Intranasal: Children 6 years of age and Adults: Management of symptoms of seasonal or perennial rhinitis

Nebulization: Children 12 months to 8 years: Maintenance and prophylactic treatment of asthma

Oral capsule: Treatment of active Crohn's disease (mild to moderate) involving the ileum and/or ascending colon

Oral inhalation: Maintenance and prophylactic treatment of asthma; includes patients who require corticosteroids and those who may benefit from systemic dose reduction/elimination

Inhalation: Contraindicated in primary treatment of status asthmaticus, acute episodes of asthma; not for relief of acute bronchospasm

Controlled clinical studies have shown that orally-inhaled and intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients. (In studies of orally-inhaled corticosteroids, the mean reduction in growth velocity was approximately 1 centimeter per year [range 0.3-1.8 cm per year] and appears to be related to dose and duration of exposure.) To minimize the systemic effects of orally-inhaled and intranasal corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.

May suppress the immune system, patients may be more susceptible to infection. Use with caution in patients with systemic infections or ocular herpes simplex. Avoid exposure to chickenpox and measles. Corticosteroids should be used with caution in patients with diabetes, hypertension, osteoporosis, peptic ulcer, glaucoma, cataracts, or tuberculosis. Use caution in hepatic impairment. Enteric-coated capsules should not be crushed or chewed.

>10%:

Central nervous system: Oral capsule: Headache (up to 21%)

Gastrointestinal: Oral capsule: Nausea (up to 11%)

Respiratory: Respiratory infection, rhinitis

Miscellaneous: Symptoms of HPA axis suppression and/or hypercorticism (acne, easy bruising, fat redistribution, striae, edema) may occur in >10% of patients following administration of dosage forms which result in higher systemic exposure (ie, oral capsule), but may be less frequent than rates observed with comparator drugs (prednisolone). These symptoms may be rare (<1%) following administration via methods which result in lower exposures (topical).

1% to 10%:

Cardiovascular: Syncope, edema, hypertension

Central nervous system: Chest pain, dysphonia, emotional lability, fatigue, fever, insomnia, migraine, nervousness, pain, dizziness, vertigo

Dermatologic: Bruising, contact dermatitis, eczema, pruritus, pustular rash, rash

Endocrine & metabolic: Hypokalemia, adrenal insufficiency

Gastrointestinal: Abdominal pain, anorexia, diarrhea, dry mouth, dyspepsia, gastroenteritis, oral candidiasis, taste perversion, vomiting, weight gain, flatulence

Hematologic: Cervical lymphadenopathy, purpura, leukocytosis

Neuromuscular & skeletal: Arthralgia, fracture, hyperkinesis, hypertonia, myalgia, neck pain, weakness, paresthesia, back pain

Ocular: Conjunctivitis, eye infection

Otic: Earache, ear infection, external ear infection

Respiratory: Bronchitis, bronchospasm, cough, epistaxis, nasal irritation, pharyngitis, sinusitis, stridor

Miscellaneous: Allergic reaction, flu-like syndrome, herpes simplex, infection, moniliasis, viral infection, voice alteration

<1%: Aggressive reactions, alopecia, angioedema, avascular necrosis of the femoral head, depression, dyspnea, hoarseness, hypersensitivity reactions (immediate and delayed; include rash, contact dermatitis, angioedema, bronchospasm), intermenstrual bleeding, irritability, nasal septum perforation, osteoporosis, psychosis, somnolence

Postmarketing and/or case reports: Growth suppression, benign intracranial hypertension

Inhaled formulations: Symptoms of overdose include irritation and burning of the nasal mucosa, sneezing, intranasal and pharyngeal Candida infections, nasal ulceration, epistaxis, rhinorrhea, nasal stuffiness, headache.

When consumed in excessive quantities, systemic hypercorticism and adrenal suppression may occur, in those cases discontinuation and withdrawal of the corticosteroid should be done judiciously. Treatment should be symptomatic and supportive.

Cimetidine: Decreased clearance and increased bioavailability of budesonide

CYP3A4 inhibitors: Serum level and/or toxicity of budesonide may be increased; this effect was shown with ketoconazole, but not erythromycin. Other potential inhibitors include amiodarone, cimetidine, clarithromycin, delavirdine, diltiazem, dirithromycin, disulfiram, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nevirapine, propoxyphene, quinupristin-dalfopristin, ritonavir, saquinavir, verapamil, zafirlukast, zileuton.

Proton pump inhibitors (omeprazole, pantoprazole, rabeprazole): Theoretically, alteration of gastric pH may affect the rate of dissolution of enteric-coated capsules. Administration with omeprazole did not alter kinetics of budesonide capsules.

Salmeterol: The addition of salmeterol has been demonstrated to improve response to inhaled corticosteroids (as compared to increasing steroid dosage).

Food: Grapefruit juice may double systemic exposure of orally-administered budesonide. Administration of capsules with a high-fat meal delays peak concentration, but does not alter the extent of absorption.

Herb/Nutraceutical: St John's wort may decrease budesonide levels.

Nebulizer: Store upright at 20°C to 25°C (68°F to 77°F) and protect from light. Do not refrigerate or freeze. Once aluminum package is opened, solution should be used within 2 weeks. Continue to protect from light.

Nasal inhaler: Store with valve up at 15°C to 30°C (59°F to 86°F). Use within 6 months after opening aluminum pouch. Protect from high humidity.

Nasal spray: Store with valve up at 20°C to 25°C (68°F to 77°F) and protect from light. Do not freeze.

