近日，美国FDA批准Onfi（clobazam）片剂和悬浮液作为一种辅助药物用于治疗成人或2岁及以上儿童的Lennox-Gastaut综合症（LGS）相关的癫痫症状。 Lennox-Gastaut综合症是癫痫中一种严重的类型，会导致衰弱发作。Lennox-Gastaut综合征通常在4岁之前发病，若干情况均可以导致发病，包括脑畸形、头部严重受伤、中枢神经系统感染以及某些遗传退行性或代谢情况。30％至35％的患者没有找到任何病因。患者通常的发作形式多样且频繁，包括全身性强直（身体僵硬、眼睛有向上偏差，瞳孔的扩张，呼吸模式的改变）、失张力（肌张力和意识简短的丧失，造成突然跌倒）、非典型失神（神志恍惚）、肌阵挛（突然的肌肉抽搐）等。 批准日期：2011年10月24日 公司：Lundbeck公司 ONFI(氯巴占[clobazam])片，口服使用CIV ONFI(氯巴占[clobazam])悬浮液,口服使用CIV 美国初步批准:2011年 警告: 与阿片类药物同时使用的风险见完整的盒装警告的完整处方信息。 同时使用苯二氮卓类药物和阿片类药物可能导致严重的镇静、呼吸抑制、昏迷和死亡。 保留这些药物的伴随处方，以供那些替代治疗方案不充分的病人使用。 将剂量和持续时间限制在最低限度。 跟踪病人呼吸抑制和镇静的体征和症状。 作用机理 氯巴扎姆，一种1，5-苯二氮卓，确切的作用机制尚不完全清楚，但被认为涉及增强GABAA受体苯二氮卓部位结合产生的GABA能神经传递。 适应症和用法 ONFI是一种苯二氮平类药物，用于辅助治疗2岁或2岁以上的Lennox-Gastaut综合征(LGS)发作。 剂量和管理 每日剂量超过5毫克，分两次服用。 病人≤30公斤体重:启动5毫克每日和滴定容忍每天20毫克。 患者>体重30公斤:初始每日10mg，每日可耐受滴定40mg。 以下各组需要调整剂量: 老年患者。 已知CYP2C19代谢不良。 轻度或中度肝功能损害;没有关于严重肝损害的资料。 减少剂量，或逐渐停用药物。 药片:整片服用，分两半服用，或在苹果酱中混合服用。 使用提供的适配器和剂量注射器测量规定量的口服悬浮液。 片剂和口服悬浮液:可与食物同时服用或不服用。 剂型及强度 片剂:5mg,10mg, 20mg，附功能评分。 口服悬浮液:2.5mg/mL, 120mL瓶。 禁忌症 对药物或其成分过敏史。 警告和预防措施 嗜睡或镇静:监测中枢神经系统(中枢神经系统)抑郁。与此同时使用其他中枢神经抑制剂可能增加风险。 戒断:症状可能出现与迅速减少剂量或停止。逐渐停止ONFI。 严重的皮肤反应(包括史蒂文斯-约翰逊综合征和毒性表皮坏死松解):除非皮疹明显与药物无关，否则在出现皮疹的第一时间停止使用fi。 生理和心理依赖:监测有药物滥用史的患者是否有习惯和依赖的迹象。 自杀行为与意念:监控自杀想法或行为。 不良反应 与安慰剂相比，任何剂量的不良反应发生频率至少高出10%，包括便秘、嗜睡或镇静、发热、嗜睡和流口水。 药物的相互作用 酒精:血液中氯巴嗪的含量增加约50%。 CYP2D6代谢的药物:当与ONFI同时使用时，可能需要低剂量的这些药物。 强或中度CYP2C19抑制剂:可能需要调整ONFI的剂量。 用于特定人群 怀孕:根据动物数据，可能会对胎儿造成伤害。 包装供应/储存和搬运 每个ONFI片含有5毫克,10毫克或20毫克的氯巴占，是一片白色至灰白色的椭圆形片剂，一侧有功能评分，另一侧有减压的“1”和“0”或“2”和“0”。 NDC 67386-314-01：5毫克记分片，100瓶 NDC 67863-314-01：10毫克记分片，100瓶 NDC 67386-315-01：20毫克划片片，100瓶 ONFI口服悬浮液是一种浆果味的白色液体，供应于儿童瓶中。口服悬浮液包装有一个分配器组，它包含两个校准的口服给药注射器和瓶适配器。 将FI-口服混悬液置于原瓶中直立放置。在第一次打开瓶子的90天内使用，然后丢弃任何剩余物。 NDC 67 38 6 31 321：2.5毫克/毫升供应在含有120毫升悬浮液的瓶子中。 在20°C至25°C（68°F至77°F）储存片剂和口服悬浮液。参见USP控制的室温。 完整资料附件：https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/ 202067s002,203993s002lbl.pdf FDA Approves ONFI™ (clobazam) FDA Approves ONFI™ (clobazam) for the Adjunctive Treatment of Seizures Associated with Lennox-Gastaut Syndrome in Patients Two Years and Older Approval based on largest clinical trial to date evaluating pediatric and adult patients with a current or prior diagnosis of LGS U.S. Food and Drug Administration (FDA) has approved ONFI™ (clobazam) as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients two years and older.ONFI (pronounced “ON-fee”) will be available in U.S. pharmacies in early January and is a federally controlled schedule four substance (C-IV). LGS is a rare and severe form of epilepsy that is typically diagnosed in childhood and often persists into adulthood.LGS is associated with multiple types of seizures with periods of frequent seizures, and daily seizures are common.5 Some of these seizures, including atonic, tonic and myoclonic seizures, may cause falls, or “drop seizures” (also referred to as “drop attacks”), which may result in injury. “As an epileptologist treating patients with a variety of challenging seizure disorders, I’m aware of the need for new add-on therapies to address the severe and frequent seizures associated with LGS,” said Joan A. Conry, MD, professor of neurology at Children’s National Medical Center in Washington, D.C., and a principal investigator of the CONTAIN Trial. “Clobazam, now approved as ONFI, was shown to be effective as adjunctive therapy for reducing seizures associated with LGS,1 and its upcoming availability provides hope for additional seizure management to patients and their physicians, caregivers and families.” The FDA approval of ONFI was based on two multicenter controlled studies similar in terms of disease characteristics