FXR5 mg

FXR is a Farnesoid X receptor (FXR) agonist used in the treatment of primary biliary cholangitis (PBC) (formerly known as primary biliary cirrhosis), a chronic autoimmune liver disease.

Established / approved use

• Treatment of primary biliary cholangitis in adults without cirrhosis or with compensated cirrhosis and no evidence of portal hypertension, used:
  • In combination with ursodeoxycholic acid (UDCA) in patients who have had an inadequate response to UDCA alone after at least one year of therapy, or
  • As monotherapy in patients who are unable to tolerate UDCA.

Not indicated / restricted use

• FXR is not indicated for patients with decompensated cirrhosis or cirrhosis with evidence of portal hypertension because of the risk of serious hepatic decompensation (see Precautions and Warnings).

Regulatory status note

Following long-term confirmatory trial data that did not show a favourable overall benefit-risk profile as second-line PBC therapy, major regulators have taken restrictive action on FXR: the European Medicines Agency revoked its EU marketing authorisation in 2024, and the US marketing authorisation holder voluntarily withdrew FXR from the US market in 2025. Availability and approved indications for FXR can therefore vary by country; confirm current local regulatory and marketing status with a physician or pharmacist before starting or continuing treatment.

Obeticholic Acid is a semi-synthetic derivative of the naturally occurring human bile acid chenodeoxycholic acid, formulated as film-coated oral tablets. Where marketed, Obeticholic Acid tablets are typically available in 5 mg and 10 mg strengths for oral administration.

FXR is a selective agonist of the farnesoid X receptor (FXR), a nuclear receptor that plays a central role in regulating bile acid synthesis, transport, and metabolism in the liver. FXR is used specifically for the management of primary biliary cholangitis, a chronic cholestatic liver disease in which activation of FXR helps reduce the build-up of toxic bile acids in the liver and slow disease progression when used alongside standard first-line therapy.

Farnesoid X Receptor (FXR) Agonist — Bile Acid Analogue used in Primary Biliary Cholangitis

Obeticholic Acid is a potent and selective agonist of the farnesoid X receptor (FXR), a nuclear hormone receptor highly expressed in the liver and intestine. Activation of FXR by Obeticholic Acid:

• Induces release of fibroblast growth factor 19 (FGF19), which suppresses cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis — this reduces hepatic bile acid production.
• Increases expression of hepatocyte bile acid transporters, promoting export of bile acids out of hepatocytes and reducing intracellular bile acid accumulation.
• Has anti-inflammatory and anti-fibrotic effects on the liver in cholestatic disease models.

Together, these actions reduce cholestasis-related hepatocyte injury seen in primary biliary cholangitis. Obeticholic Acid is absorbed orally and undergoes extensive enterohepatic recirculation; it is conjugated in the liver to active glyco- and tauro-conjugates and eliminated mainly via biliary/faecal excretion, with minimal renal clearance.

FXR tablets are taken orally, once daily, with or without food, and should be swallowed whole. If a bile acid binding resin (e.g. cholestyramine, colestipol, colesevelam) is also prescribed, FXR should be taken at least 4–6 hours before or after the resin to avoid reduced absorption.

• Bile acid binding resins (e.g. cholestyramine, colestipol, colesevelam): bind and reduce absorption of FXR; separate dosing by at least 4–6 hours.
• CYP1A2 substrates with a narrow therapeutic index (e.g. theophylline, tizanidine): FXR may increase plasma levels of these drugs; clinical and, where applicable, drug-level monitoring is recommended.
• Warfarin: changes in INR have been observed in patients receiving FXR; INR should be monitored more closely and warfarin dose adjusted as needed.
• Bile salt export pump (BSEP) inhibitors (e.g. cyclosporine): may increase systemic exposure to FXR and the risk of hepatotoxicity; avoid combined use where possible or monitor liver function closely if co-administration is unavoidable.

The most common side effect of FXR is pruritus (itching), which is dose-related and can be severe enough to require dose reduction or discontinuation in some patients.

