Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions
Cardiac glycosides
The action of the glycoside can be potentiated by potassium deficiency.

Saluretics
Potassium excretion can be enhanced.

Pharmacokinetic interactions
Cytochrome P450
– CYP3A4 inhibitors

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Ketoconazole 200mg once daily p.o. increased the plasma concentrations of budesonide (3mg single dose) approximately 6-fold during concomitant administration. When ketoconazole was administered 12 hours after budesonide, the concentrations increased approximately 3-fold. As there are not enough data to give dose recommendations, the combination should be avoided.

Other potent inhibitors of CYP3A4 such as ritonavir, itraconazole, clarithromycin, and grapefruit juice are also likely to cause a marked increase of the plasma concentrations of budesonide. Therefore concomitant intake of budesonide should be avoided.

–   CYP3A4 inducers
Compounds or drugs such as carbamazepine and rifampicin, which induce CYP3A4, might reduce the systemic but also the local exposure of budesonide at the gut mucosa. An adjustment of the budesonide dose (using e.g. Budeson 3mg capsules) might be necessary.

–   CYP3A4 substrates
Compounds or drugs which are metabolized by CYP3A4 might be in competition with budesonide. This might lead to an increased budesonide plasma concentration if the competing substance has a stronger affinity to CYP3A4, or – if budesonide binds stronger to CYP3A4 – the competing substance might be increased in plasma and a dose-adaption/reduction of this drug might be required.

Elevated plasma concentrations and enhanced effects of glucocorticosteroids have 

been reported in women also receiving oestrogens or oral contraceptives, but this has not been observed with oral low dose combination contraceptives.

Cimetidine at recommended doses in combination with budesonide has a small but insignificant effect on the pharmacokinetics of budesonide. Omeprazole has no effect on the pharmacokinetics of budesonide.

Steroid-binding compounds
In theory, potential interactions with steroid-binding synthetic resins such as colestyramine, and with antacids cannot be ruled out. If given at the same time as Budeson, such interactions could result in a reduction in the effect of budesonide.
Therefore these preparations should not be taken simultaneously, but at least two hours apart.

Because adrenal function may be suppressed by treatment with budesonide, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).