Ursodiol
Capsule · Oral
Uses
Ursodiol is indicated 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 due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Safety of use of ursodiol beyond 24 months is not established. Ursodiol is indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss.
Dosage and administration
Gallstone Dissolution The recommended dose for ursodiol treatment of radiolucent gallbladder stones is 8 - 10 mg/kg/day given in 2 or 3 divided doses. Ultrasound images of the gallbladder should be obtained at 6-month intervals for the first year of ursodiol therapy to monitor gallstone response. If gallstones appear to have dissolved, ursodiol therapy should be continued and dissolution confirmed on a repeat ultrasound examination within 1 to 3 months. Most patients who eventually achieve complete stone dissolution will show partial or complete dissolution at the first on-treatment reevaluation. If partial stone dissolution is not seen by 12 months of ursodiol therapy, the likelihood of success is greatly reduced. Gallstone Prevention The recommended dosage of ursodiol for gallstone prevention in patients undergoing rapid weight loss is 600 mg/day (300 mg b.i.d.).
Contraindications
Ursodiol will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones. Hence, patients with such stones are not candidates for ursodiol therapy. Patients with compelling reasons for cholecystectomy including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula are not candidates for ursodiol therapy. Allergy to bile acids.
Warnings
Enteroliths in Patients with Risk for Intestinal Stenosis or Stasis There have been rare postmarketing reports of ursodiol-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 (e.g., surgical enteroanastomoses, Crohn's disease). If a patient presents with obstructive gastrointestinal symptoms, hold Actigall until a clinical evaluation has been conducted.
Precautions
Liver Tests Ursodiol therapy has not been associated with liver damage. Lithocholic acid, a naturally occurring bile acid, is known to be a liver-toxic metabolite. This bile acid is formed in the gut from ursodiol less efficiently and in smaller amounts than that seen from chenodiol. Lithocholic acid is detoxified in the liver by sulfation and, although man appears to be an efficient sulfater, it is possible that some patients may have a congenital or acquired deficiency in sulfation, thereby predisposing them to lithocholate-induced liver damage. Abnormalities in liver enzymes have not been associated with ursodiol therapy and, in fact, ursodiol has been shown to decrease liver enzyme levels in liver disease. However, patients given ursodiol should have SGOT (AST) and SGPT (ALT) measured at the initiation of therapy and thereafter as indicated by the particular clinical circumstances. Drug Interactions Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of ursodiol by reducing its absorption. Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with ursodiol in the same manner as the bile acid sequestering agents. Estrogens, oral contraceptives, and clofibrate (and perhaps other lipid-lowering drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of ursodiol. Carcinogenesis, Mutagenesis, Impairment of Fertility Ursodeoxycholic acid was tested in 2-year oral carcinogenicity studies in CD-1 mice and Sprague-Dawley rats at daily doses of 50, 250, and 1000 mg/kg/day. It was not tumorigenic in mice. In the rat study, it produced statistically significant dose-related increased incidences of pheochromocytomas of adrenal medulla in males (p = 0.014, Peto trend test) and females (p = 0.004, Peto trend test). A 78-week rat study employing intrarectal instillation of lithocholic acid and tauro-deoxycholic acid, metabolites of ursodiol and chenodiol, has been conducted. These bile acids alone did not produce any tumors. A tumor-promoting effect of both metabolites was observed when they were co-administered with a carcinogenic agent. Results of epidemiologic studies suggest that bile acids might be involved in the pathogenesis of human colon cancer in patients who had undergone a cholecystectomy, but direct evidence is lacking. Ursodiol is not mutagenic in the Ames test. Dietary administration of lithocholic acid to chickens is reported to cause hepatic adenomatous hyperplasia. Pregnancy Reproduction studies have been performed in rats and rabbits with ursodiol doses up to 200-fold the therapeutic dose and have revealed no evidence of impaired fertility or harm to the fetus at doses of 20- to 100-fold the human dose in rats and at 5-fold the human dose (highest dose tested) in rabbits. Studies employing 100- to 200-fold the human dose in rats have shown some reduction in fertility rate and litter size. There have been no adequate and well-controlled studies of the use of ursodiol in pregnant women, but inadvertent exposure of 4 women to therapeutic doses of the drug in the first trimester of pregnancy during the ursodiol trials led to no evidence of effects on the fetus or newborn baby. Although it seems unlikely, the possibility that ursodiol can cause fetal harm cannot be ruled out; hence, the drug is not recommended for use during pregnancy. Nursing Mothers It is not known whether ursodiol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ursodiol is administered to a nursing mother. Pediatric Use The safety and effectiveness of ursodiol in pediatric patients have not been established. Geriatric Use In worldwide clinical studies of ursodiol, approximately 14% of subjects were over 65 years of age (approximately 3% were over 75 years old). In a subgroup analysis of existing clinical trials, patients greater than 56 years of age did not exhibit statistically significantly different complete dissolution rates from the younger population. No age-related differences in safety and effectiveness were found. Other reported clinical experience has not identified differences in response in elderly and younger patients. However, small differences in efficacy and greater sensitivity of some elderly individuals taking ursodiol cannot be ruled out. Therefore, it is recommended that dosing proceed with caution in this population.
