Mesalamineside effects

The following clinically significant adverse reactions are described elsewhere in labeling: Renal Impairment Mesalamine-Induced Acute Intolerance Syndrome Hypersensitivity Reactions Hepatic Failure Severe Cutaneous Adverse Reactions Photosensitivity Nephrolithiasis Risks in Patients with Phenylketonuria Most common adverse reactions (≥3%) are: headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical studies 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. The data described below reflect exposure to APRISO in 557 patients, including 354 exposed for at least 6 months and 250 exposed for greater than one year. APRISO was studied in two placebo-controlled trials (n=367 treated with APRISO) and in one open-label, long-term study (n=190 additional patients). The population consisted of patients with ulcerative colitis; the mean age was 47 years, 54% were female, and 93% were white. Patients received doses of APRISO 1.5 g administered orally once per day for six months in the placebo-controlled trials and for up to 24 months in the open‑label study. In the two placebo-controlled trials, the most common reactions reported in at least 3% of APRISO-treated patients and at a greater rate than placebo are shown in Table 1 below.

Table 1: Common Adverse Reactions Reported in at least 3% of APRISO-treated patients and at a greater rate than with placebo in Clinical Trials of Adults with Ulcerative Colitis APRISO 1.5 g once daily N=367 Placebo N=185 Headache 11% 8% Diarrhea 8% 7% Upper Abdominal Pain 5% 3% Nausea 4% 3% Nasopharyngitis 4% 3% The following adverse reactions, presented by body system, were reported at a frequency less than 3% in patients treated with APRISO for up to 24 months in controlled and open-label trials.

Ear and Labyrinth Disorders: tinnitus, vertigo Dermatological Disorder: alopecia Gastrointestinal: lower abdominal pain, rectal hemorrhage Laboratory Abnormalities: increased triglycerides, decreased hematocrit and hemoglobin General Disorders and Administration Site Disorders: fatigue Hepatic: hepatitis cholestatic, transaminases increased Renal Disorders: creatinine clearance decreased, hematuria Musculoskeletal: pain, arthralgia Respiratory: dyspnea

6.2 Postmarketing

Experience The following adverse reactions have been identified during post approval use of APRISO or other mesalamine-containing products. Because many of these reactions are reported voluntarily from a population of unknown 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 Cardiovascular: pericarditis, pericardial effusion, myocarditis Gastrointestinal: pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, Kawasaki-like syndrome including changes in liver enzymes Hematologic: agranulocytosis, aplastic anemia Nervous System: intracranial hypertension Neurological/Psychiatric: peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis Renal and Urinary: nephrogenic diabetes insipidus, interstitial nephritis, renal failure, minimal change disease, nephrolithiasis Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Respiratory/Pulmonary: eosinophilic pneumonia, interstitial pneumonitis, pleurisy/pleuritis Skin: psoriasis, pyoderma gangrenosum, erythema nodosum, SJS/TEN, DRESS, and AGEP Renal/Urogenital: reversible oligospermia