Salofalk® 250mg Tablets

Mesalazine 250mg.

For excipients, see 6.1

Enteric coated tablet

Treatment of mild to moderate acute exacerbations of ulcerative colitis and for the maintenance of remission of ulcerative colitis

Method of Administration: Oral

Adults: Acute treatment: six tablets daily in three divided doses.

Maintenance Treatment: three to six tablets daily in divided doses.

Elderly: As for adults

Patients with an active peptic ulcer, blood clotting abnormalities, severe hepatic or severe renal impairment or where there is a pathological propensity to bleeding. Salofalk® should not be used in babies and young children

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.

Reports of interstitial nephritis occurring with mesalazine treatment are uncommon, however it is advisable that renal function be monitored, with serum creatinine levels measured prior to treatment start, every 3 months for the first year, 6 monthly for the next 4 years, and then annually thereafter. Use with extreme caution in patients with mild to moderate renal impairment (see section 4.3). If dehydration develops, normal electrolyte levels and fluid balance should be restored as soon as possible.

Treatment should be stopped if there is suspicion or evidence of blood dyscrasia, or if renal function deteriorates

The hypoglycaemic action of sulphonylureas can be intensified, as can gastrointestinal haemorrhage caused by coumarins. The toxicity of methotrexate can be increased. The uricosuric action of probenecid and sulfinpyrazone can be decreased, as can the diuretic action of furosemide and the action of spironolactone. The antituberculosis action of rifampicin can also be diminished.

Concomitant use with other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reactions (see section 4.4)

Animal experiments with mesalazine have produced no evidence of embryonic effects. All competent authors recommend to continue treatment with sulfasalazine, the parent drug of mesalazine, during pregnancy. Up to now, they didn't see any untoward effect on its course or on the foetus. Therefore there is no reason to prohibit Salofalk® treatment during pregnancy. No untoward effects were seen in a reproductive and fertility study with mesalazine in breast-fed rat pups. But up to now there is a limited experience in using mesalazine/ sulfasalazine during the lactation period in man. Therefore, it should be stated that the experience with Salofalk® 250 during lactation up to now is not sufficient. The acetylated form of mesalazine is found in the breast milk in slight amounts

Salofalk® is not expected to affect ability to drive and use machines

Salofalk® may cause hypersensitivity reactions. These are unrelated to dose. Mesalazine may be associated with an exacerbation of the symptoms of colitis in those patients who have previously had such problems with sulfasalazine. There have been rare reports of leucopenia, neutropenia, agranulocytosis, aplastic anaemia and thrombocytopenia, pancreatitis, abnormalities of hepatic function, hepatitis and cholestatic hepatitis, myocarditis and pericarditis, allergic lung reactions, lupus erythematosus-like reactions, bullous skin reactions including erythema multiforme, Stevens Johnson Syndrome and rash (including urticaria), interstitial nephritis, peripheral neuropathy 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. Increased methaemoglobin levels may occur

Due to the enteric nature of the formulation of Salofalk® 250mg tablets and the particular pharmacokinetic properties of mesalazine, only small amounts of the drug are available for systemic action. Consequently signs of intoxication are unlikely even after large doses. However, in principle, symptoms consistent with salicylate intoxication may occur (management of which is shown in brackets).

– Mixed Acidosis-Alkalosis (reinstatement of the acid-base balance to match the situation and electrolytic substitutions).

– Hyperventilation

– Pulmonary Oedema

– Dehydration from perspiration and vomiting (fluid intake)

– Hypoglycaemia (glucose intake)

There is no specific antidote to mesalazine but in many cases of overdose, gastric lavage and intravenous transfusion of electrolytes to promote diuresis should be implemented

The main site of action of mesalazine is the inflamed musosa in the terminal ileum and colon. The pH dependent enteric coating applied to Salofalk® tablets (Eudragit L) disintegrates above pH 6.0 ensuring that the drug is released at the site of action, where it is absorbed to a certain degree. The absorbed portion is acetylated and excreted predominantly in the acetylated form via the kidneys. A small portion (about 5% of the absorbed quantity) is excreted in the bile. In faeces, mesalazine is found particularly in unchanged form and partially in acetylated form

The elimination half-lives are 0.7-2.4 hours (mean 1.4 ± 0.6 hours). The plasma protein binding of mesalazine is 43% and of acetylated mesalazine 78%. The rapid acetylation is not reversible and, in contrast to sulfapyridine, there is no difference between slow and rapid acetylation

None Stated

Sodium carbonate, glycine, povidone, microcrystalline cellulose (E460), colloidal anhydrous silica, calcium stearate, hydroxypropylmethylcellulose (E464), methacrylic acid copolymer (Eudragit L), talc, titanium dioxide (E171), iron oxide (E172), polyethylene glycol, polymethacrylate (Eudragit E).

None stated

Three years

None.

Orange PVC/PVDC/ AI blister strips packed in cartons containing 10†, 100 or 300† tablets.

† Not currently marketed

None stated

Dr Falk Pharma UK Ltd

Bourne End Business Park

Cores End Road

Bourne End

Buckinghamshire

SL8 5AS

PL 10341/0004.

13 September 1991.

August 2008

Not applicable

Not applicable