Gallstone dissolution (capsules): Oral: 8 to 10 mg/kg/day in 2 to 3 divided doses; use beyond 24 months is not established.
Gallstone prevention (capsules): Oral: 600 mg/day in 1 or 2 divided doses.
Gallstone prevention post–bariatric surgery (off-label use): Oral: 500 to 600 mg once daily or in 2 divided doses for 6 months. Note: Doses up to 1,200 mg/day were effective but were associated with a higher incidence of nonadherence (Magouliotis 2017).
Hepatic sinusoidal obstruction syndrome associated with stem cell transplant, prevention (off-label use): Oral: 12 mg/kg/day in 2 divided doses beginning 1 day before the conditioning regimen and continuing for 90 days after transplantation (Ruutu 2002; Ruutu 2013). Refer to institutional protocols for further information.
Intrahepatic cholestasis of pregnancy (off-label use): Oral: 10 to 15 mg/kg/day in 2 to 3 divided doses (ACG [Tran 2016]; SMFM [Lee 2021]) or 500 mg twice daily, gradually increase in increments of 500 mg/day (range: 500 mg to 2,000 mg/day in divided doses) (Chappell 2019); continue until delivery.
Primary biliary cholangitis (tablets): Oral: 13 to 15 mg/kg/day in 2 to 4 divided doses (with food). Note: May be given once daily (at bedtime) to improve compliance (AASLD [Lindor 2019]).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Ursodeoxycholic acid (ursodiol): Pediatric drug information")
Biliary atresia, status post-Kasai procedure: Limited data available: Infants and Children: Oral: 10 to 20 mg/kg/day in 2 to 3 divided doses. Dosing based on small prospective and retrospective trials that included ursodiol as part of a multidrug regimen designed to reduce the risk of cholangitis (Kelly 2007; Meyers 2003; Nittono 1989; Stringer 2007; Yamashiro 1994).
Pruritus secondary to cholestasis: Limited data available: Infants, Children, and Adolescents: Oral: 15 to 20 mg/kg/day once daily or in divided doses twice daily; doses up to 30 mg/kg/day may be necessary in some patients (Dinler 1999; Narkewicz 1998; Kliegman 2016). Dosing based on long-term (2.5 years), open-label, crossover trial of 13 patients (ages 2 to 27 years) with intrahepatic cholestasis; six of the 13 patients had symptomatic improvement in pruritus (Narkewicz 1998). In another study of 24 pediatric patients (1.5 to 15 years) treated with ursodiol, all patients experienced improvement in pruritus and 16.7% had complete resolution of pruritus (Dinler 1999).
Cystic fibrosis-related liver disease: Limited data available: Infants, Children, and Adolescents: Oral: Limited data available: Initial: 20 mg/kg/day in 2 divided doses, reported range: 10 to 30 mg/kg/day in divided doses; individualize dose based on patient response (Columbo 1990; Debray 2011; Lepage 1997; Sokol 1999)
Parenteral nutrition-induced cholestasis, treatment: Limited data available: Infants and Children: Oral: 30 mg/kg/day in 3 divided doses (Chen 2004; De Marco 2006; Spagnuolo 1996)
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Actigall: 300 mg [DSC]
Actigall: 300 mg [DSC] [contains corn starch]
Reltone: 200 mg [contains corn starch]
Reltone: 400 mg [contains corn starch, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Generic: 200 mg, 300 mg, 400 mg
Tablet, Oral:
Urso 250: 250 mg
Urso Forte: 500 mg [scored]
Generic: 250 mg, 500 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Urso: 250 mg
Urso DS: 500 mg
Generic: 250 mg, 500 mg
Oral: Do not administer with aluminum-based antacids or bile acid sequestrants. If aluminum-based antacids are needed, administer 2 hours after ursodiol; some experts recommend administering ursodiol 1 hour prior to or 4 to 5 hours after bile acid sequestrants (AASLD [Lindor 2019]; Rust 2000). Urso Forte can be split into halves for appropriate dosage; do not chew. Tablets should be taken with food.
