MESASAL TABLETS 250 mg; MESASAL TABLETS 500 mg

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

MESASAL TABLETS 250 mg
MESASAL TABLETS 500 mg

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

MESASAL TABLETS 250 mg
MESASAL TABLETS 500 mg

COMPOSITION:
Mesasaltablets are controlled release, enteric coated tablets containing either 250 mg or 500 mg of mesalazine (5-amino-salicylic acid) (5-ASA).

PHARMACOLOGICAL CLASSIFICATION:
A.11.9.2 Antidiarrhoeals (other)

PHARMACOLOGICAL ACTION:
Pharmacodynamics properties:
The mode of the anti-inflammatory action of 5- ASA is unknown although there are several possibilities:

•	Inhibition of prostaglandin synthesis (via inhibition of cyclo-oxygenase) thereby down-regulating the production of inflammatory prostaglandins.
•	Inhibition of the chemotactic leukotriene synthesis (via inhibition of lipoxygenase) thereby reducing inflammation.
•	Inhibition of the macrophage and neutrophil chemotaxis in inflamed tissue
•	The scavenging of oxygen free radicals

Pharmacokinetics properties
Oral Administration
In patients with Crohn’s disease or ulcerative colitis:

•	Oral doses of 500 mg mesalazine t.i.d. steady-state plasma concentration of 5-ASA and Ac-5-ASA (its major metabolite) averaged 0.7 and 1.2 mcg/mL, respectively
•	Oral doses of 250 mg mesalazine t.i.d. steady-state concentration of 5-ASA and Ac-5- ASA averaged 0.4 and 1.0 mcg/mL, respectively

Peak drug and metabolism levels with delayed release preparations generally occur about 5 hours after drug administration.
Urinary (44%) and faecal (35%) recovery (at the higher dose) indicate that 5-ASA is available both for local and systemic action.
Fasted, healthy subjects:
Time to peak plasma concentrations of 1.3 mcg/mL and 2.3 mcg/mL of 5- ASA and Ac-5-ASA respectively were obtained after 6 hours

INDICATIONS:
Mesasalis indicated in:

1.	The treatment of acute ulcerative colitis
2.	Maintenance of remission of ulcerative colitis
3.	Acute treatment of Crohn’s Disease
4.	Maintenance of remission of Crohn’s Disease

CONTRA-INDICATIONS:
Mesasalshould not be used in cases where there is a history of hypersensitivity to salicylates.
It is not indicated in cases of existing gastric and duodenal ulcers. Safety in pregnancy has not been established. In the first three months of pregnancy, treatment is only recommended if absolutely indicated. It should not be given in the last week of pregnancy or during lactation.
Mesasalshould not be used in cases of haemorrhagic diathesis

WARNINGS:
Refer to SIDE –EFFECTS AND SPECIAL PRECAUTIONS.

DOSAGE AND DIRECTIONS FOR USE:
During the acute inflammatory stage and in the long term maintenance therapy Mesasalmust be taken reliably and consistently by the patient in order to ensure the desired therapeutic success.
The safety and effectiveness of mesalazine in children under 5 years of age has not been established.
Mesasaltablets should be taken before meals with plenty of fluids.
The following dosage regimens are recommended:

1.	For the treatment of acute ulcerative colitis and Crohn’s Disease:
	500 mg three times a day (total daily dose 1.5 grams)
2.	For prevention of relapses in the cases of ulcerative colitis:
	250 –500 mg three times a day.
3.	For maintenance of remission of Crohn’s Disease:
	500 mg three times a day.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Adverse effects:
The following events have been reported:
Gastro-intestinal system: Nausea, Abdominal pain, diarrhoea and pancreatitis. Exacerbation of symptoms of colitis has been reported.
Central Nervous System: Headache, neuropathy.
Skin and Appendages: Rash (including pruritis and urticaria).
Renal: Cases of acute and chronic interstitial nephritis and renal failure have been reported. Drug induced toxicity should be considered in patients developing renal failure during mesalazine treatment. The drug is also best avoided in patients with established renal impairment.
Hepatobiliary: In common with other salicylates, transitory abnormal liver function tests. Hepatitis.
Haematological effects: Alteration in peripheral blood counts such as leucopenia, neutropenia, thrombocytopenia and aplastic anaemia have been reported less frequently.
Hypersensitivity: Hypersensitivity reactions including pulmonary and cardiac changes have been reported. These reactions include fever, myalgia, arthralgia, alveolitis, myocarditis and pericarditis although these have been reported as extra-intestinal manifestation of underlying bowel disease.

Precautions:
Caution should be exercised when administering the mesalazine to patients:

•	With severe renal and hepatic impairment ( given that 5-ASA is primarily eliminated through acetylation and subsequent urinary excretion)
•	With a history of hypersensitivity to sulphasalazine, although in general, hypersensitivity reactions to mesalazine appear to be less frequent than those observed for sulphasalazine.

Mesalazine should not be given with lactulose or similar preparations which lower stool pH and may prevent release of mesalazine.

Drug interactions:
Interaction of mesalazine with coumarins, probenecid, sulfinpyrazone, sulphonylureas, spironolactone, furosemide and rifampicin cannot be excluded. Mesalazine may delay the excretion of methotrexate.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Symptoms of overdosage include that of salicylism. Treatment consists of gastric lavage/ vomiting, together with supportive and symptomatic measures. There is no specific antidote.

IDENTIFICATION:

MESASAL tablets 250 mg:	Round, biconvex, tan coated tablets.
MESASAL tablets 500 mg:	Oval, red-orange, coated tablets.

PRESENTATION:

MESASAL tablets 250 mg:	Blister packs of 100.
MESASAL tablets 500 mg:	Blister packs of 100.

STORAGE INSTRUCTIONS:
Store in a cool dry place below 25°C and protect from light
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:

MESASAL tablets 250 mg:	Y/11.9.2/6
MESASAL tablets 500 mg:	Y/11.9.2/7

NAME AND BUSINESS ADDRESS OF THE APPLICANT
PHARMACARE LTD
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton
2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
21 October 1991

New addition to this site: January 2007
Source: Pharmaceutical Industry

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PB Mesasal 254 8500 0.indd 2	30.05.2006 11:00:41Uhr