Entocord 3 mg Modified-release hard capsules

Induction of remission in patients with mild to moderate Crohn's disease involving the ileum and/or the ascending colon; in adults and children 11 years and older.

Posology
Adults: The recommended daily dose in mild to moderate active disease is 9 mg, administered as 9 mg once daily in the morning, for up to 8 weeks. Full effect is usually achieved within 2-4 weeks.
Children 11 years and above, with a body weight over 25 kg: The recommended daily dose in mild to moderate active disease is 9 mg, administered once daily in the morning, for up to 8 weeks. Full effect is usually achieved within 2-4 weeks. Once control of symptoms is achieved, treatment should be titrated to the lowest effective dose.
Special populations
Elderly: Dosage as for adults. However, experience with ENTOCORD 3 mg in the elderly is limited. NB: Treatment with ENTOCORD 3 mg should be tapered before cessation.
Method of administration
For oral administration. The capsules should be swallowed whole with water. For children and adults with difficulty swallowing, the capsules may be opened, and the content swallowed after mixing with a tablespoon of apple sauce. It is important that the contents of the capsules are not crushed or chewed.

Hypersensitivity to budesonide (the active substance) or to any of the excipients listed in section 6.1.

Side effects typical of ENTOCORD 3 mg may occur. Potential systemic effects include glaucoma.
Visual disturbance may be reported with ENTOCORD 3 mg 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.
Caution should be taken in patients with tuberculosis, systemic or local 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 glucocorticosteroids may have unwanted effects.
Particular care is required when considering the use of ENTOCORD 3 mg in patients with existing or previous history of severe affective disorders in themselves or in their first-degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.
Systemic effects of steroids 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 very rarely a wide range of psychiatric/behavioural effects (see Section 4.8).
During transferral from conventional systemic steroid therapy to ENTOCORD 3 mg, symptoms related to change in systemic steroid dose may occur, such as adrenocortical suppression. Therefore, monitoring of adrenocortical function may be considered in these patients and their dose of ENTOCORD 3 mg should be reduced cautiously.
Replacement of high systemic effect glucocorticosteroid treatment with ENTOCORD 3 mg, sometimes unmasks allergies, e.g., rhinitis and eczema, which were previously controlled by the systemic medicine.
Chicken pox and measles can have a more serious course in patients on oral glucocorticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chicken pox develops, treatment with antiviral medicines may be considered.
Glucocorticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic glucocorticosteroid is recommended.
Some patients 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 such as ENTOCORD 3 mg is sometimes necessary.
Reduced liver function may affect the elimination of ENTOCORD 3 mg. 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. The intravenous pharmacokinetics of budesonide however was similar in cirrhotic patients and in healthy subjects.
Co-treatment with CYP3A inhibitors, including ketoconazole and cobicistat-containing products, is expected to increase the risk of systemic side effects. If treatment with ketoconazole together with ENTOCORD 3 mg is indicated, the period between treatments should be as long as possible and a reduction of the ENTOCORD 3 mg dose should be considered if side effects typical of systemic glucocorticosteroids occur (see also section 4.5).
After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinal mucosa), the systemic exposure for oral ENTOCORD 3 mg increased about 2 times. As with other medicines primarily being metabolised through CYP3A4, ingestion of grapefruit or juice of it, should be avoided in connection with ENTOCORD 3 mg administration as the bioavailability of ENTOCORD 3 mg is doubled with the combination (other juices such as orange juice or apple juice do not inhibit CYP3A4). (See section 4.5).
When ENTOCORD 3 mg capsules are used chronically, systemic glucocorticosteroid effects such as hypercorticism and adrenal suppression may appear. This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially u2018sodium-freeu2019. Contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose mal-absorption or sucrase-isomaltase insufficiency should not take ENTOCORD 3 mg.

Although not studied, concomitant administration of colestyramine may reduce ENTOCORD 3 mg uptake, in common with other medicines. 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 has a slight but clinically insignificant effect. The metabolism of budesonide is primarily mediated by CYP3A4, a subfamily of cytochrome 450. Inhibition by budesonide on other medicines metabolism via CYP3A4 is unlikely, since budesonide has a low affinity to the enzyme. Inhibition of CYP3A4 by e.g. ketoconazole and grapefruit juice can however increase the systemic exposure to budesonide. (See section 4.4). Concomitant treatment with CYP3A4 inducers such as carbamazepine may reduce budesonide exposure, which may require a dose increase of ENTOCORD 3 mg. Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

Pregnancy
Safety in pregnancy has not been established. In pregnant animals, administration of budesonide is associated with abnormalities of foetal development.
Breastfeeding
ENTOCORD 3 mg is excreted in breast milk. Based on data from inhaled budesonide, at therapeutic doses of ENTOCORD 3 mg exposure to the suckling child is anticipated to be low.

There is no information available regarding the effects of ENTOCORD 3 mg on the ability to drive and use of machines. An influence is however unlikely.

System Organ Class Frequency Reaction
Cardiac disorders: Common: (1 % to 10 %) Palpitations
Endocrine disorders: Common: (1 % to 10 %) Cushingoid features
Very Rare: Growth retardation (< 0,01 %) Gastrointestinal disorders: Common: (1 % to 10 %) Dyspepsia
Eye disorders: Common: (1 % to 10 %) Blurred vision
Rare: (< 0,1 %) Glaucoma, cataract including subcapsular cataract (see also section 4.4)
Musculoskeletal and connective tissue disorders: Common: (1 % to 10 %) Muscle cramps
Skin and subcutaneous tissue disorders: Common: (1 % to 10 %) Exanthema; urticaria
Rare: (< 0,1 %) Ecchymosis
Psychiatric disorders: Common: (1 % to 10 %) Behavioural changes such as nervousness; insomnia; mood swings and depression
Uncommon: (0,1 % to 1 %) Anxiety
Rare: (< 0,1 %) Aggression
Reproductive system and breast disorders: Common: (1 % to 10 %) Menstrual disorders
Metabolism and nutrition disorders: Common: (1 % to 10 %) Hypokalaemia
Nervous system disorders: Uncommon: (0,1 % to 1 %) Tremor, psychomotor hyperactivity
Immune system disorders: Very Rare: (< 0,01 %) Anaphylactic reaction
Unknown: Hypersensitivity reactions such as angioedema
Side effects typical of systemic glucocorticosteroids (e.g., cushingoid features and growth retardation) may occur. These side effects are dependent on dose, treatment time, concomitant and previous glucocorticosteroid intake, and individual sensitivity. Very rarely a wide range of psychiatric/ behavioural effects may occur, when systemic steroids such as ENTOCORD 3 mg are prescribed at high doses and for prolonged periods. (See section 4.4)

Reports of acute toxicity and/or death following overdosage of glucocorticosteroids are rare. Thus, acute overdosage with ENTOCORD 3 mg, even in excessive doses, is not expected to be a clinical problem. In the event of acute overdosage, no specific antidote is available. Treatment consists of supportive and symptomatic therapy. Chronic overdosage may lead to systemic corticosteroid effects, such as Cushingoid features. If such changes occur, the dose of ENTOCORD 3 mg should be gradually reduced until treatment is discontinued, in accordance with normal procedures for the discontinuation of prolonged oral glucocorticosteroid therapy.