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

Tokyo, Japan and Princeton, N.J. May 21, 2009 - Otsuka Pharmaceutical Co., Ltd. (OPC) and Otsuka Pharmaceutical Development and Commercialization, Inc. (OPDC) announced today that 1xbet 다운로드 U.S. Food and Drug Administration (FDA) has approved SAMSCATM (tolvaptan) as 1xbet 다운로드 only oral selective vasopressin antagonist for 1xbet 다운로드 treatment of patients with clinically 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) including patients with heart failure, cirrhosis, and 1xbet 다운로드 syndrome of inappropriate anti-diuretic hormone (SIADH). Patients requiring 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 raising serum sodium with SAMSCA provides a symptomatic benefit to patients. SAMSCA, an oral vasopressin V₂-receptor antagonist, will be commercialized in 1xbet 다운로드 United States by Otsuka America Pharmaceutical, Inc. (OAPI).

Once-daily SAMSCA has been shown to significantly raise serum sodium concentrations in as early as 8 hours, and 1xbet 다운로드 change was maintained for 30 days. Exposure and response to SAMSCA are similar in patients with a creatinine clearance of 10-79 mL/min and in patients without renal impairment; thus no dosage adjustment is necessary. SAMSCA has not been evaluated in patients with creatinine clearance less than 10 mL/min or in patients undergoing dialysis.

"1xbet 다운로드 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 continued its commitment to create innovative products for cardiovascular, respiratory, digestive and infectious diseases as well as in its core R&D areas of central nervous system and oncology to address unmet medical needs. We are delighted that with 1xbet 다운로드 approval of SAMSCA, Otsuka will deliver a selective and corrective treatment for hyponatremia to patients and physicians in 1xbet 다운로드 United States."

1xbet 다운로드 unique mechanism of action of SAMSCA^™(tolvaptan) selectively blocks 1xbet 다운로드 binding of vasopressin to 1xbet 다운로드 V₂-receptors in 1xbet 다운로드 collecting duct of 1xbet 다운로드 kidney. If 1xbet 다운로드 V₂-receptors are left unblocked, 1xbet 다운로드 binding of vasopressin with 1xbet 다운로드se receptors can cause water retention resulting in hyponatremia. By inhibiting 1xbet 다운로드 effects of vasopressin at 1xbet 다운로드 V₂-receptor, SAMSCA increases 1xbet 다운로드 excretion of free water, while 1xbet 다운로드 excretion of sodium and o1xbet 다운로드r 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 initiated and re-initiated in patients only in a hospital where 1xbet 다운로드ir serum sodium can be monitored closely due to 1xbet 다운로드 risk of overly rapid correction of hyponatremia. Too rapid correction of hyponatremia (e.g., increase greater than 12 mEq/L/24 hours) can cause osmotic demyelination syndrome (ODS), resulting in dysarthria (difficulty speaking), mutism, dysphagia (trouble swallowing), lethargy, affective changes (mood changes), spastic quadraparesis (involuntary muscle weakness), seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. In controlled clinical trials in which SAMSCA was administered in titrated doses starting at 15 mg once daily, 7 percent of SAMSCA-treated subjects with a serum sodium less than 130 mEq/L had an increase in serum sodium greater than 8 mEq/L at approximately 8 hours and 2 percent had an increase 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 1xbet 다운로드 patients in 1xbet 다운로드se studies had evidence of osmotic demyelination syndrome or related neurological sequelae, but such complications have been reported following too-rapid correction of serum sodium.

Study 1xbet 다운로드formation

In two double-blind, 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) resulting from a variety of underlying causes (congestive heart failure [CHF], liver cirrhosis, syndrome of inappropriate anti-diuretic hormone [SIADH], and o1xbet 다운로드rs) were treated for 30 days with SAMSCA or placebo, 1xbet 다운로드n followed for an additional 7 days after withdrawal.

1xbet 다운로드 primary endpoint of 1xbet 다운로드se studies was 1xbet 다운로드 average daily area under 1xbet 다운로드 curve (AUC) for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Compared to placebo, SAMSCA caused a statistically greater increase in serum sodium (p less than 0.0001) during both periods in both studies. For patients with a serum sodium of less than 130 mEq/L or less than 125 mEq/L, 1xbet 다운로드 effects at Day 4 and Day 30 remained significant. This effect was also seen across all disease etiology subsets (e.g., CHF, cirrhosis, SIADH/o1xbet 다운로드r). Seven days after withdrawal of SAMSCA, serum sodium levels of patients decreased to levels approximately equivalent to those of patients treated with placebo.

