IMPORTANT SAFETY INFORMATIONU.S. FULL PRESCRIBING INFORMATION, including Boxed WARNING and Medication Guide

SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable. SAFETY INFORMATION CONTINUED BELOW

Samsca

Effective Correction of Serum Sodium Concentration

Use the following links to explore this section in further detail:

Significant increase in as early as 8 hours
Results consistent across etiologies
Reduced need for fluid restriction
Importance of appropriate correction
Long-term use

Significant increase in as early as 8 hours

Proven in two identical randomized, placebo-controlled, double-blind phase 3 studies (Study of Ascending Levels of Tolvaptan in hyponatremia 1 and 2) [SALT-1 and SALT-2]¹

Results consistent among patients with heart failure, cirrhosis, and SIADH

The average rates of serum sodium correction during the treatment initiation (first 24 hours) were 3.83 mEq/L for SAMSCA (15 mg) and 0.30 mEq/L for placebo²

Too rapid correction of serum sodium (e.g., >12 mEq/L/24 hours) can cause serious neurologic sequelae, including osmotic demyelination syndrome (ODS)

A total of 424 patients with euvolemic and hypervolemic hyponatremia (serum sodium <135 mEq/L) were treated for 30 days with tolvaptan or oral placebo, then followed for an additional 7 days after withdrawal. The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to day 4 (tolvaptan, 4.0 mEq/L vs placebo, 0.4 mEq/L) and baseline to day 30 (tolvaptan, 6.2 mEq/L vs placebo, 1.8 mEq/L) in patients with a serum sodium <135 mEq/L. Patients received either tolvaptan or placebo, at a starting dose of 15 mg. The dosage of tolvaptan or placebo was increased to 30 mg or 60 mg, if necessary. During the 7-day discontinuation/follow-up period, serum sodium concentrations in patients treated with tolvaptan declined to placebo-like levels.^1,2

Reduced need for fluid restriction

Fluid restriction during the first 24 hours of therapy with SAMSCA may increase the likelihood of overly rapid correction of serum sodium and should generally be avoided
Significantly fewer patients treated with SAMSCA (30/215, 14%) required fluid restriction compared with the placebo group (51/206, 25%) (P<0.01)

Importance of appropriate serum sodium correction

Too-rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, 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 placebo-controlled clinical trials in patients with hyponatremia, 2% of SAMSCA-treated patients with serum sodium <130 mEq/L had an increase greater than 12 mEq/L at 24 hours, while no patient receiving placebo had a rise greater than 12 mEq/L at 24 hours
In controlled clinical trials at 8 hours (serum sodium <130 mEq/L), 7% of SAMSCA-treated patients had an increase in serum sodium greater than 8 mEq/L vs 1% of placebo-treated patients
None of the patients in these studies had evidence of osmotic demyelination syndrome (ODS) or related neurologic sequelae but such complications have been reported following too-rapid correction of serum sodium
Subjects with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium.
In patients receiving SAMSCA who develop too-rapid rise in serum sodium, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid

Long-term use of SAMSCA maintained serum sodium concentrations

SALTWATER trial was a 4-year sequential, open-label extension of the randomized, placebo-controlled, double-blind Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2)³
Improvements sustained in many patients for at least 1 year and in some patients for up to 4 years³

In SALTWATER, a multicenter, open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2), hyponatremic patients (N=111) received oral tolvaptan for a mean follow-up of 701 days, providing 77,369 patient-days of exposure³
A total of 111 patients previously on tolvaptan or placebo therapy in SALT-1 or SALT-2 were given tolvaptan as a titrated regimen (15 to 60 mg once daily) after having returned to standard care for at least 7 days; 94 of these patients were hyponatremic (serum sodium <135 mEq/L). By the time of study entry, patients' baseline mean serum sodium concentration had fallen to between their original baseline and post-placebo therapy level

Click the following links to explore the site further:

References:

Schrier RW, Gross P, Gheorghiade M, et al; SALT Investigators. Tolvaptan, a selective oral vasopressin V₂-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099-2112.
Data on file. Otsuka America Pharmaceutical, Inc.
Berl T, Quittnat-Pelletier F, Verbalis JG, et al; SALTWATER Investigators. Oral tolvaptan is safe and effective in chronic hyponatremia.
J Am Soc Nephrol. 2010;21(4):705-712.

INDICATION

SAMSCA is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).

Important Limitations

Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with SAMSCA.
It has not been established that raising serum sodium with SAMSCA provides a symptomatic benefit to patients

IMPORTANT SAFETY INFORMATION

SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too-rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable.

SAMSCA is contraindicated in the following conditions:

— Urgent need to raise serum sodium acutely
— Inability of the 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 – During initiation and after titration monitor patients to assess serum sodium concentrations and neurologic status. Subjects with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium. In patients receiving SAMSCA who develop too rapid a rise in serum sodium, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction during the first 24 hours with SAMSCA may increase the likelihood of overly-rapid correction of serum sodium, and should generally be avoided.
Gastrointestinal Bleeding in Patients With Cirrhosis – Use in cirrhotic patients only when need to treat outweighs this risk
Dehydration and Hypovolemia – In patients who develop medically significant signs or symptoms of hypovolemia, discontinuation is recommended. Dehydration and hypovolemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted
Co-administration With Hypertonic Saline – Not recommended
Other Drugs Affecting Exposure to SAMSCA

— CYP 3A Inhibitors – Do not use with strong inhibitors of CYP 3A; avoid concomitant use with moderate CYP 3A inhibitors
— CYP 3A Inducers – Avoid concomitant use with CYP 3A inducers. If co-administered, the dose of SAMSCA may need to be increased
— P-gp Inhibitors – The dose of SAMSCA may have to be reduced if co-administered with P-gp inhibitors

Hyperkalemia or Drugs that Increase Serum Potassium – Monitor serum potassium levels in patients with a serum potassium >5 mEq/L and in patients receiving drugs known to increase serum potassium levels

Pregnancy and Nursing Mothers – SAMSCA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants from SAMSCA, a decision should be made to discontinue nursing or SAMSCA, taking into consideration the importance of SAMSCA to the mother.

Commonly observed adverse reactions – (SAMSCA incidence ≥5% more than placebo, respectively): thirst (16% vs 5%), dry mouth (13% vs 4%), asthenia (9% vs 4%), constipation (7% vs 2%), pollakiuria or polyuria (11% vs 3%) and hyperglycemia (6% vs 1%).

Please see U.S. FULL PRESCRIBING INFORMATION, including Boxed WARNING, and Medication Guide.

Manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan.
Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850.
SAMSCA is a registered trademark of Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan.

Tell a Colleague

You are now leaving www.samsca.com