From the Guidelines
Treatment of euvolemic hypoosmolar hyponatremia should prioritize the use of vasopressin receptor antagonists, such as tolvaptan, while closely monitoring patients in a hospital setting to avoid too rapid correction and risk of osmotic demyelination syndrome. When managing patients with hyponatremia due to SIADH, it is essential to consider the potential benefits and risks of available treatments, including hepatotoxicity associated with tolvaptan 1.
Key Considerations
- Symptom severity and underlying cause guide the treatment approach
- For severe hyponatremia, careful correction with hypertonic saline may be necessary to prevent cerebral edema
- Asymptomatic patients may be managed with fluid restriction
- Medications like tolvaptan, demeclocycline, and loop diuretics can be considered for SIADH-related hyponatremia
- Monitoring serum sodium levels regularly is crucial to avoid overly rapid correction
Treatment Options
- Vasopressin receptor antagonists: tolvaptan, starting at 15 mg daily, titrating up to 60 mg if needed
- Oral urea: 15-60 g/day
- Demeclocycline: 300-600 mg twice daily
- Loop diuretics: furosemide, 20-40 mg daily
- Discontinuation of contributing medications, such as SSRIs, carbamazepine, and thiazide diuretics, is also important
Monitoring and Precautions
- Close monitoring in a hospital setting to avoid too rapid correction of severe hyponatremia
- Risk of osmotic demyelination syndrome with overly rapid correction
- Hepatotoxicity associated with tolvaptan use 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. Patients should be in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death
Treatment of Euvolemic Hyponatremia:
- Tolvaptan is indicated for the treatment of euvolemic hyponatremia.
- The recommended starting dose is 15 mg once daily, which can be increased to 30 mg once daily after at least 24 hours, and to a maximum of 60 mg once daily as needed.
- Key Considerations:
- Initiation and re-initiation of therapy should be done in a hospital setting.
- Monitor serum sodium levels closely to avoid too rapid correction of hyponatremia.
- Avoid fluid restriction during the first 24 hours of therapy.
- Important Safety Information:
- Too rapid correction of hyponatremia can cause serious neurologic sequelae, including osmotic demyelination syndrome.
- Tolvaptan is contraindicated in patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS. 2
From the Research
Treatment of Euvolemic Hypoosmolar Hyponatremia
Euvolemic hypoosmolar hyponatremia, often associated with the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), requires careful management to correct serum sodium levels without causing overly rapid correction, which can lead to osmotic demyelination syndrome. The treatment approach includes:
- Identifying and treating the underlying cause of hyponatremia 3
- Using therapeutic modalities such as fluid restriction, hypertonic saline, urea, demeclocycline, and vasopressin receptor antagonists (vaptans) 4
- Vaptans, including tolvaptan, have been shown to be effective in treating euvolemic hyponatremia by increasing free water excretion and thereby increasing serum sodium concentration 5, 6, 7
Vasopressin Receptor Antagonists (Vaptans)
Vaptans are a class of drugs that have been introduced as a specific and direct therapy for SIADH and other forms of euvolemic and hypervolemic hyponatremia. Key points about vaptans include:
- Tolvaptan is an oral vasopressin V₂-receptor antagonist approved for raising sodium levels in hypervolemic and euvolemic hyponatremia 5
- Vaptans can correct hyponatremia with similar efficacy and less risk for overcorrection compared to higher doses 6
- The use of vaptans allows for long-term therapies that can be continued at the patient's home under close monitoring 7
Considerations for Treatment
When treating euvolemic hypoosmolar hyponatremia, it is crucial to:
- Limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent overly rapid correction and osmotic demyelination syndrome 4
- Monitor serum sodium levels closely, especially during the initial 24 hours of treatment with vaptans 4, 5
- Avoid fluid restriction during the first 24 hours of treatment with vaptans to prevent overly rapid correction of hyponatremia 5