Side effects
The nature and frequency of adverse experiences were similar across all groups. The following tables provide comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level: GALLSTONE DISSOLUTION Ursodiol Placebo 8 - 10 mg/kg/day (N = 155) (N = 159) N (%) N (%) Body as a Whole Allergy 8 (5.2) 7 (4.4) Chest Pain 5 (3.2) 10 (6.3) Fatigue 7 (4.5) 8 (5.0) Infection Viral 30 (19.4) 41 (25.8) Digestive System Abdominal Pain 67 (43.2) 70 (44.0) Cholecystitis 8 (5.2) 7 (4.4) Constipation 15 (9.7) 14 (8.8) Diarrhea 42 (27.1) 34 (21.4) Dyspepsia 26 (16.8) 18 (11.3) Flatulence 12 (7.7) 12 (7.5) Gastrointestinal Disorder 6 (3.9) 8 (5.0) Nausea 22 (14.2) 27 (17.0) Vomiting 15 (9.7) 11 (6.9) Musculoskeletal System Arthralgia 12 (7.7) 24 (15.1) Arthritis 9 (5.8) 4 (2.5) Back Pain 11 (7.1) 18 (11.3) Myalgia 9 (5.8) 9 (5.7) Nervous System Headache 28 (18.1) 34 (21.4) Insomnia 3 (1.9) 8 (5.0) Respiratory System Bronchitis 10 (6.5) 6 (3.8) Coughing 11 (7.1) 7 (4.4) Pharyngitis 13 (8.4) 5 (3.1) Rhinitis 8 (5.2) 11 (6.9) Sinusitis 17 (11.0) 18 (11.3) Upper Respiratory Tract Infection 24 (15.5) 21 (13.2) Urogenital System Urinary Tract Infection 10 (6.5) 7 (4.4) GALLSTONE PREVENTION Ursodiol Placebo 600 mg (N = 322) (N = 325) N (%) N (%) Body as a Whole Fatigue 25 (7.8) 33 (10.2) Infection Viral 29 (9.0) 29 (8.9) Influenza-like Symptoms 21 (6.5) 19 (5.8) Digestive System Abdominal Pain 20 (6.2) 39 (12.0) Constipation 85 (26.4) 72 (22.2) Diarrhea 81 (25.2) 68 (20.9) Flatulence 15 (4.7) 24 (7.4) Nausea 56 (17.4) 43 (13.2) Vomiting 44 (13.7) 44 (13.5) Musculoskeletal System Back Pain 38 (11.8) 21 (6.5) Musculoskeletal Pain 19 (5.9) 15 (4.6) Nervous System Dizziness 53 (16.5) 42 (12.9) Headache 80 (24.8) 78 (24.0) Respiratory System Pharyngitis 10 (3.1) 19 (5.8) Sinusitis 17 (5.3) 18 (5.5) Upper Respiratory Tract Infection 40 (12.4) 35 (10.8) Skin and Appendages Alopecia 17 (5.3) 8 (2.5) Urogenital System Dysmenorrhea 18 (5.6) 19 (5.8) Postmarketing Experience The following adverse reactions, presented by system organ class in alphabetical order, have been identified during post-approval use of ursodiol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders : enteroliths (bezoars)
Drug interactions
Drug Interactions Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of ursodiol by reducing its absorption. Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with ursodiol in the same manner as the bile acid sequestering agents. Estrogens, oral contraceptives, and clofibrate (and perhaps other lipid-lowering drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of ursodiol.
