ursodiol (Rx)

>10%

Headache

Dizziness

Diarrhea

Dyspepsia

Nausea/vomiting

Back pain

Upper respiratory tract infection

1-10%

Alopecia

Rash

Hyperglycemia

Flatulence

Peptic ulcer

Urinary tract infection

Leukopenia

Thrombocytopenia

Cholecystitis

>1%

Fatigue

Abdominal pain

Thrombocytopenia

Pruritus

Angioedema

Peripheral edema

Biliary pain

Postmarketing Reports

Hepatobiliary disorders: Jaundice (or aggravation of pre-existing jaundice)

Abnormal laboratory tests: Increased ALT, AST, alkaline phosphatase, bilirubin, gamma-GT

Gastrointestinal disorders: Abdominal discomfort, enteroliths (bezoars), constipation

Contraindications

Hypersensitivity

Gallstone complication requiring surgery

Known hepatocyte or bile ductal abnormalities, inflammatory bowel disease

Calcified gallstones, bile acid allergy, chronic hepatic disease

Billiary gastrointestinal fistula

Patients requiring cholecystectomy

Cautions

Only use in radiolucent, non calcified, high cholesterol content gallstone

Use caution in chronic liver disease

In nonvisualizing gallbladders use caution and discontinue therapy if gallbladder nonvisualization occurs during treatment

Liver function tests (gamma-GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored q3mo x3 months after start of therapy, and q6mo thereafter; consider treatment discontinuation if parameters increase to a level considered clinically significant in patients with history of stable liver function test levels

Patients with variceal bleeding, hepatic encephalopathy, ascites or in need of an urgent liver transplant, should receive appropriate specific treatment

Gallbladder stone dissolution may take several months of therapy and complete dissolution may not occur; reocurrence of stones may happen within 5 years in up to 50% of patients receiving therapy

Enteroliths in patients with risk for intestinal stenosis or stasis

• There are rare postmarketing reports of URSO-treated patients who developed enteroliths (bezoars) resulting in obstructive symptoms that required surgical intervention; these patients had medical conditions that predisposed them to intestinal stenosis or stasis (eg, surgical enteroanastomoses, Crohn's disease); if a patient presents with obstructive gastrointestinal symptoms, hold URSO until a clinical evaluation conducted

Pregnancy

Available published data on use of ursodiol in pregnant women derived from randomized controlled trials, observational studies, and case series collected over several decades have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes; most reported exposures to ursodiol occurred in second and third trimester of pregnancy

Animal data

• In animal reproduction studies, ursodiol had no adverse effects on embryo-fetal development when administered at doses greater than human therapeutic doses

Lactation

Ursodiol is naturally present in human milk; there are no reports of adverse effects of ursodiol on breastfed child, but reports are extremely limited; there are no data on effects of ursodiol on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from 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.

Mechanism of Action

Naturally-occurring bile acid; reduces cholesterol secretion from the liver; reduces the fractional reabsorption of cholesterol by the intestines.

Absorption

Bioavailability: 90%

Onset: Initial response for gallstone dissolution is 3-6 months

Distribution

Protein Bound: 70%

Metabolism

Taken up rapidly by the liver, conjugated with glycine or taurine, and excreted in the bile

Nonabsorbed ursodiol passes into the colon where it is 7-dehydroxylated to lithocholic acid (an intermediary compound, sometimes formed, is called chenodiol); chenodiol is then dehydroxylated to lithocholic acid

Metabolites: Glyco-ursodeoxycholic acid, tauro-ursodeoxycholic acid, 7-keto-lithocholic acid (inactive); lithocholic acid (inactive) is formed from the 7-hydroxylation of ursodiol and chenodiol; a small portion is metabolized to sulfated lithocholic acid conjugates which are excreted in bile & eliminated in feces

Elimination

Excretion: Mainly in feces