Balsalazideside 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 Upper Gastrointestinal Tract Obstruction Photosensitivity Nephrolithiasis Most common adverse reactions (≥3%) are: headache, abdominal pain, diarrhea, nausea, vomiting, respiratory infection, and arthralgia. Adverse reactions in pediatric patients were similar. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 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.

Adult Ulcerative Colitis: During clinical development, 259 adult patients with active ulcerative colitis were exposed to 6.75 g/day balsalazide in 4 controlled trials. In the 4 controlled clinical trials patients receiving a balsalazide dose of 6.75 g/day most frequently reported the following adverse reactions: headache (8%), abdominal pain (6%), diarrhea (5%), nausea (5%), vomiting (4%), respiratory infection (4%), and arthralgia (4%). Withdrawal from therapy due to adverse reactions was comparable among patients on balsalazide and placebo. Adverse reactions reported by 1% or more of patients who participated in the 4 well-controlled, Phase 3 trials are presented by treatment group (Table 1). The number of placebo patients, however, is too small for valid comparisons. Some adverse reactions, such as abdominal pain, fatigue, and nausea were reported more frequently in women than in men. Abdominal pain, rectal bleeding, and anemia can be part of the clinical presentation of ulcerative colitis.

Table 1: Adverse Reactions Occurring in ≥1% of Adult Balsalazide Patients in Controlled Trials Adverse reactions occurring in at least 1% of balsalazide patients which were less frequent than placebo for the same adverse reaction were not included in the table. Adverse Reaction Balsalazide 6.75 g/day [N=259] Placebo [N=35] Abdominal pain 16 (6%) 1 (3%) Diarrhea 14 (5%) 1 (3%) Arthralgia 9 (4%) 0% Rhinitis 6 (2%) 0% Insomnia 6 (2%) 0% Fatigue 6 (2%) 0% Flatulence 5 (2%) 0% Fever 5 (2%) 0% Dyspepsia 5 (2%) 0% Pharyngitis 4 (2%) 0% Coughing 4 (2%) 0% Anorexia 4 (2%) 0% Urinary tract infection 3 (1%) 0% Myalgia 3 (1%) 0% Flu-like disorder 3 (1%) 0% Dry mouth 3 (1%) 0% Cramps 3 (1%) 0% Constipation 3 (1%) 0% Pediatric Ulcerative Colitis: In a clinical trial in 68 pediatric patients aged 5 to 17 years with mildly to moderately active ulcerative colitis who received 6.75 g/day or 2.25 g/day balsalazide for 8 weeks, the most frequently reported adverse reactions were headache (15%), abdominal pain upper (13%), abdominal pain (12%), vomiting (10%), diarrhea (9%), colitis ulcerative (6%), nasopharyngitis (6%), and pyrexia (6%). One patient who received balsalazide 6.75 g/day and 3 patients who received balsalazide 2.25 g/day discontinued treatment because of adverse reactions. In addition, 2 patients in each dose group discontinued because of a lack of efficacy. Adverse reactions reported by 3% or more of pediatric patients within either treatment group in the Phase 3 trial are presented in Table 2.

Table 2: Treatment-Emergent Adverse Reactions Reported by ≥3% of Patients in Either Treatment Group in a Controlled Study of 68 Pediatric Patients Balsalazide Adverse Reaction 6.75 g/day [N = 33] 2.25 g/day [N = 35] Total [N = 68] Headache 5 (15%) 5 (14%) 10 (15%) Abdominal pain upper 3 (9%) 6 (17%) 9 (13%) Abdominal pain 4 (12%) 4 (11%) 8 (12%) Vomiting 1 (3%) 6 (17%) 7 (10%) Diarrhea 2 (6%) 4 (11%) 6 (9%) Colitis ulcerative 2 (6%) 2 (6%) 4 (6%) Nasopharyngitis 3 (9%) 1 (3%) 4 (6%) Pyrexia 0 (0%) 4 (11%) 4 (6%) Hematochezia 0 (0%) 3 (9%) 3 (4%) Nausea 0 (0%) 3 (9%) 3 (4%) Influenza 1 (3%) 2 (6%) 3 (4%) Fatigue 2 (6%) 1 (3%) 3 (4%) Stomatitis 0 (0%) 2 (6%) 2 (3%) Cough 0 (0%) 2 (6%) 2 (3%) Pharyngolaryngeal pain 2 (6%) 0 (0%) 2 (3%) Dysmenorrhea 2 (6%) 0 (0%) 2 (3%)

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of balsalazide, or other products which contain or are metabolized to 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.

Cardiovascular and Vascular: Myocarditis, pericarditis, vasculitis Respiratory: pleural effusion, pneumonia (with and without eosinophilia), alveolitis, pleurisy/pleuritis Renal: renal failure, interstitial nephritis, nephrolithiasis Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach Gastrointestinal: pancreatitis Dermatologic: pruritus, alopecia Hepatic: hepatotoxicity, elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, hepatocellular damage including liver necrosis and liver failure, Kawasaki-like syndrome including hepatic dysfunction Skin: SJS/TEN, DRESS, and AGEP