Tokyo, Japan and Uxbridge, England (ots/PRNewswire) -
Otsuka Pharmaceutical Co., Ltd. and Otsuka Pharmaceutical Europe Ltd.
(OPEL) announced today that the European Commission has approved the
Marketing Authorisation Application for the company's oral once-daily
medication Samsca(TM)(tolvaptan), a selective V2-vasopressin receptor
antagonist, for the treatment of hyponatraemia secondary to syndrome
of inappropriate antidiuretic hormone secretion (SIADH) in adults.
Samsca is the first oral vasopressin receptor antagonist available in
"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 Prof. 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."
Results from the SALT-1 and SALT-2 (Study of Ascending Levels of
Tolvaptan in Hyponatraemia -1 and -2 ) trial programme showed that
once-daily oral tolvaptan was effective in increasing serum sodium
concentrations(1) in patients with SIADH.
Hyponatraemia is the most common electrolyte disorder encountered
in hospitalised patients and is defined as serum sodium of < 135
mmol/L.(2) The syndrome of inappropriate antidiuretic hormone
secretion (SIADH) is a common cause of hyponatraemia.(2)
Vasopressin and the V2 receptor play a central role 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.(2) 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 plays a role in the
kidney's regulation of fluid excretion. Samsca is designed to promote
aquaresis, the excretion of electrolyte-free water.(3)
Detailed recommendations for use of this product will be
described in the Summary of Product Characteristics (SmPC) which will
be published in the European Public Assessment Report (EPAR); these
will be available in all official European Languages.
Hyponatraemia, characterised by low concentrations of sodium in
the blood, is a known predictor of poor outcome in patients with
serious underlying illnesses.(1) Hyponatraemia has long been
associated with neurological symptoms including in its worst forms
seizure and coma, and in its mildest forms decreased concentration
and memory.(4) Normal serum sodium is between 135 to 145 mmol/L,
whereas patients diagnosed with hyponatraemia have sodium levels of
less than 135 mmol/L.
SIADH is characterised by inappropriate antidiuresis.(2)
Vasopressin helps regulate the amount of water in the body by
controlling how much water is excreted by the kidneys.(2)
Vasopressin activates the V2-receptors on the collecting ducts cells
in the kidneys, stimulating the insertion of aquaporin-2 water
channels and the reabsorption of water.(3) In SIADH the body retains
excess water, thus reducing the plasma osmolality, diluting sodium
and causing hyponatraemia.(2,6) Current treatments include fluid
restriction, urea, demeclocycline and intravenous infusion of
Samsca works by removing free water (water without sodium and
other electrolytes) - this is known as aquaresis.
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 (aquaresis) (3).
About Otsuka Pharmaceutical Co., Ltd.
Founded in 1964, Otsuka Pharmaceutical Co., Ltd. is a global
healthcare company with the corporate philosophy: 'Otsuka-people
creating new products for better health worldwide.' Otsuka
researches, develops, manufactures and markets innovative and
original products, with a focus on pharmaceutical products for the
treatment of diseases and consumer products for the maintenance of
everyday health. Otsuka is committed to being a corporation that
creates global value, adhering to the high ethical standards required
of a company involved in human health and life, maintaining a dynamic
corporate culture, and working in harmony with local communities and
the natural environment.
Otsuka Pharmaceutical Co., Ltd. is a wholly owned subsidiary of
Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group.
The Otsuka Group comprises 153 companies and employs approximately
36,000 people in 23 countries and regions worldwide. Otsuka and its
consolidated subsidiaries earned Yen955.9 billion (approx. US $9.7
billion*) in annual revenues in fiscal 2008.
* Exchange rate as of March 31, 2009.
For additional information, visit http://www.otsuka-global.com
1. Schrier RW, Gross P, Gheorghiade M et al. Tolvaptan, a
Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia.
(SALT-1, SALT-2). NEJM. 2006; 355(20):2099-112
2. Ellison DH, Berl T. Clinical practice. The syndrome of
inappropriate antidiuresis. NEJM. 2007;356:2064-2072
3. Miyazaki T, Fujiki H, et al. Tolvaptan, an orally active
vasopressin V(2)-receptor antagonist-pharmacology and clinical
trials. Cardiovascular Drug Reviews.2007;25(1):1-13
4. Renneboog B, Musch W, Vandemergel S et al.:Mild chronic
hyponatremia is associated with falls, unsteadiness and attention
deficits . Am J Med 119:71e1 - 71e8 , 2006
5. Gheorghiade M, Gottlieb SS, Udelson JE et al. Vasopressin V2
Receptor Blockade with Tolvaptan versus Fluid Restriction in the
Treatment of Hyponatraemia. Am J Cardiol 2006; 97:1064-1067
6. Verbalis JG, Goldsmith SR, et al. Hyponatraemia treatment
guidelines 2007: expert panel recommendations. Am J Med.
Date of preparation: August 2009
ots Originaltext: Otsuka Pharmaceutical Europe Ltd.
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