Pregnancy
Pregnancy Reproduction studies have been performed in rats and rabbits with ursodiol doses up to 200-fold the therapeutic dose and have revealed no evidence of impaired fertility or harm to the fetus at doses of 20- to 100-fold the human dose in rats and at 5-fold the human dose (highest dose tested) in rabbits. Studies employing 100- to 200-fold the human dose in rats have shown some reduction in fertility rate and litter size. There have been no adequate and well-controlled studies of the use of ursodiol in pregnant women, but inadvertent exposure of 4 women to therapeutic doses of the drug in the first trimester of pregnancy during the ursodiol trials led to no evidence of effects on the fetus or newborn baby. Although it seems unlikely, the possibility that ursodiol can cause fetal harm cannot be ruled out; hence, the drug is not recommended for use during pregnancy.
Pediatric use
Pediatric Use The safety and effectiveness of ursodiol in pediatric patients have not been established.
Geriatric use
Geriatric Use In worldwide clinical studies of ursodiol, approximately 14% of subjects were over 65 years of age (approximately 3% were over 75 years old). In a subgroup analysis of existing clinical trials, patients greater than 56 years of age did not exhibit statistically significantly different complete dissolution rates from the younger population. No age-related differences in safety and effectiveness were found. Other reported clinical experience has not identified differences in response in elderly and younger patients. However, small differences in efficacy and greater sensitivity of some elderly individuals taking ursodiol cannot be ruled out. Therefore, it is recommended that dosing proceed with caution in this population.
Overdosage
Neither accidental nor intentional overdosing with ursodiol has been reported. Doses of ursodiol in the range of 16 - 20 mg/kg/day have been tolerated for 6 to 37 months without symptoms by 7 patients. The LD 50 for ursodiol in rats is over 5000 mg/kg given over 7 to 10 days and over 7500 mg/kg for mice. The most likely manifestation of severe overdose with ursodiol would probably be diarrhea, which should be treated symptomatically.
Description
Ursodiol is a bile acid available as 300 mg capsules suitable for oral administration. Ursodiol USP (ursodeoxycholic acid) is a naturally occurring bile acid found in small quantities in normal human bile and in the biles of certain other mammals. It is a bitter-tasting, white powder freely soluble in ethanol, methanol, and glacial acetic acid; sparingly soluble in chloroform; slightly soluble in ether; and insoluble in water. The chemical name for ursodiol is 3α,7β-Dihydroxy-5β-cholan-24-oic acid (C 24 H 40 O 4 ). Ursodiol, USP has a molecular weight of 392.57. Its structure is shown below: Inactive Ingredients: Colloidal silicon dioxide, magnesium stearate, and starch (corn). Gelatin capsules contain gelatin and titanium dioxide. The capsules are printed with edible ink containing black iron oxide. structural formula
How supplied
Ursodiol Capsules USP, 300 mg are opaque white capsules imprinted WATSON on one half and 3159 on the other half of the capsule in black. Bottles of 100 (NDC 0591-3159-01) are supplied with child-resistant closures. Store at 20°C to 25°C (68°F to 77°F). [See USP controlled room temperature.] Dispense in a tight container (USP). Keep out of reach of children. Rx only Manufactured for: Teva Pharmaceuticals Parsippany, NJ 07054 © 2023 Teva Pharmaceuticals, Inc. URS-001 Rev. 7/2023
Label text from the FDA structured product label by Actavis Pharma, Inc. (revised Jul 31, 2023). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
Ursodiol NDC products (44)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 60687-527 | Ursodiol 250 mg/1 Tablet | American Health Packaging | ANDA |
| 60687-100 | Ursodiol 300 mg/1 Capsule | American Health Packaging | ANDA |
| 69238-1540 | Ursodiol 300 mg/1 Capsule | Amneal Pharmaceuticals NY LLC | ANDA |
