Introduction to the Chinese instructions for obeticholic acid

1. Common name:Obeticholic acid

Product name:Ocaliva

All names:Obeticholic acid, obeticholic acid, Ocaliva

2. Indications:

Obeticholic acid (Obeticholic acid) is suitable for the treatment of adult patients with primary biliary cholangitis (PBC), including two types of patients: 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 an inadequate response to ursodeoxycholic acid (UDCA) or as monotherapy in patients who cannot tolerate UDCA.

3. Usage and dosage:

Before starting obeticholic acid, doctors will evaluate the patient's liver function to ensure that the patient does not have symptoms of decompensated cirrhosis (such asChild-Pugh class B or C) or compensated cirrhosis with portal hypertension (such as ascites, gastroesophageal varices, and sustained thrombocytopenia). In these cases, the use of obeticholic acid is contraindicated.

1. Recommended dose: For PBC patients without cirrhosis or compensated cirrhosis, the recommended starting dose is 5 mg orally once daily for 3 months. These patients need to ensure that they have no evidence of portal hypertension and have not had an adequate biochemical response to an appropriate dose of UDCA for at least 1 year or are intolerant to UDCA. After 3 months of initial treatment, if the patient does not experience a significant decrease in ALP and/or total bilirubin levels and is able to tolerate treatment, the dose may be increased to a maximum dose of 10 mg once daily.

2. Dose adjustment: During treatment, if the patient develops laboratory or clinical evidence of decompensated liver function, or signs of compensated cirrhosis accompanied by portal hypertension, or significant hepatic adverse reactions, or complete biliary obstruction, the drug must be stopped immediately. In addition, for patients who cannot tolerate a dose of 5 mg once daily, it is recommended to adjust the dose to 5 mg every other day, or for patients who cannot tolerate 10 mg once daily, adjust the dose back to 5 mg once daily. At the same time, there is also the option of temporarily interrupting obeticholic acid treatment for up to 2 weeks, and then restarting and gradually titrating the dose based on the patient's biochemical response and tolerance.

3. Medication management: Obeticholic acid can be taken with or without food. For patients taking bile acid-binding resins, doses should be taken at least 4 hours before or 4 hours after taking obeticholic acid, or as long as possible.

4. Adverse reactions:

In clinical studies, the most common adverse reactions of obeticholic acid include itching, fatigue, abdominal pain and discomfort, rash, joint pain, sore throat, dizziness, constipation, peripheral edema, palpitations, fever, thyroid dysfunction and eczema. Among them, itching may lead to the interruption of treatment, and in most cases the itching occurs within the first month of treatment and usually decreases gradually as treatment continues. In addition, adverse reactions such as hepatic failure, new-onset cirrhosis, increases in direct and total bilirubin, and new or worsening jaundice have been reported post-marketing.

5. Supply and storage:

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

6. Taboo:

Obeticholic acid is contraindicated in the following categories of patients:

1. Patients with decompensated cirrhosis (such asChild-Pugh class B or C) or patients with past decompensation events.

2. Patients with compensated cirrhosis with evidence of portal hypertension (such as ascites, gastroesophageal varices, sustained thrombocytopenia).

3. 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 a key nuclear receptor that plays an important role in regulating bile acid, inflammation, fibrosis, and metabolic pathways. Activation of FXR can reduce the concentration of bile acids in hepatocytes by inhibiting the de novo synthesis of cholesterol and increasing the transport of bile acids from hepatocytes, thereby limiting the overall size of the circulating bile acid pool, promoting bile secretion, and reducing the liver's exposure to bile acids.

8. Overdose:

In clinical trials, PBC patients taking obeticholic acid 25 mg once daily (2.5 times the highest recommended dose) or 50 mg once daily (5 times the highest recommended dose) had a dose-dependent increase in the incidence of liver adverse reactions, including elevated liver biochemical tests, ascites, jaundice, portal hypertension, and episodes of primary cholangitis.

In PBC patients with decompensated cirrhosis, there have been post-marketing reports of serious hepatic adverse reactions when obeticholic acid is administered more frequently than the recommended dose; these adverse reactions have also been reported in some patients receiving the recommended dose. In the event of overdose, the patient should be carefully observed and given supportive care as appropriate.

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