Does oral Budesonide (corticosteroid) cause systemic side effects?

From the Guidelines

Oral budesonide can cause systemic issues, particularly at doses greater than 6 mg/day, due to systemic immunosuppression. According to the ECCO guidelines on the prevention, diagnosis, and management of infections in inflammatory bowel disease 1, topical oral budesonide at doses greater than 6 mg/day can lead to systemic immunosuppression. This is in contrast to lower doses, where long-term maintenance treatment with topical oral budesonide up to 6 mg/day did not result in higher rates of infections compared to placebo.

The potential systemic effects of oral budesonide include adrenal suppression, increased risk of infections, mood changes, sleep disturbances, elevated blood glucose, and decreased bone mineral density. Patients with liver disease may be at higher risk for systemic effects due to reduced first-pass metabolism. The typical dosage ranges from 3-9 mg daily depending on the condition being treated.

To minimize systemic absorption, patients should take budesonide as directed and avoid grapefruit juice, which can interfere with metabolism. Regular monitoring by a healthcare provider is important, especially for those on long-term therapy or higher doses, to assess for potential systemic effects. A study published in the Journal of Crohn's and Colitis in 2020 1 also supports the use of budesonide for the induction of clinical remission in patients with active mild-to-moderate Crohn’s disease, highlighting its efficacy and safety profile compared to conventional steroids.

Key considerations for minimizing systemic effects include:

• Dose: keeping the dose as low as possible, ideally below 6 mg/day
• Duration: limiting the duration of treatment to minimize the risk of systemic immunosuppression
• Monitoring: regular monitoring for potential systemic effects, particularly in patients with liver disease or those on long-term therapy
• Patient education: instructing patients to take budesonide as directed and avoid grapefruit juice to minimize systemic absorption.

From the FDA Drug Label

Advise patients that budesonide extended-release tablets may cause systemic glucocorticosteroid effects of hypercorticism and adrenal suppression Taper slowly from systemic corticosteroids if transferring to budesonide extended-release tablets [see Warnings and Precautions (5.1)and (5. 2)] If glucocorticosteroids are used at excessive doses for prolonged periods, systemic glucocorticosteroid effects, such as hypercorticism and adrenal suppression may occur

Systemic Issues with Oral Budesonide:

• Hypercorticism: Oral budesonide may cause hypercorticism, a condition characterized by an excess of cortisol in the body.
• Adrenal Suppression: Oral budesonide may also cause adrenal suppression, a condition where the adrenal glands do not produce enough cortisol.
• Immunosuppression and Increased Risk of Infection: Oral budesonide may increase the risk of infection, including fungal and threadworm (Strongyloides) infections. Oral budesonide can cause systemic issues, including hypercorticism and adrenal suppression, especially when used at excessive doses for prolonged periods 2, 2, 2

From the Research

Systemic Issues with Oral Budesonide

• Oral budesonide is designed to reduce systemic adverse events (AEs) due to its limited systemic bioavailability 3, 4, 5.
• Studies have shown that budesonide is safer than conventional steroids, with fewer corticosteroid-related AEs 3, 4.
• The risk of abnormal adrenocorticotropic hormone (ACTH) tests is increased with budesonide treatment, but less than with conventional steroids 3, 4.
• Budesonide does not appear to have significant adverse safety implications when used at low doses to maintain remission, except for slight reductions in cortisol levels on rare occasions 5.
• Long-term safety and efficacy of budesonide in treating ulcerative colitis have been demonstrated, with a similar AE profile to placebo 6, 7.

Adverse Events

• The most common AEs associated with budesonide are gastrointestinal- and endocrine systems-related 7.
• The incidence of endocrine disorders is higher with budesonide than with placebo, due to a higher overall occurrence of cutaneous glucocorticosteroid symptoms 7.
• Clinically important or serious AEs associated with systemic glucocorticosteroids, such as sepsis, cataracts, and adrenal insufficiency, are rare and similar between budesonide and placebo groups 7.

Safety Profile

• Budesonide's safety profile is similar to that of placebo, with only rare occurrences of clinically important AEs associated with systemic glucocorticosteroids 7.
• The percentage of patients with normal adrenal function is significantly lower at 13 weeks, but not at 52 weeks, in the budesonide versus placebo groups 7.
• Budesonide treatment for up to 1 year is well-tolerated in Crohn's disease patients, with an AE profile similar to placebo 7.