Introduction
Budesonide is a glucocorticoid that is a mix of the 22R and 22S epimer used to treat inflammatory conditions of the lungs and intestines such as asthma, COPD, Crohn's disease, and ulcerative colitis.
Uses
Budesonide is a corticosteroid used to treat Crohn's disease, asthma, COPD, hay fever and allergies, and ulcerative colitis.
Budesonide extended release capsules are indicated for the treatment and maintenance of mild to moderate Crohn’s disease. Various inhaled budesonide products are indicated for prophylactic therapy in asthma and reducing exacerbations of COPD. A budesonide nasal spray is available over the counter for symptoms of hay fever and upper respiratory allergies. Extended release capsules are indicated to induce remission of mild to moderate ulcerative colitis and a rectal foam is used for mild to moderate distal ulcerative colitis.
Associated Conditions
Pharmacodynamics
Budesonide is a glucocorticoid used to treat respiratory and digestive conditions by reducing inflammation. It has a wide therapeutic index, as dosing varies highly from patient to patient. Patients should be counselled regarding the risk of hypercorticism and adrenal axis suppression.
Mechanism of Action
The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.
Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.
Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.
Absorption
Extended release oral capsules are 9-21% bioavailable. A 9mg dose reaches a Cmax of 1.50±0.79ng/mL with a Tmax of 2-8h and an AUC of 7.33ng*hr/mL. A high fat meal increases the Tmax by 2.3h but otherwise does not affect the pharmacokinetics of budesonide.
180-360µg metered inhaled doses of budesonide are 34% deposited in the lungs, 39% bioavailable, and reach a Cmax of 0.6-1.6nmol/L with a Tmax of 10 minutes.
A 1mg nebulized dose is 6% bioavailable, reaching a Cmax of 2.6nmol/L with a Tmax of 20 minutes.
A 9mg oral extended release tablet reaches a Cmax of 1.35±0.96ng/mL with a Tmax of 13.3±5.9h and an AUC of 16.43±10.52ng*hr/mL.
Budesonide rectal foam 2mg twice daily has an AUC of 4.31ng*hr/mL.
Volume of Distribution
The volume of distribution of budesonide is 2.2-3.9L/kg.
Protein Binding
Corticosteroids are generally bound to corticosteroid binding globulin and serum albumin in plasma. Budesonide is 85-90% protein bound in plasma.
Route of Elimination
Approximately 60% of a budesonide dose is recovered in the urine as the major metabolites 6beta-hydroxybudesonide, 16alpha-hydroxyprednisolone, and their conjugates. No unchanged budesonide is recovered in urine.
Half Life
Budesonide has a plasma elimination half life of 2-3.6h. The terminal elimination half life in asthmatic children 4-6 years old is 2.3h.
Clearance
Budesonide has a plasma clearance of 0.9-1.8L/min. The 22R form has a clearance of 1.4L/min while the 22S form has a clearance of 1.0L/min. The clearance in asthmatic children 4-6 years old is 0.5L/min.
Toxicity
Acute overdose of corticosteroids is rare, however prolonged high dosing of corticosteroids can lead to hypercorticism and adrenal axis suppression. In the case of overdose, reduce the dosage of corticosteroids temporarily.
A 200mg oral dose is lethal to female mice while a 400mg oral dose is lethal to male mice.
Food Interactions
- Take with or without food. Food delays drug absorption, but not to a clinically significant extent.
Dosage
Initial dosage: The initial dose should be tailored to the severity of the disease and thereafter should be adjusted on an individual basis. The following doses are recommended but the minimum effective dose should always be sought.
- Children aged 6 months and above: 0.25-1.0 mg daily. For patients in maintenance therapy with oral steroids a higher initial dosage up to 2.0 mg daily should be considered.
- Adults (including the elderly) and children/adolescents over 12 years of age: 0.5-2 mg daily. In very severe cases the dosage may be increased further.
- Children aged 6 months and above: 0.25-1.0mg daily.
- Adults (including the elderly) and children/adolescents over 12 years of age: 0.5-2.0 mg daily. In very severe cases the dose may be further increased.
Onset of effect: An improvement of the asthma following administration of budesonide may occur within 3 days after initiation of therapy. The maximum effect will only be obtained after 2-4 weeks of treatment.
Patients in maintenance therapy with oral glucocorticosteroids:
Asthma: Budesonide Nebuliser suspension may permit replacement or significant reduction in dosage of oral glucocorticosteroids while maintaining asthma control. When transferral from oral steroids to budesonide Nebuliser suspension is started, the patient should be in a relatively stable phase. A high dose of budesonide Nebuliser suspension is then given in combination with the previously used oral steroid dose for about 10 days.
After that, the oral steroid dose should be gradually reduced (by for example 2.5 milligrams prednisolone or the equivalent each month) to the lowest possible level. In many cases, it is possible to completely substitute the oral steroid with budesonide Nebuliser suspension. For further information on the withdrawal of corticosteroids, when tapering off systemic corticosteroids some patients will experience steroid withdrawal symptoms, e.g. joint and/or muscle pain, lack of energy and depression or even a decreased lung function. Such patients must be advised to continue the inhaled budesonide therapy, but they should also be examined for any objective signs of adrenocortical insufficiency. If such signs are present, the dose of the systemic corticosteroid should be temporarily increased and then tapered off even more slowly. In periods of stress or severe asthma attacks, patients in the transition phase may require treatment with systemic corticosteroids.
Pseudocroup: In infants and children with pseudocroup, the commonly used dose is 2 mg of nebulised budesonide. This is given as a single administration, or as two 1 mg doses separated by 30 minutes. Dosing can be repeated every 12 hours for a maximum of 36 hours or until clinical improvement.
