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

From the Guidelines

The management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should prioritize treating the underlying cause while addressing hyponatremia, with first-line treatment involving fluid restriction to less than 1 L/day, as recommended by expert opinion 1. The goal of treatment is to correct hyponatremia while preventing complications such as osmotic demyelination syndrome.

• For asymptomatic mild SIADH, fluid restriction is the primary treatment.
• For acute, severe, or symptomatic hyponatremia (sodium <120 mEq/L or neurological symptoms), 3% hypertonic saline should be administered intravenously with careful monitoring to avoid rapid correction, as supported by recent studies 1. Key considerations in managing SIADH include:
• Regular monitoring of serum sodium, fluid status, and neurological symptoms
• Adjusting sodium correction rates to prevent complications
• Addressing the underlying condition causing SIADH Pharmacological options for chronic SIADH may include:
• Vasopressin receptor antagonists such as tolvaptan, which has been shown to be effective in improving serum sodium concentration in patients with SIADH 1
• Oral salt tablets and loop diuretics to enhance free water excretion
• Urea to induce osmotic diuresis It is essential to note that the safety and efficacy of these treatments may vary depending on the individual patient and the underlying cause of SIADH, and therefore, treatment should be tailored to the specific needs of each patient, as highlighted in recent clinical practice 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) 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.

Management of SIADH with tolvaptan involves:

• Initiating treatment in a hospital to monitor serum sodium levels
• Starting with a dose of 15 mg once daily and titrating up to 30 mg or 60 mg as needed
• Avoiding fluid restriction during the first 24 hours of therapy
• Monitoring for changes in serum electrolytes and volume status
• Limiting treatment to 30 days to minimize the risk of liver injury 2 Key considerations:
• Too rapid correction of hyponatremia can cause osmotic demyelination syndrome
• Slower rates of correction may be advisable in susceptible patients, such as those with severe malnutrition, alcoholism, or advanced liver disease

From the Research

Management of SIADH

• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia, accounting for approximately one-third of all cases 3.
• Diagnosis of SIADH requires ascertaining the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements 3.
• Treatment of SIADH aims to cure symptoms, with therapeutic modalities including nonspecific measures such as fluid restriction, hypertonic saline, urea, and demeclocycline, as well as specific therapy with vasopressin receptor antagonists, called vaptans 3.

Treatment Options

• Vaptans, such as tolvaptan, have been introduced as a specific and direct therapy for SIADH, offering advantages such as no need for fluid restriction and efficient correction of hyponatremia 3, 4, 5.
• Low-dose tolvaptan (3.75-7.5mg) has been shown to effectively increase serum sodium in SIADH-associated hyponatremia, with reduced risk of overcorrection compared to higher doses 4, 5.
• Long-term low-dose tolvaptan therapy has been found to be safe and effective in SIADH treatment, with no cases of overcorrection or osmotic demyelination syndrome reported 6.

Safety and Efficacy

• The use of vaptans in SIADH treatment has been associated with mild side effects such as thirst, polydipsia, and frequency of urination 3, 6.
• Close monitoring of sodium levels is recommended when initiating tolvaptan therapy, particularly in high-risk patients 5.
• Further clinical trials are needed to determine the optimal dosing, proper monitoring, and adequate precautions for the use of vaptans in SIADH patients 7.