Obetic

Starting Dosage: The recommended starting dosage of Obeticholic Acid is 5 mg orally once daily in adult patients who have not achieved an adequate biochemical response to an appropriate dosage of Ursodeoxycholic Acid (UDCA) for at least 1 year or are intolerant to UDCA.

Dosage Titration: If an adequate reduction in alkaline phosphatase (ALP) and/or total bilirubin has not been achieved after 3 months of Obeticholic Acid 5 mg once daily, and the patient is tolerating Obeticholic Acid, increase the dosage of Obeticholic Acid to 10 mg once daily.

Maximum Dosage: The maximum recommended dosage of Obeticholic Acid is 10 mg once daily.

Management of Patients with Intolerable Pruritus on Obeticholic Acid: For patients with intolerable pruritus on Obeticholic Acid, consider one or more of the following:

Add an antihistamine or bile acid binding resin. Reduce the dosage of Obeticholic Acid to:

• 5 mg every other day, for patients intolerant to 5 mg once daily
• 5 mg once daily, for patients intolerant to 10 mg once daily

Temporarily interrupt Obeticholic Acid dosing for up to 2 weeks followed by restarting at a reduced dosage

Increase the dosage of Obeticholic Acid to 10 mg once daily, as tolerated, to achieve optimal response. Consider discontinuing Obeticholic Acid treatment in patients who continue to experience persistent, intolerable pruritus.

The most common side effects of Obeticholic Acid include: Pruritus, Fatigue & Stomach pain and discomfort. Other common side effects include rash, arthralgia (joint pain), oropharyngeal pain (pain in the middle part of the throat), dizziness, constipation, abnormal thyroid function, and eczema (inflammation of the skin).

In PBC patients who received Obeticholic Acid 25 mg once daily (2.5 times the highestrecommended dosage) or 50 mg once daily (5 times the highest recommended dosage), a dose-dependent increase in the incidence of liver-related adverse reactions, including elevations in liver biochemical tests, ascites, jaundice, portal hypertension, and primary biliary cholangitis flare, was reported. In the case of over dosage, patients should be carefully observed and supportive care administered, as appropriate.

Obeticholic Acid 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, cholestatic liver disease & non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH).

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 following clinically significant reactions are described:

• Liver-Related Adverse Reactions
• Severe Pruritus
• Reduction in high density lipoprotein-cholesterol (HDL-C)

Special monitoring is essential for the patient with such type of problems

Farnesoid X Receptor Agonists