Asacol Tablets

Ulcerative Colitis : ASACOL is used for the treatment and maintenance of remission in ulcerative colitis.

The tablets should be swallowed whole with a glass of water one hour before food intake. They must not be chewed, crushed or broken before swallowing. If one or more doses have been missed, the next dose is to be taken as usual.

ADULTS: Ulcerative Colitis: ASACOL 400 mg: Induction of remission : 2,4 g (six tablets) once daily or divided in 2 - 3 times daily. If required, the dose may be increased to 4,8 g (twelve tablets) divided in 2 - 3 times daily. 2,4 g may be taken once daily or in divided doses. Above 2,4 g should be taken in divided doses. Maintenance of remission : 1,6 to 2,4 g (4 to 6 tablets) once daily or divided in 2 - 3 times daily. The dose can be adjusted in accordance with the response to the treatment.

ASACOL 800 mg: u2022 Mild acute disease : 2,4 g (three tablets) once daily or divided in 2 - 3 times daily, with concomitant corticosteroid therapy where clinically indicated. u2022 Moderate acute disease : 2,4 g to 4,8 g (three to six tablets) divided in 2 - 3 times daily, with concomitant corticosteroid therapy where clinically indicated. 2,4 g may be taken once daily or in divided doses. Above 2,4 g should be taken in divided doses. u2022 Maintenance therapy : 1,6 g to 2,4 g (two to three tablets) taken once daily or in divided doses. The maximum adult dose should not exceed six tablets a day and not exceed 3 tablets taken together at any one time.

ELDERLY: The normal adult dosage may be used unless renal or liver function is severely impaired (see CONTRAINDICATIONS and WARNINGS AND SPECIAL PRECAUTIONS).

Hypersensitivity to mesalazine or to any of the other ingredients of ASACOL tablets

Sensitivity to salicylates

Severe renal impairment (GFR less than 30 mu2113 per minute)

Severe liver impairment

Gastric and duodenal ulcers

Bleeding tendency

Blood tests (differential blood count, liver function parameters such as ALT or AST; serum creatinine) and urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating medical practitioner. As a guideline, follow-up tests are recommended 14 days after commencement of treatment and then every 4 weeks for the following 12 weeks. If the findings are normal, follow-up tests should be carried out every three months. If additional signs appear, these tests should be performed immediately.

Renal impairment: Not recommended in patients with renal impairment. Caution should be exercised in patients with a raised blood urea or proteinuria. The possibility of ASACOL-induced nephrotoxicity should be suspected in patients developing impairment of renal function during treatment. Treatment with ASACOL should be stopped immediately if there is evidence of renal impairment and patients should seek immediate medical advice.

Liver impairment: There have been reports of increased liver enzyme levels in patients taking ASACOL. Caution is advised if ASACOL is given to patients with liver impairment (see CONTRAINDICATIONS).

Blood dyscrasia: Serious blood dyscrasia has been reported. Treatment with ASACOL should be stopped immediately if a blood dyscrasia (signs of unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat) is suspected or present and patients should seek immediate medical advice (see SIDE EFFECTS).

Pulmonary disease: Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment with ASACOL tablets.

Cardiac hypersensitivity reactions: Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported with ASACOL. In case of previous mesalazine-induced cardiac hypersensitivity ASACOL must not be reintroduced. Caution should be used in patients with previous myo- or pericarditis of allergic background regardless of its origin.

Hypersensitivity to Sulphasalazine: In patients with a history of hypersensitivity to sulphasalazine, therapy should be initiated only under close medical supervision. Treatment must be stopped immediately if acute symptoms of intolerance occur such as cramps, abdominal pain, fever, severe headache or rash.

Tablets in stool: A limited number of reports of intact tablets in the stool have been received. What appear to be intact tablets may in some cases represent largely empty shells of the tablet coating. ASACOL tablets release their content in the lower gut even if the coating does not dissolve entirely. Once pH 7,0 is reached, cracks in the coating are sufficient for the release of mesalazine from the tablets. This process is irreversible from here on and mesalazine will therefore be released continuously, independent of intestinal pH. If tablets are observed in the stool repeatedly, the patient should consult his/her medical practitioner.

Elderly patients: Use in elderly patients should be handled with caution and ASACOL should only be prescribed to patients having a normal renal and hepatic function (see CONTRAINDICATIONS).

Paediatric patients: There is only limited documentation for an effect in children (age 6 - 18 years).

Gastric and duodenal ulcers: In case of existing gastric or duodenal ulcers treatment should begin with caution based on theoretical grounds.

Co-administration of immunosuppressive agents such as azathioprine or 6-MP can precipitate leucopenia (see INTERACTIONS).

Concurrent use of NSAIDs or azathioprine may increase the risk of renal reactions (see INTERACTIONS).

ASACOL should not be given with preparations which lower stool pH, e.g. lactulose, and which prevent release of the active ingredient.

