Ursodiol

Bile acid Hepatoprotective agent; choleretic; gallstone dissolution agent

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 10-15 mg/kg q12h (every 12 hours) Duration: Long-term (months to lifelong)
Notes: Administer with food to enhance absorption. For gallbladder mucocele, use 15 mg/kg q12h. Monitor liver enzymes and bile acids periodically.
Cat PO 10-15 mg/kg q24h (every 24 hours) or divided q12h Duration: Long-term (months to lifelong)
Notes: Often used in hepatic lipidosis with other supportive care. Administer with food. Some cats may require lower initial doses to avoid GI upset.
Horse PO 10-20 mg/kg q12h or q24h Duration: Long-term (weeks to months)
Notes: Use with caution in horses with hepatic encephalopathy. Monitor liver function tests.
Cattle PO 10-15 mg/kg (off-label) q24h Duration: Variable
Notes: Not FDA-approved for cattle. Use with veterinary oversight. Withdrawal times must be established.
Small Ruminants (sheep, goats) PO 10-15 mg/kg (off-label) q24h Duration: Variable
Notes: Limited data; use with caution.
Rabbit PO 10-15 mg/kg q12h Duration: Long-term
Notes: May be used in hepatic lipidosis. Administer with a small amount of food.
Birds/Poultry PO Not established N/A Duration: N/A
Notes: No standard dosing; use only with expert consultation.
Exotic/Other PO 10-15 mg/kg (extrapolated) q12h Duration: Variable
Notes: Use with caution; limited pharmacokinetic data.

Clinical Indications & Species Uses

General Indications
  • Cholestatic liver disease
  • Chronic hepatitis
  • Biliary sludge
  • Gallbladder mucocele (adjunctive)
  • Hepatic lipidosis (adjunctive)
Dog (Canine)
  • Chronic hepatitis (idiopathic, copper-associated, drug-induced)
  • Cholangiohepatitis
  • Cholecystitis and biliary sludge
  • Gallbladder mucocele (adjunctive therapy)
  • Primary biliary cholangitis (rare)
  • Hepatic lipidosis (adjunctive)
  • Prevention of cholesterol gallstones (uncommon)
Cat (Feline)
  • Hepatic lipidosis (adjunctive therapy)
  • Cholangiohepatitis (lymphocytic or neutrophilic)
  • Cholecystitis and biliary sludge
  • Chronic hepatitis
  • Gallbladder mucocele (rare)
Horse (Equine)
  • Cholangiohepatitis
  • Hepatic lipidosis (hyperlipemia)
  • Chronic hepatitis
  • Biliary obstruction (adjunctive)
Cattle (Bovine)
  • Potential for hepatic lipidosis in dairy cows (off-label)
Rabbit & Small Mammals
  • Hepatic lipidosis (adjunctive)
  • Cholangiohepatitis (rare)
Exotic & Other Species
  • Hepatic lipidosis in small mammals (e.g., guinea pigs, chinchillas) - off-label
  • Cholangiohepatitis in reptiles (off-label)

Pharmacology & Mechanism of Action

Drug Class: Bile acid | Pharmacological Group: Hepatoprotective agent; choleretic; gallstone dissolution agent

Mechanism of Action: Ursodiol (ursodeoxycholic acid, UDCA) is a hydrophilic bile acid that reduces the concentration of hydrophobic, hepatotoxic bile acids in the bile. It displaces toxic bile acids from the enterohepatic circulation, decreases intestinal absorption of cholesterol, and reduces biliary cholesterol secretion. It also has cytoprotective, anti-apoptotic, and immunomodulatory effects on hepatocytes and cholangiocytes. It improves bile flow (choleresis) and may help dissolve cholesterol gallstones by forming liquid crystals with cholesterol.

Pharmacodynamics: Ursodiol reduces the hydrophobicity index of the bile acid pool, thereby decreasing the detergent-like damage to hepatocyte membranes. It also inhibits apoptosis of hepatocytes induced by toxic bile acids, stabilizes mitochondrial membranes, and reduces oxidative stress. In cholestatic liver disease, it improves liver enzyme parameters and may slow disease progression. It also has anti-inflammatory effects by modulating cytokine release and reducing MHC class I expression on hepatocytes.

