近日，美国FDA已批准新药每天一次口服口服的Ongentys（opicapone）胶囊作为左旋多巴/卡比多巴的辅助疗法，治疗经历“关闭”期（“off” episodes）的帕金森病患者。随着疾病的进展，服用左旋多巴/卡比多巴的患者可能开始出现“关闭”期，在此期间患者的震颤、运动减慢和行走困难的发生率会增加。Ongentys是唯一一款获批的可减少“关闭”期时间且不会引起运动障碍的儿茶酚氧位甲基转移酶（COMT）抑制剂。
帕金森病是一种慢性神经退行性疾病，在全球约有600万名患者。帕金森病目前还没有治愈的方法，患者通常需要使用左旋多巴治疗，替代丢失的多巴胺。长期使用这种药物会导致严重的运动能力波动。这种波动分为两个阶段——在“开启”期，患者的运动能力正常；而在“关闭”期，患者的运动能力明显下降，通常表现为运动缓慢、僵硬、行走障碍、震颤和姿势不稳定，极大地影响了患者的日常生活。
Ongentys是一种口服、选择性儿茶酚氧位甲基转移酶（COMT）抑制剂，它有助于阻断分解左旋多巴的COMT酶。Ongentys通过减少左旋多巴在血液中的分解，使更多的左旋多巴到达大脑，延长其临床效果，帮助患者实现运动症状控制。
批准日期：2020年4月27日 公司：Neurocrine Biosciences
ONGENTYS（阿片哌酮[opicapone]）胶囊，口服使用
美国初次批准：2020年
作用机理
opicapone是儿茶酚-O-甲基转移酶（COMT）的选择性和可逆抑制剂。
COMT催化S-腺苷-L-蛋氨酸的甲基向含有邻苯二酚结构的底物的酚基转移。COMT的生理底物包括DOPA，儿茶酚胺（多巴胺，去甲肾上腺素和肾上腺素）及其羟基代谢物。当卡比多巴阻止左旋多巴的脱羧时，COMT成为左旋多巴的主要代谢酶，催化其代谢为3-甲氧基-4-羟基-L-苯丙氨酸（3-OMD）。
适应症和用途
ONGENTYS是一种儿茶酚-O-甲基转移酶（COMT）抑制剂，适用于帕金森病（PD）发作“休”的患者的左旋多巴/卡比多巴的辅助治疗。
剂量和给药
•建议剂量为每天睡前口服一次50mg。
•服用ONGENTYS之前1小时和之后至少1小时，患者不应进食。
•中度肝功能不全患者的推荐剂量为每天睡前口服25mg；避免在有严重肝功能不全的患者中使用。
剂量形式和强度
胶囊：25mg和50mg。
禁忌症
•并用非选择性单胺氧化酶（MAO）抑制剂。
•嗜铬细胞瘤，副神经节瘤或其他儿茶酚胺分泌性肿瘤的病史。
警告和注意事项
•伴随使用儿茶酚-O-甲基转移酶（COMT）代谢的药物的心血管效应：可能导致心律不齐，心跳加快和血压过度变化。与COMT代谢产物同时治疗时，监测患者。
•在日常生活中入睡：在治疗前建议患者。
•低血压/晕厥：如果发生，请考虑停止使用ONGENTYS或调整其他可降低血压的药物的剂量。
•运动障碍：可能导致或加剧运动障碍；考虑左旋多巴或多巴胺能药物减量。
•幻觉和精神病：考虑停止发生GENISTYS。
•冲动控制/强迫症：考虑停止发生ONGENTYS。
•戒断急需的高热和精神错乱：停止ONGENTYS时，应监测患者并考虑根据需要调整其他多巴胺能疗法。
不良反应
最常见的不良反应（≥4％，>安慰剂）：运动障碍，便秘，血肌酸激酶升高，低血压/晕厥和体重减轻。
要报告可疑的不良反应，请致电877-641-3461与NeurocrineBiosciences，Inc.或致电1-800-FDA-1088与FDA联系，或访问www.fda.gov/medwatch。
在特定人群中的使用
•怀孕：根据动物数据，可能会造成胎儿伤害。
包装供应/存储和处理方式
供应方式
ONGENTYS（opicapone）胶囊的可用形式为：
•50毫克明胶硬胶囊，大小1；深蓝色不透明帽和深粉红色不透明体；在瓶盖和阀体上用白色墨水在“ 50”以上轴向打印“ OPC”
− 30瓶，带有防儿童进入的瓶盖：NDC 70370-3050-2
•25毫克明胶硬胶囊，大小1； 浅蓝色不透明帽和浅粉红色不透明主体；在盖子和阀体上轴向用“ OPC”和“ 25”以上的蓝色墨水轴向打印
−带儿童安全盖的30瓶：NDC 70370-3025-2
储存和处理
存放在低于30°C（86°F）的温度下。
完整说明资料附件：
http://www.neurocrine.com//assets/ongentyspi.pdf
FDA Approval of Once-Daily ONGENTYS(opicapone)as an Add-On Treatment for Patients with Parkinson’s Disease Experiencing “Off” Episodes
U.S. Food and Drug Administration(FDA)has approved once-daily oral ONGENTYS(opicapone)25mg and 50mg capsules as an add-on treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. As the disease progresses, patients taking levodopa/carbidopa may begin to experience “off” time between treatment doses, during which an increase in Parkinson’s disease motor symptoms such as tremor, slowed movement and difficulty walking occur.ONGENTYS also increases “on” time without troublesome dyskinesia, the time when the motor symptoms of a patient with Parkinson’s disease are better controlled.
About ONGENTYS(opicapone)Capsules
ONGENTYS is a novel, once-daily, oral, peripheral, selective and reversible catechol-O-methyltransferase (COMT) inhibitor approved by the U.S. Food and Drug Administration (FDA) as an add-on treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. ONGENTYS inhibits the COMT enzyme, which breaks down levodopa, making more levodopa available to reach the brain.