Sulphasalazine decreases the absorption of digoxin. There are no data on interaction of digoxin with ASACOL.

There is weak evidence that ASACOL might decrease the anticoagulant effect of warfarin, frequent INR monitoring is advisable.

ASACOL can increase the immunosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine. Life-threatening infection can occur. Patients should be closely observed for signs of infection and immunosuppression. Haematological parameters, such as leukocyte and lymphocyte cell counts should be monitored regularly (weekly), especially at initiation of such combination therapy (see WARNINGS AND SPECIAL PRECAUTIONS). If white blood cells are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by 3 monthly monitoring intervals appears to be justified.

The concurrent use of known nephrotoxic medicines, such as NSAIDs or azathioprine, may increase the risk of renal reactions. However, no adverse events proving such interactions have been reported (see WARNINGS AND SPECIAL PRECAUTIONS).

The uricosuric activity of sulfinpyrazone, and the diuretic effect of furosemide can be reduced.

Safety in pregnancy and lactation has not been established.

ASACOL tablets may influence the ability to drive and use machines. The tablets contain lactose monohydrate. Patients with the rare hereditary conditions of galactose intolerance, e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption should not take ASACOL.

Side effects are presented by system organ class according to the following frequencies:

Very common: u2265 10 % patients

Common: u2265 1 % and < 10 % patients

Uncommon: u2265 0,1 % and < 1 % patients

Rare: u2265 0,01 % and < 0,1 % patients

The only very common side effect was headache, which occurred in approximately 17,8 % of patients. The following common side effects were reported: nausea (8,4 %), dyspepsia (7,5 %), abdominal pain (4,3 %), dizziness (4,0 %), rash (2,8 %), vomiting (2,5 %), arthralgia (2,3 %), diarrhoea (1,8 %) and fever (1,7 %).

Tabulated summary of side effects:

System Organ Class Common Uncommon Rare Very rare Frequency not known

Blood and the lymphatic system disorders anaemia eosinophilia (as part of an allergic reaction) altered blood counts (aplastic anaemia, agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia) bone marrow depression, blood disorder

Immune system disorders hypersensitivity reactions such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis

Nervous system disorders paraesthesia tinnitus headache, dizziness peripheral neuropathy vertigo

Cardiac disorders myocarditis, pericarditis

Respiratory, thoracic and mediastinal disorders allergic and fibrotic lung reactions (including dyspnoea, cough bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), interstitial pneumonia, eosinophilic pneumonia, lung disorder pleurisy pneumonia, chest pain

Gastrointestinal disorders dyspepsia abdominal pain, diarrhoea, flatulence, nausea, vomiting acute pancreatitis exacerbation of the symptoms of colitis

Hepato-biliary disorders changes in liver function parameters (increase in transaminases and cholestasis parameters), hepatitis, cholestatic hepatitis hepatic function abnormal/ abnormal liver function tests, increased blood bilirubin

Skin and subcutaneous tissue disorders rash pruritus, urticaria photo= sensitivity* alopecia Stevens Johnson syndrome, erythema multiforme, bulbous skin reactions

Musculoskeletal, connective tissue and bone disorders myalgia, arthralgia lupus-like syndrome with pericarditis and pleuropericarditis as prominent symptoms as well as rash and arthralgia

Renal and urinary disorders impairment of renal function including acute and chronic interstitial nephritis, renal insufficiency, nephrotic syndrome and renal failure which may be reversible on early withdrawal

Reproductive system and breast disorders oligospermia (reversible)

General disorders and administrative site conditions pyrexia, chest pain intolerance to mesalazine with C-reactive protein increased and/or exacerbation of symptoms of underlying disease

Investigations increased blood creatinine, amylase, red blood cell sedimentation rate, lipase and BUN decreased weight and creatinine clearance

Description of selected adverse reactions: An unknown number of the above mentioned undesirable effects are probably associated to the underlying IBD rather than ASACOL medicine. This holds true especially for gastrointestinal undesirable effects, arthralgia, and alopecia. To avoid blood dyscrasia resulting from developing bone marrow depression patients should be monitored with care (see WARNINGS AND SPECIAL PRECAUTIONS). Under co-administration of mesalazine contained in ASACOL with myelosuppressive drugs, such as azathioprine, or 6-MP, or thioguanine, life-threatening infection can occur (see INTERACTIONS).

*Photosensitivity: More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.

Paediatric population: There is only limited safety experience with the use of ASACOL tablets in the paediatric population. It is expected that the target organs of possible adverse reactions in the paediatric population are the same as for adults (heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue).

Symptoms of overdosage include that of salicylism: mixed acidosis-alkalosis, hyperventilation, pulmonary oedema, dehydration as a result of sweating and vomiting, and hypoglycaemia. There is no specific antidote. Treatment is symptomatic and supportive.