日本Astellas制药美国分公司宣布，美国食品及药品管理局（the U.S. Food and Drug Administration）批准了该公司的VAPRISOL(R) （研究名：YM087，通用名：盐酸考尼伐坦）。Vaprisol为精氨酸后叶加压素（AVP）拮抗剂，用于治疗住院患者低钠血症的静脉注射治疗。Vaprisol由Astellas公司研发和制造，是第一个专门治疗低血钠的药物。当身体中的血钠水平明显低于正常值时便会潜在的威胁生命。FAD同时颁发了Vaprisol治疗高容量性低钠血症的批准函。Astellas正积极与FDA联系，努力争取获得将Vaprisol应用于临床治疗高容量性低钠血症的批文。在美国每年有4%的住院患者深受这种疾病的困扰。
- 尽管很多低钠血症患者的症状都不明显，但严重时会导致脑水肿、呼吸停止甚至死亡。癌症、甲状腺功能减退、使用某些药物（如某些抗抑郁药）等，极易造成全身体液增加而钠不增加，出现低钠血症。
- “Vaprisol有助于医生有效地治疗这种无明显症状但预后非常严重的疾病。” Astellas 制药美国分公司的总裁Ph.D. Makoto Nishimura说，“Vaprisol获得批准进一步证明了Astellas公司研发创新药品以推动健康事业发展的决心。”
在一项随机、双盲、使用安慰剂的对照研究中，静脉注射Vaprisol，4天，40毫克/天，可有效校正轻度和中度住院患者体内的水钠平衡。治疗的首日就可显著提高患者的血清钠浓度。Vaprisol最常见的不良反应是注射部位反应，通常是轻度的，不需要停止用药。
“目前使用的限制水分、使用利尿药、生理盐水等治疗手段，普遍存在疗效不佳的问题。”乔治敦大学医学中心（Georgetown University Medical Center）医疗部主席、医学博士Joseph Verbalis说，“Vaprisol能有效校正低钠血症患者的水钠平衡，更好的管理这种无明显症状但预后非常严重的疾病。”
关于低钠血症
低钠血症通常是由于精氨酸后叶加压素（AVP）水平升高引起，AVP可以调整体内水盐平衡。临床医学上，低钠血症是最常见的电解质紊乱，也是最难治疗的疾病之一。抗利尿激素分泌过多综合征(SIADH)、晚期肾功能衰竭、甲状腺功能减退、癌症、慢性高血压通常会引起低钠血症。稀释性低钠血症最为常见，包括等容量性低钠血症和高容量性低钠血症。当人体只能留住水分而无法留住钠时便会出现这种症状。
关于Vaprisol
Vaprisol是由日本Astellas制药公司研发和制造的，公司总部设在日本东京。此药是一种抑制AVP活性的新颖药物，能增加尿排泄而不损失诸如钠和钾等有价值的电解质，即“利水作用”（aquaresis），有助于校正因体液增加导致的低钠血症患者（稀释型）的血清钠浓度。 Vaprisol是首个安全有效的AVP拮抗剂，通过“利水作用”改善对等容量性低钠血症患者水盐平衡的管理。
Vaprisol疗法在负荷剂量给药时，开始剂量为４ｍｌ（２０ｍｇ）；此后的持续剂量给药阶段，以20mg剂量为标准，输液时间为24小时。
在第一天的治疗之后，再以20mg/天的剂量持续输液1—3天。如果血清钠浓度没有上升，可将剂量加大到40mg/天持续输液。
住院病人患等容量性低钠血症（如抗利尿激素分泌过多综合征，或甲状腺机能减退、肾上腺机能不足、肺部疾病等），表明必须用Vaprisol来治疗。
Vaprisol不适用于低容量性高钠血症和任何形式的过敏症，也不能与CYP3A4的强效抑制剂合用，例如酮康唑、伊曲康唑、克拉霉素、利托那韦和印地那韦等。
常见的不良反应包括注射部位反应、低钾血症、头痛、口渴、呕吐等，大部分为轻度的，不需要停止用药。
将Vaprisol用于肝损伤患者（如肝腹水、 肝硬化或门静脉高压等）还没有进行系统的评价。Vaprisol不用于治疗充血性心力衰竭。
FDA Approves Astellas' Vaprisol(R) For Treatment Of Euvolemic Hyponatremia
Astellas Pharma US, Inc announced that the U.S. Food and Drug Administration (FDA) has approved VAPRISOL(R) (investigational name: YM087, generic name: conivaptan hydrochloride injection), an arginine vasopressin (AVP) antagonist for the intravenous treatment of euvolemic hyponatremia in hospitalized patients. VAPRISOL, discovered and developed by Astellas, is the first drug specifically indicated for the treatment of euvolemic hyponatremia, apotentially life-threatening condition that occurs when the body's blood sodium level falls significantly below normal. The FDA also issued an approvable letter for VAPRISOL as a treatment for hypervolemic hyponatremia. Astellas plans on working closely with the FDA to obtain an approval for VAPRISOL's use in patients with hypervolemic hyponatremia. Hyponatremia is estimated to affect up to 4 percent of hospitalized patients in the United States each year.
