The FDA along with the manufacturer, Otsuka, notified healthcare professionals of significant liver injury associated with the use of Samsca. Samsca is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (a metabolic condition in which there is not enough sodium (salt) in the body fluids outside the cells). Samsca is not approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD).
In a double-blind, 3-year, placebo-controlled trial in about 1400 patients with 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. In the trials, the maximum daily dose of Samsca administered (90 mg in the morning and 30 mg in the afternoon) was higher than the maximum 60 mg daily dose approved for the treatment of hyponatremia.
Most of the liver enzyme abnormalities were observed during the first 18 months of therapy. Following discontinuation of treatment, all three patients improved. 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.
These data are not adequate to exclude the possibility that patients receiving Samsca for its indicated use of clinically significant hypervolemic and euvolemic hyponatremia are at a potential increased risk for irreversible and potentially fatal liver injury.
Healthcare providers should 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. If hepatic injury is suspected, Samsca should be promptly discontinued, appropriate treatment should be instituted, and investigations should be performed to determine probable cause. Samsca should not be re-initiated in patients unless the cause for the observed liver injury is definitively established to be unrelated to treatment with Samsca.
See the FDA Safety Alert