FDA warns of liver injury risk associated with hyponatremia drug

The FDA today issued a warning regarding the potential for hyponatremia treatment Samsca to cause liver injury.

Samsca (tolvaptan, Otsuka America Pharmaceutical), a selective vasopressin V2-receptor antagonist, led to significant increases to serum ALT and total bilirubin levels in three participants in a 3-year, double-blind, placebo-controlled trial, the FDA warning said. The study involved approximately 1,400 patients with autosomal dominant polycystic kidney disease (ADPKD). These results suggest the possibility of “irreversible and potentially fatal” injury to the liver as a result of Samsca use, according to the FDA and Otsuka.

A letter to health care providers from Otsuka also indicates that significant ALT elevations (three times the upper limit of normal or higher) occurred in more treated patients (4.4%) than placebo recipients (1%) during the study. Most abnormalities occurred within 18 months of treatment initiation, and all improved after discontinuation of Samsca.

“The ability to recover from liver injury may be impaired in patients with hyponatremia in the setting of underlying liver disease, including cirrhosis,” the company said in the letter. “… Health care 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.”

The FDA warning contains a request that patients and health care professionals submit a report to the MedWatch Safety Information and Adverse Event Reporting Program in the event of adverse events during treatment with Samsca.