Common

• Pruritus (very common)
• Fatigue
• Abdominal pain and discomfort
• Joint pain (arthralgia)
• Throat irritation, dizziness, constipation
• Rash, eczema
• Reduced HDL cholesterol
• Elevated liver enzymes

Serious (see Precautions and Warnings)

• Hepatic decompensation/liver failure — particularly in patients with cirrhosis, requiring urgent medical attention.

Pregnancy: Data on the use of FXR in pregnant women are limited. FXR should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus. A physician should be consulted before use in pregnancy.

Lactation: It is not known whether FXR or its metabolites pass into human breast milk. Because many drugs are excreted in breast milk and the effect on a nursing infant is unknown, a decision should be made in consultation with a physician whether to discontinue breastfeeding or discontinue FXR, taking into account the benefit of treatment to the mother.

Serious hepatic decompensation and liver failure

FXR carries a serious risk of hepatic decompensation and liver failure, which can occur even in patients without pre-existing cirrhosis, and is particularly high in patients with cirrhosis, especially those with evidence of portal hypertension. Cases of liver transplantation and liver-related death have been reported in association with FXR use. FXR should be used only under specialist (hepatology) supervision, with baseline and regular monitoring of liver function throughout treatment. Treatment should be discontinued if signs of hepatic decompensation (e.g. jaundice, ascites, confusion/encephalopathy, variceal bleeding) develop.

Regulatory restrictions

Because of this hepatic safety signal and subsequent long-term trial data, regulatory authorities have taken significant restrictive action on FXR: use in decompensated cirrhosis/portal hypertension has been restricted since 2021, the European Medicines Agency revoked the EU marketing authorisation for FXR in 2024 after a confirmatory trial did not demonstrate a favourable benefit-risk profile, and FXR was voluntarily withdrawn from the US market in 2025. Patients should discuss the current approval and availability status of FXR in their country with their physician.

Dose-related pruritus

Pruritus is common and dose-related; management options include dose reduction, temporary interruption, or addition of an antihistamine or bile acid-binding resin, under medical advice.

Lipid changes

FXR can reduce HDL cholesterol and increase LDL cholesterol in some patients; lipid profiles should be monitored periodically.

Complete biliary obstruction

Do not use in patients with complete biliary obstruction (see Contraindications).

There is limited clinical experience with FXR overdose. In case of suspected overdose, patients should be closely monitored for signs of hepatotoxicity, worsening pruritus, and other adverse effects, and should seek immediate medical attention or contact emergency services/a poison control centre. There is no specific antidote; treatment is supportive, guided by a physician based on the patient's clinical status, and may include monitoring of liver function.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Hepatic impairment

FXR requires cautious, specialist-supervised use in any degree of hepatic impairment and is not indicated in decompensated cirrhosis or cirrhosis with portal hypertension (see Contraindications and Precautions and Warnings).

Renal impairment

FXR has not been extensively studied in patients with significant renal impairment; use with caution and appropriate monitoring, as clearance is primarily hepatobiliary rather than renal.

Elderly

Limited data are available in patients over 65 years; use with routine caution, considering the greater likelihood of hepatic or other organ impairment and concomitant disease/medication in this age group.

Pediatric use

Safety and efficacy of FXR in patients under 18 years of age have not been established (see Pediatric Uses).

FXR is typically used as a long-term, chronic therapy for primary biliary cholangitis, with treatment response reassessed periodically (e.g. around 3 months after starting or adjusting the dose) using liver biochemistry. Continued treatment should be reviewed regularly by the treating physician, weighing ongoing benefit against hepatic safety risk, and taking into account current local regulatory and availability status of FXR. Treatment should not be stopped or changed without medical advice.

Farnesoid X Receptor (FXR) Agonists; Semi-synthetic Bile Acid Analogues

Obeticholic Acid selectively activates the farnesoid X receptor (FXR), reducing hepatic bile acid synthesis (via FGF19-mediated suppression of CYP7A1) and increasing bile acid export from hepatocytes, thereby lowering the toxic intracellular bile acid burden that drives liver injury in cholestatic disease such as primary biliary cholangitis.

The safety and efficacy of FXR have not been established in pediatric patients (under 18 years of age). FXR is therefore not recommended for use in children or adolescents outside of a clinical trial setting, and should only be considered under specialist pediatric hepatology guidance if no alternative exists.