Novel Agents for the Treatment of Hyponatremia A Review of Conivaptan and Tolvaptan

Hyponatremia is the most commonly encountered electrolyte abnormality. If uncorrected, it can lead to seizure, coma, or death due to brain stem herniation. Once the serum osmolality and volume status of the patient is determined, treatment should be initiated to correct the serum sodium by 8 to 12 mEq/L within the first 24 hours. Arginine vasopressin (AVP) antagonists represent a new class of drugs indicated to treat hypervolemic and euvolemic hyponatremia. Conivaptan is a nonselective AVP antagonist that is available intravenously, and tolvaptan is a V-2 selective AVP antagonist that is available as an oral tablet. Both agents produce highly effective and safe aquaresis to increase serum Na+ levels. Both agents have limited data in heart failure patients, but have been shown to produce significant decreases in pulmonary capillary wedge pressure, body weight, and signs and symptoms of heart failure. Neither drug has been approved for the treatment of heart failure, to date. There were no cases of osmotic demyelination syndrome with these agents, and the most common adverse events during studies were dry mouth and thirst. Overall, both conivaptan and tolvaptan are promising agents that can be used in hospitalized patients. Further studies are needed to assess the appropriateness of their use in symptomatic hyponatremic patients, and to determine their benefits in terms of disease outcome and length of stay to justify the high acquisition costs.