Onset of action: Respules®: 2-8 days; Rhinocort® Aqua®: ~10 hours; Turbuhaler®: 24 hours

Peak effect: Respules®: 4-6 weeks; Rhinocort® Aqua®: ~2 weeks; Turbuhaler®: 1-2 weeks

Absorption: Capsule: Rapid and complete

Distribution: 2.2-3.9 L/kg

Protein binding: 85% to 90%

Metabolism: Hepatic via CYP3A4 to two metabolites: 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide; minor activity

Bioavailability: Limited by high first-pass effect; Capsule: 9% to 21%; Respules®: 6%; Turbuhaler®: 6% to 13%; Nasal: 34%

Half-life elimination: 2-3.6 hours

Time to peak: Capsule: 30-600 minutes (variable in Crohn's disease); Respules®: 10-30 minutes; Turbuhaler®: 1-2 hours; Nasal: 1 hour

Excretion: Urine (60%) and feces as metabolites

Nasal inhalation: (Rhinocort® Aqua®): Children 6 years and Adults: 64 mcg/day as a single 32 mcg spray in each nostril. Some patients who do not achieve adequate control may benefit from increased dosage. A reduced dosage may be effective after initial control is achieved.

Maximum dose: Children <12 years: 128 mcg/day; Adults: 256 mcg/day

Nebulization: Children 12 months to 8 years: Pulmicort Respules®: Titrate to lowest effective dose once patient is stable; start at 0.25 mg/day or use as follows:

Previous therapy of bronchodilators alone: 0.5 mg/day administered as a single dose or divided twice daily (maximum daily dose: 0.5 mg)

Previous therapy of inhaled corticosteroids: 0.5 mg/day administered as a single dose or divided twice daily (maximum daily dose: 1 mg)

Previous therapy of oral corticosteroids: 1 mg/day administered as a single dose or divided twice daily (maximum daily dose: 1 mg)

Oral inhalation:

Children 6 years:

Previous therapy of bronchodilators alone: 200 mcg twice initially which may be increased up to 400 mcg twice daily

Previous therapy of inhaled corticosteroids: 200 mcg twice initially which may be increased up to 400 mcg twice daily

Previous therapy of oral corticosteroids: The highest recommended dose in children is 400 mcg twice daily

Adults:

Previous therapy of bronchodilators alone: 200-400 mcg twice initially which may be increased up to 400 mcg twice daily

Previous therapy of inhaled corticosteroids: 200-400 mcg twice initially which may be increased up to 800 mcg twice daily

Previous therapy of oral corticosteroids: 400-800 mcg twice daily which may be increased up to 800 mcg twice daily

NIH Guidelines (NIH, 1997) (give in divided doses twice daily):

Children:

"Low" dose: 100-200 mcg/day

"Medium" dose: 200-400 mcg/day (1-2 inhalations/day)

"High" dose: >400 mcg/day (>2 inhalation/day)

Adults:

"Low" dose: 200-400 mcg/day (1-2 inhalations/day)

"Medium" dose: 400-600 mcg/day (2-3 inhalations/day)

"High" dose: >600 mcg/day (>3 inhalation/day)

Oral: Adults: Crohn's disease: 9 mg once daily in the morning; safety and efficacy have not been established for therapy duration >8 weeks; recurring episodes may be treated with a repeat 8-week course of treatment

Note: Treatment may be tapered to 6 mg once daily for 2 weeks prior to complete cessation. Patients receiving CYP3A4 inhibitors should be monitored closely for signs and symptoms of hypercorticism; dosage reduction may be required.

Dosage adjustment in hepatic impairment: Monitor closely for signs and symptoms of hypercorticism; dosage reduction may be required.

Inhalation: Inhaler should be shaken well immediately prior to use; while activating inhaler, deep breathe for 3-5 seconds, hold breath for ~10 seconds and allow 1 minute between inhalations. Rinse mouth with water after use to reduce aftertaste and incidence of candidiasis.

Nebulization: Shake well before using. Use Pulmicort Respules® with jet nebulizer connected to an air compressor; administer with mouthpiece or facemask. Do not use ultrasonic nebulizer. Do not mix with other medications in nebulizer. Rinse mouth following treatments to decrease risk of oral candidiasis (wash face if using face mask).

Oral capsule: Capsule should be swallowed whole; do not crush or chew.

Oral capsule: Swallow whole; do not crush or chew capsule.

Inhalation/nebulization: This is not a bronchodilator and will not relieve acute asthma attacks. It may take several days for you to realize full effects of treatment. If you are also using an inhaled bronchodilator, wait 10 minutes before using this steroid aerosol. Take 5-10 deep breaths. Use inhaler on inspiration. Hold breath for 5-10 seconds after inhalation. Allow 1 full minute between inhalations. You may experience dizziness, anxiety, or blurred vision (rise slowly from sitting or lying position and use caution when driving or engaging in tasks requiring alertness until response to drug is known); or taste disturbance or aftertaste (frequent mouth care and mouth rinses may help). Rinse mouth with water following oral treatments to decrease risk of oral candidiasis (wash face if using a face mask).

Capsule, enteric coated (Entocort™ EC): 3 mg

Powder for oral inhalation (Pulmicort Turbuhaler®): 200 mcg/inhalation (104 g) [delivers ~160 mcg/inhalation; 200 metered doses]

Additional dosage strengths available in Canada: 100 mcg/inhalation, 400 mcg/inhalation

Suspension, nasal spray (Rhinocort® Aqua®): 32 mcg/inhalation (8.6 g) [120 metered doses]

Suspension for oral inhalation (Pulmicort Respules®): 0.25 mg/2 mL (30s), 0.5 mg/2 mL (30s)

Expert Panel Report 2, "Guidelines for the Diagnosis and Management of Asthma,"Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 94-4051, April, 1997.