Budesonide

Budesonide can increase the efficacy of inhaled beta-2-sympathomimetics.

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 might be necessary.

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.

The metabolism of budesonide is primarily mediated by CYP3A4. Inhibitors of this enzyme, e.g. ketoconazole and itraconazole, can therefore increase systemic exposure to budesonide several times. Since there are no data to support dosage recommendations, the combination should be avoided. If this is not possible, the period between treatments should be as long as possible and a reduction of the budesonide dose could also be considered.

Limited data about this interaction for high-dose inhaled budesonide indicate that marked increases in plasma levels (on average four-fold) may occur if itraconazole, 200 mg once daily, is administered concomitantly with inhaled budesonide (single dose of 1000 µg).

Other potent CYP3A4 inhibitors such as erythromycin, clarithromycin, ritonavir and saquinavir are also likely to markedly increase plasma concentrations of budesonide.

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 doseadaption/reduction of this drug might be required.

In patients with severe hepatic dysfunction, treatment with inhaled budesonide can result in a reduced elimination rate and hence enhanced systemic availability. Possible systemic effects may then result and therefore HPA axis function in these patients should be monitored at regular intervals.

The action of the glycoside can be potentiated by potassium deficiency.

Potassium excretion can be enhanced.

Raised plasma concentrations of and enhanced effects of corticosteroids have been observed in women also treated with oestrogens and contraceptive steroids, but no effect has been observed with budesonide and concomitant intake of low dose combination oral contraceptives.

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 budesonide, 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.

Cimetidine had a weak but clinically insignificant inhibiting effect on hepatic metabolism of budesonide.

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

Caution is required in patients with tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, family history of diabetes, family history of glaucoma, or any other condition in which glucocorticosteroids may have undesirable effects.

Administration during pregnancy should be avoided unless there are compelling reasons for therapy with budesonide. There are few data of pregnancy outcomes after oral administration of budesonide in humans. Although data on the use of inhaled budesonide in a large number of exposed pregnancies indicate no adverse effect, the maximal concentration of budesonide in plasma has to be expected to be higher in the treatment with capsules/rectal foam compared to inhaled budesonide. It is important for both foetus and mother to maintain an adequate asthma treatment during pregnancy. In pregnant animals, budesonide, like other glucocorticosteroids, has been shown to cause abnormalities of fetal development. The relevance of this to man has not been established.

Results from prospective epidemiological studies and from worldwide post marketing experience indicate no increased risk for overall congenital malformations from the use of inhaled or intranasal budesonide during early pregnancy. Animal studies have shown reproductive toxicity. The potential risk for humans is unknown. As with other drugs the administration of budesonide during pregnancy requires that the benefits for the mother are weighed against the risks for the foetus.

Budesonide is excreted in human milk (data on excretion after inhalative use is available). However, only minor effects on the breast-fed child are anticipated after budesonide intake within the therapeutic range. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from budesonide therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Maintenance treatment with inhaled budesonide (200 or 400 mcg twice daily) in asthmatic nursing women results in negligible systemic exposure to budesonide in breast-fed infants.

In a pharmacokinetic study, the estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th of the concentrations observed in maternal plasma, assuming complete infant oral bioavailability. Budesonide concentrations in infant plasma samples were all less than the limit of quantification.

Based on data from inhaled budesonide and the fact that budesonide exhibits linear PK properties within the therapeutic dosage intervals after nasal, inhaled, oral and rectal administrations, at therapeutic doses of budesonide, exposure to the suckling child is anticipated to be low.

Fertility

There are no data on the effect of budesonide on human fertility. Fertility was unaffected following budesonide treatment in animal studies.

This medicine may have a moderate influence on the ability to drive and use machines. This medicine may cause blurred vision, patients should therefore be cautioned about engaging in activities such as driving a car or operating machinery, until they have established their own response to the drug.

No studies on the effects on the ability to drive and use machines have been performed.