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.
Exacerbation of the symptoms of colitis has been reported in 3% of -treated patients in controlled clinical trials. This acute reaction, characterized by cramping, abdominal pain, bloody diarrhea, and occasionally by fever, headache, malaise, pruritus, rash, and conjunctivitis, has been reported after the initiation of tablets as well as other mesalamine products. Symptoms usually abate when tablets are discontinued.
Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to tablets or to other compounds which contain or are converted to mesalamine.
Renal:
Asacol
Therefore, caution should be exercised when using Asacol (or other compounds which contain or are converted to mesalamine or its metabolites) in patients with known renal dysfunction or history of renal disease. It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol tablets and periodically while on Asacol therapy.
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Use in Hepatic Impairment:
Asacol
Patients with ulcerative colitis should be made aware that ulcerative colitis rarely remits completely, and that the risk of relapse can be substantially reduced by continued administration of at a maintenance dosage.
Drug Interactions:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Asacol
in vitro
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Pregnancy: Teratogenic Effects:
Nursing Mothers:
Pediatric Use:
Asacol
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when prescribing this drug therapy. As stated in the section, it is recommended that all patients have an evaluation of renal function prior to initiation of tablets and periodically while on therapy.
In two short-term (6 weeks) placebo-controlled clinical studies involving 245 patients, 155 of whom were randomized to tablets, five (3.2%) of the patients discontinued therapy because of adverse events as compared to two (2.2%) of the placebo patients. Adverse reactions leading to withdrawal from 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 -treated patients at a frequency of 2% or greater in the two short-term, double-blind, placebo-controlled trials mentioned above are listed in below. Overall, the incidence of adverse events seen with tablets was similar to placebo.
Of these adverse events, only rash showed a consistently higher frequency with increasing dose in these studies.
In a 6-month placebo-controlled maintenance trial involving 264 patients, 177 of whom were randomized to tablets, six (3.4%) of the patients discontinued therapy because of adverse events, as compared to four (4.6%) of the placebo patients. Adverse reactions leading to withdrawal from 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 tablets was similar to that seen with placebo. In addition to events listed in , the following adverse events occurred in -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:
For the treatment of mildly to moderately active ulcerative colitis:
For the maintenance of remission of ulcerative colitis:
Two Asacol 400 mg tablets have not been shown to be bioequivalent to one Asacol HD 800 mg tablet.
