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 placebocontrolled 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
||GIAZO 6.6 g/day
|Urinary Tract Infection
Data collected from all three trials (placebo-controlled,
active-controlled, and openlabel) 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:
Gastrointestinal Disorders: abdominal pain,
constipation, defecation urgency, diarrhea, dry mouth, hard feces, flatulence,
gastroesophageal reflux disease, vomiting
Hepatobiliary Disorders: increased aspartate
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
Because 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. These
adverse reactions have been chosen for inclusion due to a combination of
seriousness, frequency of reporting, or potential causal connection to products
which contain or are metabolized to mesalamine, including balsalazide.
Cardiovascular and Vascular: myocarditis,
Respiratory: alveolitis, pleural effusion,
pneumonia (with and without eosinophilia)
Renal: interstitial nephritis, renal failure.
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
Based on in vitro studies, balsalazide and its
metabolites [5-aminosalicylic acid (5- ASA), N-acetyl-5-aminosalicylic acid
(N-Ac-5-ASA), 4-aminobenzoyl-Ã-alanine (4-ABA), and
N-acetyl-4-aminobenzoyl-Ã-alanine (N-Ac-4-ABA)] are not expected to inhibit the
metabolism of other drugs that are substrates of CYP1A2, CYP2C9, CYP2C19,
CYP2D6, or CYP3A4/5.