Oral: Do not administer with aluminum-based antacids or bile acid sequestrants. If aluminum-based antacids are needed, administer 2 hours after ursodiol; administer ursodiol 5 hours or more after bile acid sequestrants (Rust 2000). Urso Forte can be split into halves for appropriate dosage; do not chew. Urso and Urso Forte should be taken with food.
Gallstones (capsules only):
Treatment of patients with radiolucent, noncalcified gallbladder stones <20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk caused by systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Safety for use of ursodiol beyond 24 months is not established.
Prevention of gallstone formation in obese patients experiencing rapid weight loss.
Primary biliary cholangitis (tablets only): Treatment of patients with primary biliary cholangitis (PBC) (previously referred to as primary biliary cirrhosis).
Gallstone prevention post–bariatric surgery; Hepatic sinusoidal obstruction syndrome associated with stem cell transplant, prevention; Intrahepatic cholestasis of pregnancy
Ursodiol may be confused with ulipristal
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Headache (≤25%), dizziness (17%)
Gastrointestinal: Diarrhea (≤27%), constipation (≤26%), dyspepsia (≤17%), nausea (≤17%)
Neuromuscular & skeletal: Back pain (≤12%)
Respiratory: Upper respiratory tract infection (≤16%)
1% to 10%:
Dermatologic: Alopecia (5%), skin rash (3%)
Endocrine & metabolic: Hyperglycemia (1%)
Gastrointestinal: Vomiting (≤10%), peptic ulcer (1%)
Genitourinary: Urinary tract infection (7%)
Hematologic & oncologic: Leukopenia (3%), thrombocytopenia (1%)
Hepatic: Cholecystitis (5%)
Hypersensitivity: Hypersensitivity reaction (5%)
Infection: Viral infection (9%)
Neuromuscular & skeletal: Arthritis (6%), musculoskeletal pain (6%)
Renal: Increased serum creatinine (1%)
Respiratory: Pharyngitis (≤8%), bronchitis (7%), cough (7%), flu-like symptoms (7%)
<1%, postmarketing, and/or case reports: Abdominal distress, abdominal pain, abnormal hepatic function tests, angioedema, anorexia, biliary colic, esophagitis, facial edema, fever, hepatobiliary disease, increased gamma-glutamyl transferase, increased liver enzymes, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin, jaundice, laryngeal edema, malaise, metallic taste, myalgia, peripheral edema, pruritus, transaminases increased, urticaria, weakness
Hypersensitivity to ursodiol or any component of the formulation (tablet); not to be used with calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones; patients with unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula; allergy to bile acids
Canadian labeling: Additional contraindications (not in US labeling): Complete biliary obstruction of extrahepatic origin; widespread intrahepatic obstruction
Concerns related to adverse effects:
• Biliary obstruction: Maintain bile flow during therapy to prevent biliary obstruction.
Disease-related concerns:
• Hepatic effects: Use with caution in patients with chronic liver disease. Monitor LFTs; consider discontinuing therapy in patients with significant elevations in LFTs.
Other warnings/precautions:
• Appropriate use: Gallbladder stone dissolution may take several months of therapy; complete dissolution may not occur and recurrence of stones within 5 years has been observed in up to 50% of patients. Patients should be cautiously selected for therapy, consider alternative treatments. Specific treatments should be initiated in patients with ascites, hepatic encephalopathy, variceal bleeding, or if an urgent liver transplant is necessary.
• Nonvisualizing gallbladder: Use with caution in patients with a nonvisualizing gallbladder; therapy should be discontinued if gallbladder nonvisualization occurs during treatment.
None known.
