Treatment with SAMSCA® (tolvaptan)

SAMSCA is indicated 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

Our patient selection guide can help you identify appropriate patients for SAMSCA therapy.

Important steps in the treatment of patients with hyponatremia is to determine whether their disease is acute(defined as duration of <48 hours) or chronic(defined as duration of ≥48 hours),1 and to take into account the rate of serum sodium correction.2 The risk of hyponatremia-associated complications then must be balanced against the risk of serum sodium correction. Factors that should be considered before treating include the rapidity of onset of hyponatremia; degree, duration, and symptomatology of hyponatremia; and the presence or absence of risk factors for neurologic complications.1

Treatment of Acute vs Chronic Hyponatremia

Because of the different effects of acute versus chronic hyponatremia on the brain, the treatment strategy for each will differ. Tap on the disease states below to see treatment options.

Patients requiring an urgent need to raise serum sodium to prevent or treat serious neurological symptoms should not be treated with SAMSCA.

Limit duration of therapy to 30 days.

In acute severe and rapidly developing hyponatremia, treatment should begin as soon as the problem is identified. The goal of treatment is to increase the serum sodium level by 1.5 to 2 mEq/L/hour until symptoms subside or until the sodium concentration is >118 to 120 mEq/L, with the primary focus to minimize the risk of seizure. Even in symptomatic patients, the sodium level should not be increased by >12 mEq/L in the first 24 hours, or by >18 mEq/L in the first 48 hours, to avoid osmotic demyelination syndrome (ODS).1

When patients become asymptomatic and sodium levels rise above 118 mEq/L, correction should be slowed to no more than 8 mEq/L in 24 hours to achieve the target sodium concentration. In all cases, close and frequent monitoring of serum sodium and electrolytes is mandatory until sodium levels increase and symptoms of hyponatremia resolve.1

In hyponatremia of unknown duration, sodium correction should be managed cautiously because of brain adaptation to prolonged hyponatremia. In patients presenting with severe symptoms, treatment should be similar to that for acute symptomatic hyponatremia.1

Careful monitoring is critical because of increased risk of irreversible osmotic demyelination. Correction should be limited to no more than 10 to 12 mEq/L during the first 24 hours of treatment and <6 mEq/L/day subsequently. In patients presenting with mild to moderate symptoms, slower correction is required. Once the desired correction is achieved, fluid restriction may be employed.1

When treating asymptomatic hyponatremia, the goal is to prevent further decreases in serum sodium levels and to keep levels as close to normal as possible.1

Effects of hyponatremia on the brain and adaptive responses

The brain’s adaptation process during hyponatremia may be associated with the rare but serious consequence of osmotic demyelination syndrome (ODS) if the rate of correction of sodium is too rapid. ODS can develop 1 to several days after aggressive treatment of hyponatremia (e.g., too rapid correction), even with water restriction alone.3

Treat hyponatremia appropriately to avoid osmotic demyelination2
Image showing how hyponatremia effects the brain, and how osmotic demyelination occurs.

Adapted from Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581-1589. Copyright © 2000 Massachusetts Medical Society. All rights reserved.

  1. Hypotonic hyponatremia results in water entering the brain.3
  2. Water gain leads to cerebral edema, intracranial hypertension, and a risk of brain injury.3
  3. Within hours, however, solutes exit the brain tissues, inducing loss of water.3
  4. This loss of water relieves the swelling of the brain. This adaptation process helps explain why even patients with severe hyponatremia may have few symptoms if the condition develops slowly.3
  5. Rapid correction of the hypotonic state can lead to shrinkage of the brain. Shrinkage of the brain leads to demyelination of pontine and extrapontine neurons, which can cause neurologic dysfunction in the form of quadriplegia, pseudobulbar palsy, seizures, coma, or even death. Patients with potassium depletion and malnutrition are at increased risk of this complication.3

Expert recommendations to avoid ODS in the management of hyponatremia

Experts advise that correction should be of an appropriate rate to reverse the manifestation of hypotonicity, but not to impose a risk of ODS.3 According to the expert panel recommendations for treating hyponatremia, the rate of correction of hyponatremia should be limited to <10 to 12 mEq/L in 24 hours and <18 mEq/L in 48 hours.2,3

As always, physicians must use their clinical judgment when treating patients with hyponatremia.