2010年3月23日，勃林格殷格翰制药公司宣布，美国食品药品管理局(FDA)已批准米拉帕缓释制剂(普拉克索)用于治疗特发性帕金森病(PD)的症状和体征。该药为口服缓释片剂，每日服用1次，早期或晚期PD患者均适用。先前获准的米拉帕(普拉克索)为速释型，每日服用3次。 FDA批准米拉帕缓释制剂用于治疗晚期PD患者是依据一项随机、双盲、安慰剂对照、3个平行组临床研究的疗效数据。该临床试验共纳入517例晚期PD患者，分别接受不同剂量的米拉帕缓释片或米拉帕治疗，或者安慰剂处置。 研究结果表明，晚期PD患者接受米拉帕缓释片治疗后，症状相对于安慰剂对照组有较大缓解。另外，与安慰剂对照组相比，米拉帕缓释片治疗组患者与米拉帕片剂治疗组患者均有收益且两治疗组的收益相近。米拉帕缓释片治疗组患者症状复发时间亦较对照组显著缩短。 在本研究中，联合左旋多巴治疗的晚期PD患者最常见的不良事件(发生率≥5%且高于安慰剂对照组)为运动障碍、恶心、便秘、幻觉、头痛及厌食。 早期PD患者服用米拉帕缓释片后最常见的不良事件为嗜睡、恶心、呕吐、便秘、头晕、乏力、幻觉、口干、肌肉痉挛及水肿。 药品英文名 Pramipexole 药品别名 米拉帕、Trivastal MIRAPEX 药物剂型 片剂：125μg，250μg。   药理作用 本品是人工合成的氨苯噻唑(aminobenzothiazole)的衍生物。具有D2-受体激动剂活性。采用UPDRS评分评估本品对早期帕金森病的作用，与安慰剂对照组相比，用药组患者生活能力显著改善，呈“关”状态的时间明显缩短，但两组患者的运动功能检查评分没有差别。 药动学 空腹口服后可迅速吸收，2h可达血药峰值；进食时口服本品后，3h达血药峰值。消除t1/2约9h，生物利用度＞90%，只有小部分被代谢，几乎全部经肾排出。 适应证 本品主要用于治疗帕金森病及其综合征。可单用或与左旋多巴合用。 禁忌证 哺乳者禁用。 注意事项 1.肾功能不全者慎用。 2.可引起睡眠发作，因此开车和机械操作者应特别注意。 不良反应 有幻觉、嗜睡、运动障碍、口干、恶心、便秘等。 用法用量 在开始第1周中，口服125μg，每天3次，第2周，口服250μg，每天3次；以后每周增加750μg，达最高每天4.5mg。   药物相应作用 西咪替丁可减少本品的清除。 专家点评 本品为一种选择性作用于多巴胺D3受体的多巴胺激动剂。可明显减少帕金森病静息时的震颤。晚期帕金森病用该药与左旋多巴共同治疗时，可使患者对左旋多巴需要量减少，并可延长症状最佳控制时间平均每天2h。有报道表明，虽然本品可用于治疗帕金森氏病及其综合征，但临床效果不肯定。 DESCRIPTION MIRAPEX tablets contain pramipexole, a nonergot dopamine agonist. The chemical name of pramipexole dihydrochloride is (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate. Its empirical formula is C10H17N3S • 2HCl • H2O, and its molecular weight is 302.27. The structural formula is:  Pramipexole dihydrochloride is a white to off-white powder substance. Melting occurs in the range of 296°C to 301°C, with decomposition. Pramipexole dihydrochloride is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane. MIRAPEX tablets, for oral administration, contain 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, or 1.5 mg of pramipexole dihydrochloride monohydrate. Inactive ingredients consist of mannitol, corn starch, colloidal silicon dioxide, povidone, and magnesium stearate. INDICATIONS Parkinson's Disease MIRAPEX (pramipexole dihydrochloride) tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease. The effectiveness of MIRAPEX tablets was demonstrated in randomized, controlled trials in patients with early Parkinson's disease who were not receiving concomitant levodopa therapy as well as in patients with advanced disease on concomitant levodopa (see CLINICAL STUDIES). Restless Legs Syndrome MIRAPEX tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). Key diagnostic criteria for RLS are: an urge to move the legs usually accompanied or caused by uncomfortable and unpleasant leg sensations; symptoms begin or worsen during periods of rest or inactivity such as lying or sitting; symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues; and symptoms are worse or occur only in the evening or night. Difficulty falling asleep may frequently be associated with symptoms of RLS. DOSAGE AND ADMINISTRATION Parkinson's Disease In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension. MIRAPEX tablets should be titrated gradually in all patients. The dosage should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth. Dosing in Patients with Normal Renal Function Initial Treatment Dosages should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage schedule that was used in clinical studies is shown in the following table: Table 7 Ascending Dosage Schedule of MIRAPEX tablets for Parkinson's Disease Week Dosage (mg) Total Daily Dose (mg) 1 0.125 TID 0.375 2 0.25 TID 0.75 3 0.5 TID 1.50 4 0.75 TID 2.25 5 1.0 TID 3.0 6 1.25 TID 3.75 7 1.5 TID 4.50 Maintenance Treatment MIRAPEX (pramipexole dihydrochloride) tablets were effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses three times per day with or without concomitant levodopa (approximately 800 mg/day). In a fixed-dose study in early Parkinson's disease patients, doses of 3 mg, 4.5 mg, and 6 mg per day of MIRAPEX tablets were not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. However, in the same fixed-dose study, the following adverse events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence reported with pramipexole at a dose of 1.5 mg/day