Mesalamineside effects

The following clinically significant adverse reactions are described elsewhere in the labeling:

Renal impairment

Mesalamine-induced acute intolerance syndrome

Hypersensitivity reactions

Hepatic failure

Severe cutaneous adverse reactions

Photosensitivity

Nephrolithiasis Most common adverse reactions are nausea and vomiting (1%). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8748 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials 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 practice. More than 2,100 patients were exposed to mesalamine in clinical trials of ulcerative colitis or another gastrointestinal condition. The most common adverse reactions (i.e., greater than or equal to 1%) were diarrhea (3%), headache (2%), nausea (2%), abdominal pain (2%), dyspepsia (2%), vomiting (2%), and rash (1%). The safety of mesalamine was evaluated in two randomized, double-blind, placebo-controlled, dose-response trials (UC-1 and UC-2) of 624 patients with mildly to moderately active ulcerative colitis for up to 8 weeks of treatment. The most common adverse reaction was nausea and vomiting: 1% in the mesalamine group (N = 451) and 0% in the placebo group (N = 173). Withdrawal from therapy due to adverse reactions was 7% in the mesalamine group and 4% in the placebo group. The following adverse reactions, presented by body system, were reported in less than 1% of patients in UC-1, UC-2, and clinical trials for another gastrointestinal condition. Blood and lymphatic system disorders: thrombocythemia, thrombocytopenia Cardiac Disorders: palpitations, pericarditis, vasodilation Gastrointestinal Disorders: abdominal distention, constipation, duodenal ulcer, dysphagia, eructation, esophageal ulcer, fecal incontinence, GI bleeding, mouth ulcer, pancreatitis, rectal bleeding, stool abnormalities (color or texture change) General disorders and administration site conditions: fever, malaise Infections and infestations: oral moniliasis, conjunctivitis Investigations: GGTP increase, increased alkaline phosphatase, LDH increase, SGOT increase, SGPT increase, lipase increase, amylase increase Metabolism and nutritional disorders: anorexia, edema, thirst Musculoskeletal and connective tissue disorders: arthralgia, leg cramps, myalgia Nervous System Disorders: dizziness, insomnia, somnolence, paresthesia Psychiatric disorders: depression, asthenia Renal and urinary disorders: albuminuria, hematuria, urinary frequency Reproductive system and breast disorders: amenorrhea, breast pain, hypomenorrhea, menorrhagia, metrorrhagia Respiratory, Thoracic and Mediastinal Disorders: pulmonary infiltrates, one week after completion of an 8-week ulcerative colitis study, a 72-year-old male, with no previous history of pulmonary problems, developed dyspnea. The patient was subsequently diagnosed with interstitial pulmonary fibrosis without eosinophilia by one physician and bronchiolitis obliterans with organizing pneumonitis by a second physician. Skin and Subcutaneous Tissue Disorders: acne, alopecia, dry skin, eczema, erythema nodosum, nail disorder, photosensitivity, pruritus, sweating, urticaria, ecchymosis, lichen planus

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of mesalamine. 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. Cardiac Disorders: chest pain, fatal myocarditis, pericarditis, T-wave abnormalities Hematologic Disorders: agranulocytosis, anemia, aplastic anemia, leukopenia, pancytopenia Hepatic Disorders: cirrhosis, jaundice, including cholestatic jaundice; hepatotoxicity, hepatitis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. One case of Kawasaki-like syndrome which included hepatic function changes was also reported. Immune System Disorders: anaphylactic reaction, angioedema, lupus-like syndrome, systemic lupus erythematosus Nervous System Disorders: intracranial hypertension Renal and Urinary Disorders: acute renal failure, chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, nephrotic syndrome

Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach Reproductive System and Breast Disorders: reversible oligospermia Respiratory, Thoracic and Mediastinal Disorders: hypersensitivity pneumonitis (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis), interstitial lung disease, pleurisy/pleuritis, pneumonitis Skin and Subcutaneous Tissue Disorders: AGEP, DRESS, SJS/TEN