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

Euvolemic Hyponatremia

About Hyponatremia Prevalence and Prognosis Etiology and Pathogenesis Role of Vasopressin in Hyponatremia Hypervolemic Hyponatremia Pathophysiology of Hyponatremia in Heart Failure Pathophysiology of Hyponatremia in Cirrhosis Euvolemic Hyponatremia Pathophysiology of SIADH in Hyponatremia Management of Hyponatremia Acute vs Chronic Hyponatremia The Role of Vasopressin Receptor Antagonists

Hyponatremia in SIADH
Alpesh Amin, MD

Dilutional Hyponatremia: SIADH and Edematous States
Joseph G. Verbalis, MD

SIADH: A Major Cause of Euvolemic Hyponatremia

Euvolemic Hyponatremia

Euvolemic hyponatremia is characterized by normal or excess extracellular fluid volume.¹ The most common cause of this is the syndrome of inappropriate antidiuretic hormone (SIADH).¹ Other causes include excessive drinking, renal failure, hormonal abnormalities, hypothyroidism, extreme exercising during which overhydration has occurred, and low solute intake.¹

There are 4 conditions associated with SIADH: cancer, nonmalignant lung disease, medication use, and central nervous system (CNS) disorders.²

Causes of SIADH

Cancer. Tumors are the most common condition associated with SIADH. Lung tumors (small cell type) and head and neck tumors are the 2 tumor types most frequently associated with this syndrome. It has been noted that the lungs of patients with small cell cancer synthesize and secrete vasopressin.²

Nonmalignant lung disease has also been associated with SIADH. The pathophysiology, decreased oxygen, and increased CO₂ that increase plasma vasopressin may decrease systemic resistance. This process impairs water clearance and may lead to dilutional hyponatremia.²

Medication use. Antipsychotic drugs, antidepressants, anticonvulsants, narcotics, sulfonylureas, and angiotensin-converting enzyme inhibitors are among the various classes of drugs that can cause SIADH by causing inappropriate release of vasopressin.²

CNS disorders. The last group of conditions that cause SIADH comprises CNS disorders, such as trauma, infection, and hydrocephalus. These conditions are caused by alteration of the usual signaling pathway from the hypothalamus and brainstem, which regulate pituitary release of vasopressin.²

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Pathophysiology of SIADH in Hyponatremia

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References:

Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11, suppl 1):S1-S21.
Siragy HM. Hyponatremia, fluid-electrolyte disorders, and the syndrome of inappropriate antidiuretic hormone secretion: diagnosis and treatment options. Endocr Pract. 2006;12(4):446-457.

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.

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Euvolemic Hyponatremia

SIADH: A Major Cause of Euvolemic Hyponatremia

Euvolemic Hyponatremia

Causes of SIADH

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

Click the following links to explore the site further:

References:

INDICATION

Important Limitations

IMPORTANT SAFETY INFORMATION

SAMSCA is contraindicated in the following conditions: