Ursodeoxycholic acid (UDCA)

Overview

Ursodeoxycholic acid (UDCA) (Ursofalk®, Cholurso®) is a relatively hydrophilic bile acid used in veterinary medicine as adjunctive therapy for hepatobiliary disease in dogs and cats, particularly when cholestasis is present. It has cytoprotective, choleretic, and immunomodulatory effects within the biliary system.

UDCA helps reduce the concentration of toxic hydrophobic bile acids within the bile acid pool, thereby protecting hepatocyte and biliary cell membranes from injury. It is commonly incorporated into long-term management protocols for chronic liver and biliary disorders.

Mechanism of Action (MOA): Ursodeoxycholic acid inhibits ileal absorption of hydrophobic bile acids, reducing their accumulation and toxicity within the hepatobiliary system. It also promotes bile flow, stabilizes hepatocyte membranes, exerts anti-inflammatory and mildly immunomodulatory effects, and is antiapoptotic via stimulation of cell-survival pathways. UDCA acts as a molecular chaperone protecting against endoplasmic-reticulum-mediated cellular stress and as an antioxidant against mitochondrial oxidative stress. Cholehepatic shunting allows recirculation of UDCA from cholangiocytes back to hepatocytes.

Indications

Ursodeoxycholic acid is used in dogs and cats as adjunctive therapy for hepatobiliary disease, particularly when cholestasis or impaired bile flow is present.

• Cholestatic liver disease: Used to improve bile flow and reduce accumulation of toxic bile acids.
• Chronic hepatobiliary disorders: Commonly incorporated into long-term management protocols for inflammatory or cholestatic liver disease.
• Adjunctive hepatoprotective therapy: Provides cytoprotective support for hepatocytes and biliary epithelial cells.
• Biliary sludge / microlithiasis: Aspecific UDCA indication is a medical treatment of biliary sludge (microlithiasis) — resolution of biliary sludge accumulation in dogs and cats with cholestatic disorders.
• Gallbladder mucocele — ADJUNCT (surgery for mature): Gallbladder mucocele: UDCA may protect against hepatobiliary epithelial damage as part of medical management (10–15 mg/kg PO divided BID with food), but medical therapy is NOT advised to resolve mature mucoceles — surgical cholecystectomy is indicated in most patient. Naïve unmonitored choleretic use can result in ruptured GB.

Dosage (Reference)

Dog

In dogs, ursodeoxycholic acid is used as adjunctive therapy for hepatobiliary disease and cholestatic disorders. Treatment is often continued long-term depending on the underlying condition and clinical response.

Cat

In cats, ursodeoxycholic acid is used as adjunctive therapy for cholestatic and inflammatory hepatobiliary disease. Treatment is generally well tolerated when appropriately selected.

Warnings & Precautions

Ursodeoxycholic acid is generally well tolerated in dogs and cats, but appropriate patient selection is important because administration during complete biliary obstruction may worsen hepatobiliary injury.

• Biliary obstruction: Contraindicated in patients with complete occlusion of the biliary tract.
• Underlying hepatobiliary disease: Monitor liver enzymes and clinical response during long-term therapy.
• Xylitol-containing formulations: Some oral suspensions contain xylitol and should be used cautiously in dogs and cats.
• Limited veterinary safety data: Formal safety studies in dogs and cats are limited, although adverse effects appear uncommon clinically.
• Cholestatic patients: Use only after confirming that bile flow is present and extrahepatic obstruction has been excluded.
• Vanishing bile duct syndrome — contraindicated: Vanishing bile duct syndrome is a specific contraindication to UDCA.
• Hypersensitivity contraindication: UDCA is contraindicated in patients hypersensitive to it or to other bile acid products.
• Hepatic ductopenic disorders — caution: Use UDCA with caution in dogs and cats with histologically confirmed hepatic ductopenic disorders (e.g. cholangitis, cholangiohepatitis) — UDCA may lead to PROGRESSIVE biliary damage,recommended liver biopsy BEFORE empiric UDCA in cats with suspected chronic CCHS.
• Will NOT dissolve dog/cat choleliths: UDCA is approved in humans to dissolve CHOLESTEROL choleliths, but it will NOT dissolve the typical canine choleliths (calcium carbonate) or feline choleliths (calcium bilirubinate). UDCA may facilitate dissolution if the stone is composed of cholesterol — but this is uncommon in small animals. Do not prescribe UDCA expecting it to dissolve typical canine or feline choleliths.
• Bile peritonitis — contraindicated: UDCA is contraindicated in BILE PERITONITIS or in uncorrected extrahepatic biliary obstruction. Confirm bile peritonitis has been ruled out before starting UDCA in patients with acute hepatobiliary signs.
• Cholelithiasis without identifiable cause — lifelong therapy: For cholelithiasis without an identifiable underlying cause, UDCA therapy is often continued LIFELONG to augment choleresis and thwart bile stasis. Counsel owners that this may be a long-term commitment.
• Pregnancy / lactation — safe: UDCA does NOT cross the placenta and has been safely used for intrahepatic cholestasis of pregnancy in women. Minimal systemic absorption makes clinical effects on nursing offspring unlikely. No impaired fertility or fetal harm in pregnant rabbits/rats at 7-22× human dose.

