Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Tillotts Pharma UK Limited., Wellingore Hall, Wellingore, Lincolnshire, LN5 0HX, United Kingdom
ATC Code: A07EAO6
Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect.
A 4-week single-blind, randomized, reference-controlled, parallel-group study compared the clinical efficacy and safety of glucocorticosteroid enemas in 47 children with ulcerative colitis. 23 children (range 7-15 years) were randomized and treated with Entocort Enema and 24 children (range 6 -15 years) with Pred-Clysma enema. The primary efficacy variable was remission, defined by endoscopic improvement and absence of clinical symptoms of ulcerative colitis. The remission rate after 4 weeks was 50% in the Entocort group and 71% in the Pred-Clysma group. The difference was not statistically significant. The primary safety variable was adrenal suppression, defined by changes in plasma cortisol levels after ACTH-stimulation. There was a statistically significant difference in the percentage of patients with normal adrenal function at week 4 (Entocort 73%, Pred-Clysma 33%). (Study LD-008-0003).
The mean maximal plasma concentration after rectal administration of 2 mg budesonide is 3 nmol/L (range 1–9 nmol/L), reached within 1.5 hours. Budesonide undergoes an extensive degree (~90%) of biotransformation in the liver to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.
The metabolism of budesonide is primarily mediated by CYP3A4, a subfamily of cytochrome P450.
At recommended doses, budesonide causes no or small suppression of plasma cortisol.
The mean maximal plasma concentration after rectal administration of 2 mg budesonide is 3 nmol/L (range 1-9 nmol/L), reached within 1.5 hours.
Results from acute, subacute and chronic toxicity studies show that the systemic effects of budesonide, e.g. decreased body-weight gain and atrophy of lymphoid tissues and adrenal cortex, are less severe or similar to those observed after administration of other glucocorticosteroids.
Budesonide evaluated in six different test systems did not show any mutagenic or clastogenic effects.
An increased incidence of brain gliomas in male rats in a carcinogenicity study could not be verified in a repeat study, in which the incidence of gliomas did not differ between any of the groups with active treatment (budesonide, prednisolone, triamcinolone acetonide) and the control groups.
Liver changes (primary hepatocellular neoplasms) found in male rats in the original carcinogenicity study were noted again in a repeat study with budesonide as well as with the reference glucocorticosteroids. These effects are most probably related to a receptor effect and thus represent a class-effect.
Available clinical experience shows that there are no indications that budesonide or other glucocorticosteroids induce brain gliomas or primary hepatocellular neoplasms in man.
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