美国FDA于2009年5月19日批准了日本大冢制药(Otsuka Pharm)的新分子化合药——托伐普坦片(Tolvaptan Tablets,商品名:Samsca)用于治疗高容或等容性低钠血症伴心力衰竭、肝硬化、抗利尿激素分泌异常综合征。
INDICATIONS AND USAGE
SAMSCA is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia [serum sodium < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction], including patients with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).
Important Limitations:
• Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological
symptoms should not be treated with SAMSCA.
• It has not been established that SAMSCA provides a symptomatic benefit to patients.
DOSAGE AND ADMINISTRATION
• SAMSCA should be initiated and re-initiated in a hospital.
• The recommended starting dose is 15 mg once daily. Dosage may be increased at intervals ≥24 hr to 30 mg once daily, and to a maximum of 60 mg once daily as needed to raise serum sodium. Monitor serum sodium and volume status.
DOSAGE FORMS AND STRENGTHS
• Tablets: 15 mg and 30 mg
CONTRAINDICATIONS
• Do not administer to patients requiring urgent intervention to raise serum sodium acutely.
• Do not use in patients who are unable to sense or to respond appropriately to thirst.
• Do not use in patients with hypovolemic hyponatremia.
• Do not use with strong CYP 3A inhibitors.
• Do not administer to patients who are anuric as no benefit is expected.
WARNINGS/PRECAUTIONS
• Monitor serum sodium and neurologic status as serious neurologic sequelae can result from
over rapid correction of sodium.
• Because of the potential increased risk of gastrointestinal bleeding in patients with cirrhosis,
use in patients with cirrhosis only when the need to treat outweighs this risk.
• Dehydration and hypovolemia may require intervention.
• Avoid use with hypertonic saline.
• Avoid use with CYP 3A inducers and moderate CYP 3A inhibitors.
• Consider dose reduction if co-administered with P-gp inhibitors.
• Monitor serum potassium in patients with potassium > 5 mEq/L or on drugs known to increase potassium.
ADVERSE REACTIONS
Most common adverse reactions (≥ 5% placebo) are thirst, dry mouth, asthenia, constipation,
pollakiuria or polyuria, and hyperglycemia.
SAMSCA TAB 15MG 10 15MG TABLET
SAMSCA TAB 30MG 10 30MG TABLET
【英文名】tolvaptan Tablet
【汉语拼音】TuoFaPuTanPian
【化学名】N-[4-[(5R)-7-氯-5-羟基-2,3,4,5-四氢-1-苯并氮杂卓-1-甲酰基]-3-甲基苯基]-2-甲基苯甲酰胺。
其结构式为：
【分子式】C26H25ClN2O3
【分子量】448.94
【主要成分】托伐普坦
【性状】白色片剂。
【适应症】
治疗由充血性心衰、肝硬化以及抗利尿激素分泌不足综合征导致的低钠血症。
【用法用量】
15mg/片，一次/日。或尊医嘱。
【药理毒理】
一种血管加压素V2受体拮抗药(非肽类AVP2受体拮抗剂),可以升高血浆中钠离子浓度，帮助多余的水分从尿液排出。增强肾脏处理水的能力。多囊肾细胞内环磷酸腺苷（cAMP）积聚，其通过刺激囊液分泌和内衬细胞增生促进囊肿生长。托伐普坦是2型加压素受体拮抗剂，可抑制cAMP生成和聚积。在多种PKD动物模型研究中，托伐普坦显示出良好疗效。
【药代动力学】（详见说明书。）
【不良反应】口干、渴感、晕眩、恶心、低血压等。
【注意事项】详见说明书。
【禁忌】对本品过敏者禁用。（详见说明书。）
【批准文号】尚未在国内上市。
【规格】
15mg；30mg；60mg/片
【生产企业】
日本大冢制药公司；美国诺华
FDA批准托伐普坦片治疗低钠血症
FDA 已经批准托伐普坦片（tolvaptan，Samsca）治疗低钠血症，本品是唯一获准治疗该症的口服型选择性加压素拮抗剂。Samsca在美国地区的销售由Otsuka美国分公司负责。
