Mesalamine Information
Mesalamine () Description
The active ingredient in Mesalamine () rectal suspension USP, 4 g/60 mL, a disposable (60 mL) unit, is Mesalamine () , also known as 5-aminosalicylic acid (5-ASA). Chemically, Mesalamine () is 5-amino-2-hydroxybenzoic acid.
The structural formula is:
CHNO M.W. 153.14
Each rectal suspension unit contains 4 grams of Mesalamine () . In addition to Mesalamine () the preparation contains the inactive ingredients carbomer 934P, edetate disodium, potassium acetate, potassium metabisulfite, purified water and xanthan gum. Sodium benzoate is added as a preservative. The disposable unit consists of an applicator tip protected by a polyethylene cover and lubricated with USP white petrolatum. The unit has a one-way valve to prevent back flow of the dispensed product.
Mesalamine () Clinical Pharmacology
Sulfasalazine is split by bacterial action in the colon into sulfapyridine (SP) and Mesalamine () (5-ASA). It is thought that the Mesalamine () component is therapeutically active in ulcerative colitis [A.K. Azad Khan , 2:892-895 (1977)]. The usual oral dose of sulfasalazine for active ulcerative colitis in adults is two to four grams per day in divided doses. Four grams of sulfasalazine provide 1.6 g of free Mesalamine () to the colon. Each Mesalamine () rectal suspension USP delivers up to 4 g of Mesalamine () to the left side of 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.
Mesalamine () Indications And Usage
Mesalamine () rectal suspension is indicated for the treatment of active mild to moderate distal ulcerative colitis, proctosigmoiditis or proctitis.
Mesalamine () Contraindications
Mesalamine () rectal suspension is contraindicated for patients known to have hypersensitivity to the drug or any component of this medication.
Mesalamine () Warnings
Mesalamine () rectal suspension contains potassium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low. Sulfite sensitivity is seen more frequently in asthmatic or in atopic nonasthmatic persons.
Epinephrine is the preferred treatment for serious allergic or emergency situations even though epinephrine injection contains sodium or potassium metabisulfite with the above-mentioned potential liabilities. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite(s) in epinephrine injection should not deter the administration of the drug for treatment of serious allergic or other emergency situations.
Mesalamine () Precautions
Mesalamine () has been implicated in the production of an acute intolerance syndrome characterized by cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache and a rash; in such cases prompt withdrawal is required. The patient's history of sulfasalazine intolerance, if any, should be re-evaluated. If a rechallenge is performed later in order to validate the hypersensitivity it should be carried out under close supervision and only if clearly needed, giving consideration to reduced dosage. In the literature one patient previously sensitive to sulfasalazine was rechallenged with 400 mg oral Mesalamine () ; within eight hours she experienced headache, fever, intensive abdominal colic, profuse diarrhea and was readmitted as an emergency. She responded poorly to steroid therapy and two weeks later a pancolectomy was required.
Although renal abnormalities were not noted in the clinical trials with Mesalamine () rectal suspension, the possibility of increased absorption of Mesalamine () and concomitant renal tubular damage as noted in the preclinical studies must be kept in mind. Patients on Mesalamine () rectal suspension, especially those on concurrent oral products which liberate Mesalamine () and those with preexisting renal disease, should be carefully monitored with urinalysis, BUN (blood urea nitrogen), and creatinine studies.
In a clinical trial most patients who were hypersensitive to sulfasalazine were able to take Mesalamine () enemas without evidence of any allergic reaction. Nevertheless, caution should be exercised when Mesalamine () is initially used in patients known to be allergic to sulfasalazine. These patients should be instructed to discontinue therapy if signs of rash or fever become apparent.
While using Mesalamine () rectal suspension, some patients have developed pancolitis. However, extension of upper disease boundary and/or flare-ups occurred less often in the Mesalamine () rectal suspension treated group than in the placebo-treated group.
Worsening of colitis or symptoms of inflammatory bowel disease, including melena and hematochezia, may occur after commencing Mesalamine () .
Rare instances of pericarditis have been reported with Mesalamine () containing products including sulfasalazine. Cases of pericarditis have also been reported as manifestations of inflammatory bowel disease. In the cases reported with Mesalamine () rectal suspension, there have been positive rechallenges with Mesalamine () or Mesalamine () containing products. In one of these cases, however, a second rechallenge with sulfasalazine was negative throughout a 2 month follow-up. Chest pain or dyspnea in patients treated with Mesalamine () rectal suspension should be investigated with this information in mind. Discontinuation of Mesalamine () rectal suspension may be warranted in some cases, but rechallenge with Mesalamine () can be performed under careful clinical observation should the continued therapeutic need for Mesalamine () be present.
Mesalamine () Adverse Reactions
Mesalamine () rectal suspension is usually well tolerated. Most adverse effects have been mild and transient.
In addition, the following adverse events have been identified during post-approval use of products which contain (or are metabolized to) Mesalamine () in clinical practice: nephrotoxicity, pancreatitis, fibrosing alveolitis and elevated liver enzymes. Cases of pancreatitis and fibrosing alveolitis have been reported as manifestations of inflammatory bowel disease as well. Published case reports and/or spontaneous postmarketing surveillance have described rare instances of aplastic anemia, agranulocytosis, thrombocytopenia, eosinophilia, pancytopenia, neutropenia, oligospermia, and infertility in men. Anemia, leukocytosis, and thrombocytosis can be part of the clinical presentation of inflammatory bowel disease.
Mesalamine () Overdosage
There have been no documented reports of serious toxicity in man resulting from massive overdosing with Mesalamine () . Under ordinary circumstances, Mesalamine () absorption from the colon is limited.
Mesalamine () Dosage And Administration
The usual dosage of Mesalamine () rectal suspension USP in 60 mL units is one rectal instillation (4 grams) once a day, preferably at bedtime, and retained for approximately eight hours. While the effect of Mesalamine () rectal suspension USP may be seen within 3 to 21 days, the usual course of therapy would be from 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Studies available to date have not assessed if Mesalamine () rectal suspension will modify relapse rates after the 6 week short-term treatment. Mesalamine () rectal suspension USP is for rectal use only.
Patients should be instructed to shake the bottle well to make sure the suspension is homogeneous. The patient should remove the protective sheath from the applicator tip. Holding the bottle at the neck will not cause any of the medication to be discharged. The position most often used is obtained by lying on the left side (to facilitate migration into the sigmoid colon); with the lower leg extended and the upper right leg flexed forward for balance. An alternative is the knee-chest position. The applicator tip should be gently inserted in the rectum pointing toward the umbilicus. A steady squeezing of the bottle will discharge most of the preparation. The preparation should be taken at bedtime with the objective of retaining it all night. Patient instructions are included with every seven units.
Mesalamine () How Supplied
Mesalamine () rectal suspension USP, 4 g/60 mL for rectal administration is a off-white to tan colored suspension. Each disposable enema bottle contains 4 grams of Mesalamine () in 60 mL aqueous suspension. Enema bottles are supplied in boxed, foil-wrapped trays of seven. Mesalamine () rectal suspension USP, 4 g/60 mL is for rectal use only.
Patient instructions are included.
Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature]. Once the foil-wrapped unit of seven bottles is opened, any bottles remaining after 14 days should be discarded.
Manufactured By:
Sellersville, PA 18960
Rev. C 8/2008
Mesalamine ()
Mesalamine () Principal Display Panel
Mesalamine ()
RECTAL SUSPENSION, USP
4 g/60 mL
FOR RECTAL USE ONLY
7x60 mL UNIT-DOSE BOTTLES
TEVA
