Vasopressin Antagonists

Information about Vasopressin Antagonists

Tolvaptan is a vasopressin 2 receptor antagonist which is used for short term treatment of severe hyponatremia in patients with heart failure, cirrhosis or syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It has been used experimentally to prevention progression of disease in autosomal dominant polycystic kidney disease (ADPKD).

Liver toxicity of Vasopressin Antagonists

Tolvaptan recently has been implicated in causing serum aminotransferase elevations as well as clinically apparent acute liver injury during long term use.

Mechanism of action of Vasopressin Antagonists

Tolvaptan (tol vap' tan) is a vasopressin 2 receptor antagonist (vaptan) that is used for treatment of hyponatremia caused by elevated levels of arginine vasopressin (also known as antidiuretic hormone: ADH), commonly found in patients with inappropriate ADH syndrome (SIADH) or with fluid overload from heart failure or cirrhosis. Vasopressin acts on type 2 receptors in the distal renal tubules causing reabsorption of free water, without electrolytes. Inappropriate secretion of vasopressin (as occurs in some paraneoplastic syndromes) is associated with retention of water and dilutional hyponatremia that can be symptomatic and even fatal. In controlled clinical trials, tolvaptan given for 28 days resulted in an increase in serum sodium and diuresis in patients with hypervolemic hyponatremia, in patients with cirrhosis and heart failure, and euvolemic hyponatremia in patients with SIADH.

FDA approval information for Vasopressin Antagonists

Tolvaptan was approved for use in the United States in 2009 and current indications are for short term therapy of patients with hypervolemic or euvolemic hyponatremia due to SIADH, congestive heart failure or cirrhosis. Tolvaptan has also been used experimentally to prevent progression of disease in patients with autosomal dominant polycystic kidney disease (ADPKD), but has not been approved for this use in the United States.

Dosage and administration for Vasopressin Antagonists

Tolvaptan is available in tablets of 15 and 30 mg under the brand name Samsca. The recommended dose is 15 mg initially, titrating up to a maximum of 60 mg once daily, but limiting therapy to 30 days. 

Side effects of Vasopressin Antagonists

Common side effects include excessive thirst, dry mouth and urinary frequency. Rare, but more serious side effects include hypernatremia and osmotic demyelination injury.

Antihypertensive agents

• Dailymed label info on Vasopressin Antagonists
• FDA Vasopressin Antagonists