Otsuka and the FDA are notifying healthcare professionals of significant liver injury associated with the use of Samsca (tolvaptan) tablets.  Samsca is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125mEq/L or marked hyponatremia that is symptomatic and has resisted correction with fluid restriction). This includes patients with heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormone (SIADH).

In a double-blind, 3-year, placebo-controlled trial (n=1,400) evaluating patients with autosomal dominant polycystic kidney disease (ADPKD) and its open-label extension trial, three  patients treated with the drug developed significant increases in serum alanine aminotransferase (ALT) with concomitant, clinically significant increases in serum total bilirubin. The maximum daily dose of Samsca administered (90mg in the morning and 30mg in the afternoon) was higher than the maximum 60mg daily dose approved for the treatment of hyponatremia. Following discontinuation of treatment, all three patients improved.

These findings indicate that Samsca has the potential to cause irreversible and potentially fatal liver injury. Healthcare professionals are recommended to perform liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice). Samsca should be discontinued if hepatic injury is suspected, and should not be re-initiated unless the cause for observed liver injury is unrelated to treatment with Samsca.

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