近日，美国FDA批准Rytary(Carbidopa and Levodopa)用于治疗帕金森病，Rytary是帕金森病标准治疗药物卡比多巴-左旋多巴的一种长效口服胶囊剂，治疗帕金森病的特点是脑内多巴胺水平降低。 批准日期：2015年1月  公司：Impax Laboratories公司 RYTARY（卡比多巴左旋多巴 carbidopa/levodopa）缓释胶囊,为口服使用 美国首次批准：1975年 适应症和用法 RYTARY是卡比多巴（芳香氨基酸脱羧抑制剂）和左旋多巴（芳香族氨基酸）的帕金森综合征的组合表示为帕金森氏病，脑炎后帕金森综合征的治疗，并且可以遵循一氧化碳中毒或锰中毒。 用法用量 •左旋多巴初治患者：起始剂量为23.75毫克/ 95毫克，每日三次;可每日三次增加至36.25毫克/ 145毫克治疗的第四天。 •用于将采取立即释放卡比多巴 - 左旋多巴RYTARY患者说明见表1; RYTARY的剂量是不能互换与其他卡比多巴 - 左旋多巴产品 •最大推荐剂量为每日RYTARY是612.5毫克/2450毫克 •RYTARY可采取或没有食物;不嚼，分割或粉碎 剂型和规格 缓释胶囊：卡比多巴左旋多巴和23.75毫克/95毫克，36.25毫克/145毫克，48.75毫克/195毫克，61.25毫克/245毫克 禁忌 非选择性MAO抑制剂。 警告和注意事项 •可能导致在日常生活活动入睡。 •避免突然停药或迅速减少剂量，以减少戒断后出现高热和混乱的风险。 •心血管事件：监控患者的心血管疾病史。 •幻觉/精神病，可能会出现。 •冲动控制障碍：如果发生考虑减少剂量或停止RYTARY。 •可能引起或加重运动障碍：考虑减少剂量。 不良反应 •早期帕金森病：最常见的不良反应（发生率≥5％和大于安慰剂）的有恶心，头晕，头痛，失眠，梦异常，口干，运动障碍，焦虑症，便秘，呕吐，体位性低血压。 •先进的帕金森氏病：最常见的不良反应（发生率≥5％和大于口服速释卡比多巴 - 左旋多巴）是恶心和头痛。 要报告疑似不良反应，请联系的Impax实验室在1-877-99-IMPAX或FDA电话1-800-FDA-1088或www.fda.gov/medwatch 药物相互作用 铁盐和多巴胺D2受体拮抗剂，包括胃复安：可以减少RYTARY的有效性。 特殊人群中使用 妊娠：根据动物实验数据，可能对胎儿造成伤害。 包装规格 RYTARY CAP  61.25/245  100   CARBIDOPA/LEVODOPA     64896-0664-01      RYTARY CAP  23.75/95    240   CARBIDOPA/LEVODOPA     64896-0661-43      RYTARY CAP  36.25/145  240   CARBIDOPA/LEVODOPA     64896-0662-43     RYTARY CAP  48.75/195  240   CARBIDOPA/LEVODOPA     64896-0663-43  RYTARY CAP  61.25/245  240   CARBIDOPA/LEVODOPA     64896-0664-43  RYTARY CAP  23.75/95    100   CARBIDOPA/LEVODOPA     64896-0661-01 RYTARY CAP  36.25/145  100   CARBIDOPA/LEVODOPA     64896-0662-01  RYTARY CAP  48.75/195  100   CARBIDOPA/LEVODOPA     64896-0663-01  FDA Approves Rytary for Parkinson's Disease Impax announced that the Food and Drug Administration (FDA) has approved Rytary (carbidopa/levodopa) extended-release capsules for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication and/or manganese intoxication. Rytary capsules contain both immediate-release and extended-release beads in a fixed 1:4 carbidopa to levodopa ratio. The capsules may also be opened and the beads sprinkled on applesauce for patients who have trouble swallowing. RELATED: Parkinsonism Treatments The approval of Rytary was based on the Rytary clinical program that evaluated patients with early (levodopa-naive) to advanced Parkinson's disease. Results from the APEX-PD (Study 1) study of 381 levodopa-naive patients met the study's primary efficacy endpoint of mean change from baseline in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (activities of daily living) score and UPDRS Part III (motor skills) score vs. placebo at Week 30. In ADVANCE-PD (Study 2), treatment with Rytary decreased the percent of "off" time from 36.9% to 23.8% from baseline vs. immediate-release carbidopa/levodopa (36.05 to 29.8%) during waking hours to end of study. Rytary will be available in 23.75mg/95mg, 36.25mg/145mg, 48.75mg/195mg, and 61.25mg/245mg capsules. It is expected to launch in February 2015. INDICATION RYTARY (rye-TAR-ee) (carbidopa and levodopa) extended-release capsules are indicated for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication. IMPORTANT SAFETY INFORMATION • RYTARY is contraindicated in patients who are currently taking or have recently (within 2 weeks) taken a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine). Hypertension can occur if these drugs are used concurrently. • Patients treated with levodopa (a component of RYTARY) have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence while on levodopa, some perceived that they had no warning signs (sleep attack), such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported more than 1 year after initiation of treatment. Before initiating treatment with RYTARY, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with RYTARY such as concomitant sedating medications or the presence of a sleep disorder. Prescribers should consider discontinuing RYTARY in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.). If a decision is made to continue RYTARY, patients should be advised not to drive and to avoid other potentially dangerous activities that might result in harm if the patients become somnolent. • A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. Avoid sudden discontinuation or rapid dose reduction in patients taking RYTARY. If the decision is made to discontinue RYTARY, the dose should be tapered to reduce the risk of hyperpyrexia and confusion.  • Cardiovascular ischemic events have occurred in patients taking RYTARY. In patients with a history of myocardial infarction who have residual atrial, nodal, or ventricular arrhythmias, cardiac function should be monitored in an intensive cardiac care facility during the period of initial dosage adjustment.  • There is an increased risk for hallucinations and psychosis in patients taking RYTARY. Hallucinations present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa. Hallucinations may be accompanied by confusion, insomnia, and excessive dreaming. Abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.  Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with RYTARY. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of RYTARY.  • Case reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications, including RYTARY, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with RYTARY. Consider a dose reduction or stopping the medication if a patient develops such urges while taking RYTARY.  • RYTARY can cause dyskinesias that may require a dosage reduction of RYTARY or other medications used for the treatment of Parkinson’s disease.  • Treatment with RYTARY may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer and may cause increased intraocular pressure in patients with glaucoma.  • Early Parkinson’s disease: Most common adverse reactions (incidence ≥ 5 % and greater than placebo) are nausea, dizziness, headache, insomnia, abnormal dreams, dry mouth, dyskinesia, anxiety, constipation, vomiting, and orthostatic hypotension.  • Advanced Parkinson’s disease: Most common adverse reactions (incidence ≥ 5 % and greater than oral immediate-release carbidopa-levodopa) are nausea and headache.  • RYTARY should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when RYTARY is administered to a nursing woman.  Overdosage • The acute symptoms of levodopa/dopa decarboxylase inhibitor overdosage can be expected to arise from dopaminergic overstimulation (cardiovascular and central nervous system disturbances).  Drug Interactions: • Monitor patients taking selective MAO-B inhibitors and carbidopa-levodopa. The combination may be associated with orthostatic hypotension. RYTARY should be co-administered cautiously with: dopamine D2 antagonists (metoclopramide), isoniazid, and iron salts.  Dosing Information: • Dosages of RYTARY are not interchangeable with other carbidopa-levodopa products. The starting dose for levodopa-naïve patients is 23.75 mg / 95 mg three times daily; may increase to 36.25mg/145mg three times daily on the fourth day of treatment. See Full PrescribingInformation for instructions for starting patients on RYTARY and converting patients from immediate-release carbidopa and levodopa to RYTARY.  • Doses and dosing intervals may be adjusted depending upon individual therapeutic response and adverse reactions. Maintain patients on the lowest dosage required to achieve symptomatic control and minimize adverse reactions such as dyskinesia and nausea.  • RYTARY should not be chewed, divided, or crushed. • The maximum recommended daily dose of RYTARY is 612.5 mg / 2450 mg. http://rytaryhcp.com/clinical-trial-results http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6c1f7cd4-de56-45c1-a734-5e77b4aeb6f7