Budeson

/ Rafa

Crohn’s disease: Adults (over 18 years): The recommended daily dose is 9 mg budesonide: three capsules once daily in the morning or one capsule three times daily (morning, midday, evening), if this is more convenient to the patient, about ½ hour before meals.
Collagenous colitis: Adults (over 18 years): The recommended daily dose is three capsules once daily in the morning before breakfast (corresponding to a daily dose of 9 mg budesonide).
Autoimmune hepatitis: Adults (over 18 years):
Induction of remission: For the induction of remission (i.e. for the normalisation of laboratory parameters), the recommended daily dose is 1 capsule 3 times daily (morning, midday and evening, equivalent to a total daily dose of 9 mg budesonide).
Maintenance of remission: Once remission has been achieved, a daily dose of 1 capsule twice daily (morning and evening, equivalent to a total daily dose of 6 mg budesonide) is recommended. If the transaminases ALT and/or AST increase during this treatment, the dose should be increased to 3 capsules daily, as for induction of remission (equivalent to a total daily dose of 9 mg budesonide).
In patients who tolerate azathioprine, budesonide should be combined with this drug for the induction and maintenance of remission.
Children: Budeson should not be taken by children younger than 12 years due to insufficient experience and possibly increased risk of adrenal suppression in this age group.
Adolescent patients: The safety and efficacy of Budeson in children aged 12 to 18 years have not yet been established. Currently available data in adolescent patients (12 – 18 years) with Crohn’s disease or autoimmune hepatitis are described in the doctor’s leaflet but no recommendation on a posology can be made.
Method of administration: The capsules should be swallowed whole, not chewed, and taken with plenty of liquid (e.g. a glass of water), about ½ hour before meals.
Patients with swallowing difficulties can open the capsules and take the gastro-resistant granules directly, without chewing and with plenty of liquid.
Duration of administration:
Crohn’s disease and collagenous colitis: The usual duration of treatment is 8 weeks. The full effect is usually reached after 2-4 weeks.
Autoimmune hepatitis: After remission has been achieved, treatment of autoimmune hepatitis should be continued for at least 24 months. If the biochemical remission is stable and liver biopsy does not reveal any signs of acute inflammation, treatment can be concluded.
Termination of treatment: Budeson should not be stopped abruptly, but withdrawn gradually (tapering doses). In the first week, the dosage should be reduced to two capsules daily (one in the morning, one in the evening). In the second week, only one capsule should be taken in the morning. Treatment can subsequently be stopped.
See prescribing information for full details.

Acute mild to moderate Crohn’s disease with involvement of the ileum (twisted intestine) and/or ascending colon (part of large bowel). Collagenous colitis. Autoimmune hepatitis.

Hypersensitivity, hepatic cirrhosis.

Treatment with Budeson results in lower systemic steroid levels than conventional oral steroid therapy. Switch from other steroid therapy may result in symptoms relating to the change in systemic steroid levels. Special 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 glucocorticoids may have undesirable effects. Systemic effects of corticosteroids may occur, particularly when prescribed at high doses and for prolonged periods. Such effects may include Cushing’s syndrome, adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma and a wide range of psychiatric/behavioural effects.
Infections: Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The risk of deterioration of bacterial, fungal, amoebic and viral infections during glucocorticoid treatment should be carefully considered. The clinical presentation may often be atypical and serious infections such as sepsis and tuberculosis may be masked, and therefore may reach an advanced stage before being recognised.
Visual disturbance: Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
See prescribing information for full details.

Occasionally, side effects may occur which are typical for systemic glucocorticosteroids. These side effects depend on the dosage, the period of treatment, concomitant or previous treatment with other glucocorticosteroids and the individual sensitivity.
Clinical studies showed that the frequency of glucocorticosteroid-associated side effects is lower with Budeson than with oral treatment of equivalent dosages of prednisolone.
An exacerbation or the reappearance of extraintestinal manifestations (especially affecting skin and joints) can occur on switching a patient from the systemically acting glucocorticosteroids to the locally acting budesonide.
See prescribing information for full details.

Pharmacodynamic interactions
Cardiac glycosides: The action of 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 200 mg once daily p.o. increased the plasma concentrations of budesonide (3 mg single dose) approximately 6-fold during concomitant administration. When ketoconazole was administered approximately 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 should be avoided.
CYP3A inductors: 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.
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).

Pregnancy: Administration during pregnancy should be avoided unless there are compelling reasons for therapy with this product. There are few data of pregnancy outcomes after oral administration of budesonide in humans.
See prescribing information for full details.
Lactation: 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 intake of Budeson 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.

To date, no cases of overdosage with budesonide are known.

Storage: Store below 25°C.