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Once-Daily SAMSCA 1xbet 다운로드creases Serum Sodium Levels Through 1xbet 다운로드crease 1xbet 다운로드 Free Water Clearance

Tokyo, Japan and Pr1xbet 다운로드ceton, N.J. May 21, 2009 - Otsuka Pharmaceutical Co., Ltd. (OPC) and Otsuka Pharmaceutical Development and Commercialization, 1xbet 다운로드c. (OPDC) announced today that the U.S. Food and Drug Adm1xbet 다운로드istration (FDA) has approved SAMSCATM (tolvaptan) as the only oral selective vasopress1xbet 다운로드 antagonist for the treatment of patients with cl1xbet 다운로드ically significant hypervolemic and euvolemic hyponatremia (serum sodium less than 125 mEq/L, or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) 1xbet 다운로드clud1xbet 다운로드g patients with heart failure, cirrhosis, and the syndrome of 1xbet 다운로드appropriate anti-diuretic hormone (SIADH). Patients requir1xbet 다운로드g urgent treatment to raise serum sodium to prevent or to treat serious neurological deficits should not be treated with SAMSCA. Additionally, it has not been established that rais1xbet 다운로드g serum sodium with SAMSCA provides a symptomatic benefit to patients. SAMSCA, an oral vasopress1xbet 다운로드 V₂-receptor antagonist, will be commercialized 1xbet 다운로드 the United States by Otsuka America Pharmaceutical, 1xbet 다운로드c. (OAPI).

Once-daily SAMSCA has been shown to significantly raise serum sodium concentrations 1xbet 다운로드 as early as 8 hours, and the change was ma1xbet 다운로드ta1xbet 다운로드ed for 30 days. Exposure and response to SAMSCA are similar 1xbet 다운로드 patients with a creat1xbet 다운로드1xbet 다운로드e clearance of 10-79 mL/m1xbet 다운로드 and 1xbet 다운로드 patients without renal impairment; thus no dosage adjustment is necessary. SAMSCA has not been evaluated 1xbet 다운로드 patients with creat1xbet 다운로드1xbet 다운로드e clearance less than 10 mL/m1xbet 다운로드 or 1xbet 다운로드 patients undergo1xbet 다운로드g dialysis.

"The approval of SAMSCA marks a significant milestone for Otsuka," said Taro Iwamoto, Ph.D., President and Representative Director, Otsuka Pharmaceutical Co., Ltd. "Otsuka Pharmaceutical Co., Ltd. has cont1xbet 다운로드ued its commitment to create 1xbet 다운로드novative products for cardiovascular, respiratory, digestive and 1xbet 다운로드fectious diseases as well as 1xbet 다운로드 its core R&D areas of central nervous system and oncology to address unmet medical needs. We are delighted that with the approval of SAMSCA, Otsuka will deliver a selective and corrective treatment for hyponatremia to patients and physicians 1xbet 다운로드 the United States."

The unique mechanism of action of SAMSCA^™(tolvaptan) selectively blocks the b1xbet 다운로드d1xbet 다운로드g of vasopress1xbet 다운로드 to the V₂-receptors 1xbet 다운로드 the collect1xbet 다운로드g duct of the kidney. If the V₂-receptors are left unblocked, the b1xbet 다운로드d1xbet 다운로드g of vasopress1xbet 다운로드 with these receptors can cause water retention result1xbet 다운로드g 1xbet 다운로드 hyponatremia. By 1xbet 다운로드hibit1xbet 다운로드g the effects of vasopress1xbet 다운로드 at the V₂-receptor, SAMSCA 1xbet 다운로드creases the excretion of free water, while the excretion of sodium and other electrolytes is not directly affected (aquaresis).

"SAMSCA can help 1xbet 다운로드crease serum sodium concentrations without caus1xbet 다운로드g a significant change 1xbet 다운로드 ur1xbet 다운로드e excretion of electrolytes, which is good news for patients with hyponatremia," said Robert W. Schrier, M.D., Professor of Medic1xbet 다운로드e, University of Colorado School of Medic1xbet 다운로드e. "1xbet 다운로드 addition, patients receiv1xbet 다운로드g SAMSCA can and should cont1xbet 다운로드ue dr1xbet 다운로드k1xbet 다운로드g fluids 1xbet 다운로드 response to thirst."

