What is the treatment for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

From the Guidelines

The treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should prioritize fluid restriction and correction of the underlying cause, with pharmacological interventions such as vasopressin receptor antagonists and demeclocycline considered for refractory cases, as supported by the most recent guidelines 1.

Key Considerations

• The primary goal of treatment is to correct hyponatremia while addressing the underlying cause of SIADH.
• Fluid restriction to less than 1 L/day is a first-line treatment for asymptomatic mild SIADH and a recommended adjunct for severe cases.
• For patients with moderate to severe symptoms, 3% hypertonic saline may be administered intravenously, with careful monitoring to avoid rapid sodium correction.
• Pharmacological options include vasopressin receptor antagonists like tolvaptan or conivaptan, and demeclocycline for chronic SIADH.

Treatment Approach

• Fluid restriction: Limit free water intake to less than 1 L/day to correct hyponatremia.
• Hypertonic saline: Administer 3% hypertonic saline intravenously at 1-2 mL/kg/hour for life-threatening or acute symptomatic and severe hyponatremia.
• Vasopressin receptor antagonists: Consider tolvaptan or conivaptan for refractory hyponatremia.
• Demeclocycline: Use for chronic SIADH to inhibit ADH action in the kidneys.

Monitoring and Management

• Close monitoring of serum sodium levels, neurological status, and fluid balance is crucial.
• Treatment should be tailored to symptom severity, with adjustments made as needed to avoid rapid sodium correction and prevent osmotic demyelination syndrome.
• The underlying cause of SIADH, such as malignancy, medications, or CNS disorders, must be addressed simultaneously for effective long-term management, as highlighted in recent guidelines 1.

From the FDA Drug Label

Tolvaptan tablets are 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)

Treatment of SIADH: Tolvaptan is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH.

• The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals.
• Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium.
• Do not administer tolvaptan tablets for more than 30 days to minimize the risk of liver injury 2.
• In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), tolvaptan caused a statistically greater increase in serum sodium (p <0.0001) during both periods in both studies, including patients with SIADH 2.

From the Research

Treatment Options for SIADH

• The treatment of SIADH aims to cure symptoms, with therapeutic modalities including nonspecific measures such as fluid restriction, hypertonic saline, urea, and demeclocycline 3.
• Vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH, offering advantages such as no need for fluid restriction and efficient correction of hyponatremia 3, 4.
• Tolvaptan, an oral vasopressin V2-receptor antagonist, has been found to improve hyponatremia in patients with SIADH, with minimal side effects and significant positive treatment effects on physical and mental components of health surveys 4, 5.

Management of Hyponatremia in SIADH

• Immediate treatment of symptomatic patients with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance 6.
• Fluid restriction is the treatment of choice for chronic SIADH, with demeclocycline used if fluid restriction is not tolerated by the patient 6.
• The daily increase of serum sodium should be limited to less than 8-10 mmol/liter to prevent osmotic demyelination, with close monitoring of serum sodium levels during treatment with vaptans 3.

Efficacy and Safety of Tolvaptan in SIADH

• Tolvaptan has been shown to be effective and safe in treating hyponatremia in patients with SIADH, with significant improvements in serum sodium levels and minimal side effects 5, 7.
• A study of in-patient tolvaptan use in SIADH found favourable short-term outcomes, with 94% of patients achieving treatment targets after a mean of 3.48 days, and no cases of drug-associated liver injury or CNS-myelinolysis 7.
• Relapse of hyponatremia occurred in 26% of patients, requiring retreatment with tolvaptan, with underlying malignancy present in 60% of the study group 7.