OBETICHOLIC ACID
Clinical safety rating
cautionComprehensive clinical and safety monograph for OBETICHOLIC ACID (OBETICHOLIC ACID).
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.
| 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. |
| Molecular Weight | 420.6 |
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. |
| 1st trimester | Obeticholic acid is teratogenic in animal studies (rats and rabbits) with increased mortality and reduced fetal body weight. There are no adequate human studies in first trimester; use only if benefit outweighs risk. |
| 2nd trimester | Safety in second trimester not established. Animal studies show adverse effects; use only if clearly needed. |
| 3rd trimester | May increase risk of fetal harm based on animal data. Use in third trimester only if potential benefit justifies risk to fetus. |
Clinical note
Comprehensive clinical and safety monograph for OBETICHOLIC ACID (OBETICHOLIC ACID).
| Placental transfer | Based on molecular weight and animal data, placental transfer is likely. In rats, radioactivity crossed placenta after oral administration of radiolabeled obeticholic acid. |
| Breastfeeding | No data on presence in human milk. Animal studies indicate excretion into milk. Because of potential for serious adverse reactions in nursing infants, breast-feeding is not recommended during therapy for 5 weeks after last dose. |
| Lactation Rating | L5 |
| 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 | Monitor liver function tests (AST, ALT, bilirubin) monthly. Monitor for pruritus worsening. Fetal ultrasound for growth and amniotic fluid index in third trimester. |
| Fertility Effects | No human data on fertility. Animal studies showed no impairment of fertility at clinically relevant doses. |
■ 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.
| Serious Effects |
Complete biliary obstruction
| 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). |
| Food/Dietary | No specific food interactions are reported, but alcohol should be avoided due to potential hepatotoxicity. Bile acid binding resins (e.g., cholestyramine) may reduce absorption; separate administration by at least 4-6 hours. |
| Clinical Pearls | Obeticholic acid is a farnesoid X receptor agonist used for primary biliary cholangitis (PBC). It increases bile acid excretion and may cause dose-dependent pruritus; start at 5 mg daily and titrate to 10 mg if tolerated. Monitor hepatic function closely due to risk of liver decompensation. Contraindicated in patients with complete biliary obstruction. |
| Patient Advice | Take obeticholic acid exactly as prescribed, usually once daily with or without food. · Common side effects include itching (pruritus), which may be severe; inform your doctor if it becomes bothersome. · Report any symptoms of liver problems such as jaundice, dark urine, or abdominal pain immediately. · Avoid alcohol while taking this medication. · Do not take additional bile acid binding resins (e.g., cholestyramine) within 4-6 hours of obeticholic acid. · Inform your healthcare provider of all other medications you are taking, especially warfarin or other blood thinners. · If you are pregnant, planning to become pregnant, or breastfeeding, discuss with your doctor before starting this medication. |
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