Which aquaretics are approved for euvolemic and hypervolemic hyponatremia and how are they used?

Updated: Jun 17, 2019
  • Author: Eric E Simon, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
  • Print

A new class of drugs, AVP receptor antagonists, designed specifically to promote aquaresis (ie, electrolyte-sparing excretion of free water), has been evaluated in clinical trials for the treatment of hyponatremia. [37, 38] The first agent to be approved was conivaptan, a V1A and V2 vasopressin receptor antagonist. It is available only for intravenous use and is approved for use in the hospital setting for euvolemic and hypervolemic hyponatremia. It is contraindicated in hypovolemic patients. It induces both a water and sodium diuresis with improvement in plasma sodium levels. Most of the clinical experience has been in heart failure. It is effective in raising serum sodium levels; however, conivaptan has not been shown to improve heart failure per se. Close monitoring of the rate of correction is needed and is approved for treatment for only 4 days.

In addition, the effects in patients with renal and hepatic impairment have not been well studied and caution is advised with use in this population. There are several drug interactions that need close monitoring and the use of conivaptan with CYP3A4 inhibitors is contraindicated.

Tolvaptan, a selective V2 receptor antagonist, can be taken orally and has been approved for use in the treatment of euvolemic and hypervolemic hyponatremia, including cases associated with cirrhosis and heart failure. Tolvaptan treatment must be initiated in the hospital to avoid the possibility of too rapid correction (although there have not been reported cases). It shows great promise but because of the requirement for hospitalization for initiation or reintroduction and the expense of the drug, its use at this time is limited. It also interacts with CYP3A inhibitors and use with such drugs is contraindicated. In April 2013, the FDA limited use of tolvaptan to no more than 30 days and indicated that it should not be used in patients with underlying liver disease. This decision was based on reports of liver injury, including those potentially leading to liver transplant or death. [39]

The use of these vaptans is limited and exact benefits have yet to be determined. There are reports that even mild hyponatremia can cause gait instability and possibly increase the risk of falls and hip fractures. In this setting, vaptans may be beneficial to improve hyponatremia and gait.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!