- What Is Drug Used For?
- Pharmacology / Actions
- Before you take Drug
- Contraindications / Precautions / Warnings
- Adverse Effects
- Reproductive / Nursing Safety
- Overdosage / Acute Toxicity
- Drug Interactions
- Laboratory Considerations
- How to use Drug
- Client Information
- Chemistry / Synonyms
- Storage / Stability
- Dosage Forms / Regulatory Status
URSODIOL (Actigall, Ursodeoxycholic acid)
Highlights of Prescribing Information
- Bile acid that may be useful for treatment of hepatobiliary disease in dogs/cats. May also be used for cholesterol containing gallstones
- Contraindications: Rabbits & other hindgut fermenters. Caution: Complications associated with gallstones (e.g., biliary obstruction, biliary fistulas, cholecystitis, pancreatitis, cholangitis)
- Adverse Effects: Appears to be well tolerated in dogs/cats
What Is Drug Used For?
In small animals, ursodiol may be useful as adjunctive therapy for the medical management of cholesterol-containing gallstones and/or in patients with chronic liver disease, particularly where cholestasis (bile toxicity) plays an important role. Ursodiol’s benefit in treating canine or feline hepatobiliary disease is unknown at the time of writing (studies are ongoing), but it may be of help in slowing the progression of inflammatory hepatic disorders, particularly autoimmune hepatitis and acute hepatotoxicity.
Pharmacology / Actions
After oral administration, ursodiol suppresses hepatic synthesis and secretion of cholesterol. Ursodiol also decreases intestinal absorption of cholesterol. By reducing cholesterol saturation in the bile, it is thought that ursodiol allows solubilization of cholesterol-containing gallstones. Ursodiol also increases bile flow and in patients with chronic liver disease, it apparently reduces the hepatocyte toxic effects of bile salts by decreasing their detergent action, and may protect hepatic cells from toxic bile acids (e.g., lithocholate, deoxycholate, and chenodeoxycholate).
Ursodiol is well absorbed from the small intestine after oral administration. In humans, up to 90% of dose is absorbed. After absorption, it enters the portal circulation. In the liver, it is extracted and combined (conjugated) with either taurine or glycine and secreted into the bile. Only very small quantities enter the systemic circulation and very little is detected in the urine. After each entero-hepatic cycle, some quantity of conjugated and free drug undergoes bacterial degradation; eventually most of the drug is eliminated in the feces after being oxidized or reduced to less soluble compounds. Ursodiol detected in the systemic circulation is highly bound to plasma proteins.
Before you take Drug
Contraindications / Precautions / Warnings
Ursodiol is contraindicated in rabbits and other hindgut fermenters as it is converted into lithocholic acid (toxic). Patients sensitive to other bile acid products may also be sensitive to ursodiol. The benefits of using ursodiol should be weighed against its risks in patients with complications associated with gallstones (e.g., biliary obstruction, biliary fistulas, cholecystitis, pancreatitis, cholangitis). While ursodiol may be useful in treating patients with chronic liver disease, some patients may experience further impairment of bile acid metabolism.
While ursodiol use in animals has been limited, it appears to be well tolerated in dogs and cats. Although hepatotoxicity has not been associated with ursodiol therapy, some human patients have an inability to sulfate lithocholic acid (a naturally occurring bile acid and also a metabolite of ursodiol). Lithocholic acid is a known hepatotoxin; veterinary significance is unclear. Diarrhea and other GI effects have rarely been noted in humans taking ursodiol. Ursodiol will not dissolve calcified radiopaque stones or radiolucent bile pigment stones.
Reproductive / Nursing Safety
In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) It is not known whether ursodiol is excreted in breast milk.
Overdosage / Acute Toxicity
Overdosage of ursodiol wouldmost likely cause diarrhea. Treatment, if required, could include supportive therapy; oral administration of an aluminum-containing antacid (e.g., aluminum hydroxide suspension); gastric emptying (if large overdose) with concurrent administration of activated charcoal or cholestyramine suspension.
The following drug interactions have either been reported or are theoretical in humans or animals receiving ursodiol and may be of significance in veterinary patients:
■ ALUMINUM-CONTAINING ANTACIDS: May bind to ursodiol, thereby reducing its efficacy
■ CHOLESTYRAMINE RESIN: May bind to ursodiol, thereby reducing its efficacy
■ As ursodiol is detected by many serum bile acid tests, bile acids may remain falsely elevated. One study in normal dogs did not show any effects, however.
How to use Drug
Drug dosage for dogs:
For adjunctive treatment of chronic hepatitis:
a) 5-15 mg/kg PO divided q12h, with immunosuppressive therapy. (Note: Use of this drug at this dose is preliminary, but promising) ()
b) 10-15 mg/kg PO once daily ()
c) For use in chronic active hepatitis, fibrosis and cirrhosis. May use as primary or adjunctive therapy. Dose: 11-15.4 mg/kg PO either once daily or divided twice daily ()
Drug dosage for cats:
For adjunctive treatment of chronic hepatitis:
a) 10-15 mg/kg PO once daily ()
b) For use in chronic active hepatitis, fibrosis, and cirrhosis. May use as primary or adjunctive therapy. Dose: 11-15.4 mg/kg PO either once daily or divided twice daily. Cats usually get l/6th of a capsule mixed with a small amount of food. Cats may still eat their food even if drug is sprinkled on top. ()
c) 10 mg/kg/day PO ()
■ Efficacy (ultrasonography for gallstones; improved liver function tests for chronic hepatic disease)
■ Monitoring of SGPT/SGOT (AST/ALT) on a routine basis (in humans these tests are recommended to be performed at the initiation of therapy and at 1 and 3 months after starting therapy; then every 6 months).
■ Because ursodiol dissolves more rapidly in the presence of bile or pancreatic juice, it should be given with food.
Chemistry / Synonyms
A naturally occurring bile acid, ursodiol, also known as ursodeoxycholic acid has a molecular weight of 392.6.
Ursodiol may also be known as: acidum ursodeoxycholicum, UDCA, ursodesoxycholic acid; many trade names are available.
Storage / Stability
Unless otherwise specified by the manufacturer, ursodiol capsules should be stored at room temperature (15-30°C) in tight containers.
Dosage Forms / Regulatory Status
Veterinary-Labeled Products: None
Ursodiol Capsules: 300 mg; Actigall & generic (Watson); (Rx)
Ursodiol Tablets: 250 mg & 500 mg; URSO 250 & -Forte (Axcan Pharma); (Rx)
Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008