POM: Prescription only medicine
This information is intended for use by health professionals
ADULTS:Mild acute exacerbations of ulcerative colitis: Three tablets (2.4g) a day in divided doses.Moderate acute exacerbations of ulcerative colitis: Six tablets (4.8g) a day in divided doses.Maintenance of remission of ulcerative colitis: Up to three tablets (2.4g) a day once daily or in divided doses. Maintenance of remission of Crohn's ileocolitis: Up to three tablets (2.4g) a day in divided doses. ELDERLY: The normal adult dosage may be used unless renal function is impaired (see section 4.4).CHILDREN: Not recommended.
Geriatric UseUse in the elderly should be cautious and subject to patients having normal renal function
IntoleranceDiscontinue treatment immediately if acute symptoms of intolerance occur including vomiting, abdominal pain or rash. This medicine contains lactose. Patients with the rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine because of the presence of lactose monohydrate.Mesalazine inhibits the thiopurine methyl-transferase (TPMT) activity in vitro and may therefore impair the metabolism of azathioprine and 6-mercaptopurine. Standard haematological indices (including the white cell count) should be monitored repeatedly in patients taking azathioprine, especially at the beginning of such combination therapy, whether or not mesalazine is prescribed.
Renal disorderMesalazine 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. Asacol 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 every 6 months 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.
Blood DyscrasiasSerious blood dyscrasias (some with fatal outcome) have been reported very rarely with mesalazine. Haematological investigations including a complete blood count may be performed prior to initiation and whilst on therapy according to the physician's judgement. Such tests should be done immediately 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.
PregnancyMesalazine is known to cross the placental barrier, but the limited data available on its use in pregnant women do not allow accurate assessment of possible adverse effects. Mesalazine should therefore be used with caution during pregnancy and lactation when the potential benefit outweighs the possible hazards in the opinion of the physician. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
LactationLow concentrations of mesalazine and higher concentrations of its N-acetyl metabolite have been detected in human milk. While the clinical significance of this has not been determined, caution should be exercised when mesalazine is administered to a nursing woman. Hypersensitivity reactions like diarrhoea cannot be excluded. Therefore, if the suckling neonate develops suspected adverse reactions consideration should be given to discontinuation of breast-feeding or discontinuation of treatment of the mother.
|Adverse Event*||Asacol 800 mg (4.8 g/day) N = 213 (%)||Mesalazine 400 mg (2.4 g/day) N = 235 (%)|
|HeadacheAbdominal painDiarrhoea Nausea Respiratory infectionExacerbation of colitisDyspepsiaVomiting FlatulenceRectal disorderFlu syndromeRashIncreased cough SinusitisRhinitis||16 (7.5%) 9 (4.2%) 8 (3.8%) 8 (3.8%)7 (3.3%) 6 (2.8%) 6 (2.8%)6 (2.8%) 5 (2.3%) 4 (1.9%)3 (1.4%) 3 (1.4%) 1 (0.5%) 1 (0.5%)0 (0.0%)||14 (6.0%)12 (5.1%)9 (3.8%) 4 (1.7%) 4 (1.7%)6 (2.6%)5 (2.1%) 2 (0.9%) 7 (3.0%) 6 (2.6%)8 (3.4%)5 (2.1%)9 (3.8%)5 (2.1%)7 (3.0%)|
Moderately active ulcerative colitis:Two active-controlled trials enrolled a total of 687 patients comparing Asacol 4.8 g/day (800 mg formulation) with mesalazine enteric coated tablets 2.4 g/day (400 mg formulation) in patients with mildly to moderately active ulcerative colitis. Both studies were of six weeks duration. Treatment success was defined on the basis of the Physician's Global Assessment (PGA), which took into consideration clinical assessments of rectal bleeding, stool frequency, and the patient's functional assessment and sigmoidoscopic examination. Across the two studies 4.8 g/day provided superior efficacy in patients with moderately active disease.In the first study a total of 301 patients with mildly to moderately active UC were enrolled. Of these, 169 patients with moderately active disease were assessed for efficacy in a pre-defined subgroup analysis. In these patients, 4.8 g/day gave greater treatment success than 2.4 g/day (72% treatment success compared with 57%).In the second study a total of 386 patients with mildly to moderately active ulcerative colitis were randomly assigned to treatment. In the 254 patients with moderately active disease, the pre-defined primary efficacy analysis showed that 4.8 g/day gave greater treatment success than 2.4 g/day (72% treatment success compared to 59%). In both studies, more patients showed improvement on 4.8 g/day compared to 2.4 g/day across the clinical assessments (stool frequency, rectal bleeding, sigmoidoscopy and PGA). In combined studies, 4.8 g/day showed statistically significant superiority in the sigmoidoscopy and PGA scores.At Week 3, more patients with moderately active disease achieved treatment success on 4.8 g/day compared with 2.4 g/day in each study and in the combined analysis (62% vs. 53%). These differences were not statistically significant.In combined studies among patients with moderately active disease, the efficacy benefit of 4.8 g/day over 2.4 g/day was consistent across various subgroups including age, gender, race, ulcerative colitis disease history, prior medication usage and extent of disease (proctitis, proctosigmoiditis, left-sided colitis and pancolitis).
|Core||lactose monohydratesodium starch glycolatetalcpovidonemagnesium stearatecolloidal anhydrous silica|
|Coating||methacrylic acid methyl methacrylate copolymer (1:2)talcdibutyl sebacateferric oxide red (E172)methacrylic acid methyl methacrylate copolymer (1:1)ferric oxide yellow (E172)macrogol|
|Black ink containing||propylene glycol ferric oxide black (E172) ammonium hydroxide ethanol shellac glaze (bleached, de-waxed)|