Asacol HD

Asacol tablets are indicated for the treatment of mildly to moderately active ulcerative colitis and for the maintenance of remission of ulcerative colitis.

For the treatment of mildly to moderately active ulcerative colitis: The usual dosage in adults is two 400 mg tablets to be taken three times a day for a total daily dose of 2.4 grams for a duration of 6 weeks.

For the maintenance of remission of ulcerative colitis: The recommended dosage in adults is 1.6 grams daily, in divided doses. Treatment duration in the prospective, well-controlled trial was 6 months.

Two Asacol 400 mg tablets have not been shown to be bioequivalent to one Asacol® HD (mesalamine) delayed-release 800 mg tablet.

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 listed in Table 1 below. Overall, the incidence of adverse events seen with Asacol tablets was similar to placebo.

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 listed 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 listed 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.

Drug Interactions:

There are no known drug interactions.

Each Asacol® delayed-release tablet for oral administration contains 400 mg of mesalamine, an anti-inflammatory drug. The Asacol delayed-release tablets are coated with acrylic based resin, Eudragit S (methacrylic acid copolymer B, NF), which dissolves at pH 7 or greater, releasing mesalamine in the terminal ileum and beyond for topical anti-inflammatory action in the colon. Mesalamine has the chemical name 5-amino-2-hydroxybenzoic acid; its structural formula is:

Inactive Ingredients: Each tablet contains colloidal silicon dioxide, dibutyl phthalate, edible black ink, iron oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate, methacrylic acid copolymer B (Eudragit S), polyethylene glycol, povidone, sodium starch glycolate, and talc.

Mesalamine is thought to be the major therapeutically active part of the sulfasalazine molecule in the treatment of ulcerative colitis. Sulfasalazine is converted to equimolar amounts of sulfapyridine and mesalamine by bacterial action in the colon. The usual oral dose of sulfasalazine for active ulcerative colitis is 3 to 4 grams daily in divided doses, which provides 1.2 to 1.6 grams of mesalamine to the colon.

The mechanism of action of mesalamine (and sulfasalazine) is unknown, but appears to be topical rather than systemic. Mucosal production of arachidonic acid (AA) metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs), is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin (PG) production in the colon.

Clinical Studies:

Asacol® (mesalamine) Delayed-Release Tablets are available as red-brown, capsule-shaped tablets containing 400 mg mesalamine and imprinted “0752 DR” in black.

They are supplied by State of Florida DOH Central Pharmacy as follows:

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Manufactured by:
Warner Chilcott Deutschland GmbH
D-64331 Weiterstadt
Germany

Marketed by:
Warner Chilcott (US), LLC
Rockaway, NJ 07866
1-800-521-8813

Under license from Medeva Pharma Suisse AG (registered trademark owner).

U.S. Patent Nos. 5,541,170 and 5,541,171

To report SUSPECTED ADVERSE REACTIONS, contact Warner Chilcott at 1-800-521-8813 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

This Product was Repackaged By:

State of Florida DOH Central Pharmacy
104-2 Hamilton Park Drive
Tallahassee, FL 32304
United States