| 59651-421 | Ursodiol 300 mg/1 Capsule | Aurobindo Pharma Limited | ANDA |
| 42291-931 | Ursodiol 500 mg/1 Tablet, Film Coated | AvKARE | ANDA |
| 50268-864 | Ursodiol 300 mg/1 Capsule | AvPAK | ANDA |
| 50268-797 | Ursodiol 300 mg/1 Capsule | AvPAK | ANDA |
| 68001-378 | Ursodiol 500 mg/1 Tablet | BluePoint Laboratories | ANDA |
| 68001-377 | Ursodiol 250 mg/1 Tablet | BluePoint Laboratories | ANDA |
| 72162-1500 | Ursodiol 250 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 72162-1501 | Ursodiol 500 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 72162-2168 | Ursodiol 300 mg/1 Capsule | Bryant Ranch Prepack | ANDA |
| 72162-2619 | Ursodiol 300 mg/1 Capsule | Bryant Ranch Prepack | ANDA |
| 63629-2287 | Ursodiol 500 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 63629-2286 | Ursodiol 250 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 55154-2633 | Ursodiol 250 mg/1 Tablet, Film Coated | Cardinal Health 107, LLC | ANDA |
| 62135-430 | Ursodiol 300 mg/1 Capsule | Chartwell RX, LLC | ANDA |
| 42806-503 | Ursodiol 300 mg/1 Capsule | Epic Pharma, LLC | ANDA |
| 68462-474 | Ursodiol 500 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-473 | Ursodiol 250 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 51407-754 | Ursodiol 300 mg/1 Capsule | Golden State Medical Supply, Inc. | ANDA |
| 10702-237 | Ursadiol 300 mg/1 Capsule | KVK-Tech, Inc. | ANDA |
| 0527-1326 | Ursodiol 300 mg/1 Capsule | Lannett Company, Inc. | ANDA |
| 42385-946 | Ursodiol 300 mg/1 Capsule | Laurus Labs Limited | ANDA |
| 0904-6221 | Ursodiol 300 mg/1 Capsule | Major Pharmaceuticals | ANDA |
| 0904-6890 | Ursodiol 250 mg/1 Tablet, Film Coated | Major Pharmaceuticals | ANDA |
| 72603-613 | Ursodiol 300 mg/1 Capsule | NorthStar Rx LLC | ANDA |
| 49884-413 | Ursodiol 500 mg/1 Tablet, Film Coated | Par Health USA, LLC | ANDA |
| 49884-412 | Ursodiol 250 mg/1 Tablet, Film Coated | Par Health USA, LLC | ANDA |
| 43063-871 | Ursadiol 300 mg/1 Capsule | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 24658-999 | Ursodiol 300 mg/1 Capsule | PuraCap Laboratories, LLC | ANDA |
| 24658-780 | Ursodiol 300 mg/1 Capsule | PuraCap Laboratories, LLC | ANDA |
| 64380-918 | Ursodiol 250 mg/1 Tablet | Strides Pharma Science Limited | ANDA |
| 64380-919 | Ursodiol 500 mg/1 Tablet | Strides Pharma Science Limited | ANDA |
| 64380-844 | Ursodiol 300 mg/1 Capsule | Strides Pharma Science Limited | ANDA |
| 72664-217 | Ursodiol 300 mg/1 Capsule | VGYAAN Pharmaceuticals LLC | ANDA |
| 70771-1408 | Ursodiol 500 mg/1 Tablet | Zydus Lifesciences Limited | ANDA |
| 70771-1524 | Ursodiol 300 mg/1 Capsule | Zydus Lifesciences Limited | ANDA |
| 70771-1407 | Ursodiol 250 mg/1 Tablet | Zydus Lifesciences Limited | ANDA |
| 70710-1483 | Ursodiol 300 mg/1 Capsule | Zydus Pharmaceuticals (USA) Inc. | ANDA |
| 70710-1128 | Ursodiol 500 mg/1 Tablet | Zydus Pharmaceuticals (USA) Inc. | ANDA |
| 70710-1127 | Ursodiol 250 mg/1 Tablet | Zydus Pharmaceuticals (USA) Inc. | ANDA |
| 0591-3159 | Ursodiol 300 mg/1 Capsule | Actavis Pharma, Inc. | NDA AUTHORIZED GENERIC |
| 42291-923 | Ursodiol 300 mg/1 Capsule | AvKARE | NDA AUTHORIZED GENERIC |
Frequently asked questions
What is Ursodiol used for?
Ursodiol is indicated 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 due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Safety of use of ursodiol beyond 24 months is not…
What are the side effects of Ursodiol?
The nature and frequency of adverse experiences were similar across all groups. The following tables provide comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level: GALLSTONE DISSOLUTION Ursodiol Placebo 8 - 10 mg/kg/day (N = 155) (N = 159) N (%) N (%) Body as a Whole Allergy 8 (5.2) 7 (4.4) Chest Pain 5 (3.2) 10 (6.3) Fatigue 7 (4.5) 8 (5.0) Infection… See the full label for the complete list.
Who makes Ursodiol?
Ursodiol is listed by 25 labelers in the FDA NDC directory, including American Health Packaging, Amneal Pharmaceuticals NY LLC, Aurobindo Pharma Limited, AvKARE.