Urso 250 and Urso Forte - Product Information
|Manufacture:||Forest Laboratories, Inc.|
|Condition:||Biliary Cirrhosis, Gallbladder Disease|
|Class:||Gallstone solubilizing agents|
|Ingredients:||ursodiol, microcrystalline cellulose, povidone, sodium starch glycolate, magnesium stearate, ethylcellulose, dibutyl sebacate, carnauba wax, hydroxypropyl methylcellulose, PEG 3350, PEG 8000, cetyl alcohol, sodium lauryl sulfate, hydrogen peroxide|
Indications and Usage
URSO 250 and URSO Forte (ursodiol) tablets are indicated for the treatment of patients with primary biliary cirrhosis (PBC).
Dosage and Administration
General Dosing Information
The recommended adult dosage for URSO 250 and URSO Forte in the treatment of PBC is 13-15 mg/kg/day administered in two to four divided doses with food. Dosing regimen should be adjusted according to each patient’s need at the discretion of the physician.
Liver Function Tests
Liver function tests (γ-GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored every month for three months after start of therapy, and every six months thereafter [see Warnings and Precautions ].
Scoring the URSO Forte Tablet
The URSO Forte scored tablet can be broken in halves to provide recommended dosage.
To break URSO Forte scored tablet easily, place the tablet on a flat surface with the scored section on top. Hold the tablet with your thumbs placed close to the scored part of the tablet (groove). Then apply gentle pressure and snap the tablet segments apart (segments breaking incorrectly should not be used). The segments should be washed down unchewed, with water, keeping the segments in the mouth can reveal a bitter taste. Due to the bitter taste, segments should be stored separately from whole tablets. [see How Supplied/Storage and Handling ].
Dosage Forms and Strengths
- URSO 250: 250 mg tablet
- URSO Forte: 500 mg scored tablet
Patients with complete biliary obstruction and known hypersensitivity or intolerance to ursodiol or any of the components of the formulation.
Warnings and Precautions
Patients with variceal bleeding, hepatic encephalopathy, ascites or in need of an urgent liver transplant, should receive appropriate specific treatment.
Abnormal Liver Function Tests
Liver function tests (γ-GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored every month for three months after start of therapy, and every six months thereafter. This monitoring will allow the early detection of a possible deterioration of the hepatic function. Treatment discontinuation should be considered if the above parameters increase to a level considered clinically significant in patients with stable historical liver function test levels.
Caution has to be exercised to maintain the bile flow of the patients taking ursodiol.
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The following table summarizes the adverse reactions observed in the two placebo-controlled clinical trials.
|ADVERSE REACTIONS||VISIT AT 12 MONTHS||VISIT AT 24 MONTHS|
|Elevated creatinine||---||---||1 (1.32)||---|
|Elevated blood glucose||1 (1.18)||---||1 (1.32)||---|
|Peptic ulcer||---||---||1 (1.32)||---|
|Skin rash||---||---||2 (2.63)||---|
|Note: Those adverse reactions occurring at the same or higher incidence in the placebo as in the UDCA group have been deleted from this table (this includes diarrhea and thrombocytopenia at 12 months, nausea/vomiting, fever and other toxicity).|
UDCA = Ursodeoxycholic acid = Ursodiol
In a randomized, cross-over study in sixty PBC patients, seven patients (11.6%) reported nine adverse reactions: abdominal pain and asthenia (1 patient), nausea (3 patients), dyspepsia (2 patients) and anorexia and esophagitis (1 patient each). One patient on the twice a day regimen (total dose 1000 mg) withdrew due to nausea. All of these nine adverse reactions except esophagitis were observed with the twice a day regimen at a total daily dose of 1000 mg or greater. However, an adverse reaction may occur at any dose.
The following adverse reactions, presented by system organ class in alphabetical order, have been identified during postapproval 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: abdominal discomfort, abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting.
- General disorders and administration site conditions: malaise, peripheral edema, pyrexia.
- Hepatobiliary disorders: jaundice (or aggravation of pre-existing jaundice).
- Immune System Disorders: Drug hypersensitivity to include facial edema, urticaria, angioedema and laryngeal edema.
- Abnormal Laboratory Tests: ALT increased, AST increased, blood alkaline phosphatase increased, blood bilirubin increased, γ-GT increased, hepatic enzyme increased, liver function test abnormal, transaminases increased.
- Musculoskeletal and connective tissue disorders: myalgia.
- Nervous system disorders: dizziness, headache.
- Respiratory, thoracic and mediastinal disorders: cough.
- Skin and subcutaneous tissue disorder: alopecia, pruritus, rash.
Bile Acid Sequestering Agents
Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of URSO 250 and URSO Forte by reducing its absorption.
Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with URSO 250 and URSO Forte in the same manner as the bile acid sequestering agents.
Drugs Affecting Lipid Metabolism
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 URSO 250 and URSO Forte.
Use in Specific Populations
Pregnancy Category B. Reproduction studies have been performed in pregnant rats at oral doses up to 22 times the recommended maximum human dose (based on body surface area) and in pregnant rabbits at oral doses up to 7 times the recommended maximum human dose (based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to ursodiol.
There are no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
It is not known whether ursodiol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when URSO 250 and URSO Forte are administered to a nursing mother.
The safety and effectiveness of URSO 250 and URSO Forte in pediatric patients have not been established.
There have been no reports of accidental or intentional overdosage with ursodiol. Single oral doses of ursodiol at 10 g/kg in mice and dogs, and 5 g/kg in rats were not lethal. A single oral dose of ursodiol at 1.5 g/kg was lethal in hamsters. Symptoms of acute toxicity were salivation and vomiting in dogs, and ataxia, dyspnea, ptosis, agonal convulsions and coma in hamsters.
How Supplied/Storage and Handling
Each URSO 250 elliptical, biconvex, film-coated tablet, white, engraved with "URS785", contains 250 mg of ursodiol. Available in bottles of 100 tablets (NDC 58914-785-10).
Each URSO Forte elliptical, biconvex, scored, film-coated tablet, white, engraved with "URS790", contains 500 mg of ursodiol. Available in bottles of 100 tablets (NDC 58914-790-10).
Store at 20°C to 25°C (68°F to 77°F). Dispense in a tight container.
Half-tablets (scored URSO Forte 500 mg tablets broken in half) maintain acceptable quality for up to 28 days when stored in the current packaging (bottles) at 20°C to 25°C (68°F to 77°F). Due to the bitter taste, the halved segments should be stored separately from the whole tablets [see Dosage and Administration ].
Patient Counseling Information
Patients with the following conditions should be instructed to receive appropriate management measures: variceal bleeding, hepatic encephalopathy, ascites, in need of an urgent liver transplant or hepatic function deterioration. [see Warnings and Precautions ].
Caution has to be exercised to maintain the bile flow of the patients taking ursodiol.
Patients should be informed that adsorption of URSO 250 and URSO Forte may be reduced if they are taking bile acid sequestering agents, such as cholestyramine and colestipol, or aluminum-based antacids, or drugs known to alter the metabolism of cholesterol. [see Drug Interactions ].
Manufactured in Canada for
Aptalis Pharma US, Inc.
100 Somerset Corporate Boulevard
Bridgewater, NJ, 08807 USA