Note: Extemporaneously compounded oral suspensions are available in multiple concentrations (eg, 20 mg/mL, 25 mg/mL, 50 mg/mL, 60 mg/mL); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mg of ursodiol (ie, not in mL or number of tablets).
Biliary atresia, status post-Kasai procedure: Limited data available: Term neonates: Usual dose: Oral: 10 to 20 mg/kg/day in 2 to 3 divided doses. Dosing based on small prospective and retrospective trials of neonates and very young infants that included ursodiol as part of a multidrug regimen designed to reduce the risk of cholangitis (Kelly 2007; Meyers 2003; Nittono 1989; Stringer 2007). Some centers have reported higher doses (Wong 2019); a range of 20 to 36 mg/kg/day (mean: 25 mg/kg/day) in divided doses was reported in neonates and infants (n=16) following Kasai procedures at a median age of 54 days (range: 14 to 89 days) (Willot 2008).
Parenteral nutrition-induced cholestasis: Limited data available:
Treatment: Efficacy results variable: Preterm and term neonates: Reported range: Oral: 10 to 30 mg/kg/day in 3 divided doses; dosing based on reported retrospective studies that included preterm and term neonates (Chen 2004; Levine 1999).
Neonates who were treated with ursodiol had a significantly shortened duration of cholestasis (62.8 ± 10.7 days vs 92.4 ± 8.8 days) and decreased peak direct bilirubin (5.3 ± 0.6 mg/dL vs 8.7 ± 1.1 mg/dL) compared to no treatment (Chen 2004); improvement of bilirubin was seen after 2 weeks and 50% of patients saw a decrease in transaminases (Levine 1999). However, in another large retrospective trial (n=64), neonates receiving ursodiol (mean dose: 24.9 mg/kg/day) had a significantly prolonged resolution of cholestasis compared to controls (median: 79 vs 50 days); authors attribute this to smaller, more premature patients in the treatment group and possibly due to a delay in treatment with ursodiol (time from onset of cholestasis to treatment: median: 24 days) (Thibault 2014).
Prevention: Reported regimens variable: Preterm neonates: Oral: 20 to 25 mg/kg/day in 2 to 4 divided doses (Arslanoglu 2008; Gokmen 2012; Liu 2022). In a randomized, placebo-controlled trial of 102 preterm neonates (n=42 treatment group), ursodiol doses of 20 to 25 mg/kg/day in 2 divided daily doses were shown to significantly prevent neonatal cholestasis (0% vs 11.7%) with significantly lower peak direct and total bilirubin levels (Liu 2022). In a smaller prospective, randomized, controlled study of neonates who received parenteral nutrition for at least 12 days and were receiving <75 mL/kg/day of enteral feeds by day of life 14, 24 neonates received ursodiol at 20 mg/kg/day in 4 divided doses starting at day of life 14; results showed ursodiol was more effective at preventing cholestasis compared to erythromycin or placebo (Gokmen 2012). Dose titration was reported in a double-blind, placebo-controlled study of 15 premature neonates requiring parenteral nutrition during the first few days of life; ursodiol was initiated at 5 mg/kg/day in 4 divided doses beginning on day of life 3 with initiation of parenteral nutrition; increase dose to 10 mg/kg/day in 4 divided doses with initiation of enteral feeding; increase dose to 20 mg/kg/day in 4 divided doses when full enteral feedings reached (Arslanoglu 2008).
Note: Extemporaneously compounded oral suspensions are available in multiple concentrations (eg, 20 mg/mL, 25 mg/mL, 50 mg/mL, 60 mg/mL); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mg of ursodiol (ie, not in mL or number of tablets).
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). Some patients may require higher doses (Wong 2019); a range of 20 to 36 mg/kg/day (mean: 25 mg/kg/day) in divided doses was reported in neonates and infants (n=16) following Kasai procedures at a median age of 54 days (range: 14 to 89 days) (Willot 2008).
Cystic fibrosis-related liver disease: Limited data available: Infants, Children, and Adolescents: Oral: 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; Kappler 2012; Lepage 1997; Sokol 1999; Warner 2021).
Parenteral nutrition-induced cholestasis, treatment: Limited data available (ASPEN [Wales 2014]): Infants and Children: Oral: 30 mg/kg/day in 3 divided doses (Chen 2004; De Marco 2006; Spagnuolo 1996).
