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

Swallow whole with water. Do not break, crush or chew the tablets before swallowing.

Adults:

Acute disease: 6 tablets a day in divided doses, with concomitant corticosteroid therapy where clinically indicated.

Maintenance therapy: 3-6 tablets a day in divided doses.

Elderly:

The normal adult dosage may be used unless renal function is impaired (see section 4.4).

Children:

There is no dosage recommendation.

Route of administration:

Oral.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

A history of sensitivity to salicylates or renal sensitivity to sulphasalazine.

Confirmed severe renal impairment (GFR less than 20 ml/min). Children under 2 years of age.

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs), including Drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment.

Mesalazine should be discontinued, at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.

Use in the elderly should be cautious and subject to patients having normal renal function.

Renal disorder: Mesalazine is excreted rapidly by the kidney, mainly as its metabolite, N-acetyl-5-aminosalicylic acid. In rats, large doses of mesalazine injected intravenously produce tubular and glomerular toxicity. Mesalazine should be used with extreme caution in patients with confirmed mild to moderate renal impairment (see section 4.3). Patients on mesalazine should have renal function monitored, (with serum creatinine levels measured) prior to treatment start. Renal function should then be monitored periodically during treatment, for example every 3 months for the first year, then 6 monthly for the next 4 years and annually thereafter, based on individual patient history. Physicians should take into account risk factors such as prior and concomitant medications, duration and severity of disease and concurrent illnesses. Treatment with mesalazine should be discontinued if renal function deteriorates. If dehydration develops, normal electrolyte and fluid balance should be restored as soon as possible.

Mesalazine may produce red-brown urine discoloration after contact with sodium hypochlorite bleach (e.g., in toilets cleaned with sodium hypochlorite contained in certain bleaches)

Serious blood dyscrasias have been reported very rarely with mesalazine. Haematological investigations should be performed if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat. Treatment should be stopped if there is suspicion or evidence of blood dyscrasia.

Cases of nephrolithiasis have been reported with the use of mesalazine including stones with a 100% mesalazine content. It is recommended to ensure adequate fluid intake during treatment.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. is essentially "sodium-free".

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).

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

No information is available with regard to teratogenicity; however, negligible quantities of mesalazine are transferred across the placenta and are excreted in breast milk following sulphasalazine therapy. Use during pregnancy should be with caution, and only if the potential benefits are greater than the possible hazards. Mesalazine should, unless essential, be avoided by nursing mothers.

Not applicable.

Severe cutaneous adverse reactions (SCARs), including Drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment (see section 4.4).

The side effects are predominantly gastrointestinal, including nausea, diarrhoea, vomiting and abdominal pain. 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, pleurisy, 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 has 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 of colitis, Stevens Johnson syndrome and erythema multiforme.

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

Skin and subcutaneous tissue disorders

Frequency not known:

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN)

Renal and urinary disorders

Frequency not known: nephrolithiasis*

* See section 4.4 for further information

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Following overdose, gastric lavage, intravenous transfusion of electrolytes to promote diuresis and standard supportive measures are recommended. There is no specific antidote.

Mesalazine (5-aminosalicylic acid) is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter which is responsible for the majority of the side effects associated with sulphasalazine therapy whilst mesalazine is known to be the active moiety 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.

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.

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.

Not applicable.

36 months.

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

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

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

No special requirements.