Obeticholic

Obeticholic acid is a synthetic bile acid derivative and a potent agonist of the farnesoid X receptor (FXR). By activating FXR in the liver and intestine, it reduces bile acid synthesis and modulates bile acid transport and lipid metabolism, offering therapeutic effects in certain liver diseases.

Medical uses: In adults with primary biliary cholangitis (PBC) who have an inadequate response to or intolerance of ursodeoxycholic acid (UDCA), obeticholic acid is indicated as add-on therapy to UDCA. It is not approved as a stand-alone treatment for PBC.

Dosing and administration: It is taken orally. The typical starting dose is 5 mg once daily, with the option to increase to 10 mg once daily if tolerated and the response remains insufficient. Dose adjustments or discontinuation may be needed in patients with hepatic impairment or significant pruritus.

Clinical efficacy and monitoring: In PBC, adding obeticholic acid to UDCA improves biochemical markers such as alkaline phosphatase and may slow disease progression, but it is not curative. Liver function tests should be monitored regularly, and dose reductions or discontinuation considered if signs of liver injury appear.

Safety and adverse effects: Pruritus is the most common adverse effect, followed by fatigue, nausea, and abdominal pain. There is a risk of worsening cholestasis and liver injury; it is contraindicated in complete biliary obstruction and used with caution in decompensated cirrhosis. Absorption can be affected by bile acid sequestrants and other hepatically metabolized drugs.

Regulatory status: Obeticholic acid was approved by the U.S. FDA in 2016 for PBC in adults with inadequate UDCA response or intolerance, marketed as Ocaliva by Intercept Pharmaceuticals. As of 2024, approval for NASH has not been granted; research continues in other liver diseases.