The most serious adverse reactions seen in DELZICOL
clinical trials or with other products that contain or are metabolized to
- Renal impairment, including renal failure [see WARNINGS
- Acute intolerance syndrome [see WARNINGS AND
- Hypersensitivity reactions [see WARNINGS AND
- Hepatic failure [see WARNINGS AND PRECAUTIONS]
The data presented in Section 6.1 are from clinical
trials conducted with mesalamine delayed-release tablets. DELZICOL is
bioequivalent to these mesalamine delayed-release tablets.
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.
In total, mesalamine delayed-release 400 mg tablets have
been evaluated in 2690 patients with ulcerative colitis in controlled and
open-label trials. Adverse events presented in the following sections may occur
regardless of length of therapy and similar events have been reported in
short-and long-term studies and in the postmarketing setting.
Clinical studies supporting mesalamine delayed-release
tablets use for the treatment of mildly to moderately active ulcerative colitis
included two 6-week, placebo-controlled, randomized, double-blind studies in
adults with mildly to moderately active ulcerative colitis (Studies 1 and 2),
and one 6-week, randomized, double-blind, study of 2 dose levels in children
with mildly to moderately active ulcerative colitis. Clinical studies
supporting the use of mesalamine delayed-release tablets in the maintenance of
remission of ulcerative colitis included a 6-month, randomized, double-blind,
placebo-controlled, multicenter study and four active-controlled maintenance
trials comparing mesalamine delayed-release with sulfasalazine. Mesalamine
delayed-release tablets have been evaluated in 427 adults and 82 children with
ulcerative colitis in these controlled studies.
Treatment of Mildly to Moderately Active Ulcerative
Colitis in Adults
In two 6-week placebo-controlled clinical studies
(Studies 1 and 2) involving 245 patients, 155 of whom were randomized to
mesalamine delayed-release tablets [see Clinical Studies], 3.2% of the
mesalamine delayed-release tablets-treated patients discontinued therapy
because of adverse reactions as compared to 2.2% of the placebo-treated
patients. The average age of patients in Study 1 was 42 years and 48% of
patients were male. The average age of patients in Study 2 was 42 years and 59%
of patients were male. Adverse reactions leading to withdrawal from mesalamine
delayed-release tablets included (each in one patient): diarrhea and colitis
flare; dizziness, nausea, joint pain, and headache; rash, lethargy and
constipation; dry mouth, malaise, lower back discomfort, mild disorientation,
mild indigestion and cramping; headache, nausea, aching, vomiting, muscle
cramps, a stuffy head, plugged ears, and fever.
Adverse reactions in patients treated with mesalamine
delayed-release tablets occurring at a frequency of at least 2% and at a rate
greater than placebo in 6-week, double-blind, placebo-controlled trials
(Studies 1 and 2) are listed in Table 1 below.
Table 1 : Adverse Reactions Reported in Two Six-Week
Placebo-Controlled Trials (Studies 1 and 2) Experienced by at Least 2% of
patients in the mesalamine delayed-release tablets Group and at a Rate Greater
||% of Patients with Adverse Reactions
|mesalamine delayed-release tablets
(n = 152)
(n = 87)
Treatment of Mildly to Moderately Active Ulcerative
Colitis in Pediatric Patients 5 to 17 Years Old
A randomized, double-blind, 6-week study of 2 dose levels
of mesalamine delayed-release 400 mg tablets (Study 3) was conducted in 82
pediatric patients 5 to 17 years of age with mildly to moderately active
ulcerative colitis. All patients were divided by body weight category (17 to
less than 33 kg, 33 to less than 54 kg, and 54 to 90 kg) and randomly assigned
to receive a low dose (1.2, 2.0, and 2.4 g/day for the respective body weight
category) or a high dose (2.0, 3.6, and 4.8 g/day).
The high dose is not an approved dosage because it was
not found to be more effective than the approved dose [see DOSAGE AND
ADMINISTRATION and Clinical Studies].
Duration of exposure to mesalamine among the 82 patients
in the study ranged from 12 to 50 days (mean of 40 days in each dose group).
The majority (88%) of patients in each group were treated for more than 5
weeks. Table 2 provides a summary of the specific reported adverse reactions
Table 2: Adverse Reactions Reported in One Six-Week
Trial (Study 3) Experienced by at Least 5% of Patients in the Low Dose Group or
High Dose Group
||% of Patients with Adverse Reactions
|Low Dose = mesalamine 400mg delayed-release tablet 1.2 –
2.4 g/day; High Dose = mesalamine 400mg delayed-release tablet 2.0 – 4.8 g/day.
Dosage was dependent on body weight.
