pms-Ursodiol C

pms-Ursodiol C Adverse Reactions

ursodeoxycholic acid




Full Prescribing Info
Adverse Reactions
Adverse Drug Reaction Overview: Adverse events observed in clinical trials are tabulated and described as follows. In a 180 patient placebo-controlled trial in primary biliary cirrhosis, the common adverse events (i.e. ≥1 %) included leukopenia, skin rash, diarrhea, blood creatinine increased, blood glucose increased, and peptic ulcer. In a second trial with 60 patients, the frequency of treatment-emergent adverse event reporting was higher with the most common (defined as ≥5%) being asthenia, dyspepsia, edema peripheral, hypertension, nausea, GI disorder, chest pain, and pruritus. In this second trial there were 4 serious adverse events: 1 patient with diabetes mellitus, 1 patient with breast nodule and 2 patients with fibrocystic breast disease. None of these events were considered related to the medication. At the recommended dosage, ursodiol is well-tolerated and has no significant adverse events.
Clinical Trial Adverse Drug Reactions: Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
The adverse reactions in Table 3 as follows were observed in clinical trials in primary biliary cirrhosis with 180 patients (89 randomized to ursodiol treatment, 91 to placebo treatment). Adverse events are reported regardless of attribution to the test medication. Adverse reactions occurring at a rate of 1% or higher in the ursodiol group, and that are higher than placebo are included in Table 3. Diarrhea and thrombocytopenia at 12 months, nausea/vomiting, fever and other side effects are not included, because they occurred at the same rate or a lower rate than placebo. (See Table 3.)

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In a randomized, cross over study in sixty PBC patients, four patients experienced one serious adverse event each (diabetes mellitus, breast nodule, and fibrocystic breast disease (2 patients)). No deaths occurred in the study. Forty-three patients (43/71.7%) experienced at least one treatment-emergent adverse event (TEAEs) during the study. The most common (defined as ≥5%) TEAEs were asthenia, (11.7%), dyspepsia (10%), edema peripheral (8.3%), hypertension (8.3%), nausea (8.3%), GI disorders (5%), chest pain (5%), and pruritus (5%). These nine TEAEs included abdominal pain and asthenia (1 patient), nausea (3 patients), dyspepsia (2 patients), and anorexia and esophagitis (1 patient each). One patient on the BID regimen (total dose 1000 mg) withdrew due to nausea. All of these nine TEAEs except esophagitis were observed with the BID regimen at a total daily dose of 1000 mg or greater. (See Table 4.)

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Less Common Clinical Trial Adverse Drug Reactions (<1%): Analysis of the data in the trial with 180 patients (Table 3) revealed no reports of adverse events at rates <1% with the exception of those adverse events that occurred at the same or at a higher incidence in the treatment group than placebo. No data for TEAEs occurring at rates <1% in the trial of 60 patients (Table 4) are available due to the small sample size.
Abnormal Hematologic and Clinical Chemistry Findings: In the placebo-controlled trial with 180 patients, change from baseline in hematologic parameters and non-hepatic clinical chemistry were analyzed. Statistically significant differences from baseline are reported in Tables 5 and 6.
There was a significant decrease (p<0.01) in WBC and platelets in the UDCA-treated group from baseline and a significant (p<0.05) decrease in platelets in the placebo group. There was no significant change in hemoglobin. (See Table 5.)

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All the non-hepatic clinical chemistries at baseline were not significantly different (p>0.05) between the UDCA- and placebo-treated groups. In the UDCA group there was a significant (p>0.05) decrease from baseline in calcium, cholesterol and total thyroxine and a significant increase (p>0.05) in creatinine and triglycerides. In the placebo group there was a significant (p>0.05) decrease in cholesterol and significant increase (p>0.05) in calcium and creatinine. There was no significant change seen for sodium, potassium, phosphorus, HDL, and AMA. (See Table 6.)

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Post-Market Adverse Drug Reactions: 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.
Blood and lymphatic system disorders: anemia, eosinophilia, leukopenia, neutropenia, thrombocytopenia.
Cardiac disorders: palpitations.
Gastrointestinal disorders: abdominal discomfort, abdominal pain, cheilitis, 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: angioedema and laryngeal edema, drug hypersensitivity to include facial edema, urticaria.
Investigations: blood glucose increased, blood urine present, weight decreased, weight increased, ALT increased, AST increased, blood alkaline phosphatase increased, blood bilirubin increased, γ-GT increased, transaminases increased. Rare instances of severe liver injury (elevated values for ALT/AST, ALP, γ-GTP and total bilirubin) have been reported with ursodiol.
Musculoskeletal and connective tissue disorders: myalgia.
Nervous system disorders: dizziness, headache.
Respiratory, thoracic and mediastinal disorders: cough, interstitial lung disease.
Skin and subcutaneous tissue disorder: alopecia, dermatitis exfoliative, drug eruption, erythema, lichenoid keratosis, photosensitivity reaction, pruritus, rash.
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