The FDA instructed physicians to limit the use of tolvaptan, a drug sometimes prescribed to heart failure patients, to no more than 30 days due to possible liver damage that could lead to organ transplantation or death.
Tolvaptan (Samsca, Otsuka Pharmaceuticals) is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. A selective vasopression V2-receptor antagonist, it was approved in 2009 to treat hyponatremia associated with congestive heart failure, liver cirrhosis and the syndrome of inappropriate antidiuretic hormone secretion.
Tolvaptan helps raise serum sodium levels by removing extra water in the urine. Its approval included a boxed warning to initiate treatment only in a hospital where blood sodium could be monitored closely.
The FDA recommends discontinuing treatment in patients who develop signs of liver disease; avoiding treatment in patients with underlying liver disease, including cirrhosis; and limiting treatment to 30 days or less.
The agency warned that an increased risk of liver injury was reported in TEMPO, a randomized clinical trial that enrolled 1,445 patients with autosomal dominant polycystic kidney disease. TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) found a higher frequency of elevated liver enzyme levels than had been observed in previous studies (N Engl J Med 2012; 367:2407-2418).