2018年4月27日，新药“托伐普坦”tolvaptan（商标名 Jynarque 大冢制药）已获美国FDA批准上市，作为第一种缓解成人肾功能下降的药物快速发展为常染色体显性多囊肾病（ADPKD）的风险，成为全球获批的首个ADPKD治疗药物。
  托伐普坦（Jynarque）是一种血管加压素V2受体拮抗剂，每日口服2次。该药具有一种独特的作用机制，仅促进水的排泄而不会影响其他电解质如钠离子的排泄。而在ADPKD患者中，血管加压素水平明显高于正常人群。高水平的血管加压素能促进囊肿的生长，从而使肾脏肿胀体积增大。托伐普坦通过阻断血管加压素的作用，减缓肾囊肿的生长速度。
  托伐普坦（Jynarque）的疗效在两项关键试验中得到证实。在为期一年的REPRISE研究中，与安慰剂相比，该药在一年中使用肾脏中的肾小球滤过率（GFR）作为生物标志物减少了大约35％，从而减缓了肾功能的下降。
  为期三年的TEMPO 3：4研究的数据显示：托伐普坦能够降低常染色体显性PKD中的总肾体积，以及肾脏疾病进展的时间（使用肌酸酐水平测量）和症状例如肾痛和高血压等症状。
  推荐剂量：对JYNARQUE的初始剂量是60mg口服每天作为45mg在醒来时服用和15mg服用8小时以后。滴定调整至60mg加30mg然后至90 mg加30mg每天如耐受滴定有间至少每周间隔。患者可能向下-滴定根据耐受性。鼓励患者饮足够水避免口渴或脱水。

https://www.otsuka-us.com/media/static/JYNARQUE-PI.pdf
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3febc0a1-9e5a-4ce0-843d-210f21d862c4

托伐普坦描述
商标名：Jynarque
活性物质：tolvaptan
持证商：Otsuka Pharmaceutical Development & Commercialization, Inc.
持证商地址：2440 Research Boulevard Rockville, MD 20850
剂型：Tablets
剂量： 15 mg, 30 mg, 45 mg, 60 mg, and 90 mg
适应症：Adults at Risk of Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease
申请编号：NDA204441
批准上市时间：04/23/2018
是否孤儿药：yes
Jynarque (Tolvaptan Tablets for Oral Use)
JYNARQUE Rx
Generic Name and Formulations:
Tolvaptan 15mg, 30mg, 45mg, 60mg, 90mg; tabs.
Company:
Otsuka America Pharmaceutical, Inc
Indications for JYNARQUE:
To slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD).
Adult:
Initially 60mg/day (45mg on waking + 15mg taken 8hrs later). Titrate to 60mg + 30mg, then to 90mg + 30mg per day if tolerated; separate titrations at least weekly. Concomitant moderate CYP3A inhibitors: reduce Jynarque dose (see full labeling); temporarily interrupt if recommended reduced doses are not available.
Children:
Not established.
Contraindications:
History, signs or symptoms of significant liver impairment or injury except uncomplicated polycystic liver disease. Concomitant strong CYP3A inhibitors. Uncorrected abnormal blood sodium concentrations or urinary outflow obstruction. Unable to sense or respond to thirst. Hypovolemia. Anuria.
Boxed Warning:
Risk of serious liver injury.
Warnings/Precautions:
Can cause serious and potentially fatal liver injury. Assess ALT/AST, bilirubin prior to treatment, at 2 and 4 weeks after initiation, then monthly for 18 months, and every 3 months thereafter. Discontinue immediately if signs/symptoms of hepatic injury occur, ALT/AST or bilirubin >2XULN; if resolves, may reinitiate (with more monitoring) if ALT/AST remains <3XULN. Do not restart if hepatic injury occurs or ALT/AST >3XULN. Ensure adequate hydration. Correct sodium concentration prior to initiation. Monitor for weight loss, tachycardia, hypotension. Suspend therapy until normalized if serum sodium increases above normal range, or hypovolemia or dehydration occurs and fluid intake cannot be increased. Elderly. Pregnancy. Nursing mothers: not recommended.
Pharmacological Class:
Selective vasopressin V2-receptor antagonist.
Interactions:
See Contraindications. Concomitant moderate CYP3A inhibitors: dose adjustment is needed (see Adult). Avoid concomitant grapefruit juice, strong CYP3A inducers, OATP1B1/3 and OAT3 substrates (eg, statins, bosentan, glyburide, nateglinide, repaglinide, methotrexate, furosemide), BCRP substrates (eg, rosuvastatin), and V2-receptor agonists (eg, desmopressin).
Adverse Reactions:
Thirst, polyuria, nocturia, pollakiuria, polydipsia; serious hepatic injury, hypernatremia, dehydration, hypovolemia.
REMS:
YES
How Supplied:
Tabs—14, 56