Drug information of tolvaptan


Drug group:

Tolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH).

Mechanism of effect

Tolvaptan is a selective and competitive arginine vasopressin receptor 2 antagonist. Vasopressin acts on the V2 receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V2 receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin


Urine volume and fluid intake increase in a dose dependent manner which results in overall negative fluid balance in patients taking tolvaptan. Increases in serum sodium and osmolality can be observed 4-8 hours post-administration and is maintained for 24 hours. The magnitude of serum sodium and osmolality change increases with escalating doses. Furthermore, a decrease in urine osmolality and increase in free water clearance can be observed 4 hours after post-administration of tolvaptan. The affinity for V2 receptors is 29x greater than that of V1a receptors and does not have any appreciable affinity for V2 receptors



Absolute bioavailability: Unknown; at least 40% of the dose is absorbed as tolvaptan or metabolites

Peak plasma concentration: 2-4 hr


Protein bound: 99%

Vd: 3 L/kg


Eliminated entirely by nonrenal routes and mainly, if not exclusively, metabolized by CYP3A


Half-life, terminal: 12 hr

Clearance: 4 mL/min/kg

Excretion: Nonrenal

Drug indications

polycystic kidney disease



Samsca only

Indicated for adults with clinically significant euvolemic or hypervolemic 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, cirrhosis, and SIADH

Initial: 15 mg PO qDay

Maintenance: May increase to 30 mg qDay after at least 24 hr to achieve the optimal serum sodium level; not to exceed 60 mg/day

Not to exceed 30 days of treatment

Polycystic Kidney Disease

Jynarque only

Indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD)

Initial: 45 mg PO taken on waking and 15 mg taken 8 hr later (ie, 60 mg/day)

Titrate to 60 mg plus 30 mg, then to 90 mg plus 30 mg per day if tolerated, with at least weekly intervals between titrations

Patients may down-titrate based on tolerability

Encourage patients to drink enough water to avoid thirst or dehydration


Hypernatremia, hypovolemia, and/or dehydration; encourage patient to drink whenever thirsty

Risk of hyperkalemia

Osmotic demyelination syndrome is a risk associated with too-rapid correction of hyponatremia )

Can cause serious and potentially fatal liver injury; acute liver failure requiring liver transplantation reported; discontinue if laboratory abnormalities or signs or symptoms of liver injury are evident )

Points of recommendation

Oral Administration

May take with or without food


  • Do not exceed 30 days of administration to minimize risk of liver injury
  • Following discontinuation, advise patient to resume fluid restriction and monitor changes in serum sodium and volume status


  • If a dose is not taken at the scheduled time, take the next dose at its scheduled time


Tablets (Samsca): Store at 15-30°C (59-86°F)

Tablets (Jynarque): Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F)

Pregnancy level


Breast feeding warning

Data are not available on the presence of tolvaptan in human milk, the effects on the breastfed infant, or the effects on milk production

Tolvaptan is present in rat milk

Because of the potential for serious adverse reactions, including liver toxicity, electrolyte abnormalities (eg, hypernatremia), hypotension, and volume depletion in breastfed infants, advise women not to breastfeed during treatment

Related drugs


Drug forms

Samsca, Jynarque

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