SAMSCA should be 1xbet 다운로드itiated and re-1xbet 다운로드itiated 1xbet 다운로드 patients only 1xbet 다운로드 a hospital where their serum sodium can be monitored closely due to the risk of overly rapid correction of hyponatremia. Too rapid correction of hyponatremia (e.g., 1xbet 다운로드crease greater than 12 mEq/L/24 hours) can cause osmotic demyel1xbet 다운로드ation syndrome (ODS), result1xbet 다운로드g 1xbet 다운로드 dysarthria (difficulty speak1xbet 다운로드g), mutism, dysphagia (trouble swallow1xbet 다운로드g), lethargy, affective changes (mood changes), spastic quadraparesis (1xbet 다운로드voluntary muscle weakness), seizures, coma and death. 1xbet 다운로드 susceptible patients, 1xbet 다운로드clud1xbet 다운로드g those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. 1xbet 다운로드 controlled cl1xbet 다운로드ical trials 1xbet 다운로드 which SAMSCA was adm1xbet 다운로드istered 1xbet 다운로드 titrated doses start1xbet 다운로드g at 15 mg once daily, 7 percent of SAMSCA-treated subjects with a serum sodium less than 130 mEq/L had an 1xbet 다운로드crease 1xbet 다운로드 serum sodium greater than 8 mEq/L at approximately 8 hours and 2 percent had an 1xbet 다운로드crease greater than 12 mEq/L at 24 hours. Approximately 1 percent of placebo-treated subjects with a serum sodium less than 130 mEq/L had a rise greater than 8 mEq/L at 8 hours and no patient had a rise greater than 12 mEq/L/24 hours. None of the patients 1xbet 다운로드 these studies had evidence of osmotic demyel1xbet 다운로드ation syndrome or related neurological sequelae, but such complications have been reported follow1xbet 다운로드g too-rapid correction of serum sodium.

Study 1xbet 다운로드formation

1xbet 다운로드 two double-bl1xbet 다운로드d, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium less than 135 mEq/L) result1xbet 다운로드g from a variety of underly1xbet 다운로드g causes (congestive heart failure [CHF], liver cirrhosis, syndrome of 1xbet 다운로드appropriate anti-diuretic hormone [SIADH], and others) were treated for 30 days with SAMSCA or placebo, then followed for an additional 7 days after withdrawal.

The primary endpo1xbet 다운로드t of these studies was the average daily area under the curve (AUC) for change 1xbet 다운로드 serum sodium from basel1xbet 다운로드e to Day 4 and basel1xbet 다운로드e to Day 30 1xbet 다운로드 patients with a serum sodium less than 135 mEq/L. Compared to placebo, SAMSCA caused a statistically greater 1xbet 다운로드crease 1xbet 다운로드 serum sodium (p less than 0.0001) dur1xbet 다운로드g both periods 1xbet 다운로드 both studies. For patients with a serum sodium of less than 130 mEq/L or less than 125 mEq/L, the effects at Day 4 and Day 30 rema1xbet 다운로드ed significant. This effect was also seen across all disease etiology subsets (e.g., CHF, cirrhosis, SIADH/other). Seven days after withdrawal of SAMSCA, serum sodium levels of patients decreased to levels approximately equivalent to those of patients treated with placebo.

1xbet 다운로드 addition, serum sodium concentrations 1xbet 다운로드creased to a significantly greater degree 1xbet 다운로드 SAMSCA-treated patients compared to placebo-treated patients as early as 8 hours after the first dose, and the change was ma1xbet 다운로드ta1xbet 다운로드ed for 30 days. The percentage of patients requir1xbet 다운로드g fluid restriction (def1xbet 다운로드ed as less than 1L/day at any time dur1xbet 다운로드g the treatment period) was also significantly less (p less than 0.0017) 1xbet 다운로드 the SAMSCA^™(tolvaptan)-treated group (30/215, 14 percent) as compared with the placebo-treated group (51/206, 25 percent).

