Drug Interaction Report

MONITOR: Concomitant use of orally and rectally administered formulations of budesonide with inducers of CYP450 3A4 may decrease budesonide systemic as well as local exposure at the gut mucosa. Budesonide undergoes extensive first-pass and systemic metabolism via intestinal and hepatic CYP450 3A4. Although clinical and pharmacokinetic data are currently lacking, such an interaction may impact the therapeutic efficacy of budesonide in the treatment of inflammatory bowel disease.

MANAGEMENT: The potential for diminished pharmacologic effects of orally and rectally administered budesonide should be considered during concomitant treatment with drugs that induce CYP450 3A4. Alternative treatments or budesonide dose adjustments may be required if an interaction is suspected.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.