adverse reactions
To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 1-888-380-3276 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ADVERSE REACTIONS: Olsalazine has been evaluated in ulcerative colitis patients in remission, as well as those with acute disease. Both sulfasalazine-tolerant and intolerant patients have been studied in controlled clinical trials. Overall, 10.4% of patients discontinued olsalazine because of an adverse experience compared with 6.7% of placebo patients. The most commonly reported adverse reactions leading to treatment withdrawal were diarrhea or loose stools (olsalazine 5.9%; placebo 4.8%), abdominal pain, and rash or itching (slightly more than 1% of patients receiving olsalazine). Other adverse reactions to olsalazine leading to withdrawal occurred in fewer than 1% of patients ( Table 1 ). Table 1 Adverse Reactions Resulting In Withdrawal From Controlled Studies Total Olsalazine (N = 441) Placebo (N = 208) Diarrhea/Loose Stools 26 (5.9%) 10 (4.8%) Nausea 3 2 Abdominal Pain 5 (1.1%) 0 Rash/Itching 5 (1.1%) 0 Headache 3 0 Heartburn 2 0 Rectal Bleeding 1 0 Insomina 1 0 Dizziness 1 0 Anorexia 1 0 Light Headedness 1 0 Depression 1 0 Miscellaneous 4 (0.9%) 3 (1.4%) Total Number of Patients Withdrawn 46 (10.4%) 14 (6.7%) For those controlled studies, the comparative incidences of adverse reactions reported in 1% or more patients treated with olsalazine or placebo are provided in Table 2 . Table 2 Comparative Incidence (%) of Adverse Effects Reported By One Percent Or More of Ulcerative Colitis Patients Treated With Olsalazine Or Placebo in Double Blind Controlled Studies Adverse Event Olsalazine (N = 441) % Placebo (N = 208) % Gastrointestinal Disorders Diarrhea 11.1 6.7 Abdominal Pain/Cramps 10.1 7.2 Nausea 5.0 3.9 Dyspepsia 4.0 4.3 Bloating 1.5 1.4 Vomiting 1.0 - Stomatitis 1.0 - Increased Blood in Stool - 3.4 Metabolism and Nutrition Disorders Anorexia 1.3 1.9 Nervous System Disorders Headache 5.0 4.8 Insomnia - 2.4 General Disorders and Administration Site Conditions Fatigue/Drowsiness/Lethargy 1.8 2.9 Psychiatric Disorders Depression 1.5 - Ear and Labyrinth Disorders Vertigo/Dizziness 1.0 - Skin and Subcutaneous Tissue Disorders Rash 2.3 1.4 Itching 1.3 - Musculoskeletal and Connective Tissue Disorders Arthralgia/Joint Pain 4.0 2.9 Infections and Infestations Upper Respiratory Infection 1.5 - Over 2,500 patients have been treated with olsalazine in various controlled and uncontrolled clinical studies. In these as well as in post-marketing experience, olsalazine was administered mainly to patients intolerant to sulfasalazine. There have been rare reports of the following adverse effects in patients receiving olsalazine. These were often difficult to distinguish from possible symptoms of the underlying disease or from the effects of prior and/or concomitant therapy. A causal relationship to the drug has not been demonstrated for some of these reactions. Blood and Lymphatic System Disorders: Anemia, Eosinophilia, Hemolytic anemia, Interstitial pulmonary disease, Leukopenia, Lymphopenia, Neutropenia, Reticulocytosis, Thrombocytopenia Cardiac Disorders: Chest pains, Heart block second degree, Myocarditis, Palpitations, Pericarditis, Peripheral edema, Shortness of breath, Tachycardia A patient who developed thyroid disease 9 days after starting DIPENTUM was given propranolol and radioactive iodine and subsequently developed shortness of breath and nausea. The patient died 5 days later with signs and symptoms of acute diffuse myocarditis. Ear and Labyrinth Disorders: Tinnitus Eye Disorders: Dry eyes, Vision blurred, Watery eyes Gastrointestinal Disorders: Abdominal pain (upper), Diarrhea with dehydration, Dry mouth, Epigastric discomfort, Flare in symptoms, Flatulence, Increased blood in stool, Pancreatitis, Rectal bleeding, Rectal discomfort In a double-blind, placebo-controlled study, increased frequency and severity of diarrhea were reported in patients randomized to olsalazine 500 mg B.I.D. with concomitant pelvic radiation. Rare cases of granulomatous hepatitis and nonspecific, reactive hepatitis have been reported in patients receiving olsalazine. Additionally, a patient developed mild cholestatic hepatitis during treatment with sulfasalazine and experienced the same symptoms two weeks later after the treatment was changed to olsalazine. Withdrawal of olsalazine led to complete recovery in these cases. General Disorders and Administration Site Conditions: Fever chills, Hot flashes, Irritability, Rigors Immune System Disorders: Bronchospasm, Erythema nodosum Laboratory: ALT (SGPT) or AST (SGOT) elevated beyond the normal range. Musculoskeletal and Connective Tissue Disorders: Muscle cramps Nervous System Disorders: Insomnia, Paraesthesia, Tremors Psychiatric Disorders: Mood swings Renal and Urinary Disorders: Dysuria, Hematuria, Interstitial nephritis, Nephrotic syndrome, Proteinuria, Urinary frequency Reproductive System and Breast Disorders: Impotence, Menorrhagia Skin and Subcutaneous Tissue Disorders: Alopecia, Erythema, Photosensitivity reaction Vascular Disorders: Hypertension, Orthostatic hypotension Postmarketing The following events have been identified during post-approval use of products that contain (or are metabolized to) mesalamine in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to mesalamine: Blood and Lymphatic System Disorders: Aplastic anemia, Pancytopenia General Disorders and Administration Site Conditions: Pyrexia Hepatobiliary Disorders: Hepatic enzyme increased, Hepatitis, Increased bilirubin Reports of hepatotoxicity, including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, 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. Musculoskeletal and Connective Tissue Disorders: Myalgia Respiratory, Thoracic and Mediastinal Disorders: Dyspnoea, Interstitial lung disease Skin and Subcutaneous Tissue Disorders: Angioneurotic oedema Nervous System Disorders: Paraesthesia, Peripheral neuropathy Renal and Urinary Disorders: Interstitial nephritis