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. In controlled clinical trials in which tolvaptan was administered in titrated doses starting at 15 mg once daily, 7% of tolvaptan-treated subjects with a serum sodium <130 mEq/L had an increase in serum sodium greater than 8 mEq/L at approximately 8 hours and 2% had an increase greater than 12 mEq/L at 24 hours
The management of SIADH after a stroke involves the use of tolvaptan, a medication that helps to correct hyponatremia. The recommended starting dose is 15 mg once daily, which can be increased to a maximum of 60 mg once daily as needed. It is essential to monitor serum sodium levels closely to avoid too rapid correction, which can cause osmotic demyelination. Patients should be advised to continue ingestion of fluid in response to thirst, and fluid restriction should be avoided during the first 24 hours of therapy 1.
- Key considerations:
- Initiate and re-initiate tolvaptan in a hospital setting
- Monitor serum sodium levels closely
- Avoid too rapid correction of hyponatremia
- Use with caution in patients with severe malnutrition, alcoholism, or advanced liver disease
- Do not use in patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS 1
From the Research
The management of SIADH after stroke should prioritize correcting hyponatremia while addressing the underlying condition, with fluid restriction and pharmacological intervention as needed, according to the most recent and highest quality study 2. The goal of treatment is to improve symptoms and prevent complications such as osmotic demyelination syndrome.
- Fluid restriction of 800-1000 mL/day is the first-line treatment, as limiting free water intake helps correct sodium levels.
- For mild to moderate cases (sodium >125 mEq/L), fluid restriction alone may be sufficient.
- In more severe cases (sodium <125 mEq/L) or when symptoms are present, pharmacological intervention is warranted, with options including tolvaptan, a vasopressin receptor antagonist, which can be initiated at 15 mg daily and titrated up to 60 mg daily based on sodium response 3.
- Alternatively, demeclocycline (300-600 mg twice daily) or urea (15-60 g/day) may be used.
- For severe symptomatic hyponatremia, hypertonic saline (3%) may be administered at 1-2 mL/kg/hour with careful monitoring to avoid rapid correction.
- Sodium correction should not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as emphasized in the study 2. Regular monitoring of serum sodium (every 4-6 hours initially), fluid balance, and neurological status is essential, as highlighted in the study 4. SIADH following stroke typically resolves within days to weeks as brain edema subsides, allowing for gradual discontinuation of treatment. The underlying mechanism involves brain injury triggering inappropriate ADH release from the posterior pituitary, leading to excessive water retention and dilutional hyponatremia, as discussed in the study 5.