A. Menarini
Full Prescribing Info
1 gastro-resistant capsule of Budenofalk (capsule with gastro-resistant pellets) contains 3 mg Budesonide.
Excipients/Inactive Ingredients: Povidone K25, lactose monohydrate, sucrose, talc, maize starch, methacrylic acid-methyl methacrylate copolymer (1:1), methacrylic acid-methyl methacrylate copolymer (1:2), ammonio methacrylate copolymer type B, ammonio methacrylate copolymer type A (= Eudragit L, S, RS and RL), triethyl citrate, titanium dioxide (E171), purified water, gelatin, erythrosine (E127), iron (II, III) oxide (E172), iron (III) oxide (E172), sodium laurylsulphate.
Pharmacotheraputic Group: Corticosteroids acting locally. ATC Code: A07EA06.
Pharmacology: The exact mechanism of action of Budesonide in the treatment of Crohn's disease is not fully understood. Data from clinical pharmacology studies and controlled clinical trials strongly indicate that the mode of action of Budesonide is predominantly based on a local action in the intestine. Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect. At doses clinically equivalent to systemically acting glucocorticosteroids, Budesonide causes significantly less suppression of the hypothalamo-pituitary-adrenal axis and has a lower impact on inflammatory markers.
Budenofalk 3 mg capsules show a dose-dependent influence on cortisol plasma levels which is at the recommended dose of 3 x 3 mg budesonide/day significantly smaller than that of clinically equivalent effective doses of systemic glucocorticosteroids.
Pharmacokinetics: Due to the special gastro-resistant film-coating of the pellets contained in Budenofalk 3 mg hard capsules, absorption occurs after a lag phase of 2-3 hours. Mean peak plasma levels of approximately 1-2 ng/mL Budesonide were measured at about 5 hours after a dose of 1 capsule of Budenofalk 3 mg before meals. Concomitant intake of food can delay gastrointestinal passage by approx. 2-3 hours.
Budesonide has a high volume of distribution (approx. 3 L/kg). Plasma protein binding averages 85-90%. It undergoes extensive biotransformation in the liver (approx. 90%) to metabolites with low glucocorticoid activity. The average elimination half-life is about 3-4 hours. Oral bioavailability both in healthy volunteers and in fasting patients with Crohn's disease is approx. 9-13%. Budesonide clearance is approx. 10-15 L/min.
Specific Patient Populations: Liver Diseases: A relevant proportion of budesonide is metabolised in the liver. The systemic exposure of budesonide might be increased in patients with impaired hepatic functions due to a decrease in budesonide metabolism by CYP3A4. This is dependent on the type and severity of liver disease.
Budenofalk is used in the treatment of mild to moderate active Crohn's disease affecting the ileum and/or the ascending colon (part of the large intestine) and in the treatment of collagenous colitis. Please note that treatment with Budenofalk 3 mg does not appear useful in patients with Crohn's disease affecting the upper gastrointestinal tract. Extraintestinal symptoms, e.g. involving the skin, eyes or joints, are unlikely to respond to Budenofalk 3 mg because of its local action. Also used in the treatment of patients, aged 18 years and older, with autoimmune hepatitis.
Dosage/Direction for Use
Adults (Over 18 Years): Crohn's Disease: The recommended daily dose is three capsules once daily in the morning or one capsule three times daily (morning, midday, evening) about 30 minutes before meals if this is more convenient to the patient.
Collagenous Colitis: 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: Induction of Remission: For the induction of remission (i.e. for the normalisation of elevated liver enzymes), the recommended daily dose is 1 hard 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 hard 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 hard 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.
Patients with Renal Impairment: There are no specific dosage recommendations for patients with renal insufficiency (see Pharmacology: Pharmacokinetics under Actions).
Patients with Hepatic Impairment: Caution is urged in patients with mild to moderate hepatic impairment.
Children: Budenofalk 3 mg should not be given due to the lack of experience in this age group.
Adolescents: The safety and efficacy of Budenofalk 3 mg in children aged 12 to 18 years have not been established. Currently available data on adolescent patients (12 to 18 years of age) with autoimmune hepatitis are described in Pharmacology: Pharmacodynamics under Actions and Side Effects. No dosage recommendations can be given, however.
Or as prescribed by the physician.
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.
Administration: The hard 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 hard capsules and take the gastro-resistant granules directly, without chewing and with plenty of liquid. This does not impair the efficacy of Budenofalk 3 mg.
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.
