过血脑屏障的通透性降低和流出量增加，与P-gp底物性质有关，nns对naloxegol的渗透在推荐剂量水平下是可以忽略不计的，这限制了对中枢介导的阿片类镇痛的潜在干扰。 适应症和用法 MOVANTIK是一种阿片类药物拮抗剂，用于治疗成人慢性非癌性疼痛患者的阿片类药物引起的便秘(OIC)，包括与既往癌症相关的慢性疼痛患者或其治疗不需要频繁(如每周)阿片类药物剂量增加的患者。 剂量和管理 管理: •在动手术前停止维持通便治疗;如果患者在服用莫凡替克3天后出现OIC症状，可继续服用泻药。 •启动MOVANTIK之前不需要改变镇痛给药方案。 •服用阿片类药物少于4周的患者对MOVANTIK的反应可能较差。 每天第一餐前1小时或饭后2小时空腹进食。 •对于不能完全吞下MOVANTIK药片的患者，可将药片压碎口服或经鼻胃管给药，详见处方说明。 避免食用葡萄柚或葡萄柚汁。 如果阿片类止痛药的治疗也停止了，则停止使用。 建议用量: •25毫克每天一次;如果不能耐受，每天一次减少到12.5毫克。 •肾脏损害(CLcr<60mL/min): 12.5mg，每日1次;如果耐受，每天一次增加到25mg，监测不良反应。 剂型及强度 •片剂:12.5mg, 25mg 禁忌症 •已知或怀疑存在消化道梗阻且复发性梗阻风险增加的患者。 •与强CYP3A4抑制剂(如克拉霉素、酮康唑)一起使用。 •已知对MOVANTIK或其赋形剂的严重或严重过敏反应。 警告和预防措施 •阿片类药物戒断:考虑血脑屏障受损患者的总体风险收益。监测阿片类药物戒断症状。 •严重的腹痛和/或腹泻:在使用MOVANTIK治疗后监测症状的发展，如果出现严重症状则停止治疗。如果合适的话，可以考虑每天12.5毫克重新启动MOVANTIK。 •胃肠道穿孔:考虑已知或可疑胃肠道病变患者的总体风险收益。监测严重、持续或恶化的腹痛;如果出现症状停止。 不良反应 在临床试验中最常见的不良反应(≥3%)是:腹痛、腹泻、恶心、肠胃气胀、呕吐,头痛。 要报告疑似不良反应，请致电1-800-236-9933与或1-800-FDA-1088或www.fda.gov/medwatch与FDA联系。 药物的相互作用 •适度的CYP3A4抑制剂(例如diltiazem，红霉素，维拉帕米):增加纳洛西格尔浓度;避免同时使用;如果不可避免，每天一次减少剂量至12.5毫克，并监测不良反应。 •强CYP3A4诱导物(如利福平):纳洛昔洛格浓度降低;不建议同时使用。 •其他阿片类拮抗剂:潜在的附加效应和阿片类药物戒断风险增加;避免同时使用。 用于特定人群 •妊娠:可导致孕妇和胎儿阿片类物质的提取。 •哺乳期:不建议母乳喂养。 •肝脏损害:避免严重损害。 包装提供/存储和处理 MOVANTIK(naloxegol)药片供应如下: •NDC 0310-1969-30: 12.5毫克，每瓶30片 •NDC 0310-1969-90: 12.5毫克，一瓶90片 •NDC 0310-1969-39: 12.5 mg，单位剂量100片起泡盒(仅适用于HUD) •NDC 0310-1970-30: 25mg，每瓶30片 •NDC 0310-1970-90: 25mg，一瓶90片 •NDC 0310-1970-39: 25mg，单位剂量100片起泡盒(仅适用于HUD) 存储 MOVANTIK储存在20 - 25°C(68 - 77°F)。远足允许15 - 30°C(59 - 86°F)(见USP室温控制)。 完整说明附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f49c6978-ca7b-4a66-919b-757f8f92ef64 US Food and Drug Administration (FDA) approved MOVANTIK as the first once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) medication for the treatment of opioid-induced constipation (OIC) in adult patients with chronic, non-cancer pain. IMPORTANT SAFETY INFORMATION ABOUT MOVANTIK MOVANTIK is contraindicated in: Patients with known or suspected gastrointestinal (GI) obstruction and patients at increased risk of recurrent obstruction due to the potential for GI perforation Patients receiving strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms Patients with a known serious or severe hypersensitivity reaction to MOVANTIK or any of its excipients Cases of GI perforation have been reported with the use of another peripherally acting opioid antagonist in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract. Monitor for severe, persistent, or worsening abdominal pain; discontinue if this symptom develops Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning, occurred in patients treated with MOVANTIK. Patients receiving methadone as therapy for their pain condition in the clinical trials were observed to have a higher frequency of GI adverse reactions that may have been related to opioid withdrawal than patients receiving other opioids. Patients with disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. These patients were not enrolled in the clinical studies. Take into account the overall risk-benefit profile when using MOVANTIK in such patients. Monitor for symptoms of opioid withdrawal when using MOVANTIK in such patients Avoid concomitant use of moderate CYP3A4 inhibitors (eg, diltiazem, erythromycin, verapamil) because they may increase the risk of adverse reactions. Use of strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John’s Wort) is not recommended because they may decrease the efficacy of MOVANTIK, Avoid use of MOVANTIK with another opioid antagonist due to the increased risk of opioid withdrawal The use of MOVANTIK during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier. MOVANTIK should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Due to the potential for serious adverse reactions, including opioid withdrawal in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother The most common adverse reactions with MOVANTIK as compared to placebo in clinical trials were abdominal pain (21% vs. 7%), diarrhea (9% vs. 5%), nausea (8% vs 5%), flatulence (6% vs 3%), vomiting (5% vs 4%), headache (4% vs. 3%), and hyperhidrosis (3% vs. >1%) About MOVANTIK™ (naloxegol) Tablets MOVANTIK™ (naloxegol) Tablets is the first FDA approved once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) specifically designed for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. In the Phase III clinical studies, MOVANTIK was administered as a once-daily tablet and was designed to block the binding of opioids to opioid receptors in tissues such as the gastrointestinal (GI) tract. MOVANTIK is part of the exclusive worldwide licence agreement announced on 21 September 2009 between AstraZeneca and Nektar Therapeutics. MOVANTIK was developed using Nektar’s oral small molecule polymer conjugate technology.