Dosing & Uses
Dosage Forms & Strengths
tablet
- 5mg
- 10mg
Primary Biliary Cholangitis
Indicated for 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) in adults with an inadequate response to UDCA for at least 1 yr or as monotherapy in adults intolerant to UDCA
Before initiating, determine if patient has the following:
- Decompensated cirrhosis (eg, Child-Pugh class B or C)
- Had prior decompensation event
- Compensated cirrhosis with evidence of portal hypertension (eg, ascites, gastroesophageal varices, persistent thrombocytopenia)
Dosage regimen
- 5 mg PO qDay for first 3 months
- After 3 months, for patients tolerating drug, but have an inadequate reduction in alkaline phosphatase (ALP) and/or total bilirubin (TB), may increase dose up to 10 mg/day
Dosage Modifications
Intolerable pruritus
-
Consider 1 or more of the following options:
- Add an antihistamine or bile-acid binding resin
- Reduce dosage to 5 mg every other day if intolerant to 5 mg qDay OR 5 mg qDay if intolerant to 10 mg qDay
- Temporarily interrupt dosing for up to 2 weeks, restart at reduced dosage
- For patients whose dosage is reduced or interrupted, titrate dosage based on biochemical response and tolerability
- Consider discontinuing treatment in patients who continue to experience persistent, intolerable pruritus despite management strategies
Renal impairment
- Mild-to-severe (eGFR 15-89 mL/min/1.73 m2): No meaningful effect observed on obeticholic acid and its conjugated metabolites
Hepatic impairment
-
Contraindicated in
- Moderate-to-severe (Child-Pugh B or C)
- Prior decompensated hepatic event
- Compensated cirrhosis with evidence of portal hypertension (eg, ascites, gastroesophageal varices, persistent thrombocytopenia)
-
Closely monitor
- Compensated cirrhosis
- Concomitant hepatic disease
- Severe intercurrent illness for new evidence of portal hypertension
Safety and efficacy not established
No overall differences in safety or effectiveness were observed between subjects older than 65 yr, but sensitivity in some older individuals cannot be ruled out
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (5)
- cholestyramine
cholestyramine will decrease the level or effect of obeticholic acid by drug binding in GI tract. Modify Therapy/Monitor Closely. Administer obeticholic acid at least 4 hr before or 4 hr after taking a bile acid binding resins.
- colesevelam
colesevelam will decrease the level or effect of obeticholic acid by drug binding in GI tract. Modify Therapy/Monitor Closely. Administer obeticholic acid at least 4 hr before or 4 hr after taking a bile acid binding resins.
- colestipol
colestipol will decrease the level or effect of obeticholic acid by drug binding in GI tract. Modify Therapy/Monitor Closely. Administer obeticholic acid at least 4 hr before or 4 hr after taking a bile acid binding resins.
- theophylline
obeticholic acid will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. CYP1A2 substrates that have a narrow therapeutic index should be monitored closely and the dose adjusted accordingly.
- tizanidine
obeticholic acid will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. CYP1A2 substrates that have a narrow therapeutic index should be monitored closely and the dose adjusted accordingly.
Minor (0)
Adverse Effects
>10%
Pruritus (56-70%)
Fatigue (19-25%)
Severe pruritus (19-23%)
Reduced HDL-C (9-20%)
Abdominal pain and discomfort (10-19%)
1-10%
Rash (7-10%)
Arthralgia (6-10%)
Oropharyngeal pain (7-8%)
Dizziness (7%)
Constipation (7%)
Peripheral edema (3-7%)
Palpitations (3-7%)
Pyrexia (7%)
Thyroid function abnormality (4-6%)
Eczema (3-6%)
Postmarketing Reports
Hepatobiliary disorders: Liver failure, new onset cirrhosis, increased direct and total bilirubin, new or worsening of jaundice
Warnings
Black Box Warnings
Hepatic decompensation and failure in primary biliary cholangitis with cirrhosis
- Hepatic decompensation and failure, in some cases fatal or resulting in liver transplant, reported in patients with primary biliary cholangitis (PBC) with either compensated or decompensated cirrhosis
- Contraindicated in PBC with decompensated cirrhosis, prior decompensation event, or with compensated cirrhosis in patients who have evidence of portal hypertension
- Permanently discontinue 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 during treatment
Contraindications
Complete biliary obstruction
Decompensated cirrhosis (eg, Child-Pugh Class B or C) or a prior decompensation event
Compensated cirrhosis with evidence of portal hypertension (eg, ascites, gastroesophageal varices, persistent thrombocytopenia)
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 reduction in HDL-C; for patients who do not respond after 1 yr at the highest recommended dosage that can be tolerated (ie, 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 (eg, 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, 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 with compensated cirrhosis, concomitant hepatic disease (eg, autoimmune hepatitis, alcoholic liver disease), and/or with severe intercurrent illness for new evidence of portal hypertension (eg, 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 (eg, ascites, jaundice, variceal bleeding, hepatic encephalopathy)
- Have compensated cirrhosis and develop evidence of portal hypertension (eg, ascites, gastroesophageal varices, persistent thrombocytopenia)
- Experience clinically significant hepatic adverse reactions.
- Develop complete biliary obstruction
FDA MedWatch alert
- On May 26, 2021, FDA restricted 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 requiring 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 (eg, encephalopathy, coagulopathy) or portal hypertension (eg, ascites, gastroesophageal varices, persistent thrombocytopenia)
- Advise patients to contact prescriber immediately if any symptoms develop
- Monitor for clinically significant liver-related adverse reactions that may manifest as 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 INR
-
CYP1A2 substrates with narrow therapeutic index
- Monitor CYP1A2 substrates with narrow therapeutic index
- Obeticholic acid may increase exposure of CYP1A2 substrates
-
Bile salt efflux pump (BSEP) inhibitors
- Avoid coadministration
- BSEP inhibitors may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms
Pregnancy
Pregnancy
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 presence in 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 from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Farnesoid X receptor (FXR) agonist
FXR is a nuclear receptor expressed in the liver, intestine, kidney, and adipose tissue that regulates a wide variety of target genes critically involved in the control of bile acid synthesis and transport, lipid metabolism, and glucose homeostasis
FXR activation suppresses de novo synthesis of bile acids in hepatocytes as well as increasing transport of bile acids out of hepatocytes, thereby reducing exposure of the hepatocytes to bile acid
Absorption
Peak plasma concentration
- Obeticholic acid: 1.5 hr
- Active metabolites: 10 hr
Distribution
Protein bound: >99%
Vd: 618 L
Metabolism
Obeticholic acid is conjugated with glycine or taurine in the liver then secreted into bile
Conjugates are converted back to obeticholic acid and either reabsorbed in the small intestine for enterohepatic recirculation or excreted in feces
Elimination
Excretion: ~87% feces; <3% urine
Administration
Oral Administration
May take with or without food
Coadministration with bile-acid binding resin: Separate obeticholic acid dose by at least 4 hr before or after the bile-acid binding resin, or at as great an interval as possible
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Ocaliva oral - | 5 mg tablet |  | |
| Ocaliva oral - | 10 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
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