indication

For the treatment of mild to moderate active Crohn's disease. Also for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis.

pharmacology

Budesonide is a synthetic corticosteroid used in Crohn's disease to decrease the symptoms and inflammation associated with the disease, especially at times of flare up. Budesonide has a high topical glucocorticosteroid (GCS) activity and a substantial first pass elimination. The formulation contains granules which are coated to protect dissolution in gastric juice, but which dissolve at pH >5.5, ie, normally when the granules reach the duodenum. Thereafter, a matrix of ethylcellulose with budesonide controls the release of the drug into the intestinal lumen in a time-dependent manner.

mechanism of action

The exact mechanism of action of budesonide in the treatment of Crohn's disease is not fully understood. However, being a glucocorticosteroid, budesonide has a high local anti-inflammatory effect.

toxicity

Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.

biotransformation

Following absorption, budesonide is subject to high first pass metabolism (80-90%). In vitro experiments in human liver microsomes demonstrate that budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6b-hydroxy budesonide and 16a- hydroxy prednisolone. The glucocorticoid activity of these metabolites is negligible (<1/100) in relation to that of the parent compound.

absorption

Absorption is complete following oral administration.

half life

2.0 and 3.6 hours

route of elimination

Budesonide is excreted in urine and feces in the form of metabolites.

drug interactions

Bicalutamide: CYP3A4 Inhibitors like bicalutamide may increase the serum concentration of budesonide. The clinical significance of this interaction is greater for oral budesonide than for orally inhaled budesonide. Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor.

Clotrimazole: CYP3A4 Inhibitors (Moderate) such as clotrimazole may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a moderate CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess.

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). onsider reducing the oral budesonide dose when used together with a strong CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a strong CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess.

Itraconazole: Itraconazole may increase levels/effect of budesonide.

Ketoconazole: Ketoconazole may increase levels/effect of budesonide.

Telithromycin: Telithromycin may reduce clearance of Budesonide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Budesonide if Telithromycin is initiated, discontinued or dose changed.

Tipranavir: Tipranavir may increase the plasma concentration of Budesonide. Monitor for toxic Budesonide effects during concomitant administration.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of budesonide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of budesonide if voriconazole is initiated, discontinued or dose changed.