Mesalamineside effects

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

Renal impairment, including renal failure

Mesalamine-induced acute intolerance syndrome

Hypersensitivity reactions

Hepatic failure

Severe cutaneous adverse reactions

Upper gastrointestinal tract obstruction

Photosensitivity

Nephrolithiasis Most common adverse reactions in:

adults (≥2%) are headache, flatulence, liver function test abnormal, abdominal pain, and diarrhea.

pediatric patients (≥5%) are abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection. To report SUSPECTED ADVERSE REACTIONS, contact Annora Pharma Private Limited at 1-866-495-1995 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. Adults Induction The most common adverse reactions occurring in at least 1% of mesalamine-or placebo-treated adult patients with mildly to moderately active ulcerative colitis in two eight-week, randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) are listed in Table 2.

Table 2: Adverse Reactions* in Two Eight-Week, Placebo-Controlled Trials of Induction Therapy (Study 1 and Study 2) in Adults with Mildly to Moderately Active Ulcerative Colitis Adverse Reaction Mesalamine 2.4 g once daily (n=177) Mesalamine 4.8 g once daily (n=179) Placebo (n=179) Headache 6% 3% <1% Flatulence 4% 3% 3% Liver Function Test Abnormal <1% 2% 1% Alopecia 0 1% 0 Pruritus <1% 1% 1% *Reported in at least 1% of patients in at least one mesalamine group and greater than placebo Pancreatitis occurred in less than 1% of patients during induction in clinical trials and resulted in discontinuation of therapy with mesalamine in patients experiencing this event. Maintenance of Remission A mesalamine dosage of 2.4 g/day, administered as either 1.2 g twice daily or 2.4 g once daily, was evaluated for safety in three maintenance trials in patients with mildly to moderately active ulcerative colitis: a 6-month double-blind, active-controlled study (Study 3) and two 12- to 14-month open-label studies. The most common adverse reactions with mesalamine in these maintenance trials are listed in Table 3.

Table 3: Adverse Reactions* in Three Trials of Maintenance of Remission in Adults with Ulcerative Colitis Mesalamine 2.4 g/day † (n=1082) Adverse Reaction % Headache 3% Liver function test abnormal 2% Abdominal pain 2% Diarrhea 2% Abdominal distension 1% Abdominal pain upper 1% Dyspepsia 1% Back pain 1% Rash 1% Arthralgia 1% Fatigue 1% Hypertension 1% *Reported in at least 1% of patients †Administered either as 1.2 g twice daily or 2.4 g once daily The following adverse reactions, presented by body system, were reported in less than 1% of mesalamine -treated patients with ulcerative colitis in either induction or maintenance trials: Cardiac Disorder: tachycardia Ear and Labyrinth Disorders: ear pain Gastrointestinal Disorders: abdominal distention, colitis, diarrhea, flatulence, nausea, pancreatitis, rectal polyp, vomiting General Disorders and Administrative Site Disorders: asthenia, face edema, fatigue, pyrexia Investigations: decreased platelet count Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain Nervous System Disorders: dizziness, somnolence, tremor Respiratory, Thoracic and Mediastinal Disorders: pharyngolaryngeal pain Skin and Subcutaneous Tissue Disorders: acne, prurigo, rash, alopecia, pruritus, urticaria Vascular Disorders: hypertension, hypotension Pediatrics Mesalamine was evaluated in 105 pediatric patients 5 through 17 years of age with mildly to moderately active ulcerative colitis. The adverse reaction profile was similar to that of adults. The most common adverse reactions reported in at least 5% of pediatric patients treated with mesalamine were: abdominal pain, upper respiratory tract infection, vomiting, anemia, headache, and viral infection.

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of mesalamine or other mesalamine-containing products. 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. Body as a Whole: lupus-like syndrome, drug fever Cardiac Disorders: pericarditis, pericardial effusion, myocarditis Gastrointestinal: cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, hepatotoxicity, Kawasaki-like syndrome including changes in liver enzymes Hematologic: agranulocytosis, aplastic anemia Immune System Disorders: anaphylactic reaction, angioedema Musculoskeletal and Connective Tissue Disorders: myalgia, lupus-like syndrome Neurological/Psychiatric: peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis, intracranial hypertension Renal Disorders: renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis

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