Ursodiol

Description

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

What Is Ursodiol Used For?

INDICATIONS AND USAGE 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

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.).

Side Effects (Adverse Reactions)

ADVERSE REACTIONS 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) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993; email [email protected]; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

Contraindications

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.

Pregnancy and Breastfeeding

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.

Overdosage

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.

How Supplied

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 42291-923-01) are supplied with child-resistant closures. Store at 20-25°C (68-77°F). [See USP controlled room temperature.] Dispense in a tight container (USP). Keep out of reach of children. Rx only Manufactured for: AvKARE Pulaski, TN 38478 Mfg. Rev. 11/20 AV 07/23 (P)