Does Tolvaptan (Vasopressin V2 receptor antagonist) cause diuresis?

From the Guidelines

Yes, tolvaptan causes diuresis, as evidenced by its mechanism of action as a vasopressin V2-receptor antagonist, which increases excretion of free water without significant loss of electrolytes. Tolvaptan works by preventing the reabsorption of water in the collecting ducts of the kidneys, resulting in the production of more dilute urine and increased urine output, as seen in trials such as the EVEREST trial, where tolvaptan use resulted in better decongestion, including lower body weight and improvement in oedema 1. The diuretic effect of tolvaptan is a key aspect of its therapeutic use, particularly in conditions like heart failure, where it is used to correct dilutive hyponatraemia. Some key points about tolvaptan's diuretic effect include:

• Increased excretion of free water without significant loss of electrolytes
• Onset of diuretic effect typically within 1-2 hours after administration
• Duration of diuretic effect can last for several hours, depending on the dose prescribed
• Importance of adequate fluid intake to prevent dehydration while taking tolvaptan, as instructed by a healthcare provider. The use of tolvaptan in clinical settings, such as in the TACTICS-HF trial, has shown significant weight and fluid loss in patients with acute heart failure, further supporting its diuretic properties 1.

From the FDA Drug Label

When taken orally, 15 to 60 mg doses of tolvaptan antagonize the effect of vasopressin and cause an increase in urine water excretion that results in an increase in free water clearance (aquaresis), a decrease in urine osmolality, and a resulting increase in serum sodium concentrations. Tolvaptan tablets therapy induces copious aquaresis, which is normally partially offset by fluid intake.

Tolvaptan causes aquaresis, which is an increase in urine water excretion. This can be considered a form of diuresis, as it increases urine production. However, it's more specifically aquaresis, as it increases the excretion of free water, leading to an increase in serum sodium concentrations.

• Key points:
  • Tolvaptan increases urine water excretion
  • Tolvaptan induces aquaresis, which can lead to dehydration and hypovolemia if not managed properly
  • The effects of tolvaptan are limited to aquaresis and the resulting increase in sodium concentration 2 2 2

From the Research

Tolvaptan and Diuresis

• Tolvaptan is a vasopressin V2 receptor antagonist that increases free water clearance, thereby correcting low serum sodium levels 3.
• Studies have shown that tolvaptan has a diuretic effect in patients with heart failure, increasing urine volume and decreasing body weight 4, 5.
• In patients with chronic kidney disease and chronic heart failure, tolvaptan decreased body weight and increased urine volume, with a significant decrease in urine osmolality 4.
• Tolvaptan has also been shown to improve hyponatremia in patients with heart failure, with a significant increase in serum sodium levels 3, 6.

Comparison with Other Diuretics

• A study comparing tolvaptan with furosemide-based diuretic regimens in patients hospitalized for heart failure with hyponatremia found that tolvaptan was associated with similar, but not superior, diuresis compared with intravenous furosemide 7.
• Another study found that early administration of tolvaptan in patients with hyponatremia secondary to acutely decompensated heart failure was associated with a lower length of hospitalization and a higher increase in serum sodium levels 6.

Mechanism of Action

• Tolvaptan works by blocking the binding of arginine vasopressin to V2 receptors, leading to an increase in free water clearance and a decrease in urine osmolality 5.
• This mechanism of action is thought to be responsible for the diuretic effect of tolvaptan, as well as its ability to improve hyponatremia in patients with heart failure.