Budesonide - Drug Monograph

Introduction

Budesonide is a synthetic corticosteroid with potent anti-inflammatory properties that is widely used in the management of respiratory, gastrointestinal, and allergic conditions. As a glucocorticoid receptor agonist, it offers targeted therapeutic effects with reduced systemic exposure compared to traditional corticosteroids, making it a valuable option for both acute and maintenance therapy across various clinical settings.

Mechanism of Action

Budesonide exerts its therapeutic effects through binding to cytoplasmic glucocorticoid receptors. The drug-receptor complex translocates to the cell nucleus where it modulates gene transcription, leading to:

• Inhibition of inflammatory cytokine production (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, TNF-α, GM-CSF)
• Upregulation of anti-inflammatory proteins (lipocortin-1)
• Reduction in inflammatory cell migration and activation
• Stabilization of lysosomal membranes
• Decreased capillary permeability

The high first-pass metabolism (80-90%) of orally administered budesonide contributes to its favorable safety profile in gastrointestinal applications.

Indications

• Asthma maintenance treatment (inhalation formulation)
• Allergic rhinitis (nasal spray)
• Crohn's disease maintenance (oral controlled ileal release)
• Eosinophilic esophagitis (oral viscous suspension)
• Ulcerative colitis (rectal foam/enema)

• Chronic obstructive pulmonary disease (COPD)
• Autoimmune hepatitis
• Pediatric Crohn's disease
• Microscopic colitis
• Post-transplant immunosuppression

Dosage and Administration

• Adults: 180-360 mcg twice daily (maintenance), up to 720 mcg twice daily in severe cases
• Children 6-17 years: 180-360 mcg twice daily

• Adults: 64 mcg per nostril once daily or 32 mcg twice daily
• Children ≥6 years: 32 mcg per nostril once daily

• Adults: 9 mg once daily in morning for up to 8 weeks
• Children: 0.45 mg/kg/day (max 9 mg) for 8 weeks

• 2 mg/60 mL enema nightly for 2-4 weeks
• 2 mg foam applicator nightly

• Hepatic impairment: Use with caution, consider dose reduction
• Renal impairment: No adjustment typically needed
• Elderly: Start at lower end of dosing range
• Pediatrics: Age-specific dosing recommendations apply

Pharmacokinetics

• Oral: ~10-15% systemic bioavailability due to extensive first-pass metabolism
• Inhalation: ~39% lung deposition, 6-13% systemic absorption
• Nasal: Minimal systemic absorption (<2%)
• Rectal: Variable absorption depending on disease activity

• Volume of distribution: 2.2-3.9 L/kg
• Protein binding: 85-90% (primarily albumin)
• Crosses placenta and enters breast milk

• Extensive hepatic metabolism via CYP3A4
• Forms two primary metabolites: 16α-hydroxyprednisolone and 6β-hydroxybudesonide
• Metabolites have <1% glucocorticoid activity

• Half-life: 2-3 hours
• Excretion: Primarily feces (60%), urine (10-15%)
• Clearance: 0.9-1.8 L/min

Contraindications

• Hypersensitivity to budesonide or any component of formulation
• Active untreated infections (tuberculosis, fungal, bacterial, viral)
• Status asthmaticus or other acute asthma episodes requiring intensive measures
• Moderate to severe hepatic impairment (Child-Pugh B and C) for oral formulations
• Concomitant use with strong CYP3A4 inhibitors when systemic effects are undesirable

Warnings and Precautions

• Adrenal suppression may occur with high doses or prolonged use
• Increased risk of infections (bacterial, viral, fungal, parasitic)
• Reduced growth velocity in children (monitor height regularly)
• Ocular effects: Cataracts, glaucoma, intraocular pressure increase

• Not for relief of acute bronchospasm
• Caution in patients with diabetes mellitus (may worsen hyperglycemia)
• Monitor for signs of hypercorticism
• Risk of osteoporosis with long-term use
• May mask signs of infection

• Requires gradual tapering to avoid adrenal insufficiency
• Monitor for signs of corticosteroid withdrawal

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): ↑ budesonide levels
• Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin): ↓ budesonide levels
• Other corticosteroids: Additive systemic effects
• Live vaccines: Avoid administration during treatment

• Estrogen-containing contraceptives: May ↑ budesonide levels
• Macrolide antibiotics: Potential ↑ budesonide exposure

Adverse Effects

• Headache
• Pharyngitis
• Nasopharyngitis
• Upper respiratory infection
• Oral candidiasis (inhalation)
• Nausea (oral)
• Sinusitis

• Cough
• Hoarseness
• Dyspepsia
• Abdominal pain
• Epistaxis (nasal)
• Voice alteration

• Adrenal insufficiency
• Severe allergic reactions
• Increased intraocular pressure
• Glaucoma
• Cataracts
• Osteoporosis
• Psychiatric reactions (agitation, depression)
• Hypercorticism

Monitoring Parameters

• Asthma control: PFTs, symptom diaries, rescue medication use
• Inflammatory bowel disease: Clinical symptoms, endoscopic evaluation
• Allergic rhinitis: Symptom assessment, nasal examination

• Height and weight in children (every 3-6 months)
• Bone mineral density with long-term use
• Intraocular pressure annually with prolonged therapy
• Adrenal function tests if symptoms suggest insufficiency
• Blood glucose in diabetic patients
• Signs of infection

• Elderly: Fall risk assessment, bone health monitoring
• Hepatic impairment: LFT monitoring

Patient Education

• Inhaler: Rinse mouth after use to prevent oral candidiasis
• Nasal spray: Prime before first use, clean applicator regularly
• Oral: Take in morning with food to reduce GI upset
• Do not abruptly discontinue medication

• Carry rescue medication for asthma patients
• Report signs of infection (fever, sore throat)
• Inform all healthcare providers of budesonide use
• Use calcium and vitamin D supplements for bone health

• Seek immediate care for severe allergic reactions
• Contact provider if asthma symptoms worsen
• Report vision changes or eye pain promptly

• Discuss with provider before conception
• Use during pregnancy only if clearly needed
• Small amounts excreted in breast milk - generally compatible with breastfeeding

References

1. Drugs.com. (2023). Budesonide Professional Monograph. 2. Global Initiative for Asthma. (2023). GINA Report, Global Strategy for Asthma Management and Prevention. 3. Lichtenstein, G. R., et al. (2018). ACG Clinical Guideline: Management of Crohn's Disease in Adults. American Journal of Gastroenterology, 113(4), 481-517. 4. Pfizer Laboratories. (2022). Pulmicort Flexhaler [Package Insert]. 5. Sandborn, W. J., et al. (2012). Budesonide for maintenance of remission in Crohn's disease. Cochrane Database of Systematic Reviews, (5). 6. UpToDate. (2023). Budesonide: Drug Information. 7. FDA. (2022). Budesonide prescribing information. 8. Barnes, P. J. (2010). Mechanisms and resistance in glucocorticoid control of inflammation. Journal of Steroid Biochemistry and Molecular Biology, 120(2-3), 76-85.