Samsca is the first oral vasopressin receptor antagonist available in Europe. ’It is very welcome news to learn that a licence has been granted for the use of tolvaptan in the treatment of hyponatraemia due to SIADH,’ said Professor Chris Thompson, Professor of Endocrinology at Beaumont Hospital, Dublin. ’Hyponatraemic patients are vulnerable to a vast array of symptoms and complications, and the treatments available for the treatment of hyponatraemia have had limited efficacy or significant tolerability issues. Clinicians will be aware of the excellent safety record and efficacy of tolvaptan in published trial data and will welcome the availability of a therapeutic agent which specifically treats the underlying cause of hyponatraemia.’

Hyponatraemia, which is characterized by low concentrations of sodium in the blood, is the most common electrolyte disorder encountered in hospitalized patients and is defined as serum sodium of <135 mmol/L (normal serum sodium is between 135 and 145 mmol/L) [1]. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), which is characterized by inappropriate antidiuresis, is a common cause of hyponatraemia [1]. Hyponatraemia is a known predictor of poor outcome in patients with serious underlying illnesses [2] and has long been associated with neurological symptoms, including (in its worst forms) seizure and coma and (in its mildest forms) decreased concentration and memory [3].

Results from the Study of Ascending Levels of Tolvaptan in Hyponatraemia-1 and -2 (SALT-1 and SALT-2) trial programme showed that once-daily oral tolvaptan was effective in increasing serum sodium concentrations in patients with SIADH [2].

Vasopressin and the V2 receptor play a central part in maintaining plasma osmolality. In SIADH, the body retains excess water, thus reducing the plasma osmolality by diluting sodium and causing hyponatraemia. SIADH is associated with a multitude of causes; however, cancer, central nervous system disorders and certain medications are common triggers [1]. Current treatment options are limited and often challenging to use.

Samsca is a novel molecule designed to be an orally available antagonist of the vasopressin V2 receptor, which has a role in the kidney's regulation of fluid excretion. Samsca is designed to promote aquaresis, the excretion of electrolyte-free water [4]. This is different from diuresis, in which both sodium and water are released. Samsca offers a selective treatment for hyponatraemia in SIADH. The mechanism of action of Samsca selectively blocks the binding of vasopressin to the V2 receptors in the collecting duct of the kidney. If the V2 receptors are occupied by vasopressin and the patient continues drinking, this will result in water retention, dilution of plasma osmolality and hyponatraemia. By inhibiting the effects of vasopressin at the V2 receptor, Samsca increases the excretion of free water, while the excretion of sodium and other electrolytes are not directly affected [4].

References

1 Ellison, D.H. and Berl, T. (2007) Clinical practice. The syndrome of inappropriate antidiuresis. N. Engl. J. Med. 356, 2064–2072
2 Schrier, R.W. et al. (2006) Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. (SALT-1, SALT-2). N. Engl. J. Med. 355, 2099–2112
3 Renneboog, B. et al. (2006) Mild chronic hyponatremia is associated with falls, unsteadiness and attention deficits. Am. J. Med. 119, 71e1–71e8
4 Miyazaki, T. et al. (2007) Tolvaptan, an orally active vasopressin V2-receptor antagonist-pharmacology and clinical trials. Cardiovasc. Drug Rev. 25, 1–13