1 INDICATIONS AND USAGE Ursodiol tablets, 250 mg and 500 mg are indicated for the treatment of patients with primary biliary cholangitis (PBC).

Ursodiol tablets, 250 mg and 500 mg are bile acids indicated for the treatment of patients with primary biliary cholangitis.

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6 ADVERSE REACTIONS Most common adverse reactions reported with the use of ursodiol during worldwide postmarketing and clinical experience (≥1%) are, in alphabetical order: abdominal discomfort, abdominal pain, alopecia, diarrhea, nausea, pruritus, and rash.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc.

at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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 (1.32) -- Elevated creatinine -- -- 1 (1.32) -- Elevated blood glucose 1 (1.18) -- 1 (1.32) -- Leukopenia -- -- 2 (2.63) -- Peptic ulcer -- -- 1 (1.32) -- Skin rash -- -- 2 (2.63) -- Thrombocytopenia -- -- 1 (1.32) -- 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.

6.2 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 preexisting 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.