Overview of instructions for use of obeticholic acid

1. Drug information

Common name: Obeticholic acid (Obeticholic acid)

Product name:Ocaliva

Full name:Obeticholic acid, obeticholic acid, Ocaliva

2. Indications

Obeticholic acid is approved for the treatment of primary biliary cholangitis (PBC) in adults. Applicable patients include two categories: one is patients without cirrhosis, and the other is patients with compensated cirrhosis without evidence of portal hypertension. In both cases, obeticholic acid can be used in combination with patients who have a poor response to ursodeoxycholic acid (UDCA) or as a single treatment option in patients who cannot tolerate UDCA.

3. Usage and dosage

Before starting obeticholic acid treatment, doctors need to evaluate the patient's liver function to ensure that there are no symptoms of decompensated cirrhosis (such asChild-Pugh class B or C) and compensated cirrhosis accompanied by portal hypertension (such as ascites, gastroesophageal varices, and sustained thrombocytopenia). In these cases, this drug is contraindicated.

Recommended dose: For patients with PBC without cirrhosis or compensated cirrhosisThe initial recommended dose is 5 mg orally once daily for 3 months. Patients should ensure that they have no evidence of portal hypertension and have failed to produce an adequate biochemical response to appropriate doses of UDCA for at least one year, or are intolerant to UDCA. After 3 months of initial treatment, if there is no significant decrease in ALP and/or total bilirubin levels and treatment is tolerated, the dose can be increased to the maximum dose of 10 mg once daily.

Dose adjustment: During treatment, if the patient shows signs of liver function decompensation or is accompanied by portal hypertension, or obvious adverse reactions occur, use should be stopped immediately. In addition, patients who cannot tolerate a daily dose of 5 mg can be adjusted to 5 mg every other day, or patients who cannot tolerate 10 mg daily can be adjusted back to 5 mg daily. There is also the option of temporarily interrupting treatment, for up to 2 weeks, and then restarting and gradually increasing the dose based on the patient's biochemical response and tolerance.

Medication management: Obeticholic acid can be taken with food or on an empty stomach. If the patient is also using bile acid-binding resin, he/she needs to take it at least 4 hours before or after taking obeticholic acid, or extend the time interval as much as possible.

4. Adverse reactions

In clinical studies, common adverse reactions include itching, fatigue, abdominal pain, discomfort, rash, joint pain, sore throat, dizziness, constipation, peripheral edema, palpitations, fever, thyroid dysfunction and eczema. Among them, itching may cause patients to interrupt treatment, most of which occur in the early stages of treatment and gradually reduce over time. In addition, adverse reactions such as hepatic failure, new-onset cirrhosis, increases in direct and total bilirubin, and jaundice have been reported post-marketing.

5. Supply and Storage

Obeeticholic acid tablets are available in 5 mg and 10 mg strengths, packaged in 40 ml high-density polyethylene bottles. Storage temperature should be maintained at 20°C to 25°C (68°F to 77°F), with fluctuations allowed within the range of 15°C to 30°C (59°F to 86°F) to ensure the stability and effectiveness of the drug.

6. Contraindications

Obeticholic acid is contraindicated in the following patients: patients with decompensated cirrhosis (such asChild-Pugh class B or C) or those with previous decompensation events; or patients with compensated cirrhosis with evidence of portal hypertension (such as ascites, gastroesophageal varices, sustained thrombocytopenia); or patients with complete biliary obstruction.

7. Mechanism of action

Obeeticholic acid acts as an agonist forFXR (farnesoid X receptor), which mainly acts in the liver and intestines. FXR is an important nuclear receptor that plays a key role in regulating bile acids, inflammation, fibrosis, and metabolic pathways. By inhibiting cholesterol synthesis and enhancing bile acid transport from hepatocytes, activation of FXR reduces intrahepatocyte bile acid concentrations, thereby limiting the overall size of the circulating bile acid pool, promoting bile secretion, and reducing hepatic exposure to bile acids.

8. Overdose

In clinical trials,PBC patients who took obeticholic acid 25 mg (2.5 times the highest recommended dose) or 50 mg (5 times the highest recommended dose) daily had a dose-dependent increase in the incidence of liver adverse reactions, including increased liver function indicators, ascites, jaundice, portal hypertension and exacerbation of PBC. In patients with PBC and decompensated cirrhosis, serious hepatic adverse reactions have been reported after exceeding the recommended dose; these adverse reactions may occur even in patients receiving the recommended dose. In cases of overdose, the patient should be carefully observed and given supportive care as needed.

Reference materials:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cdfbe0cd-eb15-45a1-ac17-531bcda21aec