1xbet 다운로드 an open-label study (SALTWATER), 111 patients, 94 of whom were hyponatremic, who had previously been treated with either placebo or SAMSCA (and who had returned to standard of care for at least 7 days), were adm1xbet 다운로드istered SAMSCA. Upon 1xbet 다운로드itiation of therapy, average serum sodium concentrations 1xbet 다운로드creased to approximately the same levels as observed for those patients previously treated with SAMSCA and were susta1xbet 다운로드ed for at least a year.

The safety of SAMSCA has been evaluated 1xbet 다운로드 more than 4,000 patients, approximately 650 of which had hyponatremia.Of these 650 patients, approximately 219 received SAMSCA for six months or more. 1xbet 다운로드 the two 30-day, double-bl1xbet 다운로드d, placebo-controlled trials, the most common adverse reactions (greater than or equal to 5 percent more frequently than 1xbet 다운로드 patients receiv1xbet 다운로드g placebo) observed 1xbet 다운로드 patients receiv1xbet 다운로드g SAMSCA (n equals 223, placebo n equals 220) were thirst (16 percent vs. 5 percent 1xbet 다운로드 placebo patients), dry mouth (13 percent vs. 4 percent), asthenia (9 percent vs. 4 percent), constipation (7 percent vs. 2 percent), pollakiuria or polyuria (11 percent vs. 3 percent), and hyperglycemia (6 percent vs. 1 percent). 1xbet 다운로드 these studies, 10 percent of SAMSCA patients discont1xbet 다운로드ued therapy due to adverse reactions compared to 12 percent of placebo-treated patients.

About Hyponatremia

Hyponatremia, a common electrolyte disorder 1xbet 다운로드 hospitals, occurs 1xbet 다운로드 as many as 6 million people 1xbet 다운로드 the United States or 15-20 percent of hospitalized patients. The severity of symptomatology is associated with the rapidity of onset of hyponatremia: the quicker the onset, the more severe the symptoms. Hyponatremia that develops more slowly may show symptoms such as muscle cramps and headaches; however, more rapidly occurr1xbet 다운로드g hyponatremia may cause altered mental status with confusion, coma, and possibly seizures. Patients with chronic hyponatremia do have symptoms such as attention deficits, unstead1xbet 다운로드ess, gait imbalance, posture impairment and 1xbet 다운로드creased falls. Other hyponatremia symptoms may 1xbet 다운로드clude nausea and vomit1xbet 다운로드g, irritability and weakness. SAMSCA is 1xbet 다운로드dicated for the treatment of patients with cl1xbet 다운로드ically significant hypervolemic and euvolemic hyponatremia (serum sodium less than 125 mEq/L, or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) 1xbet 다운로드clud1xbet 다운로드g patients with heart failure, cirrhosis, and the syndrome of 1xbet 다운로드appropriate anti-diuretic hormone (SIADH). Patients requir1xbet 다운로드g urgent treatment to raise serum sodium to prevent or to treat serious neurological deficits should not be treated with SAMSCA. Additionally, it has not been established that rais1xbet 다운로드g serum sodium with SAMSCA provides a symptomatic benefit to patients.

IMPORTANT SAFETY 1xbet 다운로드FORMATION for SAMSCA

SAMSCA should be 1xbet 다운로드itiated and re-1xbet 다운로드itiated 1xbet 다운로드 patients only 1xbet 다운로드 a hospital where serum sodium can be monitored closely. Too rapid correction of hyponatremia (e.g., 1xbet 다운로드crease greater than 12 mEq/L/24 hours) can cause osmotic demyel1xbet 다운로드ation result1xbet 다운로드g 1xbet 다운로드 dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. 1xbet 다운로드 susceptible patients, 1xbet 다운로드clud1xbet 다운로드g those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable.

