BUDENOFALK Rectal foam Ref.[6671] Active ingredients: Budesonide

Absorption

After oral application the systemic availability of budesonide is about 10%. After rectal administration the areas under the concentration time curves are about 1.5-fold higher than in historical controls considering the identical oral budesonide dose. Peak levels are obtained after an average of 2-3 hours after administering Budenofalk 2mg rectal foam.

Distribution

Budesonide has a high volume of distribution (about 3 L/kg). Plasma protein binding averages 85-90%.

Biotransformation

Budesonide undergoes extensive biotransformation in the liver (approximately 90%) 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.

Elimination

The average elimination half-life is about 3-4 hours. The mean clearance rate is about 10-15 L/min for budesonide, determined by HPLC-based methods.

Spread

A scintigraphic investigation with technetium-marked Budenofalk 2mg rectal foam on patients with ulcerative colitis showed that the foam spreads out over the entire sigmoid.

Specific patient populations (liver diseases)

Dependent on the type and severity of liver diseases the metabolism of budesonide might be decreased.

Preclinical investigations on dogs have shown that Budenofalk 2mg rectal foam is well tolerated locally.

Preclinical data in acute, subchronic and chronic toxicological studies with budesonide showed atrophies of the thymus gland and adrenal cortex and a reduction especially of lymphocytes. These effects were less pronounced or at the same magnitude as observed with other glucocorticosteroids. These steroid effects might also be of relevance in man.

Budesonide had no mutagenic effects in a number of in vitro and in vivo tests.

A slightly increased number of basophilic hepatic foci were observed in chronic rat studies with budesonide, and in carcinogenicity studies there was an increased incidence of primary hepatocellular neoplasms, astrocytomas (in male rats) and mammary tumours (female rats) observed. These tumours are probably due to the specific steroid receptor action, increased metabolic burden on the liver and anabolic effects, effects which are also known from other glucocorticosteroids in rat studies and therefore represent a class effect. No similar effects have ever been observed in man for budesonide, neither in clinical trials nor from spontaneous reports.

In general, preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential.

In pregnant animals, budesonide, like other glucocorticosteroids, has been shown to cause abnormalities of foetal development, but the relevance to man has not been established (see also section 4.6).