Samsca (tolvaptan) is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. It is specifically designed to address serum sodium imbalances in patients with conditions such as syndrome of inappropriate antidiuretic hormone secretion (SIADH), heart failure, and cirrhosis. By promoting aquaresis—the electrolyte-sparing excretion of free water—Samsca provides a targeted mechanism to raise serum sodium concentrations. Its use is reserved for patients under close medical supervision to mitigate risks and ensure appropriate monitoring of sodium correction rates. This agent represents a critical tool in managing complex fluid and electrolyte disorders where conventional therapies may be insufficient or contraindicated.

Features

• Contains tolvaptan, a selective vasopressin V2-receptor antagonist
• Available in 15 mg and 30 mg oral tablet formulations
• Promotes aquaresis—exclusive free water excretion without significant sodium or potassium loss
• Initiation requires inpatient setting for serum sodium monitoring
• Not indicated for hypovolemic hyponatremia
• Requires avoidance of concomitant strong CYP 3A inhibitors

Benefits

• Effectively increases low serum sodium levels in appropriate patient populations
• Provides a mechanism for controlled correction of hyponatremia
• Reduces fluid overload symptoms in hypervolemic states through aquaresis
• May improve neurological symptoms associated with hyponatremia when properly managed
• Offers an alternative to fluid restriction and saline infusion in selected cases
• Enables tailored dosing based on serum sodium response and tolerability

Common use

Samsca is primarily used in hospitalized patients for the treatment of hypervolemic and euvolemic hyponatremia. Common clinical scenarios include hyponatremia associated with congestive heart failure, liver cirrhosis with ascites, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). It is particularly valuable when rapid but controlled correction of serum sodium is warranted, or when fluid restriction alone is ineffective or poorly tolerated. Treatment should always be initiated in a setting where serum sodium can be monitored frequently, typically every 6-8 hours during the initial phase of therapy.

Dosage and direction

Initiate therapy with 15 mg orally once daily. Dose may be increased to 30 mg once daily after at least 24 hours to a maximum of 60 mg once daily, as needed to achieve the desired serum sodium level. Titration should be based on serum sodium concentrations, with a goal not to exceed 12 mEq/L in the first 24 hours or 18 mEq/L in the first 48 hours. Avoid fluid restriction during the first 24 hours of therapy. Treatment duration should be limited to 30 days due to potential liver injury risks. Administration with or without food is acceptable.

Precautions

Samsca should be used with extreme caution due to the risk of overly rapid correction of hyponatremia, which can lead to osmotic demyelination syndrome. Monitor serum sodium and volume status frequently, especially during initiation and titration. Hepatic function should be assessed before and during treatment. Dehydration and hypovolemia may occur; monitor vital signs and assess for signs of volume depletion. Use with caution in patients with renal impairment. Patients should have access to water and be advised they will experience increased urination and thirst. Avoid use in patients unable to sense or respond to thirst.

Contraindications

Samsca is contraindicated in patients with hypovolemic hyponatremia. Concomitant use with strong CYP 3A inhibitors such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir is prohibited. Additional contraindications include anuria, inability to sense or respond to thirst, and urgent need to raise serum sodium acutely. Use is also contraindicated in patients with known hypersensitivity to tolvaptan or any component of the formulation.

Possible side effects

Common adverse reactions include thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia. Serious side effects may include overly rapid correction of sodium leading to osmotic demyelination, hepatic injury, dehydration, and gastrointestinal bleeding. Less frequent but significant effects include acute renal failure, hypernatremia, and orthostatic hypotension. Patients may experience dizziness, nausea, and decreased appetite. Any signs of liver injury (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) should prompt immediate evaluation.

Drug interaction

Strong CYP 3A inhibitors significantly increase tolvaptan exposure and are contraindicated. Moderate CYP 3A inhibitors (erythromycin, fluconazole, aprepitant, diltiazem, verapamil) may increase tolvaptan levels—consider dose reduction. CYP 3A inducers (rifampin, rifabutin, rifapentine, barbiturates, phenytoin, St. John’s wort) may decrease tolvaptan efficacy. P-gp inhibitors may increase tolvaptan concentrations. Use with other medications affecting serum sodium (diuretics, especially hypertonic saline) requires careful monitoring. Concomitant use with hypertonic saline is not recommended.

Missed dose

If a dose is missed, it should be taken as soon as possible on the same day. However, if the missed dose is not remembered until the next day, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not take two doses on the same day to make up for a missed dose. Any pattern of missed doses should be discussed with the healthcare provider to assess potential impact on serum sodium control.

Overdose

Overdose may lead to pronounced aquaresis with substantial fluid loss, potentially resulting in dehydration, hypovolemia, and hypernatremia. Signs and symptoms may include excessive thirst, dry mucous membranes, hypotension, tachycardia, weakness, and altered mental status. Management involves discontinuation of Samsca, careful assessment of volume status and serum electrolytes, and appropriate supportive measures including fluid replacement based on hydration status. There is no specific antidote; treatment should be symptomatic and supportive with close monitoring of serum sodium concentrations.

Storage

Store at room temperature between 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in original container with desiccant to protect from moisture. Keep out of reach of children and pets. Do not use if the blister pack is damaged or tablets show signs of deterioration. Discard any unused medication properly according to local regulations, preferably through a medicine take-back program.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Samsca is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Treatment decisions must be made by a physician based on individual patient assessment. Patients should not initiate or discontinue therapy without medical supervision. Full prescribing information, including boxed warnings about the risk of osmotic demyelination and liver injury, should be reviewed before administration.

Reviews

Clinical trials demonstrate Samsca’s efficacy in significantly increasing serum sodium concentrations compared to placebo in patients with euvolemic and hypervolemic hyponatremia. In the SALT studies, tolvaptan produced a mean increase in serum sodium of approximately 4-6 mEq/L over placebo by day 4, with effects maintained through day 30. Most patients achieved normal or near-normal sodium levels within 7-8 days. Expert consensus guidelines recognize vasopressin receptor antagonists as valuable options for specific hyponatremia cases, particularly when careful monitoring is available. Real-world experience confirms its utility in appropriate patient populations, though emphasizes the critical importance of adherence to monitoring protocols and duration limitations.