Obeliva Tablet

Introduction

Obeticholic acid (brand name Ocaliva) is a semisynthetic bile acid analog and a member of the farnesoid X receptor (FXR) agonist family of drugs. It is an orally administered FXR agonist and is used to treat primary biliary cholangitis (PBC).

Uses for

Obeticholic acid is used to treat primary biliary cholangitis (PBC), a progressive disorder of the bile ducts in the liver. It works by blocking the abnormal buildup of bile, slowing down the growth of the cells, and reducing inflammation.

Mechanism Of Action

The primary mechanism by which obeticholic acid works is through the farnesoid X receptor (FXR). FXR is a nuclear receptor involved in the regulation of bile acid synthesis and metabolism. When activated, it increases the expression of small-hormone receptors involved in the production and excretion of bile acids from the liver. It also decreases the expression of bile acid transporters involved in reabsorption of bile acids and increases the expression of several bile acid synthesis enzymes. Obeticholic acid also has anti-inflammatory and anti-oxidant effects, which can help reduce the damage and inflammation caused by PBC.

How Long Does It Take To Work?

Obeticholic acid typically takes several weeks to become effective. Most patients begin to see an improvement in liver enzyme levels within 4-6 weeks, although the degree of improvement can vary from person to person. It is important to continue taking the medication even if no improvement is noticed, as it may take several months for the drug to reach its maximum effect.

Absorption

Obeticholic acid is easily absorbed from the gastrointestinal tract into the systemic circulation. It has an estimated bioavailability of 45%.

Route Of Elimination

Obeticholic acid is primarily eliminated via the feces. It is also metabolized by the liver and excreted in the urine.

Dosage

Important Dosage and Administration Instructions: Prior to the initiation of Obeticholic acid, healthcare providers should determine whether the patient has decompensated cirrhosis (e.g., Child-Pugh Class B or C) has had a prior decompensation event or has compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) because Obeticholic acid is contraindicated in these patients.

Recommended Dosage Regimen: The recommended dosage of Obeticholic acid for PBC patients without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least 1 year or are intolerant to UDCA follows below:

Start with a dosage of 5 mg once daily for the first 3 months.
After the first 3 months, for patients who have not achieved an adequate reduction in ALP and/or total bilirubin and who are tolerating Obeticholic acid increase to a maximum dosage of 10 mg once daily.

Monitoring to Assess Safety, Need for Obeticholic acid Discontinuation: Routinely monitor patients during Obeticholic acid treatment for biochemical response, tolerability and progression of PBC. Closely monitor patients with compensated cirrhosis, concomitant hepatic disease (e.g., autoimmune hepatitis, alcoholic liver disease) and/or severe intercurrent illness for new evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia) or increases above the upper limit of normal in total bilirubin, direct bilirubin or prothrombin time. Permanently discontinue Obeticholic acid in patients who develop laboratory or clinical evidence of hepatic decompensation, have compensated cirrhosis and develop evidence of portal hypertension, experience clinically significant hepatic adverse reactions, or develop complete biliary obstruction.

Management of Patients with Intolerable Pruritus on Obeticholic acid: For patients with intolerable pruritus on Obeticholic acid consider one or more of the following management strategies. Add an antihistamine or bile acid-binding resin.

Reduce the dosage of Obeticholic acid to:

5 mg every other day, for patients intolerant to 5 mg once daily.
5 mg once daily, for patients intolerant to 10 mg once daily.
Temporarily interrupt Obeticholic acid dosing for up to 2 weeks. Restart at a reduced dosage. For patients whose dosage is reduced or interrupted, titrate the dosage based on biochemical response and tolerability. Consider discontinuing Obeticholic acid treatment in patients who continue to experience persistent, intolerable pruritus despite management strategies.

The recommended adult dose of obeticholic acid is 10 mg once daily with food. This dose can be increased to 10 mg twice daily by the physician based on individual needs, such as the degree of liver enzyme elevation. The maximum daily dose should not exceed 20 mg.

Administration

Obeticholic acid should be taken with food to facilitate absorption. It is available as a tablet or oral suspension and should be taken as directed by the physician.

Side Effect

Common side effects of obeticholic acid include nausea, diarrhea, increased liver enzymes, fatigue, and itching. Serious side effects, such as liver damage and jaundice, have been reported in rare cases.

Toxicity

Obeticholic acid is not known to be toxic, although long-term use can lead to elevated liver enzymes. Patients should discuss any signs or symptoms of liver toxicity with their doctor. Additionally, obeticholic acid should not be given to patients with severe liver disease.

Precautions

Obeticholic acid should not be taken by patients with severe hepatic impairment, as it may aggravate liver failure. Patients with a history of gallstones should also exercise caution when taking obeticholic acid, as it may increase the risk of gallstone formation. Additionally, pregnant and breastfeeding women should consult their doctor before taking obeticholic acid.

Interaction

Obeticholic acid may interact with certain other medications, including antifungal drugs, antibiotics, uricosuric agents, and statins. Patients should discuss all medications with their doctor before taking obeticholic acid. Additionally, obeticholic acid may interact with grapefruit juice and alcohol, and these products should be avoided while taking the medication.

Disease Interactions

Obeticholic acid should not be used in patients with severe liver impairment or hepatic failure. Patients with a history of gallstones should exercise caution when taking the drug, as it may increase the risk of gallstone formation. Patients with active infections, such as HIV and hepatitis, should also exercise caution.

Drug Interactions

Obeticholic acid can interact with certain other medications, including antifungal drugs, antibiotics, uricosuric agents, and statins. Patients should discuss all medications with their doctor before taking obeticholic acid.

Food Interactions

Grapefruit juice and alcohol should be avoided while taking obeticholic acid, as these can interact with the drug and cause adverse effects. Additionally, the drug should be taken with food to facilitate absorption.

Pregnancy Use

Obeticholic acid is classified as a Pregnancy Category C medication, meaning it may or may not be safe to use during pregnancy. Patients should discuss the risks and benefits with their doctor before taking the drug during pregnancy or when planning to become pregnant.

Lactation Use

Obeticholic acid is not recommended for use in breastfeeding women, as it could pass into the milk and harm a nursing infant. Patients should discuss the risks and benefits with their doctor before taking the drug when breastfeeding.

Acute Overdose

Symptoms of an obeticholic acid overdose may include nausea, vomiting, diarrhea, and abdominal pain. Patients should seek medical attention immediately if these symptoms occur.

Contraindication

Obeticholic acid should not be used in patients with severe hepatic impairment or hepatic failure. Patients with active infections, such as HIV and hepatitis, should also exercise caution. Additionally, the drug should not be used during pregnancy or when planning to become pregnant.

Use Direction

Obeticholic acid should be taken with food to facilitate absorption. The recommended adult dose is 10 mg once daily, with the maximum daily dose not exceeding 20 mg. The dose may be increased to 10 mg twice daily based on individual needs, such as the degree of liver enzyme elevation.

Storage Condition

Obeticholic acid should be stored at room temperature between 15-30°C (59-86°F). It should be protected from light, heat, and moisture. The tablets should not be crushed or chewed.