Version December 2023
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 (Ref).
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 (Ref). Refer to institutional protocols for further information.
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 (Ref).
Primary sclerosing cholangitis (off-label use): Note: May be considered in patients who are not interested in clinical trial enrollment with persistently elevated alkaline phosphatase for at least 6 months prior to initiating therapy (Ref).
Oral: 13 to 23 mg/kg/day in 2 to 4 divided doses; continue as tolerated if there is a reduction or normalization in alkaline phosphatase and/or improvement in symptoms with 12 months of treatment (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (<1% excreted in urine (Ref)) (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (mainly distributed in bile and small intestine (Ref)): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (mainly distributed in bile and small intestine (Ref)): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Ursodeoxycholic acid (ursodiol): Pediatric drug information")
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 (Ref). Some patients may require higher doses (Ref); 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) (Ref).
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 (Ref).
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 (Ref). 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 (Ref). 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 (Ref).
Veno-occlusive disease (sinusoidal obstruction syndrome) following hematopoietic stem cell transplantation, prevention: Limited data available (Ref); efficacy results variable (Ref); 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 (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Ursodeoxycholic acid (UDCA) will precipitate from water at a pH of 8 to 8.1, and its glycine conjugated form will precipitate from water at a pH of 6.5 to 7.4 and 37ºC (98ºF), which may lead to crystalline formation within bile ducts (pH 6.5 to 8) or within the small intestine lumen (pH 6 to 8) (Ref). UDCA crystals are postulated to provide a base for enterolith/stone formation, and recurrent exposure allows additional precipitation and formation of the UDCA based enteroliths/stones (Ref). UDCA based enteroliths/stones can lead to obstruction, localized inflammation and infection and may recur with continued use of UDCA (Ref).
Mechanism: Unknown; likely related to the use of UDCA in the setting of conditions in which UDCA and its conjugated metabolites are exposed to an acidic environment, following liver first pass metabolism, for a prolonged period leading to precipitation of the conjugated metabolites or parent drug (Ref).
Onset: Delayed (ie, occurs after 30 days of drug therapy); case reports suggest may occur as early as 1 to 2 months after drug initiation or may take several months to years (Ref).
Risk factors:
• Recurrent biliary infection (eg, recurrent cholangitis) (Ref)
• History of gastrointestinal surgery with surgical anastomosis that allows for free communication between the gastrointestinal and biliary tracts (eg, choledochoduodenostomy, Roux-en-Y hepaticojejunostomy) (Ref)
• Impaired intestinal flow (bowel stasis) due to a blind loop or adhesions resulting as a complication of gastrointestinal surgery, especially in patients who undergo reoperation (Ref)
• Concomitant use of gastric acid suppression (eg, proton pump inhibitor) (Ref)
• Presence of intestinal stenosis (eg, proximal small intestine) associated with inflammatory bowel disease (Ref)
• Concomitant immunosuppression which may enhance bacterial overgrowth in the small intestine (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Constipation (10% to 26%), diarrhea (1% to 27%), dyspepsia (3% to 17%), nausea (5% to 17%)
Nervous system: Dizziness (17%), headache (25%)
Neuromuscular & skeletal: Back pain (12%)
Respiratory: Upper respiratory tract infection (12% to 16%)
1% to 10%:
Dermatologic: Alopecia (5%), skin rash (3%)
Endocrine & metabolic: Increased serum glucose (1%)
Gastrointestinal: Cholecystitis (5%), peptic ulcer (1%), vomiting (10%)
Genitourinary: Urinary tract infection (7%)
Hematologic & oncologic: Leukopenia (3%), thrombocytopenia (1%)
Hypersensitivity: Hypersensitivity reaction (5%)
Neuromuscular & skeletal: Arthritis (6%), musculoskeletal pain (6%)
Renal: Increased serum creatinine (1%)
Respiratory: Bronchitis (7%), cough (7%), flu-like symptoms (7%), pharyngitis (8%)
<1%:
Gastrointestinal: Abdominal pain, anorexia, esophagitis
Nervous System: Asthenia
Postmarketing:
Cardiovascular: Peripheral edema
Dermatologic: Pruritus
Gastrointestinal: Abdominal distress, bezoar formation
Hepatic: Increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin, jaundice
Hypersensitivity: Angioedema
Nervous system: Malaise
Neuromuscular and skeletal: Myalgia
Miscellaneous: Fever
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.
• Enteroliths (bezoars): The formation of enteroliths (bezoars) resulting in obstructive symptoms, requiring surgical intervention, have been reported, especially in patients predisposed to intestinal stenosis or stasis (eg, Crohn’s disease, surgical enteroanastomoses); hold therapy and evaluate patients presenting with obstructive GI symptoms.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
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
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Urso: 250 mg [DSC]
Urso DS: 500 mg [DSC]
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 (Ref). 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 (Ref).
Tablets: Urso Forte can be split into halves for appropriate dosage; do not chew. Urso and Urso Forte should be administered 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; Primary sclerosing cholangitis
Ursodiol may be confused with ulipristal
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.
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
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 liver chemistries (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); signs of obstructive GI symptoms.
Primary sclerosing cholangitis: Baseline liver chemistries (bilirubin, ALP, AST, platelets, and PT); repeat at 12 months (or every 6 months in high-risk patients) and as clinically indicated (EASL 2022).
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%)
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