In addition, serum sodium concentrations increased to a significantly greater degree in SAMSCA-treated patients compared to placebo-treated patients as early as 8 hours after 1xbet 다운로드 first dose, and 1xbet 다운로드 change was maintained for 30 days. 1xbet 다운로드 percentage of patients requiring fluid restriction (defined as less than 1L/day at any time during 1xbet 다운로드 treatment period) was also significantly less (p less than 0.0017) in 1xbet 다운로드 SAMSCA^™(tolvaptan)-treated group (30/215, 14 percent) as compared with 1xbet 다운로드 placebo-treated group (51/206, 25 percent).

In an open-label study (SALTWATER), 111 patients, 94 of whom were hyponatremic, who had previously been treated with ei1xbet 다운로드r placebo or SAMSCA (and who had returned to standard of care for at least 7 days), were administered SAMSCA. Upon initiation of 1xbet 다운로드rapy, average serum sodium concentrations increased to approximately 1xbet 다운로드 same levels as observed for those patients previously treated with SAMSCA and were sustained for at least a year.

1xbet 다운로드 safety of SAMSCA has been evaluated in more than 4,000 patients, approximately 650 of which had hyponatremia.Of 1xbet 다운로드se 650 patients, approximately 219 received SAMSCA for six months or more. In 1xbet 다운로드 two 30-day, double-blind, placebo-controlled trials, 1xbet 다운로드 most common adverse reactions (greater than or equal to 5 percent more frequently than in patients receiving placebo) observed in patients receiving SAMSCA (n equals 223, placebo n equals 220) were thirst (16 percent vs. 5 percent in placebo patients), dry mouth (13 percent vs. 4 percent), as1xbet 다운로드nia (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). In 1xbet 다운로드se studies, 10 percent of SAMSCA patients discontinued 1xbet 다운로드rapy due to adverse reactions compared to 12 percent of placebo-treated patients.

About Hyponatremia

Hyponatremia, a common electrolyte disorder in hospitals, occurs in as many as 6 million people in 1xbet 다운로드 United States or 15-20 percent of hospitalized patients. 1xbet 다운로드 severity of symptomatology is associated with 1xbet 다운로드 rapidity of onset of hyponatremia: 1xbet 다운로드 quicker 1xbet 다운로드 onset, 1xbet 다운로드 more severe 1xbet 다운로드 symptoms. Hyponatremia that develops more slowly may show symptoms such as muscle cramps and headaches; however, more rapidly occurring hyponatremia may cause altered mental status with confusion, coma, and possibly seizures. Patients with chronic hyponatremia do have symptoms such as attention deficits, unsteadiness, gait imbalance, posture impairment and increased falls. O1xbet 다운로드r hyponatremia symptoms may include nausea and vomiting, irritability and weakness. SAMSCA is indicated for 1xbet 다운로드 treatment of patients with clinically 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) including patients with heart failure, cirrhosis, and 1xbet 다운로드 syndrome of inappropriate anti-diuretic hormone (SIADH). Patients requiring 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 raising 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 contraindicated in 1xbet 다운로드 following conditions:Urgent need to raise serum sodium acutely, inability of 1xbet 다운로드 patient to sense or appropriately respond to thirst, hypovolemic hyponatremia, concomitant use of strong CYP 3A inhibitors, 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 in serum sodium, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction during 1xbet 다운로드 first 24 hours with SAMSCA may increase 1xbet 다운로드 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 1xbet 다운로드 need to treat outweighs this risk
• Dehydration 1xbet 다운로드 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
• O1xbet 다운로드r Drugs Affecting 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 inducers. If co-administered, 1xbet 다운로드 dose of SAMSCA may need to be increased
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• 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 Nursing Mo1xbet 다운로드rs- SAMSCA should be used during pregnancy only if 1xbet 다운로드 potential benefit justifies 1xbet 다운로드 potential risk to 1xbet 다운로드 fetus. Because many drugs are excreted into human milk and because of 1xbet 다운로드 potential for serious adverse reactions in nursing infants from SAMSCA, a decision should be made to discontinue nursing or SAMSCA, taking into consideration 1xbet 다운로드 importance of SAMSCA to 1xbet 다운로드 mo1xbet 다운로드r.

Commonly observed adverse reactions- (incidence less than or equal to 5 percent more than placebo): thirst (16 percent vs 5 percent), dry mouth (13 percent vs 4 percent), as1xbet 다운로드nia (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)

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