Last reviewed 2026-04-20 · How we verify

Samsca (TOLVAPTAN)

Samsca works by blocking the action of vasopressin, a hormone that regulates water levels in the body.

At a glance

Mechanism of action

Tolvaptan is selective vasopressin V2-receptor antagonist with an affinity for the V2-receptor that is 1.8 times that of native arginine vasopressin (AVP). Tolvaptan affinity for the V2-receptor is 29 times greater than for the V1a-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), decrease in urine osmolality, and resulting increase in serum sodium concentrations. Urinary excretion of sodium and potassium and plasma potassium concentrations are not significantly changed. Tolvaptan metabolites have no or weak antagonist activity for human V2-receptors compared with tolvaptan.

Approved indications

• Fluid retention in heart failure
• Hyponatremia
• Polycystic kidney disease, adult type
• Syndrome of inappropriate vasopressin secretion

Boxed warnings

• WARNING: RISK OF SERIOUS LIVER INJURY JYNARQUE (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported [see Warnings and Precautions (5.1) ] . Measure ALT, AST and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then monthly for the first 18 months and every 3 months thereafter [see Warnings and Precautions (5.1) ] . Prompt action in response to laboratory abnormalities, signs, or symptoms indicative of hepatic injury can mitigate, but not eliminate, the risk of serious hepatotoxicity. Because of the risks of serious liver injury, JYNARQUE is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tolvaptan for ADPKD Shared System REMS [see Warnings and Precautions (5.2) ] . WARNING: RISK OF SERIOUS LIVER INJURY See full prescribing information for complete boxed warning . JYNARQUE (tolvaptan) can cause serious and potentially fatal liver injury. Acute liver failure requiring liver transplantation has been reported ( 5.1 ) Measure transaminases and bilirubin before initiating treatment, at 2 weeks and 4 weeks after initiation, then continuing monthly for the first 18 months and every 3 months thereafter ( 5.1 ) JYNARQUE is available only through a restricted distribution program called the Tolvaptan for ADPKD Shared System REMS ( 5.2 )

Common side effects

• Mortality
• Thirst
• Polyuria or pollakiuria
• Dry mouth
• Nausea
• Asthenia
• Hyperglycemia
• Pyrexia
• Constipation
• Anorexia
• Gastrointestinal bleeding
• Disseminated intravascular coagulation

Drug interactions

• amprenavir
• aprepitant
• atazanavir
• boceprevir
• ciprofloxacin
• clarithromycin
• darunavir
• diltiazem
• fluconazole
• fosamprenavir
• fosaprepitant
• imatinib

Key clinical trials

• HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life (PHASE3)
• A Study to See Iftolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years Old withAutosomal Recessive Polycystic Kidney Disease (ARPKD) (PHASE3)
• Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration (PHASE2)
• Canadian Medical Assessment of JINARC™ Outcomes Registry
• A Study to See if Tolvaptan Can Delay Dialysis in Infants and Children Who at Enrollment Are 28 Days to Less Than 12 Weeks Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD) (PHASE3)
• Bempedoic Acid Therapy for Polycystic Kidney Disease (PHASE2)
• Post-Marketing Surveillance Study of Tolvaptan in Patients With ADPKD
• A Study of HRS-9057 in Patients With Heart Failure and Volume Overload (PHASE1)

Patents

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.