From the Guidelines
Tolvaptan is used to treat clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and resistant to fluid restriction). It works by selectively blocking vasopressin V2 receptors in the kidneys, which prevents water reabsorption and promotes free water excretion, thereby increasing serum sodium levels. The typical starting dose is 15 mg once daily, which can be titrated up to 60 mg daily based on serum sodium response. Treatment should be initiated in a hospital setting with close monitoring of serum sodium levels to prevent overly rapid correction (which can lead to osmotic demyelination syndrome) 1. Sodium levels should not increase by more than 8-12 mEq/L in 24 hours.
Key Considerations
- Tolvaptan is contraindicated in patients who need urgent sodium correction, those unable to sense or respond to thirst, and in patients with liver disease 1.
- Common side effects include thirst, dry mouth, increased urination, and potential liver injury with prolonged use.
- Patients should be advised to drink water in response to thirst but avoid excessive fluid intake during treatment.
- Tolvaptan should be used cautiously in patients with cirrhosis and is not recommended for use beyond 30 days due to risk of liver injury 1.
Monitoring and Safety
- Frequent monitoring of liver function tests (LFTs) is mandatory in people treated with tolvaptan, especially in the first 18 months of treatment 1.
- Tolvaptan use is associated with an increased risk for idiosyncratic drug-induced liver injury, and approximately 5% of people with ADPKD treated with tolvaptan displayed an increase in transaminase levels that was above 3-fold the upper limit of normal 1.
Clinical Guidelines
- The use of vasopressin antagonists, including tolvaptan, may be considered in the short term to improve serum sodium concentration in hypervolemic, hyponatremic states with either a V2 receptor selective or a nonselective vasopressin antagonist, according to the 2013 ACCF/AHA guideline for the management of heart failure 1.
From the FDA Drug Label
Tolvaptan tablets are a selective vasopressin V 2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia [serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction], including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Limitations of Use: Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with tolvaptan tablets It has not been established that tolvaptan tablets provide a symptomatic benefit to patients
Tolvaptan Use in Treating Hyponatremia:
- Tolvaptan is used to treat clinically significant hypervolemic and euvolemic hyponatremia.
- It is indicated for patients with serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction.
- Tolvaptan can be used in patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).
- However, it should not be used in patients who require urgent intervention to raise serum sodium to prevent or treat serious neurological symptoms 2.
From the Research
Tolvaptan Use in Treating Hyponatremia
- Tolvaptan is a vasopressin receptor antagonist used to treat hyponatremia, a common electrolyte disorder in hospitalized patients 3.
- It is effective in improving serum sodium levels in patients with euvolemic or hypervolemic hyponatremia related to heart failure, cirrhosis, or syndrome of inappropriate anti-diuretic hormone (SIADH) 3, 4.
- Tolvaptan has been shown to be safe and well-tolerated for long-term use in patients with chronic hyponatremia, with beneficial effects on serum sodium levels in both mild and marked hyponatremia 3.
Mechanism of Action
- Tolvaptan works by selectively increasing electrolyte-free water excretion, thereby increasing serum sodium concentrations 3, 4.
- It is an oral, nonpeptide selective vasopressin V(2)-receptor antagonist, which acts to increase free water excretion (aquaresis) and raise serum sodium concentration 4, 5.
Clinical Evidence
- Clinical trials have demonstrated the efficacy of tolvaptan in correcting hyponatremia in patients with heart failure, cirrhosis, and SIADH 4, 5, 6.
- Tolvaptan has been shown to be effective in rapidly and effectively resolving hyponatremia in these settings, with significant increases in serum sodium concentrations compared to placebo 4, 6.
- However, tolvaptan has not been associated with significant improvements in mortality in patients with heart failure compared to placebo 4.
Safety and Tolerability
- Tolvaptan is generally well-tolerated, with common adverse events including dry mouth, thirst, and polyuria, consistent with its mechanism of action 4, 6.
- However, fluid restriction should be avoided during the first 24 hours of treatment to prevent overly rapid correction of hyponatremia, and tolvaptan should not be used in patients who cannot sense/respond to thirst, anuric patients, hypovolemic patients, and/or those requiring urgent intervention to raise serum sodium acutely 5.