Important Safety Information
Contraindications
ONGENTYS is contraindicated in patients with:
Concomitant use of non-selective monoamine oxidase(MAO)inhibitors.
Pheochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.
Warnings & Precautions
Cardiovascular Effects with Concomitant Use of Drugs Metabolized by Catechol-O-Methyltransferase (COMT)
Possible arrhythmias, increased heart rate, and excessive changes in blood pressure may occur with concomitant use of ONGENTYS and drugs metabolized by COMT, regardless of the route of administration (including inhalation). Monitor patients treated concomitantly with ONGENTYS and drugs metabolized by COMT.
Falling Asleep During Activities of Daily Living and Somnolence
Patients treated with dopaminergic medications and medications that increase levodopa exposure, including ONGENTYS, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents.If a patient develops daytime sleepiness or somnolence, consider discontinuing ONGENTYS or adjusting other dopaminergic or sedating medications and advise patients to avoid driving and other potentially dangerous activities.
Hypotension/Syncope
Monitor patients for hypotension and advise patients about the risk for syncope. If these adverse reactions occur, consider discontinuing ONGENTYS or adjusting the dosage of other medications that can lower blood pressure.
Dyskinesia
ONGENTYS potentiates the effects of levodopa which may result in dyskinesia or exacerbate pre-existing dyskinesia. Reducing the patient’s levodopa dosage or the dosage of another dopaminergic drug may reduce dyskinesia that occurs during treatment with ONGENTYS.
Hallucinations and Psychosis
Consider stopping ONGENTYS if hallucinations or psychotic-like behaviors occur. Patients with a major psychotic disorder should ordinarily not be treated with ONGENTYS.
Impulse Control/Compulsive Disorders
Patients may experience intense urges(e.g., gambling, sexual, spending money, binge eating)and the inability to control them.It is important for prescribers to specifically ask patients or their caregivers about the development of new or increased urges. Re-eva luate the patient’s current therapies for Parkinson’s disease and consider stopping ONGENTYS if a patient develops such urges while taking ONGENTYS.
Withdrawal-Emergent Hyperpyrexia and Confusion
A symptom complex resembling neuroleptic malignant syndrome (elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), has been reported in association with rapid dose reduction or withdrawal of drugs that increase central dopaminergic tone. There were no reports of neuroleptic malignant syndrome in ONGENTYS controlled clinical studies. When discontinuing ONGENTYS, monitor patients and consider adjustment of other dopaminergic therapies as needed.