Aluminum Hydroxide: May decrease the serum concentration of Ursodiol. Management: Separate administration of ursodiol and aluminum-containing antacid products to prevent adsorption in the gastrointestinal tract. Risk D: Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Ursodiol. Management: Administer ursodiol 2 to 4 hours before or at least 2 to 5 hours after bile acid sequestrants to minimize the potential for any significant interaction. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants. Risk D: Consider therapy modification
Estrogen Derivatives: May diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy
Fibric Acid Derivatives: May diminish the therapeutic effect of Ursodiol. Risk C: Monitor therapy
Nitrendipine: Ursodiol may decrease the absorption of Nitrendipine. Management: Consider therapeutic alternatives. If concomitant therapy cannot be avoided, avoid simultaneous administration. Risk D: Consider therapy modification
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Ursodiol has been evaluated for treating intrahepatic cholestasis of pregnancy (ICP). Maternal symptoms (eg, itching, increased bile acid concentrations) generally occur during the second and third trimester. Fetal distress, preterm birth, and intrauterine death are also associated with ICP. Although some studies have shown a decrease in maternal symptoms (primarily itching) with ursodiol treatment, data is inconclusive regarding improvement of fetal/neonatal outcomes (ACG [Tran 2016]; Chappell 2019; Kong 2016; Ovadia 2021; Parízek 2016; Sepúlveda Marín 2016; Shen 2019; SMFM [Lee 2021]; Walker 2020; Zhang 2016).
The American College of Gastroenterology guideline for liver disease in pregnancy and the Society for Maternal-Fetal Medicine intrahepatic cholestasis of pregnancy consult series consider ursodiol a first-line therapy for the treatment of ICP during the second and third trimesters of pregnancy (ACG [Tran 2016]; SMFM [Lee 2021]).
Ursodiol may be present in breast milk (Brites 1998).
Total bile acid concentrations are increased in the colostrum of patients with intrahepatic cholestasis of pregnancy (ICP). Ursodiol treatment for ICP until delivery decreased the concentrations of total bile acid in the colostrum of 7 women compared to nontreated patients. Ursodeoxycholic acid concentrations were insignificantly elevated in the colostrum and were lower than the maternal serum (Brites 1998).
Based on limited case reports, adverse events have not been observed in breastfed infants (Brites 1998; Erol-Coskun 2018; Vítek 2010).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Urso and Urso Forte should be taken with food.
Gallstone disease: ALT, AST, ultrasound every 6 months for the first year.
Intrahepatic cholestasis of pregnancy: Serum bile acid and liver transaminase prior to therapy (SMFM [Lee 2021]).
Primary biliary cholangitis: Monitor LFTs (GGT, AST, ALT, bilirubin, and alkaline phosphatase) monthly for the first 3 months and every 6 months thereafter or as clinically necessary (90% of the improvement usually occurs within 6 to 9 months) (AASLD [Lindor 2019]); baseline vitamin D level (Guo 2015).
Ursodiol decreases the cholesterol content of bile and bile stones by reducing the secretion of cholesterol from the liver and the fractional reabsorption of cholesterol by the intestines. Mechanism of action in primary biliary cholangitis is not clearly defined. Ursodiol reduces hydrophobic bile acids; hydrophobic bile acids may be toxic to hepatic parenchymal cells in patients receiving hematopoietic stem cell transplantation (BCSH/BSBMT [Dignan 2013]; Ruutu 2002).
Absorption: 90%
Protein binding: ~70%
Metabolism: Undergoes extensive enterohepatic recycling; following hepatic conjugation and biliary secretion, the drug is hydrolyzed to active ursodiol, where it is recycled or transformed to lithocholic acid by colonic microbial flora; during chronic administration, ursodiol becomes a major biliary and plasma bile acid constituting 30% to 50% of biliary and plasma bile acids
Excretion: Feces; urine (<1%)
Capsules (Reltone Oral)
200 mg (per each): $23.94
400 mg (per each): $35.28
Capsules (Ursodiol Oral)
200 mg (per each): $50.00
300 mg (per each): $1.50 - $13.94
400 mg (per each): $70.00
Tablets (Urso 250 Oral)
250 mg (per each): $6.61
Tablets (Urso Forte Oral)
500 mg (per each): $11.71
Tablets (Ursodiol Oral)
250 mg (per each): $2.68
500 mg (per each): $4.75
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