From the Guidelines
Obeticholic acid is a potent synthetic bile acid analog that acts as a farnesoid X receptor (FXR) agonist, primarily used to treat primary biliary cholangitis (PBC) and under investigation for non-alcoholic steatohepatitis (NASH), with a recommended initial dose of 5 mg once daily, potentially increasing to 10 mg daily based on response and tolerability 1.
Mechanism of Action
Its mechanism of action involves binding to and activating FXR in the liver and intestine, which regulates bile acid synthesis, transport, and metabolism. When activated, FXR reduces bile acid production by suppressing the enzyme CYP7A1, increases bile acid excretion from hepatocytes, and reduces inflammation and fibrosis in the liver.
Uses and Dosage
For PBC, obeticholic acid is typically prescribed at 5 mg once daily initially, with potential increase to 10 mg daily based on response and tolerability, particularly for patients who have inadequate response to ursodeoxycholic acid (UDCA) or as monotherapy for those who cannot tolerate UDCA 1.
Side Effects and Monitoring
Common side effects include pruritus (itching), fatigue, abdominal pain, and elevated LDL cholesterol levels. Patients should be monitored for hepatic function, as severe liver injury has been reported in some cases 1.
Contraindications and Precautions
The medication is contraindicated in complete biliary obstruction, and dose adjustment is necessary for patients with moderate to severe hepatic impairment (Child-Pugh Class B and C) 1. Key points to consider when prescribing obeticholic acid include:
- Monitoring liver function tests and adjusting the dose as needed
- Being aware of the potential for severe liver injury and hepatotoxicity, particularly in patients with advanced liver disease
- Considering alternative treatments for patients with incomplete response to UDCA or intolerance to UDCA
- Following the recommended dosing guidelines to minimize the risk of adverse events 1.
From the FDA Drug Label
Obeticholic acid is an agonist for FXR, a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic, and metabolic pathways FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes. These mechanisms limit the overall size of the circulating bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids.
The mechanism of action of obeticholic acid is as a farnesoid X receptor (FXR) agonist, which regulates bile acid, inflammatory, fibrotic, and metabolic pathways. The uses of obeticholic acid include the treatment of primary biliary cholangitis (PBC) as evidenced by the discussion of ALP reduction and management of the disease in the provided text 2, 2. Key points about obeticholic acid include:
- It is a nuclear receptor expressed in the liver and intestine
- It decreases intracellular hepatocyte concentrations of bile acids
- It promotes choleresis, reducing hepatic exposure to bile acids
- It is used to treat primary biliary cholangitis (PBC)
From the Research
Mechanism of Action of Obeticholic Acid
- Obeticholic acid (OCA) is a highly potent farnesoid X receptor (FXR) agonist 3, 4.
- Activation of FXR leads to decreased bile acid synthesis, inflammation, and fibrosis of the liver 4.
- OCA has been shown to ameliorate deranged bile acid homeostasis and attenuate raised concentrations of liver enzymes associated with primary biliary cholangitis (PBC) 5.
Uses of Obeticholic Acid
- OCA is used as a second-line treatment for patients with primary biliary cholangitis (PBC) who are unresponsive to ursodeoxycholic acid (UDCA) 5, 3, 6.
- OCA has been shown to lead to a significant decrease in serum alkaline phosphatase, a marker for long-term survival in PBC patients 3, 4.
- OCA is used in conjunction with UDCA to improve liver biochemistries in patients with PBC who are refractory to UDCA 7.
Clinical Efficacy and Safety
- Several clinical trials have demonstrated the efficacy of OCA in reducing serum alkaline phosphatase and improving liver function in PBC patients 3, 4.
- The most clinically relevant adverse effect of OCA is dose-related pruritus 4.
- OCA has been approved by the US FDA as a second-line treatment for PBC and is incorporated into current guidelines for the treatment of PBC 4, 6.