Successful Long-Term Treatment of Hyponatremia in Syndrome of Inappropriate Antidiuretic Hormone Secretion with Satavaptan (SR121463B), an Orally Active Nonpeptide Vasopressin V2-Receptor Antagonist

Abstract

The effects of satavaptan (SR121463B), a novel long-acting orally active vasopressin V 2 -receptor antagonist, were investigated in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In the first part of this randomized, double-blind study, 34 patients first were treated with satavaptan ( V asopressin is involved in most cases of sustained hyponatremia (1). Therefore, the use of specific blockers of vasopressin receptors is a logical approach in the treatment of patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and may present advantages over current available therapies (2). Selective nonpeptide V 2 -receptor antagonists (V 2 RA) have been in development since 1992 (3-6). Oral compounds have been synthesized more recently, and, to our knowledge, publications have focused mainly on patients with SIADH that is treated with an oral V 2 RA for a short period of time (Ͻ1 wk) (7-10).In this study, we investigated the efficacy and the safety of a new oral nonpeptide V 2 RA, satavaptan (SR121463B) (11), in correcting hyponatremia in patients with SIADH of various origins. After the initial phase of the study (short-term, 1 mo), we evaluated for the first time the efficacy and the tolerance of a V 2 RA over a long-term period (12 mo). Materials and Methods PatientsFrom June 2001 to June 2003, a total of 35 patients from four countries (Belgium, Germany, Hungary, and France) were included in a randomized, double-blind, placebo-controlled study to assess the efficacy and the safety of different dosages of satavaptan in SIADH. The diagnosis of SIADH was based on several criteria: True serum hypo-osmolality; inappropriate urinary osmolality; clinical euvolemia; elevated urinary sodium excretion while on a normal salt and water intake; and normal renal, adrenal, and thyroid functions. Patients with low sodium excretion (Յ20 mmol/L) as a result of low solute intake (anorexia) were included. Drug-induced SIADH was limited to carbamazepine and antidepressants. The search for the cause of SIADH (especially neoplasia and iatrogenic) was performed carefully by each investigator before considering the origin as idiopathic.Inclusion criteria were age 18 yr or older, stable hyponatremia (serum sodium [SNa] increase Յ4 mmol/L between two measurements of 24 h apart) between 115 and 132 mmol/L during the screening period,

A Copeptin-Based Classification of the Osmoregulatory Defects in the Syndrome of Inappropriate Antidiuresis

“…A better understanding of the different forms of SIAD may influence future treatment strategies because response to therapy (e.g., with vaptans or fluid restriction) varies widely in SIAD. 6,7 Using the hypertonic saline infusion test, the present study aimed to establish quantitatively defined SIAD subtypes based on serial measurements of copeptin, a stable and easily measurable surrogate for AVP release.…”

Arginine vasopressin (AVP) and treatment with arginine vasopressin receptor antagonists (vaptans) in congestive heart failure, liver cirrhosis and syndrome of inappropriate antidiuretic hormone secretion (SIADH)

“…The efficacy of satavaptan was first evaluated in the phase II trial in patients with hyponatremia due to SIADH [65]. Satavaptan was well tolerated in clinical trials; the main adverse effects associated with the use of satavaptan included increased thirst and dry mouth.…”

“…Although the agent has demonstrated utility in animal models and improved clinical outcomes in patients with SIADH or cirrhosis [65][66][67][68], its efficacy in CHF patients has yet to be determined.…”

“…Soupart et al studied in a first part of a randomized, double-blind and placebocontrolled study the effect of satavaptan in 34 patients with hyponatremia due to SIADH [65].…”

Severe Hyponatremia During Moxifloxacin Treatment: A Case Report

“…Hipervolemik hiponatremi, genellikle artmış ekstraselüler sıvının (konjestif kalp yetmezliği, siroz ve nefrotik sendrom gibi) bir sonucudur (4,5). Normovolemik hiponatremi, uygunsuz antidiüretik hormon (ADH) sendromuyla ilişkili ve ilişkili olmayan bozukluklar olarak ayrılır (6)(7)(8).…”