Obetic

• Approved Indications:
• Treatment of primary biliary cholangitis (PBC) in adults who have an inadequate response to ursodeoxycholic acid (UDCA).
• Monotherapy for adults with PBC who are intolerant to UDCA.
• Off-label and Investigational Uses:
• Investigational treatment for nonalcoholic steatohepatitis (NASH) with liver fibrosis.
• Being studied for other cholestatic liver diseases.

• Adults (Primary Biliary Cholangitis):
• Initial dose: 5 mg orally once daily.
• After 3 months, if tolerated and response is inadequate, increase to 10 mg once daily.
• Maximum recommended dose: 10 mg daily.
• Special Populations:
• Hepatic Impairment: Contraindicated in patients with decompensated cirrhosis (Child-Pugh B or C).
• Renal Impairment: No dose adjustment required.
• Elderly: No specific dose adjustment needed; monitor closely for tolerability.
• Administration:
• Take orally with food to enhance absorption.
• Swallow tablets whole; do not crush, split, or chew.

Obeticholic acid is a synthetic bile acid analogue that acts as a potent agonist of the farnesoid X receptor (FXR), a nuclear receptor primarily expressed in the liver and intestines. Activation of FXR decreases bile acid synthesis by suppressing the rate-limiting enzyme cholesterol 7α-hydroxylase (CYP7A1). It also increases bile acid transport and detoxification. These actions reduce bile acid accumulation in the liver, thereby decreasing cholestasis, inflammation, and fibrosis in diseases such as primary biliary cholangitis.

• Absorption: Rapid oral absorption with peak plasma concentration (Tmax) within 1 to 3 hours post-dose.
• Bioavailability: Enhanced when administered with food.
• Distribution: Highly (>99%) bound to plasma proteins.
• Metabolism: Undergoes hepatic conjugation (glucuronidation and sulfation) to active metabolites.
• Elimination: Primarily excreted in bile via feces; minimal renal elimination.
• Half-life: Approximately 4 to 6 days, supporting once-daily dosing.

• Pregnancy: No adequate or well-controlled studies in pregnant women. Animal studies suggest potential fetal harm at high doses. Use only if clearly needed and after assessing risk versus benefit.
• Lactation: Unknown if excreted in human milk. Breastfeeding is not recommended during treatment due to potential risks to the infant.
• Caution: Limited human data; avoid use during pregnancy and lactation unless necessary.

• Primary Class: Bile acid derivative
• Subclass: Farnesoid X receptor (FXR) agonist

• Hypersensitivity to obeticholic acid or any excipients.
• Decompensated liver disease (Child-Pugh Class B or C cirrhosis).
• Severe hepatic impairment.
• Concomitant use with strong CYP3A4 inducers that may reduce drug levels.

• Hepatic Decompensation: Use with caution in patients with advanced liver disease due to risk of worsening liver function.
• Pruritus: Common and may worsen existing itching; may necessitate dose adjustment or discontinuation.
• Lipid Changes: Can increase low-density lipoprotein cholesterol (LDL-C); monitor lipid profiles regularly.
• Pregnancy & Lactation: Use only if benefits outweigh risks.
• Monitoring: Regular liver function tests and lipid panels are recommended during treatment.

• Common:
• Pruritus (itching)
• Fatigue
• Abdominal pain
• Arthralgia (joint pain)
• Serious:
• Hepatic decompensation in patients with advanced liver disease
• Elevated liver enzymes
• Hyperlipidemia, particularly increased LDL cholesterol
• Rare:
• Hypersensitivity reactions including rash and angioedema

• CYP3A4 Inducers (e.g., rifampin, carbamazepine): May reduce obeticholic acid plasma levels and effectiveness.
• Bile Acid Sequestrants (e.g., cholestyramine): May reduce absorption; administer obeticholic acid at least 4 hours before or after.
• Statins: Concomitant use may increase risk of liver-related adverse effects; monitor liver function.
• Alcohol: No direct interaction, but alcohol may exacerbate liver disease and should be avoided.

• Obeticholic acid was FDA-approved in 2016 for treatment of PBC in patients with inadequate response to UDCA.
• Recent hepatology guidelines recommend it as a second-line therapy for PBC.
• Clinical trials continue to evaluate its efficacy and safety in NASH and other liver diseases.
• Caution is emphasized in patients with advanced liver disease due to risk of hepatic decompensation.

• Store at room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in the original container until use.
• Do not freeze.
• Keep out of reach of children.