Drug Interactions

Clinically significant interactions with ursodeoxycholic acid are primarily related to altered absorption or effects on concurrent medications. Monitoring and dose adjustment may be necessary when combined with the following drugs.

• Aluminum-containing antacids: May bind ursodeoxycholic acid within the gastrointestinal tract and reduce its absorption and efficacy.
• Ciclosporin: Ursodeoxycholic acid may increase ciclosporin absorption and elevate serum drug concentrations.
• Cholestyramine — binds + reduces efficacy: Cholestyramine binds UDCA in the gut and reduces its efficacy. Separate doses by at least 2 hours.
• Estrogens — may diminish efficacy: Estrogens may increase hepatic cholesterol secretion and counteract UDCA effects. Veterinary significance is unknown but relevant in spayed/un-spayed comparison or estrogen-treated patients.
• Fibrates (fenofibrate / gemfibrozil): fenofibrate and gemfibrozil increase cholesterol formation and may counteract UDCA effects in humans. Veterinary significance is unknown but relevant in patients on concurrent hypertriglyceridemia therapy.
• Lab interference (BAT): UDCA may falsely elevate total serum bile acid test (BAT) results. Stop UDCA for at least 2–3 days before BAT testing. BAT is superfluous in the setting of hepatobiliary jaundice.

Side Effects & Overdose

Side Effects

Ursodeoxycholic acid is generally well tolerated in dogs and cats, and adverse effects appear to be uncommon during clinical use.

• Diarrhea: The most commonly reported adverse effect during therapy.
• Potential hepatotoxic metabolite formation: Formation of lithocholic acid metabolites may occur, although the veterinary significance remains unclear.
• Safety evidence in healthy dogs and cats: 20 healthy dogs (10–15 mg/kg × 6–8 wks) showed no hepatic US / liver enzyme / bilirubin / lipid changes; 12 healthy dogs (× 7 days) showed no BAT or histopathology changes; 2 healthy cat studies showed no CBC / biochem / UA / US / histopath changes — supports clinical safety at standard doses.

Overdose

Published information regarding acute ursodeoxycholic acid overdose in dogs and cats is limited. Significant toxicity appears uncommon, but excessive doses may increase gastrointestinal adverse effects.

• Diarrhea and GI irritation: Excessive dosing may result in diarrhea, vomiting, or abdominal discomfort.
• Dog-specific overdose signs — salivation + vomiting: In dogs UDCA overdose has additionally produced salivation and vomiting beyond the expected diarrhea.
• Overdose antidote (aluminum hydroxide / charcoal / cholestyramine): UDCA overdose can be managed with oral aluminum hydroxide suspension OR (if large overdose) gastric emptying with concurrent activated charcoal or cholestyramine suspension — both bind UDCA. Consult a 24-hour veterinary poison consultation centre.

Key Notes

Practical clinical points that help optimize the safe and effective use of ursodeoxycholic acid in dogs and cats in everyday veterinary practice:

• Adjunctive therapy: UDCA is typically used alongside treatment of the underlying hepatobiliary disorder rather than as sole therapy.
• Hydrophilic bile acid: Replacement of more toxic hydrophobic bile acids may help protect hepatocytes and biliary epithelial cells.
• Long-term administration: Many patients require prolonged or chronic therapy for sustained clinical benefit.
• Variable clinical response: Improvement in liver enzyme abnormalities and clinical signs may occur gradually over time.
• Commonly combined therapies: Frequently incorporated into multimodal liver support protocols with dietary management and hepatoprotective agents.
• Oral administration: Once-daily dosing is commonly used, although divided dosing may be selected in some patients.
• Bile acid testing: Administration does not significantly alter bile acid stimulation testing in healthy dogs.
• Give with food + bitter taste: UDCA works best when given with food, and its bitter taste can usually be masked by giving with food.
• Bile-acid pool plateau at 30-50% by 3 weeks: UDCA bile concentration plateaus at 30–50% of total bile acid pool after about 3 weeks of dosing. This explains why clinical onset is gradual and why a meaningful trial requires several weeks of continuous therapy.
• Will NOT dissolve dog/cat choleliths: UDCA dissolves cholesterol choleliths in humans but will NOT dissolve canine (calcium carbonate) or feline (calcium bilirubinate) choleliths. Manage owner expectations — UDCA is hepatoprotective, not lithotripsy.
• Half-tablet stability + storage: half-tablets maintain acceptable quality for up to 28 days when stored in the bottle at room temperature. Store half tablets separately from whole tablets because of the bitter taste. Compounded 50 mg/mL suspension retains 90% potency for 90 days.