CardioSource WorldNews December 2014 - Page 68

For 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 WHEN FLUID RESTRICTION IS NOT ENOUGH, HELP PATIENTS BREAK FREE WITH FREE WATER CLEARANCE • Too rapid correction of serum sodium can cause serious neurologic sequelae • Avoid fluid restriction during the first 24 hours of therapy INDICATION and Important Limitations • 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, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) • 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 Contraindications: 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, and hypersensitivity (e.g. anaphylactic shock, rash generalized) to tolvaptan or its components Warnings and Precautions: • 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 or develop neurologic sequelae, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction should generally be avoided during the first 24 hours • SAMSCA can cause serious and potentially fatal liver injury. Avoid use in patients with underlying liver disease, including cirrhosis, because the ability to recover may be impaired. Limit duration of therapy with SAMSCA to 30 days • Dehydration and hypovolemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted. In patients who develop medically significant signs or symptoms of hypovolemia, discontinuation is recommended • Co-administration with hypertonic saline is not recommended • Avoid concomitant use with: CYP 3A inhibitors and CYP 3A inducers. The dose of SAMSCA may have to be reduced if co-administered with P-gp inhibitors • Monitor serum potassium levels in patients with a serum potassium >5 mEq/L and in patients receiving drugs known to increase serum potassium levels Adverse Reactions - The most common 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%) Gastrointestinal Bleeding in Patients with Cirrhosis – In patients with cirrhosis in the hyponatremia trials, GI bleeding was reported in 10% of tolvaptantreated patients vs 2% for placebo Please see Brief Summary of FULL PRESCRIBING INFORMATION, including Boxed WARNING, on following page. 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. ©2014 Otsuka America Pharmaceutical, Inc. For more information please visit SAMSCA.com June 2014 07US14EBP2751