From the Guidelines
The treatment of SIADH should prioritize the use of vaptans, such as tolvaptan, due to their efficacy in improving serum sodium concentration and their relatively favorable side effect profile, as demonstrated in recent studies 1.
Key Considerations
- The management of SIADH focuses on addressing the underlying cause while correcting hyponatremia.
- For patients with severe hyponatremia (sodium <125 mmol/L), vaptans are a preferred treatment option due to their ability to selectively block the V2-receptors of AVP, thereby improving solute-free water excretion 1.
- Tolvaptan, in particular, has been approved for the treatment of SIADH in Europe and for severe hypervolemic hyponatremia in the USA, with a recommended starting dose of 15 mg/day that can be titrated up to 60 mg/day as needed 1.
Treatment Approach
- Vaptans, such as tolvaptan, should be considered as the first-line treatment for SIADH, especially in cases with severe hyponatremia or significant symptoms, due to their effectiveness in correcting serum sodium levels 1.
- Fluid restriction may be helpful in preventing further decreases in serum sodium but is rarely effective in improving serum sodium concentration on its own 1.
- Other pharmacological options, such as hypertonic saline, loop diuretics, and urea, may be considered based on the individual patient's condition and response to initial treatment.
Monitoring and Safety
- Close monitoring of serum sodium levels is crucial when initiating treatment with vaptans to avoid rapid correction and potential complications such as osmotic demyelination syndrome 1.
- Patients should be started on vaptans in a hospital setting with careful monitoring, and the treatment should be adjusted based on the patient's response and potential side effects 1.
- The risk of dehydration and hypernatremia, particularly in patients who cannot drink appropriately due to altered mental states, should be carefully managed 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 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 2.
- Key considerations:
- Initiate and re-initiate in a hospital and monitor serum sodium.
- Avoid too rapid correction of hyponatremia (> 12 mEq/L/24 hours) to prevent osmotic demyelination.
- Patients receiving tolvaptan tablets should be advised that they can continue ingestion of fluid in response to thirst.
- Do not administer tolvaptan tablets for more than 30 days to minimize the risk of liver injury.
- Clinical trials: 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 in patients with SIADH 2.
From the Research
Treatment Options for SIADH
- Fluid restriction is a common treatment for SIADH, but it has limitations and is often insufficient 3
- Hypertonic saline is used in the initial treatment of symptomatic SIADH with severe neurological deficits 4
- Demeclocycline has been used to treat chronic hyponatremia in SIADH, but it lacks broad availability and has safety concerns 4
- Urea and frusemide are also used to treat SIADH, but they have their limitations 5
Vasopressin Receptor Antagonists (Vaptans)
- Vaptans are a new class of drugs that specifically target the underlying pathophysiology of SIADH 4, 5
- They have been shown to be efficacious in the treatment of mild to moderate SIADH with an acceptable safety profile 4, 6
- Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with SIADH 6
- Vaptans have the advantage of not requiring fluid restriction and can achieve correction of hyponatremia comfortably and within a short time 7
Important Considerations
- The daily increase of serum sodium should be limited to less than 8-10 mmol/liter to avoid osmotic demyelination 7
- The serum sodium should be measured after 0,6,24, and 48 hours of treatment with vaptans to prevent overly rapid correction of hyponatremia 7
- Discontinuation of vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse 7