OBETICHOLIC ACID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OBETICHOLIC ACID (OBETICHOLIC ACID).

How it works

Obeticholic acid is a potent, selective agonist of the farnesoid X receptor (FXR), a nuclear receptor that regulates bile acid synthesis, transport, and homeostasis. Activation of FXR reduces bile acid synthesis by inhibiting CYP7A1, increases bile acid clearance, and exerts anti-inflammatory and antifibrotic effects.

What the body does with it

Metabolism	Primarily metabolized by glucuronidation via UGT1A1, UGT1A3, and UGT2B7; undergoes enterohepatic recirculation; minimal CYP450 metabolism.
Excretion	Primarily biliary, with minimal renal excretion (<3%). The drug and its conjugates are eliminated in feces following biliary secretion. Enterohepatic recirculation occurs.
Half-life	Terminal elimination half-life is approximately 24 hours (range 14–36 h) in patients with primary biliary cholangitis, allowing once-daily dosing. Steady-state is achieved in about 2 weeks.
Protein binding	≥99% bound to serum proteins, primarily albumin.
Volume of Distribution	Approximately 0.2–0.4 L/kg, indicating limited extravascular distribution, consistent with a compound undergoing extensive enterohepatic circulation.
Bioavailability	Oral bioavailability is low (~1–2%) due to extensive first-pass metabolism in the liver. Food may reduce absorption.
Onset of Action	Oral administration: Reduction in serum alkaline phosphatase (ALP) is observed after 1–2 months of daily dosing; clinical improvement (e.g., pruritus relief) may take several months.
Duration of Action	Pharmacodynamic effects (e.g., suppression of bile acid synthesis) persist for the entire dosing interval (24 h) with daily administration. Discontinuation leads to reversal of effects within weeks.

Classification & Brands

Dosing & administration

5 mg orally once daily, may increase to 10 mg once daily if tolerated after 3 months; maximum dose 10 mg daily.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2) or dialysis; use with caution.
Liver impairment	Child-Pugh Class A: No dose adjustment. Child-Pugh Class B or C: Contraindicated.
Pediatric use	Safety and efficacy not established in pediatric patients (<18 years).
Geriatric use	No specific dose adjustment recommended; use standard adult dosing with monitoring for tolerability due to potential age-related decline in hepatic function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for OBETICHOLIC ACID (OBETICHOLIC ACID).

Breastfeeding	Excretion in human milk unknown. Due to potential for serious adverse reactions in nursing infants, decision should be made to discontinue nursing or drug. M/P ratio not determined.
Teratogenic Risk	Animal studies show fetal harm at exposures similar to human therapeutic doses. No adequate human studies. Avoid use in pregnancy unless benefit outweighs risk. First trimester: potential for teratogenicity. Second/third trimester: risk of fetal bile acid toxicity.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Risk of hepatic decompensation and liver failure in patients with compensated or decompensated cirrhosis (Child-Pugh class B or C). Ocaliva is contraindicated in patients with decompensated cirrhosis or prior hepatic decompensation.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Complete biliary obstruction","Decompensated cirrhosis (Child-Pugh class B or C) or prior hepatic decompensation","Hypersensitivity to obeticholic acid or any excipients"]

Clinical Precautions

Precautions

["Hepatic decompensation and liver failure in cirrhotic patients (Child-Pugh class B or C); not recommended in such patients without appropriate dose adjustment.","Severe pruritus: Manage with antihistamines, bile acid resins, or dose reduction.","Elevation of LDL-cholesterol: Monitor lipid levels and manage according to guidelines.","Dose adjustment required for moderate to severe hepatic impairment (Child-Pugh class B and C)."]

Clinical Tips & Counseling

Drug interactions

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OBETICHOLIC ACID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OBETICHOLIC ACID (OBETICHOLIC ACID).

How it works

What the body does with it

Metabolism	Primarily metabolized by glucuronidation via UGT1A1, UGT1A3, and UGT2B7; undergoes enterohepatic recirculation; minimal CYP450 metabolism.
Excretion	Primarily biliary, with minimal renal excretion (<3%). The drug and its conjugates are eliminated in feces following biliary secretion. Enterohepatic recirculation occurs.
Half-life	Terminal elimination half-life is approximately 24 hours (range 14–36 h) in patients with primary biliary cholangitis, allowing once-daily dosing. Steady-state is achieved in about 2 weeks.
Protein binding	≥99% bound to serum proteins, primarily albumin.
Volume of Distribution	Approximately 0.2–0.4 L/kg, indicating limited extravascular distribution, consistent with a compound undergoing extensive enterohepatic circulation.
Bioavailability	Oral bioavailability is low (~1–2%) due to extensive first-pass metabolism in the liver. Food may reduce absorption.
Onset of Action	Oral administration: Reduction in serum alkaline phosphatase (ALP) is observed after 1–2 months of daily dosing; clinical improvement (e.g., pruritus relief) may take several months.
Duration of Action	Pharmacodynamic effects (e.g., suppression of bile acid synthesis) persist for the entire dosing interval (24 h) with daily administration. Discontinuation leads to reversal of effects within weeks.

Classification & Brands

Dosing & administration

5 mg orally once daily, may increase to 10 mg once daily if tolerated after 3 months; maximum dose 10 mg daily.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2) or dialysis; use with caution.
Liver impairment	Child-Pugh Class A: No dose adjustment. Child-Pugh Class B or C: Contraindicated.
Pediatric use	Safety and efficacy not established in pediatric patients (<18 years).
Geriatric use	No specific dose adjustment recommended; use standard adult dosing with monitoring for tolerability due to potential age-related decline in hepatic function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for OBETICHOLIC ACID (OBETICHOLIC ACID).

Breastfeeding	Excretion in human milk unknown. Due to potential for serious adverse reactions in nursing infants, decision should be made to discontinue nursing or drug. M/P ratio not determined.
Teratogenic Risk	Animal studies show fetal harm at exposures similar to human therapeutic doses. No adequate human studies. Avoid use in pregnancy unless benefit outweighs risk. First trimester: potential for teratogenicity. Second/third trimester: risk of fetal bile acid toxicity.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Complete biliary obstruction","Decompensated cirrhosis (Child-Pugh class B or C) or prior hepatic decompensation","Hypersensitivity to obeticholic acid or any excipients"]