and prior treatment of patients, including a pivotal Phase III study in 238 patients with a current or prior diagnosis of LGS.1 Named the CONTAIN Trial, the study’s primary endpoint was the percent reduction in the weekly frequency of drop seizures (atonic, tonic, or myoclonic), from the 4-week baseline period to the 12-week maintenance period. A Phase II dose-ranging study was also conducted (n=68) that was consistent with results of the CONTAIN Trial. The most common adverse reactions in the CONTAIN Trial included sleepiness or tiredness, fever, drooling, acting aggressive, irritability, lack of coordination and constipation. The adverse reactions leading to discontinuation in ≥ 1 percent in the CONTAIN Trial in decreasing order of frequency included tiredness, sleepiness, lack of coordination, acting aggressive, fatigue and difficulty sleeping. “The FDA approval of ONFI is a major milstone for Lundbeck as we continue our efforts to develop therapies for people with disorders of the central nervous system, including severe seizure disorders,” said Christopher Silber, M.D., vice president of U.S. clinical research and medical affairs at Lundbeck. “ONFI will be the second therapy for challenging types of epilepsy that Lundbeck has launched in the last two and a half years.” About ONFI™ (clobazam) ONFI is an oral antiepileptic drug developed in the United States by Lundbeck Inc, and will be available in 5 mg, 10 mg, and 20 mg tablets. ONFI is a 1,5 benzodiazepine. The exact mechanism of action for ONFI is not fully understood, but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor. Important Safety Information •ONFI is a prescription medicine used along with other medicines to treat seizures associated with Lennox-Gastaut syndrome in people 2 years of age or older. •ONFI can make you sleepy or dizzy and can slow your thinking and make you clumsy which may get better over time. Do not drive, operate heavy machinery, or other dangerous activities until you know how ONFI affects you. Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking ONFI without first talking to your healthcare provider as your sleepiness or dizziness may get much worse. •ONFI can cause withdrawal symptoms. Do not stop suddenly taking ONFI without first talking to a healthcare provider. Stopping ONFI suddenly can cause seizures that will not stop (status epilepticus), hearing or seeing things that are not there (hallucinations), shaking, nervousness, and stomach and muscle cramps. •ONFI can be abused and cause dependence. Physical dependence is not the same as drug addiction. Talk to your healthcare provider about the differences. ONFI is a federally controlled substance (C-IV) because it can be abused or lead to dependence. •Like other antiepileptic drugs, ONFI may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call your healthcare provider right away if you have any symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings, and especially if they are new, worse, or worry you. •If you are pregnant or plan to become pregnant, ONFI may harm your unborn baby. You and your healthcare provider will have to decide if you should take ONFI while you are pregnant. •ONFI can pass into breast milk. You and your healthcare provider should decide if you should take ONFI or breast feed. You should not do both. •The most common side effects seen in ONFI patients include: sleepiness; drooling; constipation; cough; pain with urination; fever; acting aggressive, being angry or violent; difficulty sleeping; slurred speech; tiredness and problems with breathing.