Conivaptan: a step forward in the treatment of hyponatremia?

Su Su Hline¹, Phuong-Truc T Pham², Phuong-Thu T Pham³, May H Aung¹, Phuong-Mai T Pham⁴, Phuong-Chi T Pham¹

¹Olive View-UCLA Medical Center, Department of Medicine, Nephrology Division, Sylmar, CA, USA; ²Pennsylvania State Worthington Scranton, Dunmore, PA, USA; ³David Geffen School of Medicine at UCLA Medical Center, Los Angeles, CA, USA; ⁴Mather VA Medical Center, Mather, CA, USA

Abstract: Hyponatremia is one of the most common electrolyte abnormalities linked to adverse outcomes and increased mortality in hospitalized patients. While the differential diagnosis for hyponatremia is diverse, most cases stem from arginine vasopressin (AVP) dysregulation, where hypoosmolality fails to suppress AVP synthesis and release. The physiological effects of AVP are currently known to depend on its interaction with any of 3 receptor subtypes V1A, V2, and V1B. Activation of V2 by AVP is the key in renal water regulation and maintenance of total body volume and plasma tonicity. Despite the long-recognized problem with excess AVP in euvolemic and hypervolemic hyponatremia, traditional therapeutic options have relied on nonspecific and potentially problematic strategies. More recently, a new class of drugs, introduced as “aquaretics,” has gained great attention among clinicians because of its ability to correct hyponatremia via direct competitive inhibition of AVP at V2 receptors to induce renal electrolyte-free water excretion. In this paper, we aim to review available clinical data on the only FDA-approved aquaretic, dual V1A/V2 receptor antagonist conivaptan, discuss its clinical indications, efficacy, safety profile, and comment on its clinical limitations.

Keywords: conivaptan, hyponatremia, euvolemia, hypervolemia, AVP, AVP receptor antagonist