Obeticholic Acid

Obeticholic Acid is a prescription medication used for the treatment of Primary Biliary Cholangitis.

• Obeticholic Acid is available under the following different brand names: Ocaliva

Adult dosage

Tablet

• 5mg
• 10mg

Primary Biliary Cholangitis

Adult dosage

• 5mg orally once a day for the first 3 months
• After 3 months, patients tolerating the drug, but have an inadequate reduction in alkaline phosphatase (ALP) and/or total bilirubin (TB), may increase the dose up to 10 mg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Obeticholic Acid include:

• itching
• fatigue
• abdominal pain and discomfort
• rash
• mouth and throat pain, dizziness
• constipation
• joint pain
• thyroid function abnormality
• eczema
• swelling of the extremities
• palpitations, and
• fever

Serious side effects of Obeticholic Acid include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• severe itching,
• changes in your mental status,
• confusion,
• drowsiness,
• unusual tiredness,
• fever,
• swelling around the midsection,
• rapid weight gain,
• right-sided upper stomach pain,
• nausea,
• loss of appetite,
• vomiting,
• diarrhea,
• weight loss,
• urinating less often,
• dark urine,
• yellowing of the skin or eyes (jaundice),
• bloody or tarry stools,
• coughing up blood, and
• vomit that looks like coffee grounds

Rare side effects of Obeticholic Acid include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

• Obeticholic Acid has severe interactions with no other drugs.
• Obeticholic Acid has serious interactions with no other drugs.
• Obeticholic Acid has moderate interactions with the following drugs:
  • cholestyramine
  • colesevelam
  • colestipol
  • theophylline
  • tizanidine
• Obeticholic Acid has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Complete biliary obstruction
• Decompensated cirrhosis (.g, Child-Pugh Class B or C) or a prior decompensation event
• Compensated cirrhosis with evidence of portal hypertension (.g, ascites, gastroesophageal varices, persistent thrombocytopenia)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Obeticholic Acid?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Obeticholic Acid?”

Cautions

• Patients with PBC generally exhibit hyperlipidemia characterized by a significant elevation in total cholesterol primarily due to increased levels of high-density lipoprotein-cholesterol (HDL-C); monitor for a reduction in HDL-C; for patients who do not respond after 1 year at the highest recommended dosage that can be tolerated (e.g., 10 mg/day), and who experience a reduction in HDL-C, weigh the potential risks against the benefits of continuing treatment
• Severe pruritus reported; evaluate patients with new-onset or worsening pruritus; consider treatment with bile acid-binding resins, antihistamines, dose reduction, and/or temporary dose interruption
• Hepatic impairment
  • Closely monitor patients with compensated cirrhosis, concomitant hepatic 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 to determine whether drug discontinuation is needed
  • Permanently discontinue therapy in patients who develop laboratory or clinical evidence of hepatic decompensation, have compensated cirrhosis and develop evidence of portal hypertension, or experience clinically significant hepatic adverse reactions while on treatment; interrupt treatment during severe intercurrent illness
• Hepatic decompensation and failure
• Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, are reported with 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 to determine whether drug discontinuation is needed
• Closely monitor 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 to determine whether drug discontinuation is needed
• If severe intercurrent illness occurs, interrupt treatment and monitor the patient’s liver function; after resolution of the intercurrent illness, consider the potential risks and benefits of restarting treatment
• Permanently discontinue therapy in the following patients who:
  • Develop laboratory or clinical evidence of hepatic decompensation (e.g., ascites, jaundice, variceal bleeding, hepatic encephalopathy)
  • Have compensated cirrhosis and develop evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)
  • Experience clinically significant hepatic adverse reactions.
  • Develop complete biliary obstruction
• FDA MedWatch alert
  • On May 26, 2021, FDA restricted the use of Obeticholic Acid in patients having PBC with advanced liver cirrhosis because it can cause serious harm
  • Some PBC patients with cirrhosis (especially advanced cirrhosis) developed liver failure and some require a liver transplant
  • FDA identified 25 serious liver injury cases leading to liver decompensation or liver failure associated with Obeticholic Acid in PBC patients with cirrhosis, both in those without clinical signs of cirrhosis (compensated) or in those with clinical signs of cirrhosis (decompensated)
  • Advanced cirrhosis is defined as cirrhosis with current or prior evidence of hepatic decompensation (.g, encephalopathy, coagulopathy) or portal hypertension (.g, ascites, gastroesophageal varices, persistent thrombocytopenia)
  • Advise patients to contact the prescriber immediately if any symptoms develop
  • Monitor for clinically significant liver-related adverse reactions that may manifest as the development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine; permanently discontinue if these symptoms develop
• Drug interaction overview
  • CYP3A4 inhibitor
    • Downregulation of mRNA was observed in a concentration-dependent fashion for CYP1A2 and CYP3A4 by Obeticholic Acid and its glycine and taurine conjugate
  • Bile-acid binding resins
    • Separate Obeticholic Acid dosing from bile-acid resins
    • Bile-acid binding resins may reduce the absorption, systemic exposure, and efficacy of Obeticholic Acid
  • Warfarin
    • Monitor INR and adjust warfarin dose accordingly
    • Coadministration of warfarin and Obeticholic Acid has been shown to decrease the  International normalized ratio)
  • CYP1A2 substrates with a narrow therapeutic index
    • Monitor CYP1A2 substrates with a narrow therapeutic index
    • Obeticholic Acid may increase the exposure of CYP1A2 substrates
  • Bile salt efflux pump (BSEP) inhibitors
    • Avoid coadministration
    • BSEP inhibitors may exacerbate the accumulation of conjugated bile salts in the liver and result in clinical symptoms

Pregnancy and Lactation

• Limited available human data on the use of Obeticholic Acid during pregnancy are not sufficient to inform a drug-associated risk
• Lactation
  • There is no information on the presence of human milk, effects on breastfed infants, or effects on milk production
  • Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition.