The Food and Drug Administration (FDA) has issued a safety communication restricting the use of Ocaliva (obeticholic acid) in primary biliary cholangitis patients with advanced cirrhosis of the liver because it can cause serious harm.

Ocaliva, a farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. Since its accelerated approval in 2016, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure associated with Ocaliva in PBC patients with compensated or decompensated cirrhosis. These cases were reported to the FDA Adverse Event Reporting System (FAERS) database and were described in the medical literature.

Among these 25 cases, the most common associated liver-related adverse event was worsening total bilirubin. Within months of starting Ocaliva, patients experienced accelerated deterioration leading to liver decompensation or failure. In all cases, patients were receiving treatment at recommended dosages. 

Among the 18 PBC patients with compensated cirrhosis, 4 required a liver transplant within 1.3 years after starting Ocaliva and 1 patient died from liver failure. The median time to liver decompensation (eg, new onset ascites) after starting Ocaliva was 4 months (range, 2 weeks to 10 months). 

Among the 7 PBC patients with decompensated cirrhosis, the median time to a new decompensation event (eg, hepatic encephalopathy) after starting Ocaliva was 2.5 months (range, 10 days to 8 months). Death was reported in 2 of these cases, though the FDA noted in their communication that it was difficult to distinguish whether the outcome was a result of the drug or the disease.

Given these findings, the FDA has added a new contraindication to the prescribing information stating that Ocaliva should not be used in PBC patients with advanced cirrhosis. A revised Boxed Warning will also include information about the risks associated with use in this patient population.

Prior to initiating treatment with Ocaliva, the FDA is advising health care professionals to determine whether a patient with PBC has advanced cirrhosis (defined as cirrhosis with current or prior evidence of hepatic decompensation or portal hypertension). Once treatment is initiated, patients should be monitored routinely for progression of PBC as well as for clinically significant liver-related adverse reactions. Ocaliva should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis or in those who develop symptoms of acute-on-chronic liver disease.


Due to risk of serious liver injury, FDA restricts use of Ocaliva in primary biliary cholangitis (PBC) patients with advanced cirrhosis. [press release]. Silver Spring, MD: US Food and Drug Administration; May 26, 2021.