SAMSCA

What it is

SAMSCA is tolvaptan tablets for oral use, available in 15 mg and 30 mg strengths. Tolvaptan is a selective vasopressin V2-receptor antagonist with an affinity for the V2-receptor greater than that of native arginine vasopressin.

Approved indications

— Clinically significant hypervolemic or euvolemic hyponatraemia (serum sodium less than 125 mmol/L, or less marked hyponatraemia that is symptomatic and has resisted correction with fluid restriction) including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).

Dosing overview

Treatment with SAMSCA should be initiated in hospital due to the need for a dose titration phase with close monitoring of serum sodium and volume status, and should be initiated at a dose of 15 mg, orally, once daily. The dose may be increased to a maximum of 60 mg once daily as tolerated to achieve the desired level of serum sodium, with increases from the starting dose done incrementally (first to 30 mg and then to 60 mg if required) at intervals ≥ 24 hours. SAMSCA should not be administered for more than 30 days to minimise the risk of liver injury.

Key safety warnings

Drug-induced liver injury has been observed in clinical trials investigating a different indication with long-term use of SAMSCA at higher doses than for the approved indication, with an increased incidence of alanine aminotransferase greater than three times the upper limit of normal observed in patients treated with SAMSCA (42/958 or 4.4%) compared to those receiving placebo (5/484 or 1.0%). SAMSCA can cause irreversible and potentially fatal liver injury, and acute liver failure requiring liver transplantation has been reported in postmarketing experience with tolvaptan in ADPKD. Avoid use in patients with underlying liver disease, including cirrhosis, because the ability to recover from liver injury may be impaired. Patients should be monitored frequently during initiation and after each titration for serum sodium and volume status to avoid adverse neurologic outcomes that may result from rapid increases in serum sodium, as too rapid correction of hyponatraemia can cause osmotic demyelination which may result in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. Potent aquaresis may induce hypernatremia which can lead to adverse neurologic events, and if serum sodium increases above normal range, tolvaptan dose should be adjusted and serum sodium should be carefully monitored. Dehydration and hypovolaemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted, and fluid restriction during therapy with SAMSCA may increase the risk of dehydration and hypovolaemia. Treatment with SAMSCA is associated with an acute reduction of the extracellular fluid volume which could result in increased serum potassium, and serum potassium levels should be monitored after initiation of SAMSCA treatment in patients with a serum potassium > 5 mmol/L as well as those who are receiving drugs known to increase serum potassium levels.

Contraindications

SAMSCA is contraindicated in patients hypersensitive to the active substance, benzazepine derivatives or any of the excipients; patients who are unable to sense or appropriately respond to thirst; patients suffering from hypovolaemic hyponatraemia; patients with anuria; and patients with an urgent need to raise serum sodium acutely. SAMSCA is contraindicated with ketoconazole and other strong CYP 3A inhibitors.

Regulatory history

SAMSCA tolvaptan 15 mg and 30 mg tablets were first listed on the Australian Register of Therapeutic Goods on 5 April 2012.