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; Hassan 2020; Narkewicz 1998). 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).
Veno-occlusive disease (sinusoidal obstruction syndrome) following hematopoietic stem cell transplantation, prevention: Limited data available (Al Jefri 2017; EBMT [Ruutu 2019]; Mahadeo 2020); efficacy results variable (Cheuk 2005); reported dosing regimens variable; initiate during conditioning phase; refer to specific protocols:
Infants, Children, and Adolescents: Oral: Usual reported range: 10 to 15 mg/kg/day in 2 divided doses; some centers have used doses up to 30 mg/kg/day; if a solid dosage form appropriate for the patient, doses may be rounded to next available dosage form (eg, 150 mg tablet); maximum dose: 300 mg/dose (Faraci 2019; Mahadeo 2014; Pennesi 2022; Ruutu 2002).
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): Drug information")
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.
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 #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
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; administer ursodiol 5 hours or more after bile acid sequestrants (Rust 2000).
Tablets: Urso Forte can be split into halves for appropriate dosage; do not chew. Urso and Urso Forte should be administered 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; 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.
Capsules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Tablets:
Urso: Store at 20°C to 25°C (68°F to 77°F).
Urso Forte: Store at 20°C to 25°C (68°F to 77°F). When broken in half, scored Urso Forte 500 mg tablets maintain quality for up to 28 days when kept in current packaging and stored at 20°C to 25°C (68°F to 77°F). Split tablets should be stored separately from whole tablets due to bitter taste.
Capsules: Gallbladder stone dissolution for 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, or idiosyncratic reaction to general anesthesia, or for patients who refuse surgery; prevention of gallstone formation in obese patients experiencing rapid weight loss (All indications: FDA approved in adults).
Tablets: Treatment of primary biliary cirrhosis (FDA approved in adults).
Has also been used to facilitate bile excretion in infants with biliary atresia, treat cholestasis secondary to parenteral nutrition (PN), aid fat absorption in cystic fibrosis-related liver disease, and prevent veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) following hematopoietic stem cell transplantation.
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.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
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 1 hour before or at least 4 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
Nitrendipine: Ursodiol may decrease the absorption of Nitrendipine. Risk C: Monitor therapy
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
Urso and Urso Forte should be taken with food.
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]).
Hepatic disease: Monitor liver function tests (GGT, AST, ALT, bilirubin, and alkaline phosphatase) monthly for the first 3 months and every 6 months thereafter or as clinically necessary.
Gallbladder disease: ALT, AST, sonogram.
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%)
60 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)
A 60 mg/mL ursodiol oral suspension may be made with capsules. Empty the contents of twelve 300 mg capsules into a mortar. Add small portions of glycerin and mix to a uniform paste; mix while adding simple syrup in incremental proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well" and "refrigerate". Stable for 35 days refrigerated (Johnson 1995).
20 mg/mL Oral Suspension
A 20 mg/mL ursodiol oral suspension may be made with capsules and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of methylcellulose 1% and syrup NF. Empty the contents of seventeen 300 mg capsules into a mortar. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 255 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 255 mL. Label "shake well" and "refrigerate". Stable for 91 days refrigerated (Nahata 1999).
25 mg/mL Oral Suspension
A 25 mg/mL ursodiol oral suspension may be made with capsules. Empty the contents of ten 300 mg capsules into a mortar; add 10 mL Glycerin, USP and mix until smooth. Mix while adding 60 mL Ora-Plus; transfer mixture to a light-resistant bottle, rinse mortar with a small amount of Orange Syrup, NF, and add quantity of syrup sufficient to make 120 mL. Label "shake well". Stable for 60 days at room temperature or refrigerated (Mallett 1997).
50 mg/mL Oral Suspension
A 50 mg/mL ursodiol oral suspension may be made with tablets and 60 mL of either a 1:1 mixture of Ora-Plus and strawberry syrup or a 1:1 mixture of Ora-Plus and Ora-Sweet SF. Crush twelve 250 mg tablets in a mortar and reduce to a fine powder. Add small portions of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label "shake well" and "refrigerate". Stable for 90 days refrigerated (Johnson 2002).
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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