1. While many patients with hyponatremia have no symptoms, severe cases are medical emergencies that can result in swelling of the brain, respiratory arrest and death. Euvolemic hyponatremia, which
occurs when total body water increases with little increase in sodium, is most often associated with conditions such as cancer and hypothyroidism and the use of certain drugs (such as some antidepressants).
2. "VAPRISOL will provide physicians with an important new treatment option for a serious condition" said Makoto Nishimura, Ph.D., president and chief executive officer of Astellas Pharma US, Inc., "The approval of VAPRISOL further illustrates Astellas' commitment to developing innovative pharmaceutical products that improve healthcare."
In a randomized, double-blind, placebo-controlled study, intravenous administration of VAPRISOL 40 mg/day for four days corrected the balance of sodium and water in hospitalized patients with mild to moderate euvolemic hyponatremia. Significant improvements in serum sodium levels were observed within the first day of treatment with VAPRISOL. The most common adverse events associated with VAPRISOL were infusion site reactions, most of which were mild and did not lead to discontinuation of the drug.
"Currently available treatment options for hyponatremia, such as fluid restriction, diuretics and saline solution are inconsistent in their effects, " said Joseph Verbalis, M.D., Chair, Department of Medicine, Georgetown University Medical Center. "VAPRISOL will allow us to effectively correct the sodium-water balance in patients with euvolemic hyponatremia, and will help us to better manage this common and potentially very serious condition."
About Hyponatremia
Hyponatremia often results from elevated levels of the hormone arginine vasopressin (AVP), which regulates water and salt balance in the body. It is the most common electrolyte disorder in clinical medicine and one of the most difficult to treat. Syndrome of inappropriate antidiuretic hormone (SIADH), advanced kidney failure, hypothyroidism, cancer and chronic high blood pressure are common causes of hyponatremia. Dilutional hyponatremia, which includes euvolemic and hypervolemic hyponatremia, is the most common form of the condition, and occurs when retained water dilutes serum sodium content.
About VAPRISOL
Discovered and developed by Astellas Pharma Inc. headquartered in Tokyo, Japan, VAPRISOL is a novel drug that blocks the activity of AVP, resulting in increased urine output without loss of valuable electrolytes such as sodium and potassium. This effect, known as "aquaresis," helps to correct serum sodium levels in patients with hyponatremia due to increased body water (dilutional hyponatremia). VAPRISOL is the first AVP antagonist that safely and effectively promotes aquaresis for improved management of salt and water imbalance in patients with euvolemic hyponatremia.
VARISOL therapy will begin with a loading dose of 20 mg IV administration followed by 20 mg administered as a continuous infusion over 24 hours. Following the initial day of treatment, VAPRISOL is to be administered for an additional 1 to 3 days as a continuous infusion of 20 mg/day. If serum sodium does not rise at the desired rate, VAPRISOL may be titrated upward to a daily dose of 40 mg, again administered in a continuous infusion.
VAPRISOL is indicated for the treatment of euvolemic hyponatremia (e.g., the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients. VAPRISOL is contraindicated in patients who have hypovolemic hyponatremia and in those who have hypersensitivity to any of its components. The co-administration of VAPRISOL with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir, is contraindicated. The common adverse reactions reported with VAPRISOL administration include infusion site reactions, hypokalemia, headache, thirst and vomiting. The majority of the reactions were mild and did not lead to discontinuation of the drug. The use of VAPRISOL in patients with hepatic impairment (including ascites, cirrhosis or portal hypertension) has not been systematically evaluated. VAPRISOL is not indicated for the treatment of patients with congestive heart failure.
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