ENDOFER 10 g/100 ml, roztwór do wstrzykiwań dla świń i bydła

Pharmacotherapeutic group: Intestinal anti-inflammatory agents, Corticosteroids acting locally ATC code: A07E A06 Mechanism of action The exact mechanism of action of budesonide in the treatment of UC and MC is not fully understood. In general, budesonide inhibits many inflammatory processes including cytokine production, inflammatory cell activation and expression of adhesion molecules on endothelial and epithelial cells. At doses clinically equivalent to prednisolone, budesonide gives significantly less HPA axis suppression and has a lower impact on inflammatory markers. Data from clinical pharmacology and pharmacokinetic studies indicate that the mode of action of Cortiment tablets is based on a local action in the gut. Pharmacodynamic effects MMX extended release technology is characterised by a multi-matrix structure covered by a gastro-resistant coating that dissolves in intestinal fluids having a pH greater than 7. When the dosage form is administered, the gastro-protective layer protects the dosage form during transit through the stomach and duodenum up to the lower part of the intestine. When the protective layer is lost, the intestinal fluid then comes into contact with the hydrophilic matrix polymers, which start to swell until a viscous gel matrix is formed. The solvent that penetrates into the gel matrix dissolves the active ingredient from the lipophilic matrices. Budesonide is then released into the intestinal tract at a controlled rate throughout the colon. Budesonide is a glucocorticoid used in the treatment of inflammatory bowel disease. It has a topical anti-inflammatory activity but does not reduce cortisol levels to the same extent as systemic glucocorticoids. Clinical efficacy Ulcerative colitis: Two randomised, controlled phase III clinical trials including 1022 patients with mild to moderate active UC have been performed in adult patients. Two hundred fifty five (255) patients were treated for 8 weeks with Cortiment 9 mg per day. Patients included were either treatment naïve (42% ITT) or had failed on 5-ASA (58% ITT). Both studies included a reference arm, mesalazine (Asacol) and budesonide (Entocort), respectively to show assay sensitivity. The definition of remission applied in both studies was UCDAI score of ≤ 1, with 0 score for rectal bleeding and stool frequency, normal mucosa (no friability) and ≧1 point reduction in endoscopy score. Effect of Cortiment 9mg tablet on Primary Endpoint: Study Cortiment 9 mg Remission (%) Placebo Remission (%) P= Study CB-01-02/01 17.9 7.4 0.0143 Study CB-01-02/02 17.4 4.5 0.0047 Statistical difference versus placebo was reached for Cortiment 9 mg for both studies and the difference versus placebo was 10.4% and 12.9% respectively. 5-ASA is the Standard of Care for treatment of mild to moderate disease. Results of a head to head comparison with Cortiment and 5-ASA were not available. Therefore, the place in the therapeutic work-up remains to be established. Some patients may benefit from treatment initially with Cortiment. Evidence for the indication microscopic colitis (collagenous colitis and lymphocytic colitis) is presented below. This evidence comes from studies on budesonide product Entocort. The systemic availability of this product is similar to that of budesonide product Cortiment (see section 5.2). Collagenous colitis: Two randomised, double-blind, placebo-controlled induction studies of six and eight weeks duration investigated the clinical and histological effects of budesonide 9 mg/day in the treatment of collagenous colitis. In the first study, 23 patients were randomised to budesonide 9 mg/day and 22 patients to placebo for 6 weeks. The rate of clinical remission was significantly higher (p<0.001) in the budesonide group than in the placebo group 86.9% vs. 13.6%. Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in one patient of the placebo group (4.5%; p<0.001). In the second study, 10 patients were randomised to budesonide for 8 weeks (9 mg/day 4 weeks, 6 mg/day 2 weeks, and 3 mg/day 2 weeks) and ten to placebo. All 10 patients receiving budesonide had a clinical response compared with two in the placebo group (p<0.001). Two open-label studies (run-in phase of randomised, double-blind, placebo-controlled maintenance studies) investigated the efficacy of budesonide 9 mg/day during 6 weeks. In the first study, 46 patients (96%) achieved clinical remission within 2–30 (mean 6.4) days, with marked improvements in stool consistency. In the second study, of the 42 patients who commenced the study, 34 patients (81%) were in clinical remission (mean stool frequency of three or fewer per day) at week 6. Lymphocytic colitis: Evidence for this indication is limited. One randomised, double-blind placebo-controlled study was carried out in 15 lymphocytic colitis patients. Eleven subjects were treated with budesonide 9 mg/day and four patients received placebo for 8 weeks. A clinical response (defined as at least 50% improvement in the frequency of bowel movements) was seen in 25% of the placebo group vs. 91% in the budesonide group (p=0.03). Paediatric Population Cortiment was not studied in the paediatric population.