URSO 250 / FORTE Film-coated tablet Ref.[11137] Active ingredients: Ursodeoxycholic acid

Patients with variceal bleeding, hepatic encephalopathy, ascites or in need of an urgent liver transplant, should receive appropriate specific treatment.

5.1 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.

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.

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.

7.1 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.

7.2 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.

7.3 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.

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.