The most serious adverse reactions seen in Asacol HD
clinical trials or with other products that contain or are metabolized to
mesalamine were:
- Renal impairment, including renal failure (rare) [see WARNINGS AND PRECAUTIONS]
- Acute exacerbation of colitis [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]
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.
Asacol HD has been evaluated in 896 patients with ulcerative colitis in controlled
studies. Three six-week, active-controlled studies were conducted comparing
Asacol HD 4.8 g/day with Asacol (mesalamine) 2.4 g/day as control in patients
with mildly to moderately active ulcerative colitis. In these studies, 727 patients
were dosed with the Asacol HD tablet and 732 patients were dosed with the Asacol
400 mg tablet. (One Asacol HD 800 mg tablet has not been shown to be bioequivalent
to two Asacol 400 mg tablets [see CLINICAL PHARMACOLOGY].)
The most common reactions reported in the Asacol HD group
were headache (4.7%), nausea (2.8%), nasopharyngitis (2.5%), abdominal pain
(2.3%), exacerbation of ulcerative colitis (2.3%), diarrhea (1.7%), and
dyspepsia (1.7%); Table 1 enumerates adverse drug reactions that occurred in
the three studies. The most common reactions in the primary efficacy population
of patients with moderately active ulcerative colitis (602 patients dosed with
Asacol HD and 618 patients dosed with the Asacol 400 mg tablet) were the same
as all treated patients. The majority of adverse reactions with Asacol HD in
the double-blind, active-controlled trials were mild or moderate in severity
and were reversible.
Discontinuations due to adverse reactions occurred in 3.9%
of patients in the Asacol HD group and in 4.2% of patients in the Asacol 400 mg
tablet comparator group. The most common cause for discontinuation was
gastrointestinal symptoms associated with ulcerative colitis.
Severe adverse reactions occurred in 7.6% of patients in the
Asacol HD group and in 7.6% of patients in the Asacol 400 mg tablet comparator
group. Most of these reactions were gastrointestinal symptoms related to
ulcerative colitis. Serious adverse reactions occurred in 0.8% of patients in
the Asacol HD group and in 1.8% of patients in the Asacol 400 mg tablet
comparator group. The majority involved the gastrointestinal system.
Table 1. Adverse Reactions Occurring in 1% or More of All
Treated Patients (Three studies combined; Intent-to-treat population)
| MedDRA Preferred Term |
Asacol* 2.4g/day
(400 mg Tablet)
(N=732) |
Asacol HD* 4.8g/day
(800 mg Tablet)
(N=727) |
| Headache |
4.9 % |
4.7 % |
| Nausea |
2.9 % |
2.8 % |
| Nasopharyngitis |
1.4 % |
2.5 % |
| Abdominal pain |
2.3 % |
2.3 % |
| Ulcerative Colitis |
2.7 % |
2.3 % |
| Diarrhea |
1.9 % |
1.7 % |
| Dyspepsia |
0.8 % |
1.7 % |
| Vomiting |
1.6 % |
1.4 % |
| Flatulence |
0.7 % |
1.2 % |
| Influenza |
1.2 % |
1.0 % |
| Pyrexia |
1.2 % |
0.7 % |
| Cough |
1.4 % |
0.3 % |
| N = number of patients within specified treatment group % = percentage of patients in category and treatment group *One Asacol HD 800 mg tablet has not been shown to be bioequivalent to two Asacol 400 mg tablets [see CLINICAL PHARMACOLOGY]. |
Adverse Reaction Information from Other Sources
In addition to the adverse reactions reported above in
clinical trials involving the Asacol HD tablet, the adverse events listed below
have been reported in controlled clinical trials, open label studies,
literature reports, or foreign and domestic marketing experience with Asacol
400 mg tablets or other products that 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.
Body as a Whole: Facial edema, edema,
peripheral edema, asthenia, chills, infection, malaise, pain, neck pain, chest pain, back pain, abdominal enlargement, lupus-like syndrome, drug fever (rare).
Cardiovascular: Pericarditis (rare),
pericardial effusion, myocarditis (rare), vasodilation, migraine.
Gastrointestinal: Dry mouth, stomatitis, oral
ulcers, anorexia, increased appetite, eructation, pancreatitis, cholecystitis,
gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer
(rare), constipation, hemorrhoids, rectal hemorrhage, bloody diarrhea,
tenesmus, stool abnormality.
Hepatic: There have been rare reports of
hepatotoxicity, including jaundice, cholestatic jaundice, hepatitis, and
possible hepatocellular damage including liver necrosis and liver failure. Some
of these cases were fatal. Asymptomatic elevations of liver enzymes which
usually resolve during continued use or with discontinuation of the drug have
also been reported. One case of Kawasaki-like syndrome, that included changes
in liver enzymes, was also reported.
Hematologic: Agranulocytosis (rare), aplastic
anemia (rare), anemia, thrombocytopenia, leukopenia, eosinophilia, lymphadenopathy.
Musculoskeletal: Gout, rheumatoid arthritis,
arthritis, arthralgia, joint disorder, myalgia, hypertonia.
Neurological/Psychiatric: Anxiety, depression,
somnolence, insomnia, nervousness, confusion, emotional lability, dizziness,
vertigo, tremor, paresthesia, hyperesthesia, peripheral neuropathy (rare),
Guillain-Barré syndrome (rare), and transverse myelitis (rare).
Respiratory/Pulmonary: Sinusitis, rhinitis,
pharyngitis, asthma exacerbation, pleuritis, bronchitis, eosinophilic pneumonia, interstitial pneumonitis.
Skin: Alopecia, psoriasis (rare), pyoderma
gangrenosum (rare), erythema nodosum, acne, dry skin, sweating, pruritus,
urticaria, rash.
Special Senses: Ear pain, tinnitus, ear
congestion, ear disorder, conjunctivitis, eye pain, blurred vision, vision
abnormality, taste perversion.
Renal/Urogenital: Renal failure (rare), interstitial nephritis,
minimal change nephropathy [see WARNINGS AND PRECAUTIONS],
dysuria, urinary frequency and urgency, hematuria, epididymitis, decreased libido,
dysmenorrhea, menorrhagia.
Laboratory Abnormalities: Elevated AST (SGOT)
or ALT (SGPT), elevated alkaline phosphatase, elevated GGT, elevated LDH,
elevated bilirubin, elevated serum creatinine and BUN.