was comparable to placebo. When MIRAPEX tablets is used in combination with levodopa, a reduction of the levodopa dosage should be considered. In a controlled study in advanced Parkinson's disease, the dosage of levodopa was reduced by an average of 27% from baseline. Dosing in Patients with Renal Impairment Table 8 Pramipexole Dosage in Parkinson's Disease Patients with Renal Impairment Renal Status Starting Dose (mg) Maximum Dose (mg) Normal to mild impairment (creatinine Cl > 60 mL/min) 0.125 TID 1.5 TID Moderate impairment (creatinine Cl = 35 to 59 mL/min) 0.125 BID 1.5 BID Severe impairment (creatinine Cl = 15 to 34 mL/min) 0.125 QD 1.5 QD Very severe impairment (creatinine Cl < 15 mL/min and hemodialysis patients) The use of MIRAPEX (pramipexole dihydrochloride) has not been adequately studied in this group of patients. Discontinuation of Treatment It is recommended that MIRAPEX tablets be discontinued over a period of 1 week; in some studies, however, abrupt discontinuation was uneventful. Restless Legs Syndrome The recommended starting dose of MIRAPEX tablets is 0.125 mg taken once daily 2-3 hours before bedtime. For patients requiring additional symptomatic relief, the dose may be increased every 4-7 days (Table 9). Although the dose of MIRAPEX was increased to 0.75 mg in some patients during long-term open-label treatment, there is no evidence that the 0.75 mg dose provides additional benefit beyond the 0.5 mg dose. Table 9 Ascending Dosage Schedule of MIRAPEX tablets for RLS Titration Step Duration Dosage (mg) to be taken once daily, 2-3 hours before bedtime 1 4-7 days 0.125 2* 4-7 days 0.25 3* 4-7 days 0.5 *if needed Patients with Renal Impairment The duration between titration steps should be increased to 14 days in RLS patients with severe and moderate renal impairment (creatinine clearance 20-60 mL/min) (see CLINICAL PHARMACOLOGY, Renal Insufficiency). Discontinuation of Treatment In clinical trials of patients being treated for RLS with doses up to 0.75 mg once daily, MIRAPEX tablets were discontinued without a taper. Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from light. Store in a safe place out of the reach of children. 附件  20095604133837.pdf --------------------------------------------------------------- 注：以下产品不同规格和不同价格，购买时请以电话咨询为准！ --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: MIRAPEX 1.5mg/tab 90Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 米拉帕 1.5毫克/片 90片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物 生产厂家中文参考译名: 德国勃林格殷格翰 生产厂家英文名: BOEHRINGER INGELHEIM --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: MIRAPEX 0.75mg/tab 90Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 米拉帕 0.75毫克/片 90片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物 生产厂家中文参考译名: 德国勃林格殷格翰 生产厂家英文名: BOEHRINGER INGELHEIM --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: MIRAPEX 0.5mg/tab 90Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 米拉帕 0.5毫克/片 90片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物 生产厂家中文参考译名: 德国勃林格殷格翰 生产厂家英文名: BOEHRINGER INGELHEIM --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: MIRAPEX 0.25mg/tab 90Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 米拉帕 0.25毫克/片 90片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物 生产厂家中文参考译名: 德国勃林格殷格翰 生产厂家英文名: BOEHRINGER INGELHEIM --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: MIRAPEX 0.25mg/tab 90Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 米拉帕 0.25毫克/片 90片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物 生产厂家中文参考译名: 德国勃林格殷格翰 生产厂家英文名: BOEHRINGER INGELHEIM --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: MIRAPEX 0.125mg/tab 90Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 米拉帕 0.125毫克/片 90片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物 生产厂家中文参考译名: 德国勃林格殷格翰 生产厂家英文名: BOEHRINGER INGELHEIM --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: PRAMIPEXOLE DI-HCL(MIRAPEX GENERIC) 0.125mg/tab 63Tabs/bottle 原产地英文药品名: PRAMIPEXOLE DIHYDROCHLORIDE 中文参考商品译名: 盐酸普拉克索(米拉帕仿制药) 0.125毫克/片 63片/瓶 中文参考药品译名: 盐酸普拉克索 中文参考化合物名称: 一水合二盐酸（S）-2-氨基-4，5，6，7-四氢-6-丙胺-苯并噻唑=盐酸普拉克索一水合物