⚡ Pharmacokinetics Summary

Absorption: Ursodiol is well absorbed from the small intestine after oral administration, with peak plasma concentrations occurring within 1-3 hours. Absorption is enhanced by the presence of bile salts and food. In dogs, bioavailability is approximately 70-80%.
Distribution: Ursodiol undergoes extensive first-pass hepatic extraction and is distributed into the bile. It is highly protein-bound (approximately 90-95%) in plasma. It distributes into tissues, with highest concentrations in the liver and bile.
Metabolism: Ursodiol is metabolized in the liver by conjugation with taurine and glycine. It is also partially converted to lithocholic acid by intestinal bacteria, but this is less than for other bile acids. The conjugated forms are excreted into bile and undergo enterohepatic recirculation.
Excretion: The primary route of excretion is fecal, via bile. A small amount is excreted in urine. The half-life in dogs is approximately 8-12 hours, but the pharmacological effect is prolonged due to enterohepatic recirculation.
Half-Life: Dogs: 8-12 hours; Cats: approximately 6-10 hours; Horses: not well documented, but likely similar to other species.
Bioavailability: Oral bioavailability is approximately 70-80% in dogs, but may be lower in other species due to first-pass metabolism.
Protein Binding: Approximately 90-95% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 250 mg, 500 mg (PO)
Oral Capsule 300 mg (PO)
Oral Suspension (compounded) Various (e.g., 50 mg/mL) (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to ursodiol or any bile acid
  • Complete biliary obstruction (e.g., extrahepatic bile duct obstruction) - may cause accumulation and worsen cholestasis
  • Uncontrolled hepatic encephalopathy (use with caution)
  • Patients with calcified cholesterol gallstones (not relevant in veterinary medicine but if present)
Warnings & Clinical Precautions:
  • Use with caution in patients with impaired renal function (dose adjustment may be needed).
  • May cause diarrhea, especially at high doses.
  • In patients with pre-existing GI disease, monitor for adverse effects.
  • Safety in pregnant or lactating animals has not been fully established; use only when clearly needed.
  • In food animals, withdrawal times must be observed; extra-label use requires veterinary oversight.
  • May interfere with absorption of fat-soluble vitamins (A, D, E, K) if used long-term; consider supplementation.
  • Monitor liver enzymes and bile acids periodically to assess efficacy and adjust dose.

Adverse Effects & Reactions

Common:

  • Diarrhea (dose-dependent)
  • Soft stools
  • Vomiting (less common)
  • Anorexia (transient)

Serious / Severe:

  • Worsening of cholestasis if biliary obstruction is present
  • Hepatic encephalopathy (rare, but possible in severe liver disease)
  • Pancreatitis (rare, reported in humans; not well-documented in animals)

Rare:

  • Allergic reactions (urticaria, angioedema)
  • Pruritus
  • Steatorrhea (with high doses)
  • Metabolic acidosis (in neonates, theoretical)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Cholestyramine, Colestipol Bile acid sequestrants bind ursodiol in the gut, reducing its absorption and efficacy. Moderate
Aluminum-containing antacids May bind ursodiol and reduce absorption. Mild
Ciclosporin Ursodiol may increase absorption of ciclosporin, potentially increasing its levels and toxicity. Moderate
Nitrofurantoin Ursodiol may reduce absorption of nitrofurantoin. Mild
HMG-CoA reductase inhibitors (statins) Ursodiol may reduce absorption of some statins (e.g., rosuvastatin). Mild
Oral contraceptives (hormonal) Potential for reduced efficacy of oral contraceptives (theoretical). Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Diarrhea
  • Vomiting
  • Dehydration
  • Electrolyte imbalances (with severe diarrhea)
  • In rare cases, hepatotoxicity (paradoxical)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Discontinue the drug. Provide fluid therapy to correct dehydration and electrolyte imbalances. Administer antiemetics if vomiting is severe. In cases of massive overdose, consider gastric lavage if recent ingestion. Monitor liver function and serum electrolytes. There is no specific antidote.

Food Animal Withdrawal Times

Ursodiol is not approved for use in food animals. For extra-label use in cattle, sheep, goats, or poultry, a withdrawal time must be established by the veterinarian based on pharmacokinetic data and regulatory requirements. Typically, a conservative withdrawal time of at least 7 days for meat and 72 hours for milk is suggested, but this is not officially established. Consult FARAD (Food Animal Residue Avoidance Databank) for current recommendations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C or 68-77°F), with excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Keep container tightly closed. Protect from moisture. Compounded suspensions should be stored according to the compounding pharmacy's instructions, typically refrigerated and used within 30-60 days.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (e.g., Actigall).

Extra-Label (Off-Label) Use: In the US, ursodiol is FDA-approved for humans (e.g., Actigall) but not for veterinary species. Its use in animals is extra-label (off-label) and permitted under the Animal Medicinal Drug Use Clarification Act (AMDUCA) provided a valid veterinarian-client-patient relationship exists. For food animals, extra-label use is prohibited if an approved animal drug exists that would be effective, but since no approved veterinary formulation exists, it may be used with appropriate withdrawal times.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Ursodiol is a valuable hepatoprotective agent in veterinary medicine, particularly for cholestatic liver diseases such as chronic hepatitis, cholangiohepatitis, and gallbladder mucocele. It is generally well-tolerated, with diarrhea being the most common adverse effect. It should be used as part of a comprehensive treatment plan that may include dietary modification, antioxidants (e.g., SAMe, vitamin E), and other hepatoprotectants. In cases of extrahepatic biliary obstruction, ursodiol is contraindicated. Monitoring liver enzymes, bile acids, and clinical signs is essential to assess response. In cats with hepatic lipidosis, ursodiol is often used alongside aggressive nutritional support. For food animals, extra-label use requires careful consideration of withdrawal times and regulatory compliance. Overall, ursodiol is a safe and effective adjunctive therapy for various hepatobiliary disorders in companion animals.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)