Budetide

A. Respiratory Disorders (Inhalation/Nebulization):

• Asthma (maintenance treatment of persistent asthma in adults and children ≥6 months).
• Chronic Obstructive Pulmonary Disease (COPD): As part of combination therapy (e.g., with formoterol) for maintenance treatment.
• Eosinophilic Bronchitis
• Non-Cystic Fibrosis Bronchiectasis (off-label)
• Allergic Rhinitis or Non-Allergic Rhinitis (nasal spray)

B. Gastrointestinal Disorders (Oral):

• Crohn's Disease (mild to moderate active disease involving the ileum and/or ascending colon).
• Ulcerative Colitis (mild to moderate, especially left-sided or distal disease).
• Microscopic Colitis (collagenous and lymphocytic colitis) – off-label but widely accepted.
• Eosinophilic Esophagitis (off-label)

C. Hepatic Disorders:

• Autoimmune Hepatitis (used as an alternative to systemic corticosteroids in selected patients).

D. Rectal Forms (Enemas, Foams):

• Ulcerative Proctitis
• Distal Ulcerative Colitis

A. Inhalation (via DPI, MDI, or nebulizer):

• Adults and adolescents (≥12 years): 200–800 mcg twice daily. Max: 1600 mcg/day in severe asthma.
• Children (6 months to 11 years): 100–400 mcg/day in divided doses.
• Titrate to lowest effective dose.

B. Oral (Delayed-release or MMX tablets):

• Crohn’s Disease (Adults): 9 mg once daily in the morning for up to 8 weeks.
• Microscopic Colitis: 9 mg daily for 6–8 weeks (off-label).

C. Nasal Spray (64 mcg/spray):

• Adults and children ≥6 years: 1–2 sprays in each nostril once or twice daily.

D. Rectal Foam/Enema:

• Ulcerative proctitis/proctosigmoiditis: 2 mg rectally once or twice daily.

E. Special Populations:

• Renal Impairment: No adjustment required.
• Hepatic Impairment: Use with caution; systemic exposure may increase.
• Elderly: Standard adult dose, monitor for systemic effects.

Budesonide is a potent non-halogenated corticosteroid that exerts strong glucocorticoid activity and minimal mineralocorticoid activity. It binds to intracellular glucocorticoid receptors, altering gene transcription to suppress pro-inflammatory cytokines and chemokines while enhancing anti-inflammatory protein synthesis. In respiratory tissues, this leads to reduced airway hyperresponsiveness, decreased infiltration of eosinophils and mast cells, and reduced mucus production. Its extensive first-pass metabolism contributes to its high topical-to-systemic activity ratio, especially in gastrointestinal and pulmonary applications.

• Absorption: Oral bioavailability ~10–13% due to extensive first-pass hepatic metabolism; inhaled ~39%.
• Onset of Action: Inhaled effects begin within 24 hours; full effects in 1–2 weeks.
• Distribution: Volume of distribution ~3 L/kg; high protein binding (~85–90%).
• Metabolism: Primarily via CYP3A4 in the liver to inactive metabolites.
• Elimination Half-Life: ~2–3.6 hours.
• Excretion: Mainly via urine (60%) and feces (33%) as metabolites.

• Pregnancy: Previously FDA Category C. Human data suggest low teratogenic risk. Use only if benefits outweigh risks.
• Lactation: Budesonide is excreted in small amounts into breast milk. Inhaled and rectal forms are generally considered compatible with breastfeeding due to low systemic absorption. Use caution with oral forms; monitor infants for signs of corticosteroid exposure.

• Primary Class: Corticosteroid (Glucocorticoid)
• Subclasses:
• Inhaled Corticosteroid (ICS)
• Topical Glucocorticoid for GI conditions
• Intranasal Corticosteroid

• Known hypersensitivity to Budesonide or formulation excipients.
• Active, untreated systemic infections (e.g., tuberculosis, fungal infections).
• Hepatic cirrhosis with portal hypertension (oral Budesonide).
• Patients requiring systemic corticosteroids for life-threatening conditions.

• Systemic corticosteroid effects: Adrenal suppression, Cushing’s syndrome, growth retardation in children (dose-dependent).
• Immunosuppression: Increased susceptibility to infections (e.g., varicella, measles).
• Hepatic Impairment: Increased systemic exposure; monitor closely.
• Paradoxical bronchospasm: With inhaled use; discontinue if occurs.
• Ocular effects: Cataracts, glaucoma with long-term use; recommend periodic eye exams.
• Bone health: Risk of osteoporosis with prolonged high-dose therapy.
• Withdrawal: Taper gradually if switching from systemic corticosteroids.

Common:

• Respiratory (Inhaled/Nasal): Hoarseness, sore throat, cough, nasal irritation, epistaxis.
• Gastrointestinal (Oral/Rectal): Abdominal pain, nausea, bloating.
• Systemic: Headache, fatigue.

Serious:

• Adrenal suppression
• Growth retardation (pediatric)
• Osteoporosis
• Glaucoma, cataracts
• Anaphylaxis or angioedema (rare)
• Paradoxical bronchospasm

Rare:

• Psychiatric effects (mood swings, sleep disturbances)
• Skin thinning, easy bruising (with long-term use)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): May significantly increase Budesonide systemic exposure.
• CYP3A4 inducers (e.g., rifampin, carbamazepine): May reduce efficacy.
• Grapefruit juice: Can increase systemic exposure by inhibiting CYP3A4.
• Systemic corticosteroids: Additive adrenal suppression.
• Live vaccines: Immunosuppression may reduce vaccine efficacy.

• GINA 2024 guidelines continue to support Budesonide/formoterol as preferred controller and reliever in mild to moderate asthma.
• ECCO Guidelines (2023): Budesonide remains a first-line agent in mild ileal Crohn’s disease and microscopic colitis.
• Recent FDA safety communications reaffirm low systemic risks with inhaled Budesonide at recommended doses.
• No major recent changes in indications or safety labeling.

• Inhalers/Nebules: Store at 20°C to 25°C (68°F to 77°F). Do not freeze. Protect from light.
• Oral Capsules/Tablets: Store below 30°C; protect from moisture.
• Rectal Foam/Enema: Store at 20°C to 25°C. Do not refrigerate or freeze.
• Nasal Spray: Store at room temperature; discard after expiry or 2 months after opening.
• General: Keep out of reach of children. Avoid exposure to direct sunlight or extreme heat.