Oral Medications to Increase Serum Sodium

Tolvaptan is the most effective oral medication for increasing serum sodium levels in patients with hyponatremia. 1, 2

First-Line Oral Treatment Options

Tolvaptan, an oral vasopressin V2 receptor antagonist, is FDA-approved for euvolemic and hypervolemic hyponatremia and effectively increases serum sodium levels 2, 3
The usual starting dose for tolvaptan is 15 mg once daily, which can be increased to 30 mg after 24 hours, and further to 60 mg as needed to achieve desired serum sodium levels 2
Tolvaptan should be initiated in a hospital setting with close monitoring of serum sodium to avoid too rapid correction 4, 2
Treatment duration should not exceed 30 days to minimize risk of liver injury 2

Tolvaptan works by blocking vasopressin V2 receptors in the kidneys, promoting aquaresis (excretion of electrolyte-free water) without affecting sodium and potassium excretion 5, 3
Clinical trials demonstrate significant increases in serum sodium levels within 4 days of treatment initiation and maintained improvement through 30 days of therapy 3, 6
Even a single 15 mg dose of tolvaptan can increase serum sodium by an average of 6.4 mEq/L (range 2-10 mEq/L) within 24 hours 7
After discontinuation of tolvaptan, hyponatremia typically recurs, indicating the need for addressing the underlying cause 3

Serum sodium levels should be closely monitored to avoid increases of more than 8-10 mmol/L/day, which could lead to osmotic demyelination syndrome 1, 2
Patients with advanced liver disease, alcoholism, or malnutrition require more cautious correction (4-6 mmol/L per day) due to higher risk of osmotic demyelination 1
Common side effects include thirst, dry mouth, polyuria, and potential for dehydration 2
Avoid fluid restriction during the first 24 hours of therapy to prevent overly rapid correction of serum sodium 2
Tolvaptan is contraindicated in patients who cannot sense or respond to thirst, have hypovolemic hyponatremia, are taking strong CYP3A inhibitors, or have anuria 2

For patients with uncompensated liver cirrhosis, 50% of the standard dose is recommended as metabolism is approximately 60% slower 4
In cirrhotic patients, tolvaptan has been shown to increase serum sodium in patients with baseline values ≤130 mmol/L 8
Caution is advised by manufacturers when using tolvaptan in patients with cirrhosis due to potential side effects 8

Sodium chloride tablets can be considered as an alternative oral treatment for appropriate patients with hyponatremia 1
Urea is another oral option that can be effective for SIADH and other causes of hyponatremia 1, 9
For hypervolemic hyponatremia (e.g., cirrhosis, heart failure), fluid restriction to 1-1.5 L/day is recommended for serum sodium <125 mmol/L, but this rarely improves sodium levels significantly 1

Overly rapid correction of chronic hyponatremia (>8 mmol/L in 24 hours) can lead to osmotic demyelination syndrome 1, 2
Concomitant use of tolvaptan with hypertonic saline is not recommended due to risk of overcorrection 2
Fluid restriction during the first 24 hours of tolvaptan therapy may increase the risk of overly rapid correction 2
Using tolvaptan in hypovolemic hyponatremia is contraindicated and potentially dangerous 2
Tolvaptan should not be used for more than 30 days due to risk of liver injury 2