Ipocol* 400mg MR Tablets or

Urotir 400mg MR Tablets

Each tablet contains 400mg Mesalazine.

Enteric coated tablets.

To treat mild to moderate ulcerative colitis and maintain ulcerative colitis in remission.

Adults:

Acute attack: 6 tablets daily in divided doses.

Maintenance: 3-6 tablets daily in divided doses.

Children:

There is only limited documentation for an effect in children (age 6 – 18 years).

Children 6 years of age and older

• Active disease: To be determined individually, starting with 30-50 mg/kg/day in divided doses. Maximum dose 75 mg/kg/day in divided doses. The total dose should not exceed 4 g/day (maximum adult dose).

• Maintenance treatment: to be determined individually, starting at 15-30 mg/kg/day in divided doses. The total dose should not exceed 2 g/day (recommended adult dose).

It is generally recommended that half the adult dose may be given to children up to a body weight of 40 kg; and the normal adult dose to those above 40 kg.

Elderly:

Caution should be employed in the treatment of elderly patients. Mesalazine should not be used where there is evidence of renal impairment.

Route of administration:

Oral.

Previous experience of salicylate hypersensitivity. Patients with severe renal impairment. Children under 2 years of age.

Mesalazine is predominantly metabolised via the kidney. Animal studies have reported that large doses of mesalazine produced nephrotoxicity.

Mesalazine treatment is therefore not recommended for use in patients suffering from mild to moderate renal impairment. If treatment is essential, it should be used with extreme caution (see Section 4.3 - Contraindications).

Mesalazine should also be used with caution in treatment of elderly patients. The possibility of renal impairment should also be established prior to treatment. If treatment is necessary, mesalazine should be used with care.

Patients on oral forms of mesalazine should have renal function monitored with serum creatinine levels measured prior to treatment start, every three months for the first year, then 6 monthly for the next 4 years and annually after that. Treatment with mesalazine should be discontinued if renal function deteriorates.

Patients receiving mesalazine should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment. A blood count should be performed and mesalazine stopped immediately if there is suspicion of blood dyscrasia.

If dehydration develops, normal electrolyte levels and fluid balance should be restored as soon as possible.

Concurrent use of lactulose and related agents should be avoided as this may lower luminal pH in the colon therefore inhibiting the disintegration of the coating and release of the mesalazine.

Concurrent use of other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reactions (see Section 4.4 - Special Warnings and Precautions for Use).

Possible increased risk of leucopenia when aminosalicylates are given with azathioprine or mercaptopurine.

Mesalazine crosses the placenta and is excreted in breast milk. Use during pregnancy or whilst breast-feeding is not recommended unless essential. In this case caution should be employed.

Mesalazine can cause nausea. If this occurs patients should avoid driving, operating machinery, or other activities requiring full alertness.

The side effects are predominantly gastrointestinal, including nausea, diarrhoea, vomiting, abdominal pain and exacerbation of symptoms of colitis. Headache has also been reported.

There have been rare reports of leucopenia, neutropenia, agranulocytosis, aplastic anaemia and thrombocytopenia, alopecia, peripheral neuropathy, pancreatitis, abnormalities of hepatic function and hepatitis, myocarditis and pericarditis, allergic and fibrotic lung reactions, lupus erythematosus-like reactions and rash (including urticaria), drug fever, interstitial nephritis and nephrotic syndrome with oral mesalazine treatment, usually reversible on withdrawal. Renal failure, methaemoglobinaemia, eosinophilia, fibrosing alveolitis, myalgia and arthralgia have also been reported. Mesalazine-induced nephrotoxicity should be suspected in patients developing renal dysfunction during treatment.

Mesalazine may very rarely be associated with an exacerbation of the symptoms Stevens Johnson syndrome, erythema multiforme and bullous skin reactions including erythema .

Other side effects observed with sulphasalazine such as depression of sperm count and function, have not been reported with mesalazine.

Following overdose, gastric lavage, transfusion of electrolytes and standard supportive measures are recommended.

Mesalazine (5-aminosalicylic acid) is the active moiety in sulphasalazine, a drug long used in the treatment of ulcerative colitis. It is understood that the activity of mesalazine in the treatment of ulcerative colitis may be due to its inhibitory effect on the lipoxygenase pathway. Leucotrienes formed by the lipoxygenase pathway are implicated in the pathogenesis of ulcerative colitis.

When given orally, mesalazine is readily absorbed from the small intestine with minimal amounts reaching the desired site of activity in the colon.

Therapeutic concentrations can only be produced by oral ingestion of a delayed or slow release preparation or by topical application (e.g. enema form).

Mesalazine enteric-coated tablets are designed to disintegrate above pH 7.0 to release the active drug.

Clearance of mesalazine from circulation is predominantly due to acetylation, forming n-acetyl-5-aminosalicylic acid which is then excreted via glomerular filtration and active renal tubular secretion. The half-life of mesalazine is approximately one hour.

Not required.

Microcrystalline cellulose, sodium carboxymethyl starch, corn starch, magnesium stearate, polyvinylpyrrolidone, mannitol, precipitated silica, dimethyl phthalate, methacrylic acid copolymer, dimethicone, talc, titanium dioxide, red ferric oxide.

None.

36 months.

Store at or below 25°C in a dry place and protect from light.

Blister strips composed of: 245μm PVC (PVDC coated), 20μm aluminium foil.

Pack sizes: 28, 30, 56, 60, 84, 90, 112, 120, 168 and 240.

Not applicable.

Sandoz Ltd

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

PL 04416/0244

10 March 1997

03/2011

* An individual name to be printed as appropriate for the intended recipient.