Budenofalk 3 mg should not be stopped abruptly, but withdrawn gradually (tapering doses). In the first week, the dosage should be reduced to 2 hard capsules daily (1 hard capsule in the morning and evening). In the second week, 1 hard capsule should be taken in the morning only. Treatment can subsequently be stopped.
Budenofalk 3 mg must not be used in: Hypersensitivity to budesonide or any other ingredients. Hepatic cirrhosis; children.
Special Precautions
Treatment with Budenofalk 3 mg results in lower systemic steroid levels than conventional oral steroid therapy. Transfer from other steroid therapy may therefore result in symptoms relating to the change in systemic steroid levels.
Particularly close medical supervision is required in patients suffering from one or more of the following diseases: Tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcer (gastric or duodenal), glaucoma, cataract, family history of diabetes or 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 very rarely a wide range of psychiatric/behavioural effects (see Side effects).
Infection: 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 septicaemia and tuberculosis may be masked, and therefore may reach an advanced stage before being recognised.
Chickenpox: Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed, they should seek urgent medical attention. If the patient is a child, parents must be given the above advice. Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months, if they could have become infected with chickenpox. Immunisation should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox (varicella infection) is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.
Measles: Patients with compromised immunity who have come into contact with measles should, wherever possible, receive normal immunoglobulin as soon as possible after exposure.
Live Vaccines: Live vaccines should not be given to individuals with chronic corticosteroid use. The antibody response to other vaccines may be diminished.
Patients with Liver Function Disorders: Based on the experience with patients suffering from late stage primary biliary cirrhosis (PBC) with hepatic cirrhosis, an increased systemic availability of budesonide in all patients with severely impaired hepatic function is to be expected.
However, in patients with liver disease without hepatic cirrhosis, budesonide in daily doses of 9 mg was safe and well tolerated. There is no evidence that a specific dose recommendation for patients with non-cirrhotic liver diseases or only slightly impaired liver function is necessary.
Budenofalk 3 mg can suppress the response of the hypothalamo-pituitary-adrenal axis to stress. For this reason, a supplementary systemic glucocorticoid should be given to patients undergoing surgery or other stresses.
Budenofalk 3 mg contains lactose and sucrose. Patients with rare hereditary problems of galactose or fructose intolerance, lactase deficiency, sucrase-isomaltase insufficiency or glucose-galactose malabsorption should not take this medicine.
In patients with autoimmune hepatitis, serum transaminase levels (ALT, AST) should be regularly monitored (every 2 weeks for the first month of treatment and at least every 3 months thereafter), in order to facilitate dose adjustments of budesonide.
Fertility: There are no data on the effect of budesonide on human fertility. Fertility was unaffected following budesonide treatment in animal studies.
Use In Pregnancy & Lactation
Pregnancy: Administration during pregnancy should be avoided unless there are compelling reasons for therapy with Budenofalk 3 mg. 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 Budenofalk 3 mg compared to inhaled budesonide. In pregnant animals, budesonide, like other glucocorticosteroids, has been shown to cause abnormalities of foetal development. The relevance of this to man has not been established.
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 Budenofalk 3mg 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.
Side Effects
The following frequency conventions are used in the evaluation of undesirable effects: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), including isolated cases: See table.

Click on icon to see table/diagram/image

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 Budenofalk 3 mg 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.
Undesirable Effects in Clinical Studies in Patients with Autoimmune Hepatitis: In a clinical study involving patients with autoimmune hepatitis, undesirable effects were reported in 57% of the 102 patients treated with budesonide (by comparison: in 79% of the 105 patients on prednisone). The most common undesirable effects reported in those patients on budesonide were skin changes (particularly acne) (23% of those treated), endocrine disorders, such as Cushing's symptoms (16% of those treated), gastrointestinal disorders (14% of those treated), psychiatric disorders (mainly mood swings) (14% of those treated) and headache (12% of those treated). With the exception of headache, these undesirable effects were observed more rarely with budesonide than with prednisone.
The type and frequency of undesirable effects in a subgroup of paediatric patients were comparable with those occurring in adult patients (see Pharmacology: Pharmacodynamics under Actions).
Drug Interactions
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: 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.
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. Budesonide 3 mg 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 CYP3A the competing substance might be increased in plasma and a dose adaption/reduction of this drug might then be required.
Elevated plasma concentrations and enhanced effects of corticosteroids 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 Budenofalk 3 mg, 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.
Store at temperatures not exceeding 25°C.
ATC Classification
A07EA06 - budesonide ; Belongs to the class of corticosteroids acting locally. Used in the treatment of intestinal inflammation.
EC cap 3 mg x 100's.
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