Budesonide

Pronunciation (byoo DES oh nide)

• Asthma Guidelines
• Estimated Comparative Daily Dosages for Inhaled Corticosteroids
• Inhalant Agents

U.S. Brand Names Entocort^TM EC; Pulmicort Respules^TM; Pulmicort Turbuhaler®; Rhinocort®; Rhinocort® Aqua^TM

Generic Available No

Canadian Brand Names Entocort®; Gen-Budesonide AQ; Pulmicort®; Rhinocort® Turbuhaler®

Pharmacologic Category Corticosteroid, Inhalant (Oral); Corticosteroid, Nasal; Corticosteroid, Systemic

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

Pregnancy Risk Factor C/B (Pulmicort Turbuhaler®)

Pregnancy Implications No adequate or well-controlled studies in pregnant women; use only if potential benefit to the mother outweighs the possible risk to the fetus. Hypoadrenalism has been reported in infants.

Lactation Excreted in breast milk/use caution

Contraindications Hypersensitivity to budesonide or any component of the formulation

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

Warnings/Precautions May cause hypercorticism and/or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. Particular care is required when patients are transferred from systemic corticosteroids to products with lower systemic bioavailability (ie, inhalation). May lead to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving prolonged therapy of 20 mg per day of prednisone (or equivalent) may be most susceptible. Aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.

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.

Adverse Reactions Reaction severity varies by dose and duration; not all adverse reactions have been reported with each dosage form.

>10%:

1% to 10%:

<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, psychosis, somnolence 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.

Drug Interactions CYP3A3/4 enzyme substrate

Cimetidine: Decreased clearance and increased bioavailability of budesonide

CYP3A3/4 inducers (including carbamazepine, phenytoin, phenobarbital, rifampin): May decrease budesonide levels and/or effects.

CYP3A3/4 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.

Mechanism of Action Controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes, fibroblasts, reverses capillary permeability, and lysosomal stabilization at the cellular level to prevent or control inflammation

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

Absorption: Capsule: Rapid and complete

Distribution: 2.2-3.9 L/kg

Protein binding: 85% to 90%

Metabolism: Hepatic via CYP3A3/4 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: Children 6 years and Adults:

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

Oral inhalation:

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

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^TM 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.

Monitoring Parameters Monitor growth in pediatric patients.

Dietary Considerations Avoid grapefruit juice when using oral capsules.

Patient Information Use as directed; do not increase dosage or discontinue abruptly without consulting prescriber. Report acute nervousness or inability to sleep; severe sneezing or nosebleed; difficulty breathing, sore throat, hoarseness, or bronchitis; respiratory difficulty or bronchospasms; disturbed menstrual pattern; vision changes; loss of taste or smell perception; or worsening of condition or lack of improvement. May be more susceptible to infection; avoid exposure to chickenpox and measles unless immunity has been established Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

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 face mask).

Additional Information Effects of inhaled/intranasal steroids on growth have been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally-inhaled and intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for "catch up" growth following discontinuation of treatment with inhaled corticosteroids has not been adequately studied.

Cardiovascular Considerations Inhaled steroid therapy, usually used for chronic obstructive lung disease, has the important advantage of having minimal systemic effects. The inhaled steroid, when administered appropriately, may be assumed to have pulmonary effects equivalent to about 10 mg of oral steroids but with minimal systemic consequences.

Dental Health: Effects on Dental Treatment Localized infections with Candida albicans or Aspergillus niger have occurred frequently in the mouth and pharynx with repetitive use of oral inhaler of corticosteroids. These infections may require treatment with appropriate antifungal therapy or discontinuance of treatment with corticosteroid inhaler.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions

Mental Health: Effects on Mental Status May cause nervousness and insomnia

Mental Health: Effects on Psychiatric Treatment None reported

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

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

Suspension for nasal inhalation (Rhinocort®): 50 mcg/inhalation (7 g) [delivers ~32 mcg/inhalation; 200 metered doses]

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

Suspension for oral inhalation (Pulmicort Respules^TM): 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.

International Brand Names Aerovial® (CL); Aerovial Nasal® (CL); Aircort (IT); Apulein® (CZ, HU); Benosid (DE); Bidien (IT); Bronchocux (DE); Budamax (AU); Budapp® (DE); Budecort (DE); Budefarma® (AR); Budefat (DE); Budeflam (ZA); Budenofalk® (DE, CH); Budepur® (DE); Budepur E (DE); Budes® (DE); Budeson® (AR); Budesonid® (PL); Budesonid acis® (DE); Budesonid AL® (DE); Budesonid Azupharma® (DE); !Budesonid Basic® (DE); Budesonid beta® (DE); Budesonide Inhalatiepoeder® (NL); Budesonide Nevel® (NL); Budesonid Heumann® (DE); Budesonid pädia® (DE); Budesonid-Polfa® (HU); Budesonid-ratiopharm® (DE); Budesonid Scand Pharm® (SE); Budesonid Stada® (DE); budesonid von ct® (DE); Budon® (DE); Budo-san® (AT); Butacort® (NZ); Cortivent® (FI); Cyclocaps Budesonid® (DE); Demotest (ES); Eltair® (NZ); Entocord (ZA, ES); Entocort® (AR); Entocort (AU, AT, CA, CZ, DK, FI, FR, DE, HU, IE, NL, NZ, NO, SE, CH); Entocort CIR® (CH); Entocort CR® (GB); Entocort Enema® (LU, CH); Gen-Budesonide AQ® (CA); Hayclear® (NZ); Horacort® (PL); Inflammide® (ID); Inflammide (ZA); Miflonide (DK, DE, IT, PT, CH); Neo Rinactive (ES); Neumotex® (AR); Novopulmo (DE); Olfex® (ES); Predermid® (AT); Preferid® (BE, DK, FI, GB, IE, IT, LU, NL, NO, SE); Preferid (CH); Pulmaxan® (IT); Pulmicort (AU, AT, BE, CA, CZ, FI, FR, GB, HK, HU, IN, ID, IE, LU, MX, NL, NZ, NO, PL, PT, ZA, ES, SE, CH, TR, YU); Pulmicort "Paranova"® (DK); Pulmictan® (ES); Pulmolisoflam® (AR); Rhinocort (AU, AT, BE, CA, CZ, DK, FI, FR, GB, HK, HU, IN, IE, IT, LU, MX, NL, NZ, NO, PL, ZA, ES, SE, CH, TR); Rhinocort Aqua® (CA, HU, ID, ES, SE, YU); Rhinocortol (AT); Rhinocort® Turbuhaler® (CA); Rhinosol® (DK); Ribujet (ES); Ribusol® (ES); Rinactive (ES); Spirocort® (AR, DK, SE)