Adverse Reactions reported at the 1-week telephone follow-up visit are included
Twelve percent of the patients in the low dose group and
5% of the patients in the high dose group had serious adverse reactions (ARs).
Ulcerative colitis was reported as a serious AR in one subject in each group.
Other serious ARs consisted of sinusitis, abdominal pain, decreased body mass
index, adenovirus infection, bloody diarrhea, sclerosing cholangitis, and
pancreatitis in one subject each in the low dose group and anemia and syncope
in one subject each in the high dose group.
Seven patients were withdrawn from the study because of
ARs: 5 (12%) in the low dose group (ulcerative colitis, adenovirus infection,
sclerosing cholangitis, pancreatitis) and 2 (5%) in the high dose group
(increased amylase and increased lipase, upper abdominal pain).
In general, the nature and severity of reactions in the
pediatric population was similar to those reported in adult populations of
patients with ulcerative colitis.
Maintenance of Remission of Ulcerative Colitis in Adults
In a 6-month placebo-controlled maintenance trial
involving 264 patients (Study 4) 177 of whom were randomized to mesalamine
delayed-release tablets, six (3.4%) of the patients using mesalamine
delayed-release tablets discontinued therapy because of adverse reactions, as
compared to four (4.6%) of patients using placebo [see Clinical Studies].
The average age of patients in Study 4 was 42 years and 55% of patients were
male. Adverse reactions leading to study withdrawal in patients using
mesalamine delayed-release tablets included (each in one patient): anxiety;
headache; pruritus; decreased libido; rheumatoid arthritis; and stomatitis and
In addition to reactions listed in Table 1, the following
adverse reactions occurred in patients using mesalamine delayed-release tablets
at a frequency of 2% or greater in Study 4: abdominal enlargement,
gastroenteritis, gastrointestinal hemorrhage, infection, joint disorder,
migraine, nervousness, paresthesia, rectal disorder, rectal hemorrhage, stool
abnormalities, tenesmus, urinary frequency, vasodilation, and vision
In 3342 patients in uncontrolled clinical studies, the
following adverse reactions occurred at a frequency of 5% or greater and
appeared to increase in frequency with increasing dose: asthenia, fever, flu
syndrome, pain, abdominal pain, back pain, flatulence, gastrointestinal
bleeding, arthralgia, and rhinitis.
In addition to the adverse reactions reported above in
clinical trials involving mesalamine delayed-release tablets, the adverse
reactions listed below have been identified during post-approval use of
mesalamine delayed-release tablets and other mesalamine-containing products.
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.
Body as a Whole: Neck pain, facial edema, edema, lupus-like
syndrome, drug fever.
Cardiovascular: Pericarditis, myocarditis [see
WARNINGS AND PRECAUTIONS].
Gastrointestinal: Anorexia, pancreatitis,
gastritis, increased appetite, cholecystitis, dry mouth, oral ulcers,
perforated peptic ulcer bloody diarrhea.
Hematologic: Agranulocytosis, aplastic anemia,
thrombocytopenia, eosinophilia, leukopenia, anemia, lymphadenopathy.
Nervous: Depression, somnolence, emotional
lability, hyperesthesia, vertigo, confusion, tremor, peripheral neuropathy,
transverse myelitis, Guillain-Barré syndrome.
Renal: Renal failure, interstitial nephritis,
minimal change nephropathy [see WARNINGS AND PRECAUTIONS].
Respiratory/Pulmonary: Eosinophilic pneumonia,
interstitial pneumonitis, asthma exacerbation, pleuritis.
Skin: Alopecia, psoriasis, pyoderma gangrenosus,
dry skin, erythema nodosum, urticaria.
Special Senses: Eye pain, taste perversion,
blurred vision, tinnitus.
Urogenital: Dysuria, urinary urgency, hematuria,
epididymitis, menorrhagia, reversible oligospermia.
Laboratory Abnormalities: Elevated AST (SGOT) or
ALT (SGPT), elevated alkaline phosphatase, elevated GGT, elevated LDH, elevated
bilirubin, elevated serum creatinine and BUN.
No formal drug interaction studies have been performed
using DELZICOL with other drugs. However, the following interactions between
mesalamine-containing products and other drugs have been reported.
Nephrotoxic Agents, Including Non-Steroidal
The concurrent use of mesalamine with known nephrotoxic
agents, including nonsteroidal anti-inflammatory drugs (NSAIDs) may increase
the risk of renal reactions [see WARNINGS AND PRECAUTIONS].
Azathioprine Or 6-mercaptopurine
The concurrent use of mesalamine with azathioprine or
6-mercaptopurine may increase the risk for blood disorders.