Budesonide, oral

Budesonide, Oral (Entocort EC) [Anti-inflammatory> Corticosteroid] Uses Mild-mod Crohn Dz Action Steroid, anti-inflammatory Dose Adults. Initial, 9 mg PO qAM to 8 wk max maint 6 mg PO qAM taper by 3 mo avoid grapefruit juice Contra Active TB and fungal Infxn Caution [C, /-] DM, glaucoma, cataracts, HTN, CHF Disp Caps SE HA, cough, hoarseness, Candida Infxn, epistaxis Interactions T Effects W/ erythromycin, indinavir, itraconazole, ketoconazole, ritonavir, grapefruit EMS Monitor ECG and BP for signs of electrolyte disturbances and hypovolemia OD Acute OD unlikely to cause a problem, chronic OD can reduce natural production of certain steroids symptomatic and supportive... 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Budesonide Entocort EC Induction 9 mg orally Maintenance 6 mg orally... 

Budesonide is a high-potency glucocorticoid used in CD that has low systemic bioavailability when administered orally.23 The formulation releases budesonide in the terminal ileum for treatment of disease involving the ileum or ascending colon. Due to its reduced bioavailability, budesonide may prevent some long-term adverse effects in patients who have steroid-dependent IBD.23,24... 

Budesonide 9 mg/day orally for up to 8 weeks If fistulizing disease, consider ... 

Budesonide 9 mg orally once daily for up to 8 weeks may be used for mild to moderate active CD in patients with involvement of the terminal ileum or ascending colon, with success expected in 50% to 60% of patients.23 Because the formulation releases budesonide in the terminal ileum, it is not effective in reaching sites distal to the ascending colon.23,36 Conventional oral corticosteroids such as prednisone and methylprednisolone may be used for patients who are unresponsive to aminosalicylates or budesonide. 

Patients with moderate to severe active CD may be treated with oral corticosteroids, such as prednisone 40 to 60 mg daily.2 Budesonide 9 mg orally once daily may be used for moderate active CD involving the terminal ileum or ascending colon. Infliximab is an effective alternative to corticosteroid therapy for patients with moderate to severe CD, including patients with fistulizing or perianal disease.15,37-39 The recommended regimen for induction of remission is infliximab 5 mg/kg at weeks 0, 2, and 6 it is effective in inducing remission in... 

Chanoine, F., Grenot, C., Heidmann, P., Junien, J. L., Pharmacokinetics of butixocort 21-proprionate, budesonide, and beclomethazone diproprionate in the rat after intratrachael, intravenous and oral treatments, Drug Metab. Dispos. 

Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative colitis and Crohn s disease and are used in moderate to severe disease. Prednisone is most commonly used. Budesonide is an oral controlled-release formulation that minimizes systemic effects. 

Patients with mild to moderately active Crohn disease involving the ileum or ascending colon have been switched from oral prednisolone to budesonide with no reported episodes of adrenal insufficiency. Because prednisolone should not be stopped abruptly, tapering should begin concomitantly with initiating budesonide treatment. 

Presently, inhaled steroids (up to the equivalent of BDP 1000 pg/d, budesonide 800 pg/d, fluticasone 500 pg/d) should be given to patients who show an objective response to either oral or inhaled steroids (s. corticosteroid reversibility testing). For those patients who experience no symptomatic relief, the currently available evidence does not support the use of ICS for alteration of the natural history of the disease. Nevertheless, corticosteroids are effective in treating acute exacerbations in COPD and taking patients of off their ICS regimen may lead to deterioration. Oral corticosteroids (e.g. 40 mg prednisolone for ten days) are recommended for exacerbations, if... 

Bourbeau, 1998 Budesonide 1.6 mg/d 6 months n = 19 No effect on lung function, quality of life, symptoms, or exercise capacity (only non-responder to oral steroids) No benefit... 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Budesonide is a potent synthetic analog of prednisolone that has high affinity for the glucocorticoid receptor but is subject to rapid first-pass hepatic metabolism (in part by CYP3A4), resulting in low oral bioavailability. A controlled-release oral formulation of budesonide (Entocort) is available that releases the drug in the distal ileum and colon, where it is absorbed. The bioavailability of controlled-release budesonide capsules is approximately 10%. 

Oral controlled-release budesonide (9 mg/d) is commonly used in the treatment of mild to moderate Crohn s disease involving the ileum and proximal colon. It appears to be slightly less effective than prednisolone in achieving clinical remission, but has significantly less adverse systemic effects. 

A 32-year-old woman developed irritability, anger, and insomnia after taking oral prednisone (60 mg/day) for a relapse of ileal Crohn s disease (85). The prednisone was withdrawn and replaced by budesonide (9 mg/ day), and the psychiatric adverse effects were relieved after 3 days. A good clinical response was maintained, with no relapse after 2 months of budesonide therapy. 

Budesonide has been marketed in oral form for intestinal inflammatory disease. An non-IgE-mediated anaphylactic reaction has been associated with oral budesonide (307). 

A 57-year old Caucasian man with inflammatory bowel disease was given prednisolone metasulfobenzoate sodium enemas twice daily and oral mesalazine 800 mg tds for about 5 months, without improvement. He stopped using the prednisolone enemas but continued to take mesalazine. Within 48 hours of stopping prednisolone his symptoms resolved completely. The theoretical possibility of contact allergy was entertained. Patch tests with a standard battery of contact allergens, including tixocortol pivalate and budesonide, were ++ positive with budesonide. At follow up 3 months later he was symptom free. 

In another study, ketoconazole was given orally as 200 mg od for 4 days, following a single oral dose of budesonide 3 mg either at the same time as ketoconazole or 12 hours before (483). Ketoconazole increased budesonide concentrations (Cmax and AUC) 6.8- to 7.6-fold when the two drugs were co-administered with a 12-hour separation, budesonide concentrations increased only 1.7-to 2.1-fold. 

Oral contraceptives increased budesonide concentrations by only 22%, but prednisolone concentrations increased by 131%, suggesting a clinically important interaction (495). 

Heeringa M, Zweers P, de Man RA, de Groot H. Drug Points Anaphylactic-like reaction associated with oral budesonide. BMJ 2000 321(7266) 927. 

Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn s disease results of an open, prospective, multicenter trial. 

Seidegard J, Simonsson M, Edsbacker S. Effect of an oral contraceptive on the plasma levels of budesonide and prednisolone and the influence on plasma cortisol. Clin Pharmacol Ther 2000 67(4) 373-81. 

The systemic availability of inhaled budesonide has been measured in 15 healthy volunteers, using an open crossover design. Each subject was given three treatments, intravenous budesonide 0.5 mg, inhaled budesonide (from a metered-dose inhaler with a Nebuhaler) 1 mg (200 micrograms x 5) plus oral charcoal, and inhaled budesonide 1 mg without oral charcoal. The treatment order was randomized. The mean systemic availability of inhaled budesonide compared with intravenous budesonide was 36% with charcoal and 35% without charcoal, indicating that the absorption of budesonide from the gastrointestinal tract did not contribute to its systemic availability. Pulmonary deposition was 36% with charcoal and 34% without. When the inhaler was used incorrectly, that is, the canister was shaken only before the first of the five inhalations, systemic availability fell by 50%. This shows that the performance of each inhaler is very dependent on proper use (16). 

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