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FDA on Wednesday in primary biliary cholangitis (PBC) due to the risk of serious liver injury in patients with advanced cirrhosis.

Serious side effects, such as liver failure or the urgent need for a liver transplant, were reported after use of obeticholic acid in PBC patients with advanced cirrhosis -- "cirrhosis with current or prior evidence of liver decompensation (e.g., encephalopathy, coagulopathy) or portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)," according to the agency.

FDA's new contraindication -- the strongest possible warning -- will be added to the drug's labeling information and patient education guide, and states that the drug "should not be used in PBC patients with advanced cirrhosis."

The move follows a 2018 black box warning to highlight the correct dosing with obeticholic acid, as severe adverse events were reported in certain patients taking the drug more frequently than recommended.

Obeticholic acid, a farnesoid X receptor agonist, was first approved in May 2016, as a second-line treatment for patients who did not benefit from ursodeoxycholic acid (UDCA). Obeticholic acid continues to be safe for PBC patients who are not affected by advanced cirrhosis, have shown failure with UDCA, or cannot tolerate UDCA, the agency said.

Physicians should routinely monitor patients taking obeticholic acid for PBC progression, the FDA stated. If advanced cirrhosis should develop as determined by lab testing, clinical assessment, and symptoms, obeticholic acid should be permanently discontinued.

The FDA cited 25 serious cases of liver damage in the past 5 years. Regardless of clinical signs, these cases resulted in liver decompensation or failure from use of obeticholic acid in PBC patients with advanced cirrhosis. There were 18 cases involving patients with PBC and compensated cirrhosis that resulted in liver injury and decompensation, and 10 of the 18 cases had evidence of portal hypertension at baseline -- either low albumin levels, thrombocytopenia, elevated bilirubin, or varices.

Among the 25 cases, four patients with compensated cirrhosis required a liver transplant within 1.3 years of using the drug. One patient with compensated cirrhosis died of liver failure. Median decompensation time after initiating obeticholic acid was 4 months, but decompensation could develop anywhere between 2 weeks to 10 months.

FDA recommended that patients speak with their physician if they develop any of the following symptoms: bloody/black stool, swollen stomach, jaundice, coughing blood, fever, less frequent urination or dark urine, stomach pain, weight loss, nausea, vomiting, or diarrhea, as they may be associated with advanced cirrhosis.

Healthcare professionals should report side effects to the MedWatch program, the agency said.

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