Tolvaptan (Samsca)

An agent indicated for the treatment clinically significant hypovolemic euvolemic hyponatremia with heart failure, cirrhosis, and syndrome of inappropriate ADH.

Should not be used in patients requiring urgent sodium elevation or to treat serious neurologic symptoms.

Should be administered in a hospital setting, where serum sodium can be monitored closely.

Increases sodium levels of 5 mEq/L compared to placebo at day four, and persists at 30 days (SALT Investigators).

An oral dose of 30 mg a day increases sodium level by a mean of 3.6 mmol per liter at four days and by 4.4 mmoles per liter at 30 days.

In the trial of 4133 patients hospitalized with acute decompensated heart failure, no clinical improvements in rehospitalization, renal function on mortality were observed in median follow up of 10 months (Konstam MA et al).

The risk for overcorrection of hyponatremia is approximately 1.7%.

Too rapid correction of hyponatremia, greater than 12 mEq per liter per 24 hours, can cause osmotic demyelination with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriplegia, seizures, coma and death.

Promotes free water clearance by direct antagonism of the renal V2 receptors.

Significantly increases serum sodium in as early as eight hours.

Most common adverse reactions include: first( 16%), dry mouth (13%), asthenia (9%), constipation (7%), polyuria (11%) and hyperglycemia (6%).

Has the potential of causing irreversible and potentially fatal liver injury.

Use recommended to be limited to 30 days and should not be used in liver disease except in end stage liver disease for patients waiting to be transplantated.

Starting dose 15 mg tablet per day, with a maximum of 60 mg a day.

Patients can drink in response to thirst.

Tolvaptan, Is a vasopressin V2 receptor antagonist, as compared with placebo slowed the increase in total kidney volume and declining kidney function over three year period in patients with ADPKD (Torres VE et al).

In the above study the increase in total kidney volume in the tolvaptan group was 2.8% per year, versus 5.5% per year in the placebo group.

In the above study they were fewer ADPKD-related adverse events in the treatment group but more events related to the excretion of electrolyte freewater and hepatic adverse events unrelated to the ADPKD, contributing to a higher discontinuation rate of 23% versus 14% in the placebo group.

The US Food and Drug Administration (FDA) has approved Jynarque (tolvaptan) for the treatment of adults with autosomal dominant polycystic kidney disease (ADPKD).

Jynarque is now the first FDA-approved drug treatment that can slow kidney function decline in adult patients with a high risk of rapidly progressing ADPKD.

The approval was granted following the success of 2 trials: the 1-year REPRISE study and the 3-year TEMPO study. In the REPRISE study,

treatment with tolvatapan resulted in a change in estimated glomerular filtration rate (eGFR) of -2.3 mL/min/1.73 m2/year from pretreatment baseline to post-treatment follow-up, compared with -3.6 mL/min/1.73 m2/year among those who received placebo.

During the TEMPO study, tolvaptan use was associated with a 1.0 mL /min /1.73m2 /year reduction in the rate of decline in eGFR compared with placebo among patients with earlier stages of ADPKD.

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