The most serious adverse reactions seen in Asacol HD
clinical trials or with other products that contain mesalamine or are
metabolized to mesalamine were:
- Renal Impairment [see WARNINGS AND PRECAUTIONS]
- Mesalamine-Induced Acute Intolerance Syndrome [see
WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND
- Hepatic Failure [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 grams per day with
mesalamine-delayed release tablets 2.4 grams per day in patients with mildly to
moderately active ulcerative colitis. In these studies, 727 patients were dosed
with Asacol HD tablets and 732 patients were dosed with mesalamine
The most common reactions reported in the Asacol HD group
were headache (4.7%), nausea (2.8%), nasopharyngitis (2.5%), abdominal pain
(2.3%), diarrhea (1.7%), and dyspepsia (1.7%); Table 1 enumerates adverse
reactions that occurred in the three studies. The most common reactions in
patients with moderately active ulcerative colitis (602 patients dosed with
Asacol HD and 618 patients dosed with mesalamine delayed-release 400 mg) were
the same as all treated patients.
Discontinuations due to adverse reactions occurred in
3.9% of patients in the Asacol HD group and in 4.2% of patients in the
mesalamine delayed-release tablet comparator group. The most common cause for
discontinuation was gastrointestinal symptoms associated with ulcerative
Serious adverse reactions occurred in 0.8% of patients in
the Asacol HD group and in 1.8% of patients in the mesalamine delayed-release
tablet comparator group. The majority involved the gastrointestinal system.
Table 1: Adverse Reactions Occurring in ≥1% of
All Treated Patients (Three studies combined)
||Mesalamine delayed-release 2.4 grams per day (400 mg Tablet)
(N = 732)
|Asacol HD 4.8 grams per day (800 mg Tablet)
(N = 727)
|N = number of patients within specified treatment group
Percent = percentage of patients in category and treatment group
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 postmarketing experience with other mesalamine-containing
products or products that 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) and
myocarditis (rare) [see WARNINGS AND PRECAUTIONS], pericardial effusion,
Endocrine: Nephrogenic diabetes insipidus.
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 [see WARNINGS AND PRECAUTIONS].
Hematologic: Agranulocytosis (rare), aplastic
anemia (rare), anemia, thrombocytopenia, leukopenia, eosinophilia,
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-Barre syndrome (rare), transverse myelitis (rare), and intracranial
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,
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.
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 nephrotoxicity. Monitor patients taking nephrotoxic drugs for
changes in renal function and mesalamine-related adverse reactions [see WARNINGS
Azathioprine Or 6-Mercaptopurine
The concurrent use of mesalamine with azathioprine or
6-mercaptopurine may increase the risk for blood disorders. If concomitant use
of Asacol HD and azathioprine or 6mercaptopurine cannot be avoided, monitor blood
tests, including complete blood cell counts and platelet counts.