Urso Forte Drug Information

250 and URSO Forte (ursodiol) tablets are indicated for the treatment of patients with primary biliary cholangitis (PBC). URSO 250 and URSO Forte (ursodiol) tablets are bile acids indicated for the treatment of patients with primary biliary cholangitis.

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.

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..

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 two placebo-controlled clinical trials. ADVERSE REACTIONS VISIT AT 12 MONTHS VISIT AT 24 MONTHS UDCA n (%) Placebo n (%) UDCA n (%) Placebo n (%) Diarrhea --- --- 1 --- Elevated creatinine --- --- 1 --- Elevated blood glucose 1 --- 1 --- Leukopenia --- --- 2 --- Peptic ulcer --- --- 1 --- Skin rash --- --- 2 --- Thrombocytopenia --- --- 1 --- 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 1,000 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 1,000 mg or greater. However, an adverse reaction may occur at any dose.

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 : abdominal discomfort, abdominal pain, enteroliths (bezoars), 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 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.

Pregnancy Risk Summary Available published data on the use of ursodiol in pregnant women derived from randomized controlled trials, observational studies, and case series collected over several decades have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Most of the reported exposures to ursodiol occurred in the second and third trimester of pregnancy. In animal reproduction studies, ursodiol had no adverse effects on embryo-fetal development when administered at doses greater than human therapeutic doses (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data No adverse effects on embryo-fetal development were observed with oral administration of ursodiol to pregnant rats and rabbits during organogenesis at doses up to 22 and 7 times, respectively, the maximum recommended human dose (based on body surface area).

Pediatric Use The safety and effectiveness of URSO 250 and URSO Forte in pediatric patients have not been established.

Patients with complete biliary obstruction and known hypersensitivity or intolerance to ursodiol or any of the components of the formulation. Patients with complete biliary obstruction and known hypersensitivity or intolerance to ursodiol or any of the components of the formulation.

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.