For the use of a Registered Medical Practitioner or a Hospital or a laboratory only
Mesalamine Suppositories
Composition:
Each Suppository Contains:
Mesalamine USP 500mg
Fatty Base q.s
Clinical Pharmacology:
Mesalamine is also known as mesalazine or 5-aminosalicylic acid (5-ASA). Mesalamine is an anti-inflammatory drug.
Mechanism of Action:
The mechanism of action of Mesalamine is not fully understood, but appears to be topical rather than systemic. Although the pathology of inflammatory bowel disease is uncertain, both prostaglandins and leukotrienes have been implicated as mediators of mucosal injury and inflammation. Recently, however, the role of Mesalamine as a free radical scavenger or inhibitor of tumor necrosis factor (TNF) has also been postulated.
Pharmacokinetics:
Mesalamine administered as a rectal suppository is variably absorbed. In patients with ulcerative colitis treated with Mesalamine 500 mg rectal suppositories, administered once every eight hours for six days, the mean Mesalamine peak plasma concentration (C max) was 353 ng/mL following the initial dose and 361 ng/mL at steady state. The mean minimum steady state plasma concentration (Cmax) was 89ng/mL. Absorbed Mesalamine does not accumulate in the plasma.
Mesalamine administered as rectal suppositories distributes in rectal tissue to some extent. In patients with ulcerative procititis treated with Mesalamine rectal suppositories, recta tissue concentrations for 5-ASA and N-acetyl- 5- ASA have not been rigorously quantified.
Mesalamine is extensively metabolized, mainly to N-acetyl- 5- ASA. The site of metabolism has not been elucidated. In patients with ulcerative colitis treated with one 500mg Mesalamine rectal suppository every eight hours for six days, peak concentration (C max) of n-acetyl-5- ASA ranged from 467ng/mL to 1399 ng/mL following the initial dose and from 193 ng/mL to 1304 ng/mL at steady state.
Mesalamine is eliminated from plasma mainly by urinary excretion, predominantly as N-acetyl-5-ASA. In patients with ulcerative proctitis treated with one Mesalamine 500mg rectal suppository every eight hours for six days, ≤12% of the dose was eliminated in urine as unchanged 5-ASA and 8-77% as N-acetyl-5-ASA following the initial dose. At steady state, ≤11% of the dose was eliminated as unchanged 5-ASA and 3-35% as N-acetyl-5-ASA. The mean elimination half life was five hours for 5-ASA and six hours for N-acetyl-5-ASA and N-acetyl-5-ASA.
Indications:
Mesacol suppository is indicated for the treatment of active ulcerative proctitis.
Contraindications:
Warnings and 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 preformed 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. 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 suppository, especially those on concurrent oral products which contain or release Mesalamine and those with pre-existing renal disease should be carefully monitored with urinalysis, BUN and creatinine testing.
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.
A small proportion of patients have developed pancolitis while using Mesalamine. However, extension of upper disease boundary and/or flare-ups occurred less often in the Mesalamine treated group than in the placebo treated group.
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 there have been positive rechallenges with mesalamine or with Mesalamine containing products. Chest pain or dyspnea in patient treated with mesalamine should be investigated with this information in mind. Discontinuation of mesalamine suppositories may be warranted in some cases, but rechallenge with mesalamine can be preformed under careful clinical observation should be continued therapeutic need for mesalamine be present.
Mesalamine is excreted rapidly by the kidney, mainly as its metabolite, N-acetyl-5aminosalicylic acid. Mesalamine should be used with extreme caution in patients with confirmed mild to moderate renal impairment. Treatment with mesalamine should be discontinued if renal function deteriorates. If dehydration develops, normal electrolyte and fluid balance should be restored as soon as possible.
Use of mesalamine in the elderly should be cautious and subject to patients having normal renal function.
Serious blood dyscrasias have been reported very rarely with mesalamine. Hematological investigations should be preformed if the patient develops unexplained bleeding, bruising, purpura, anemia, fever or sore throat. Treatment should be stopped if there is suspicion or evidence of blood dyscrasias.
Pregnancy and Lactation:
There are no adequate and well controlled studies in pregnant women. No information is available with regard to teratogenicity; however, negligible quantities of mesalamine are transferred across the placenta and are excreted in breast milk following sulphasalazine therapy. Use of mesalamine during pregnancy should be with caution, and only if the potential benefits are greater than the possible hazards.
It is not unknown whether mesalamine or its metabolite(s) are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when mesalamine suppositories administered to a nursing woman.
Drug Interactions:
Concurrent use of other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reactions.
Side effects:
The most commonly reported adverse effects with mesalamine suppositories were headache, abdominal pain, hair loss, diarrhea, nausea, rectal pain, acne, fever, colitis, dizziness, and rash. Rarely, local irritation may occur.
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.
Dosage and Administration :
Mesacol suppository is for rectal use only and not to be taken by mouth.
The usual dosage of mesalamine suppositories in one 500 mg rectal suppository 2 times daily with possible increase to 3 times daily if inadequate response at two weeks.
The suppository should be retained for one to three hours or longer, if possible, to achieve the maximum benefit. While the effect of mesalamine suppositories may be seen within three to twenty one days, the usual course of therapy would be from three to six weeks depending on symptoms and sigmoidoscopic findings. Studies have suggested that mesalamine suppositories will delay relapse after the six weeks short term treatment.
Elderly: The normal adult dosage may be used unless renal function is impaired.
Patients Instructions:
Note: Mesalamine suppositories will cause staining of direct contact surfaces, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel.
Please refer "How to use" section for detained patient instructions.
Storage:
Store in a cool and dry place, below 25 degrees C. Keep out of reach of children.
Presentation:
Mesacol suppositories are available in strips of 5.
Manufactured in India by:
BLISS GVS PHARMA LTD.
10, Dewan Udyog Nagar, Aliyali,
Palghar, Maharastra- 401 404
Marketed by:
Sun Pharmaceutical ind. Ltd.
Acme Plaza, Andheri-Kurla Road
Andheri (East), Mumbai- 400 059.
Mesacol Suppository
How to use: