Tolvaptan

What it is and how it works

Mechanism of Action Tolvaptan is a selective vasopressin V 2 -receptor antagonist with an affinity for the V 2 -receptor that is 1.8 times that of native arginine vasopressin (AVP). Tolvaptan affinity for the V 2 -receptor is 29 times greater than for the V 1a -receptor. When taken orally, 15 to 60 mg doses of tolvaptan antagonize the effect of vasopressin and cause an increase in urine water excretion that results in an increase in free water clearance (aquaresis), a decrease in urine osmolality, and a resulting increase in serum sodium concentrations. Urinary excretion of sodium and potassium and plasma potassium concentrations are not significantly changed.

Mechanism class: Vasopressin V2 Receptor Antagonists

Indications

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). Limitations of Use Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with tolvaptan tablets. It has not been established that raising serum sodium with tolvaptan tablets provides a symptomatic benefit to patients.

Dosage and administration (summary)

Tolvaptan tablets should be initiated and re-initiated in a hospital The recommended starting dose is 15 mg once daily. Dosage may be increased at intervals ≥24 hr to 30 mg once daily, and to a maximum of 60 mg once daily as needed to raise serum sodium. Recommended Dosage 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. The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals.

Contraindications

Tolvaptan tablets are contraindicated in the following conditions: Patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS Unable to sense or respond to thirst Hypovolemic hyponatremia Taking strong CYP3A inhibitors Anuria Hypersensitivity (e.g., anaphylactic shock, rash generalized) to tolvaptan or any components of the product Use in patients with autosomal dominant polycystic kidney disease (ADPKD) outside of FDA approved REMS Patients who are unable to…

Warnings and precautions

Liver injury: Limit treatment duration to 30 days. If hepatic injury is suspected, discontinue tolvaptan. Avoid use in patients with underlying liver disease Dehydration and hypovolemia may require intervention Avoid use with hypertonic saline Avoid use with moderate to strong CYP 3A inhibitors Monitor serum potassium in patients with potassium >5 mEq/L or on drugs known to increase potassium Urinary outflow obstruction: Urinary output must be secured Too Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae Osmotic demyelination syndrome is a risk associated with too rapid co…

Pregnancy

Pregnancy Risk Summary Available data with tolvaptan use in pregnant women are insufficient to determine if there is a drug-associated risk of adverse developmental outcomes. Tolvaptan did not cause any developmental toxicity in rats or in rabbits at exposures approximately 2.8 and 0.8 times, respectively, the exposure in congestive heart failure (…

Storage and supply

How Supplied Tolvaptan tablets are available in the following strengths and packages. Tolvaptan 15 mg tablets are blue colored, triangular, shallow convex tablets debossed with “E” on one side and “500” on the other side.

Source: Tolvaptan (Tolvaptan) — US FDA prescribing information, 2026-08-05, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.