GIAZO SIDE EFFECTS

SIDE 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

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.

The data described below reflect exposure of GIAZO in 565 ulcerative colitis patients with mildly to moderately active disease. GIAZO was evaluated in one placebo-controlled trial (168 treated with GIAZO), one active-controlled trial (210 treated with GIAZO); and a subset of these patients also participated in an uncontrolled, open-label, extension study (additional 187 treated with GIAZO). The population studied had a mean age of 43.1 (range: 18-80) years; approximately 94% of patients were < 65 years old, 49% were male, and 84% were white.

In the placebo-controlled trial, the most common adverse reactions with GIAZO in male patients were headache, nasopharyngitis, anemia, diarrhea, fatigue, pharyngolaryngeal pain, and urinary tract infection. 10% of patients in the GIAZO group and 13% of patients in the placebo group discontinued treatment due to an adverse reaction. The majority of adverse reactions were mild to moderate in severity. The most common serious adverse reactions in both the placebo and GIAZO groups were gastrointestinal disorders, which were mainly associated with symptoms of ulcerative colitis.

Adverse reactions occurring in at least 2% of male patients and at a rate numerically higher than placebo in the placebo-controlled trial are listed in Table 1.

Table 1: Adverse Reactions Experienced by at Least 2% of GIAZO–Treated Male Patients and at a Rate Numerically Greater than Placebo in a Placebo-Controlled Trial

Data collected from all three trials (placebo-controlled, active-controlled, and open-label) showed that female patients reported adverse reactions more frequently than did male patients (76% and 66%, respectively).

The following adverse reactions, presented by body system, were reported by less than 1% of GIAZO-treated ulcerative colitis patients in controlled trials.

Cardiovascular and Vascular: increased blood pressure, increased heart rate

Dermatological: erythema nodosum, rash

Respiratory, Thoracic and Mediastinal Disorders: dyspnea

Gastrointestinal Disorders: abdominal pain, constipation, defecation urgency, diarrhea, dry mouth, hard feces, flatulence, gastroesophageal reflux disease, vomiting

Hepatobiliary Disorders: increased aspartate aminotransferase

Infections and Infestations: gastroenteritis, upper respiratory infection

Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain, myalgia

Nervous System Disorders: dizziness, lethargy

General Disorders and Administrative Site Disorders: face edema, fatigue, malaise, pain, pyrexia, swelling

Postmarketing Experience

The following adverse reactions have been identified during postapproval 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: alveolitis, pleural effusion, pneumonia (with and without eosinophilia), pleurisy/pleuritis

Gastrointestinal: pancreatitis

Renal: interstitial nephritis, renal failure, nephrolithiasis

Hepatobiliary Disorders: elevated liver enzymes (AST, ALT, GGT, LDH, alkaline phosphatase), elevated bilirubin, jaundice, cholestatic jaundice, cirrhosis, hepatocellular damage including liver necrosis and liver failure, Kawasaki-like syndrome including hepatic dysfunction. Some of these cases were fatal

Dermatological: alopecia, pruritus, SJS/TEN, DRESS, and AGEP.

SRC: NLM .