Is budesonide safe?

Is Budesonide Safe?

Yes, budesonide is safe when used at recommended doses, with a superior safety profile compared to conventional systemic corticosteroids due to its high topical anti-inflammatory activity and low systemic bioavailability from extensive first-pass hepatic metabolism. 1

Safety Profile Across Indications

Crohn's Disease

• Budesonide demonstrates excellent safety in Crohn's disease, with adverse event rates comparable to placebo (RR: 0.98; 95% CI: 0.77–1.25) in meta-analyses of randomized controlled trials 1
• The safety advantage over conventional steroids like prednisolone is substantial—prednisolone carries a 5-fold higher risk of adverse events (31.8% vs 6.5%; RR: 4.89; 95% CI: 1.98–12.07) 1
• Budesonide avoids the serious systemic complications associated with conventional corticosteroids including Cushing syndrome, infection risk (particularly abdominal/pelvic abscesses), osteoporosis, cataracts, glaucoma, and growth failure in children 1

Eosinophilic Esophagitis

• Orodispersible budesonide is safe for both induction and long-term maintenance therapy in EoE, with no serious adverse events reported in 48-week placebo-controlled trials 1
• The only notable adverse effect is oral Candida albicans infection occurring in up to 22% of patients, which does not impact daily activities and does not require treatment discontinuation 1
• This safety profile extends to pediatric patients using oral viscous budesonide formulations 1

Asthma Management

• Inhaled budesonide has an established 25-year safety record with only very rare associations with adrenal crisis, reduced final height, increased fractures, or pregnancy complications 2
• At recommended doses, budesonide does not cause clinically significant systemic effects, though high doses may cause minor reductions in cortisol levels 1, 3
• Local side effects (cough, dysphonia, oral thrush) can be minimized by using spacers and mouth rinsing after inhalation 1

Safety in Special Populations

Pregnancy and Lactation

• Budesonide is the preferred inhaled corticosteroid during pregnancy, classified as FDA Pregnancy Category B with more accumulated human safety data than other inhaled corticosteroids (Category C) 1, 4
• A nationwide cohort study of nearly 52,000 pregnancies showed no increased risk of orofacial clefts with first-trimester corticosteroid exposure 4
• Four studies using Swedish birth registries demonstrated no increased risk for congenital malformations, cardiovascular defects, or adverse birth outcomes among infants exposed to inhaled budesonide during pregnancy 2
• Budesonide is safe during breastfeeding with low infant exposure risk 1, 4
• Modern nasal corticosteroids including budesonide have negligible systemic absorption and are safe for chronic rhinosinusitis maintenance during pregnancy at recommended doses 1

Pediatric Patients

• Budesonide nebulizer suspension is the only inhaled corticosteroid with FDA-approved labeling for children under 4 years of age 1, 5
• Three retrospective and one prospective study assessing final height showed no reduction in adult height among patients receiving inhaled budesonide during childhood or adolescence 2
• While transient suppression of growth velocity has been observed in children on low-to-medium doses, the clinical significance remains unclear and effects appear reversible 1

Important Safety Considerations and Caveats

Dose-Related Effects

• At high doses, systemic effects may occur, including adrenal suppression, though studies are not conclusive about clinical significance 1
• In maintenance therapy for Crohn's disease, budesonide showed higher incidence of endocrine side effects (cutaneous symptoms like acne, easy bruising, moon face, hirsutism) compared to placebo, leading to recommendations against routine maintenance use 1
• Glucocorticoid doses >5 mg/day carry dose-related risks including gestational diabetes, pregnancy-associated osteoporosis, and preterm birth 4

Drug Interactions

• Potent CYP3A4 inhibitors (ritonavir, ketoconazole) can significantly increase systemic budesonide concentrations, potentially causing clinically significant Cushing syndrome and secondary adrenal insufficiency 1
• This interaction occurs because budesonide is metabolized in the gastrointestinal tract and liver by CYP3A4 isoenzymes 1

Immunosuppression Risk

• Patients on budesonide are more susceptible to infections than healthy individuals, with chicken pox and measles potentially having more serious or fatal courses 5
• Particular care should be taken to avoid exposure in children or adults who have not had these diseases or been properly immunized 5

Local Effects

• Localized Candida albicans infections can occur in the mouth and pharynx, requiring treatment with antifungal therapy and/or discontinuation if they develop 5
• Patients should rinse their mouth after inhalation to minimize local side effects 1, 5

Contraindications

• Primary treatment of status asthmaticus or acute asthma episodes requiring intensive measures 5
• Hypersensitivity to budesonide or any ingredients, as hypersensitivity reactions including anaphylaxis, rash, contact dermatitis, urticaria, angioedema, and bronchospasm have been reported 5

Clinical Bottom Line

Budesonide's safety advantage stems from its pharmacological design: high topical anti-inflammatory activity combined with rapid first-pass hepatic metabolism results in low systemic bioavailability (approximately 10-15%), minimizing the systemic adverse effects that plague conventional corticosteroids 1, 6. This makes it particularly valuable for long-term management of gastrointestinal and respiratory conditions where conventional steroids would pose unacceptable risks 3. The key to safe use is adhering to recommended doses, monitoring for the rare occurrence of systemic effects, and being aware of drug interactions that increase systemic exposure 1, 5.