Obeticholic acid

What is Obeticholic acid?

Obeticholic acid (OCALIVA), a farnesoid X receptor (FXR) agonist used to treat primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults.

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What are the uses of this medicine?

This medicine is used for the treatment of adult patients with primary biliary cholangitis (PBC)

• without cirrhosis or
• with compensated cirrhosis who do not have evidence of portal hypertension,
• either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.

How does this medicine work?

• Obeticholic acid is an agonist for FXR, a nuclear receptor expressed in the liver and intestine.
• FXR is a key regulator of bile acid, inflammatory, fibrotic, and metabolic pathways.
• FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes.
• These mechanisms limit the overall size of the circulating bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• have PBC with liver cirrhosis with symptoms such as fluid in the stomach-area or confusion (decompensated liver cirrhosis) or with abnormalities in certain tests that check your liver.
• have a complete blockage of the bile ducts in your liver or gallbladder.
• compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia).

What drug interactions can this medicine cause?

• If taking a bile acid binding resin (eg: cholestyramine, colestipol, or colesevelam), take OCALIVA at least 4 hours before or 4 hours after taking the bile acid binding resin, or at as great an interval as possible.
• Monitor International Normalized Ratio (INR) and adjust the dosage of warfarin, as needed, to maintain the target INR range when co-administering OCALIVA and warfarin.
• Therapeutic monitoring of CYP1A2 substrates with a narrow therapeutic index (e.g., theophylline and tizanidine) is recommended when co-administered with OCALIVA.
• Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Avoid use. If concomitant use is necessary, monitor serum transaminases and bilirubin.

Is this medicine FDA approved?

• It was approved for use in the United States in 2016.

How should this medicine be used?

Recommended Dosage: Prior to the initiation of OCALIVA, 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).

The recommended starting dosage of OCALIVA, 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 who 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 OCALIVA, increase to a maximum dosage of 10 mg once daily.

Management of Patients with Intolerable Pruritus Add an antihistamine or bile acid binding resin. Reduce the dosage of OCALIVA 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 OCALIVA dosing for up to 2 weeks. Restart at a reduced dosage.

Administration

• Take OCALIVA exactly as your healthcare provider tells you to.
• Do not take more OCALIVA than your healthcare provider tells you to.
• Take OCALIVA with or without food.
• If you take a bile acid binding resin, take OCALIVA at least 4 hours before or 4 hours after you take your bile acid binding resin. If this is not possible, space the time between taking OCALIVA and your bile acid binding resin as far apart as possible.
• If you take too much OCALIVA, call your healthcare provider or get emergency medical help right away.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablets: 5 mg, 10 mg

This medicine is available in fallowing brand namesː

• OCALIVA

What side effects can this medication cause?

The most common side effects of this medicine include:

• tiredness
• stomach pain and discomfort
• rash
• joint pain
• mouth and throat pain
• dizziness
• constipation
• swelling in your hands, ankles, or feet
• fast or irregular heartbeat
• fever
• changes in how your thyroid gland works
• dryness, irritation, redness, crusting or drainage of the skin (eczema)

OCALIVA can cause serious side effects, including:

• Severe itching (pruritus)
• Lower HDL-C ("good" cholesterol)

What special precautions should I follow?

• Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with cirrhosis, either compensated or decompensated. Routinely monitor patients for progression of PBC, including hepatic adverse reactions, with laboratory and clinical assessments. Closely monitor patients at risk of hepatic decompensation. Permanently discontinue 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. Interrupt treatment in patients with severe intercurrent illness.
• Severe pruritus was reported with OCALIVA. Management strategies include the addition of bile acid binding resins or antihistamines; OCALIVA dosage reduction and/or temporary dosing interruption.
• OCALIVA may cause reduction in HDL-C. Monitor for changes in serum lipid levels during treatment.

What to do in case of emergency/overdose?

• Symptoms of overdosage may include hepatic adverse reactions, including elevations in liver biochemical tests, ascites, jaundice, portal hypertension, and primary biliary cholangitis flares.

Management for overdosage:

• In the case of overdosage, patients should be carefully observed, and supportive care administered, as appropriate.

Can this medicine be used in pregnancy?

• The limited available human data on the use of obeticholic acid during pregnancy are not sufficient to inform a drug-associated risk.

Can this medicine be used in children?

• The safety and effectiveness of OCALIVA in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: obeticholic acid
• Inactive ingredients: microcrystalline cellulose, sodium starch glycolate, magnesium stearate

Film coating: Opadry II (Yellow) containing polyvinyl alcohol-part hydrolyzed, titanium dioxide, macrogol (polyethylene glycol 3350), talc, iron oxide yellow

Who manufactures and distributes this medicine?

• Distributed by: Intercept Pharmaceuticals, Inc., New York

OCALIVA is a registered trademark of Intercept Pharmaceuticals, Inc.

What should I know about storage and disposal of this medication?

• Store OCALIVA at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep OCALIVA and all medicines out of the reach of children.

• Dailymed label info on Obeticholic acid
• FDA Obeticholic acid

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