ASACOL (mesalamine 400 mg) Dailymed

Adverse Reactions:

Asacol tablets have been evaluated in 3685 inflammatory bowel disease patients (most patients with ulcerative colitis) in controlled and open-label studies. Adverse events seen in clinical trials with Asacol tablets have generally been mild and reversible. 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 post-marketing setting.

In two short-term (6 weeks) placebo-controlled clinical studies involving 245 patients, 155 of whom were randomized to Asacol tablets, five (3.2%) of the Asacol patients discontinued Asacol therapy because of adverse events as compared to two (2.2%) of the placebo patients. Adverse reactions leading to withdrawal from Asacol 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 events occurring in Asacol-treated patients at a frequency of 2% or greater in the two short-term, double-blind, placebo-controlled trials mentioned above are uled in Table 1 below. Overall, the incidence of adverse events seen with Asacol tablets was similar to placebo.

Table 1: Frequency (%) of Common Adverse Events Reported in Ulcerative Colitis Patients Treated with Asacol Tablets or Placebo in Short-Term (6-Week) Double-Blind Controlled Studies

	Percent of Patients with Adverse Events
	Placebo	Asacol tablets
Event	(n = 87)	(n = 152)
Headache	36	35
Abdominal pain	14	18
Eructation	15	16
Pain	8	14
Nausea	15	13
Pharyngitis	9	11
Dizziness	8	8
Asthenia	15	7
Diarrhea	9	7
Back pain	5	7
Fever	8	6
Rash	3	6
Dyspepsia	1	6
Rhinitis	5	5
Arthralgia	3	5
Hypertonia	3	5
Vomiting	2	5
Constipation	1	5
Flatulence	7	3
Dysmenorrhea	3	3
Chest pain	2	3
Chills	2	3
Flu syndrome	2	3
Peripheral edema	2	3
Myalgia	1	3
Sweating	1	3
Colitis exacerbation	0	3
Pruritus	0	3
Acne	1	2
Increased cough	1	2
Malaise	1	2
Arthritis	0	2
Conjunctivitis	0	2
Insomnia	0	2

Of these adverse events, only rash showed a consistently higher frequency with increasing Asacol dose in these studies.

In a 6-month placebo-controlled maintenance trial involving 264 patients, 177 of whom were randomized to Asacol tablets, six (3.4%) of the Asacol patients discontinued Asacol therapy because of adverse events, as compared to four (4.6%) of the placebo patients. Adverse reactions leading to withdrawal from Asacol tablets included (each in one patient): anxiety; headache; pruritus; decreased libido; rheumatoid arthritis; and stomatitis and asthenia.

In the 6-month placebo-controlled maintenance trial, the incidence of adverse events seen with Asacol tablets was similar to that seen with placebo. In addition to events uled in Table 1, the following adverse events occurred in Asacol-treated patients at a frequency of 2% or greater in this study: abdominal enlargement, anxiety, bronchitis, ear disorder, ear pain, gastroenteritis, gastrointestinal hemorrhage, infection, joint disorder, migraine, nervousness, paresthesia, rectal disorder, rectal hemorrhage, sinusitis, stool abnormalities, tenesmus, urinary frequency, vasodilation, and vision abnormalities.

In 3342 patients in uncontrolled clinical studies, the following adverse events 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 events uled above, the following events have been reported in clinical studies, literature reports, and postmarketing use of products which contain (or have been metabolized to) mesalamine. Because many of these events were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to their seriousness or potential causal connection to mesalamine:

Body as a Whole: Neck pain, facial edema, edema, lupus-like syndrome, drug fever (rare).

Cardiovascular: Pericarditis (rare), myocarditis (rare).

Gastrointestinal: Anorexia, pancreatitis, gastritis, increased appetite, cholecystitis, dry mouth, oral ulcers, perforated peptic ulcer (rare), bloody diarrhea. 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 which included changes in liver enzymes was also reported.

Hematologic: Agranulocytosis (rare), aplastic anemia (rare), thrombocytopenia, eosinophilia, leukopenia, anemia, lymphadenopathy.

Musculoskeletal: Gout.

Nervous: Depression, somnolence, emotional lability, hyperesthesia, vertigo, confusion, tremor, peripheral neuropathy (rare), transverse myelitis (rare), Guillain-Barré syndrome (rare).

Respiratory/Pulmonary: Eosinophilic pneumonia, interstitial pneumonitis, asthma exacerbation, pleuritis.

Skin: Alopecia, psoriasis (rare), pyoderma gangrenosum (rare), dry skin, erythema nodosum, urticaria.

Special Senses: Eye pain, taste perversion, blurred vision, tinnitus.

Urogenital: Renal Failure (rare), interstitial nephritis, minimal change nephropathy (See also Renal subsection in PRECAUTIONS). Dysuria, urinary urgency, hematuria, epididymitis, menorrhagia.

Laboratory Abnormalities: Elevated AST (SGOT) or ALT (SGPT), elevated alkaline phosphatase, elevated GGT, elevated LDH, elevated bilirubin, elevated serum creatinine and BUN.