Tolvaptan: Vasopressin Antagonist

Tolvaptan: Vasopressin Antagonist

Tolvaptan is vasopressin antagonist which acts on the V2 receptors in the renal tubules. Activation of V2 receptors increases water permeability in the renal collecting duct resulting in passive reabsorption of water. V2 receptor antagonism causes aquaresis or free water clearance. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH), heart failure and cirrhosis can be associated with increased secretion of arginine vasopressin (AVP). This leads to water retention or inadequate water excretion and hyponatremia (dilutional hyponatremia). The drug binds to V2 receptors and induces excretion of electrolyte-free water without altering the electrolyte excretion.


Tolvaptan is indicated for the treatment of hypervolemic and euvolemic hyponatremia, with serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction. Such situations occur with heart failure, cirrhosis, and SIADH.

Adverse Effects

As expected from its therapeutic action, important adverse effects of tolvaptan are increased thirst, dryness of mouth, increased urination and sometime dehydration leading to hypotension and syncope. Gastrointestinal hemorrhage may occur in those with cirrhosis liver. Hypernatremia and hyperkalemia are potential problems and very rarely osmotic demyelination is possible due to rapid correction of hyponatremia.


Tolvaptan is not the treatment when there is an urgent need to raise serum sodium acutely. It should also be avoided in those with inability to sense or appropriately respond to thirst. Hypovolemic hyponatremia is not an indication for tolvaptan therapy. Concomitant use of strong CYP3A inhibitors can increase the effect of the drug. There is no point in giving it to anuric patients as no fluid is delivered to renal collecting ducts, the site of action of the drug.


Serum sodium has to be closely monitored while initiating tolvaptan therapy. Too rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination (the erstwhile central pontine myelinolysis). Slower rates of correction may be considered in those susceptible patients who include those with severe malnutrition, alcoholism and advanced liver disease.