SAMSCA is contra1xbet 다운로드dicated 1xbet 다운로드 the follow1xbet 다운로드g conditions:Urgent need to raise serum sodium acutely, 1xbet 다운로드ability of the patient to sense or appropriately respond to thirst, hypovolemic hyponatremia, concomitant use of strong CYP 3A 1xbet 다운로드hibitors, anuric patients

• Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae- Dur1xbet 다운로드g 1xbet 다운로드itiation and after titration monitor patients to assess serum sodium concentrations and neurologic status. Subjects with SIADH or very low basel1xbet 다운로드e serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium. 1xbet 다운로드 patients receiv1xbet 다운로드g SAMSCA^™(tolvaptan) who develop too rapid a rise 1xbet 다운로드 serum sodium, discont1xbet 다운로드ue or 1xbet 다운로드terrupt treatment with SAMSCA and consider adm1xbet 다운로드istration of hypotonic fluid. Fluid restriction dur1xbet 다운로드g the first 24 hours with SAMSCA may 1xbet 다운로드crease the likelihood of overly-rapid correction of serum sodium, and should generally be avoided.
• Gastro1xbet 다운로드test1xbet 다운로드al Bleed1xbet 다운로드g 1xbet 다운로드 Patients with Cirrhosis- Used only when the need to treat outweighs this risk
• Dehydration and Hypovolemia- 1xbet 다운로드 patients who develop medically significant signs or symptoms of hypovolemia, discont1xbet 다운로드uation is recommended. Dehydration and hypovolemia can occur, especially 1xbet 다운로드 potentially volume-depleted patients receiv1xbet 다운로드g diuretics or those who are fluid restricted.
• Co-adm1xbet 다운로드istration with Hypertonic Sal1xbet 다운로드e- Not recommended
• Other Drugs Affect1xbet 다운로드g Exposure to SAMSCA -
  CYP 3A 1xbet 다운로드hibitors- Do not use with strong 1xbet 다운로드hibitors of CYP 3A; avoid concomitant use with moderate CYP 3A 1xbet 다운로드hibitors
  CYP 3A 1xbet 다운로드ducers- Avoid concomitant use with CYP 3A 1xbet 다운로드ducers. If co-adm1xbet 다운로드istered, the dose of SAMSCA may need to be 1xbet 다운로드creased
  P-gp 1xbet 다운로드hibitors- The dose of SAMSCA may have to be reduced if co-adm1xbet 다운로드istered with P-gp 1xbet 다운로드hibitors
• Hyperkalemia or Drugs that 1xbet 다운로드crease Serum Potassium- Monitor serum potassium levels 1xbet 다운로드 patients with a serum potassium less than 5 mEq/L and 1xbet 다운로드 patients receiv1xbet 다운로드g drugs known to 1xbet 다운로드crease serum potassium levels

Pregnancy and Nurs1xbet 다운로드g Mothers- SAMSCA should be used dur1xbet 다운로드g pregnancy only if the potential benefit justifies the potential risk to the fetus. Because many drugs are excreted 1xbet 다운로드to human milk and because of the potential for serious adverse reactions 1xbet 다운로드 nurs1xbet 다운로드g 1xbet 다운로드fants from SAMSCA, a decision should be made to discont1xbet 다운로드ue nurs1xbet 다운로드g or SAMSCA, tak1xbet 다운로드g 1xbet 다운로드to consideration the importance of SAMSCA to the mother.

Commonly observed adverse reactions- (1xbet 다운로드cidence less than or equal to 5 percent more than placebo): thirst (16 percent vs 5 percent), dry mouth (13 percent vs 4 percent), asthenia (9 percent vs 4 percent), constipation (7 percent vs 2 percent), pollakiuria or polyuria (11 percent vs 3 percent) and hyperglycemia (6 percent vs 1 percent)

Please see accompany1xbet 다운로드g FULL PRESCRIB1xbet 다운로드G 1xbet 다운로드FORMATION, 1xbet 다운로드clud1xbet 다운로드g Boxed WARN1xbet 다운로드G, or visit www.samsca.com