Clinical trials have revealed drug-induced liver injury in patients taking Samsca (tolvaptan). Samsca was being tested for an unapproved use in patients diagnosed with
autosomal dominant polycystic kidney disease (ADPKD) at higher doses than the approved indication and in long-term use.
The Medicines and Healthcare products Regulatory Agency (MHRA) recommends liver function testing in patients taking Samsca who report responses that suggest liver injury. Also, treatment should be stopped when determining potential causes of liver injury, and patients should be treated with an alternate drug.
Samsca is a selective vasopressin V2-receptor antagonist approved for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. These are electrolyte disorders in which there is an imbalance in the sodium and water levels in the body. These metabolic conditions, explained PubMedHealth previously, can lead to a broad array of adverse health reactions.
A clinical trial conducted in the United States was initiated to analyze the potential use of Samsca in 1,400 patients diagnosed with ADPKD. During the trial and when compared to the placebo group, the researchers identified an increased risk of serious liver injury in adults assigned Samsca at 120 mg daily, which is twice the maximum recommended daily dose in the approved use.
In the participant group diagnosed with ADPKD
In the participant group diagnosed with ADPKD, a variety of liver enzyme abnormalities, some described as clinically significant, were seen. Most of the abnormalities were seen in the first 18 months of treatment.
Symptoms of liver injury include fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Also patients whose tests reveal enzyme abnormalities should undergo additional testing to exclude significant hepatotoxicity. When liver injury is suspected, an alternative treatment approach should be considered and Samsca treatment should be ceased.
U.S. federal officials recently said that taking Samsca for more than one month could cause serious liver injury or even death. Also at risk is anyone who takes the drug and has an underlying kidney problem.
The U.S. Food and Drug Administration (FDA) is working with the maker of Samsca to update the drug’s warning label to take this risk into account. The FDA also released its own statement, saying that no one should take the drug for more than 30 days and that treatment should cease to include Samsca if signs of liver injury are apparent. Those with a liver disease, such as cirrhosis, should also avoid Samsca, the FDA said in its statement.
The agency noted that Samsca carries a risk of liver injury, as well as of liver failure, a fatal condition. Samsca is manufactured by Otsuka America Pharmaceutical.