From” Experience Tolvaptan ” to FDA Warns of Liver Injury Risk with Tolvaptan!!!

September ,2011 stated about Samsca( Tolvaptan) 15, 30mg tablets
Experience the first and only oral vasopressin V2-receptor antagonist that increases FREE WATER CLEARANCE and serum sodium concentrations .

Pathogenic properties of patients with heart failure

Vasopressin secretion stimulated by:

— Decrease in blood volume/pressure of approximately 8% to 10%5

Vasopressin increases passive water reabsorption in the kidney, causing water retention, which may result in.:

— Increased edema.

— Hypervolemic hyponatremia


SAMSCA is 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, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH).

Important Limitations

Patients requiring intervention to raise serum sodium urgently to prevent or to treat serious neurological symptoms should not be treated with SAMSCA

It has not been established that raising serum sodium with SAMSCA provides a symptomatic benefit to patients


SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. Too-rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death. In susceptible patients, including those with severe malnutrition, alcoholism or advanced liver disease, slower rates of correction may be advisable.

SAMSCA is contraindicated in the following conditions:

— Urgent need to raise serum sodium acutely

— Inability of the patient to sense or appropriately respond to thirst

— Hypovolemic hyponatremia

— Concomitant use of strong CYP 3A inhibitors

— Anuric patients

Too-Rapid Correction of Serum Sodium Can Cause Serious Neurologic Sequelae – During initiation and after titration monitor patients to assess serum sodium concentrations and neurologic status. Subjects with SIADH or very low baseline serum sodium concentrations may be at greater risk for too-rapid correction of serum sodium. In patients receiving SAMSCA who develop too rapid a rise in serum sodium, discontinue or interrupt treatment with SAMSCA and consider administration of hypotonic fluid. Fluid restriction during the first 24 hours with SAMSCA may increase the likelihood of overly-rapid correction of serum sodium, and should generally be avoided

Gastrointestinal Bleeding in Patients With Cirrhosis – Use in cirrhotic patients only when need to treat outweighs this risk

Dehydration and Hypovolemia – In patients who develop medically significant signs or symptoms of hypovolemia, discontinuation is recommended. Dehydration and hypovolemia can occur, especially in potentially volume-depleted patients receiving diuretics or those who are fluid restricted

Co-administration With Hypertonic Saline – Not recommended

Other Drugs Affecting Exposure to SAMSCA

— CYP 3A Inhibitors – Do not use with strong inhibitors of CYP 3A; avoid concomitant use with moderate CYP 3A inhibitors

— CYP 3A Inducers – Avoid concomitant use with CYP 3A inducers. If co-administered, the dose of SAMSCA may need to be increased

— P-gp Inhibitors – The dose of SAMSCA may have to be reduced if co-administered with P-gp inhibitors

Hyperkalemia or Drugs that Increase Serum Potassium – Monitor serum potassium levels in patients with a serum potassium >5 mEq/L and in patients receiving drugs known to increase serum potassium levels

Pregnancy and Nursing Mothers – SAMSCA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants from SAMSCA, a decision should be made to discontinue nursing or SAMSCA, taking into consideration the importance of SAMSCA to the mother.

Commonly observed adverse reactions – (SAMSCA incidence ≥5% more than placebo, respectively): thirst (16% vs 5%), dry mouth (13% vs 4%), asthenia (9% vs 4%), constipation (7% vs 2%), pollakiuria or polyuria (11% vs 3%) and hyperglycemia (6% vs 1%).

January 25, 2013, Stated
FDA Warns of Liver Injury Risk with Tolvaptan

Three cases of serious but reversible increases in hepatic enzymes in a clinical trial involving tolvaptan (Samsca) have prompted the FDA to warn of potential liver injury with the drug.
According to the letter, dated Jan. 22, three patients out of some 1,400 participating in a clinical trial of tolvaptan, a selective vasopressin V2-receptor antagonist, in autosomal dominant polycystic kidney disease (ADPKD) developed increases in serum alanine aminotransferase (ALT) three times above the upper limit of normal, as well as elevated serum total bilirubin above twice the upper limit of normal.
“An external panel of liver experts assessed these three cases as being either probably or highly likely to be caused by tolvaptan. These findings indicate that Samsca (tolvaptan) has the potential to cause irreversible and potentially fatal liver injury,” Otsuka said in the letter.
Patients with underlying liver disease that may cause or contribute to hyponatremia may be less able to recover from drug-induced liver injury.


About Dr.Nabil Paktin

Cardiologist , M.D.,F.A.C.C.

Posted on January 27, 2013, in Uncategorized. Bookmark the permalink. Leave a comment.

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