Drug Class Description
Corticosteroids (steroids).

Generic Name
Budesonide

Drug Description
Each capsule contains budesonide 3 mg

Presentation
Entocort CR 3 mg Capsules: Hard gelatin capsules for oral administration with an opaque, light grey body and opaque, pink cap marked CIR 3mg in black radial print. Each capsule contains budesonide 3 mg as gastro-resistant, prolonged-release granules

Indications
Entocort CR Capsules are indicated for the induction of remission in patients with mild to moderate Crohn's disease affecting the ileum and/or the ascending colon.

Adult Dosage
Active Crohn's disease: The recommended daily dose for induction of remission is 9 mg once daily in the morning, for up to eight weeks. The full effect is usually achieved within 2–4 weeks.When treatment is to be discontinued, the dose should normally be reduced for the last 2 to 4 weeks of therapy.

Child Dosage
There are limited data on the use of Entocort CR Capsules in children. The available data are insufficient to support safety and efficacy in the paediatric population, therefore such use cannot be recommended until further data become available.

Elderly Dosage
No special dose adjustment is recommended. However, experience with Entocort CR Capsules in the elderly is limited.The capsules should be swallowed whole with water. The capsules must not be chewed.

Contra Indications
Known hypersensitivity to any of the ingredients.

Special Precautions
Use with caution in patients with infections, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts or with a family history of diabetes or glaucoma or with any other condition where the use of glucocorticosteroids may have unwanted effects.Treatment with Entocort CR Capsules results in lower systemic steroid levels than conventional oral glucocorticosteroid therapy. When patients are transferred from systemic glucocorticosteroid treatment with higher systemic effect to Entocort CR Capsules, they may have adrenocortical suppression. Therefore, monitoring of adrenocortical function may be considered in these patients and their dose of systemic steroid should be reduced cautiously.Replacement of systemic glucocorticosteroid treatment with higher systemic effect with Entocort CR Capsules, sometimes unmasks allergies, e.g. rhinitis and eczema, which were previously controlled by the systemic drug.Chicken pox and measles may follow a more serious course in patients on oral glucocorticosteroids. Particular care should be taken to avoid exposure in patients who have not previously had these diseases. If patients are infected or suspected of being infected, consider reduction or discontinuation of glucocortiocosteriods treatment and immediately consult a physician. Glucocorticosteroids may cause suppression of the HPA axis and reduce the stress response. Where patients are subject to surgery or other stresses, supplementary systemic glucocorticoid treatment is recommended.Reduced liver function may affect the elimination of glucocorticosteroids. The pharmacokinetics after oral ingestion of budesonide was affected by compromised liver function as evidenced by increased systemic availability in patients with moderately severe hepatic cirrhosis.When treatment is to be discontinued, the dose should normally be reduced for the last 2 to 4 weeks of therapy. Some patients may feel unwell in a non-specific way during the withdrawal phase, e.g. pain in muscles and joints. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of systemic glucocorticosteroids is sometimes necessary.In vivo studies have shown that oral administration of ketoconazole (a known inhibitor of CYP3A activity in the liver and in the intestinal mucosa), caused a several fold increase of the systemic exposure to oral budesonide. If treatment with ketoconazole together with budesonide is indicated, reduction of the budesonide dose should be considered if side effects typical of systemic glucocorticosteriods occur.After extensive intake of grapefruit juice (which inhibits CYP3A activity predominantly in the intestinal mucosa), the systemic exposure for oral budesonide increased about two times. As with other drugs primarily being metabolised through CYP3A, regular ingestion of grapefruit or juice of it, should be avoided in connection with budesonide administration (other juices such as orange juice or apple juice do not inhibit CYP3A).When Entocort CR Capsules are used chronically in excessive doses, systemic glucocorticosteroid effects such as hypercorticism and adrenal suppression may appear.

Interactions
Although not studied, concomitant administration of colestyramine may reduce Entocort uptake, in common with other drugs.Elevated plasma levels and enhanced effects of corticosteroids have been reported in women also receiving oestrogens or oral contraceptives. However, a low-dose combination oral contraceptive that more than doubled the plasma concentration of oral prednisolone, had no significant effect on the plasma concentration of oral budesonide.At recommended doses, omeprazole was without effect on the pharmacokinetics of oral budesonide, whereas cimetidine had a slight but clinically insignificant effect.The metabolism of budesonide is primarily mediated by CYP3A4, one of the cytochrome p450 enzymes. Inhibitors of this enzyme, e.g. ketoconazole, itraconazole and grapefruit juice, can therefore increase systemic exposure to budesonide. Other potent inhibitors of CYP3A4 are also likely to markedly increase plasma levels of budesonide. Inhibition by budesonide on other drugs metabolism via CYP3A4 is unlikely, since budesonide has low affinity to the enzyme.

Adverse Reactions
In clinical studies most adverse events were of mild to moderate intensity and of a non-serious character.Undesirable effects characteristic of systemic corticosteroid therapy, such as Cushingoid features and reduced growth velocity, may occur.In clinical trials other adverse events: dyspepsia, muscle cramps, tremor, palpitations, blurred vision, skin reactions (urticaria, exanthema),menstrual disorders, hypokalemia and behavioural changes such as nervousness, insomnia and mood swings have been reported.In clinical studies, at recommended doses, the incidence of adverse events was comparable to placebo.Clinical studies showed the frequency of steroid associated side effects for Entocort CR Capsules to be approximately half that of conventional prednisolone treatment, at equipotent doses. In studies of patients with active disease, receiving Entocort 9 mg daily, the incidence of adverse events was comparable to placebo.

Manufacturer
AstraZeneca

Drug Availability
(POM)

Updated
12 May 2009