How Do Farnesoid X Receptor Agonists Work?

Farnesoid X receptor (FXR) agonists are a semi-synthetic bile acid analog used to treat primary biliary cholangitis (PBC) in adult patients with inadequate clinical response or intolerance to UDCA (another drug called ursodeoxycholic acid). PBC is a chronic liver disease that slowly destroys the bile ducts in the liver. These ducts deliver bile (a digestive fluid produced by the liver and stored in the gallbladder) to the small intestines to help the body digest fats and nutrients. When bile ducts are damaged, harmful substances can build up in bile and scar the liver leading to cirrhosis (a late stage of scarring of the liver) and liver failure.

PBC may have no symptoms for years and is symptomatically characterized by:

• Abdominal pain
• Itchy and dark skin
• Dry eyes/mouth
• Tiredness
• Small yellow or white bumps under the skin (xanthomas) or around the eyes (xanthelasmas)

FXR agonists are administered via the oral route, usually taken once a day with or without food.

FXR agonists work in the following ways:

• FXR is expressed at high levels in the liver and intestine; one of its primary functions is suppression of cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. 
• FXR agonists work by decreasing the production of bile in the liver
• In addition, it increases the elimination of bile from the liver.

FXR agonists are indicated for the treatment of PBC with or without cirrhosis either in combination with UDCA with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.

Common side effects include:

Pruritis (itching)

• Fatigue (feeling of tiredness or lack of energy)
• Abdominal pain and discomfort
• Rash
• Mouth/throat pain

Other rare side effects may include:

• Fast/irregular heartbeat
• Dizziness (feeling faint, weak, or unsteady)
• Severe itching
• Peripheral edema (swelling in hands or lower legs)
• Constipation
• Arthralgia (pain, stiffness, and swelling in joints and muscles)
• Fever, chills, or other signs of infection
• Thyroid function abnormality
• Reduced high-density lipoprotein cholesterol (low levels)
• Vomit that looks like coffee grounds
• Bloody or tarry stools

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of farnesoid X receptor agonists include:

• Obeticholic acid
• Ocaliva