Introduction

Synthetic, non-halogenated corticosteroid; potent glucocorticoid and weak mineralocorticoid activity.

Uses for Budesonide (Systemic, Oral Inhalation)

Crohn’s Disease

Used orally for the management of an active episode of mild-to-moderate Crohn’s disease involving the ileum and/or ascending colon and for maintenance of clinical remission for up to 3 months in this condition.

Has been used for the management of mild to moderately active Crohn’s disease^{† [off-label]} in a limited number of children 9.5–18 years of age.

Asthma

Long-term prevention of bronchospasm in patients with asthma.

In corticosteroid-dependent patients, may permit a substantial reduction in daily maintenance dosage of systemic corticosteroid and gradual discontinuance of corticosteroid maintenance dosages.

Used in fixed combination with formoterol in asthmatic patients whose disease is inadequately controlled with other anti-asthma controller therapy (e.g., low-to-medium dosages of inhaled corticosteroids) or whose disease severity warrants treatment with 2 maintenance therapies.

Fixed combination with formoterol should not be used in patients whose asthma can be successfully managed with inhaled corticosteroids and occasional use of inhaled short-acting β₂-adrenergic agonists. (See Serious Asthma-related Events under Cautions.)

Use fixed combination with formoterol for shortest duration required to achieve asthma control. Assess patient at regular intervals and step down therapy (e.g., discontinue budesonide/formoterol), if possible without loss of asthma control, and maintain patient on long-term asthma controller therapy (e.g., inhaled corticosteroids).

Not indicated for management of acute bronchospasm.

Not indicated for treatment or prevention of exercise-induced bronchospasm.

Budesonide (Systemic, Oral Inhalation) Dosage and Administration

General

Asthma

• Individualize dosage carefully according to disease severity.

• Base initial and maximum dosages of oral inhalation on previous asthma therapy.

• After a satisfactory response is obtained, decrease dosage gradually to the lowest dosage that maintains an adequate clinical response. Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth. (See Pediatric Use under Cautions.)

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

• When switching from systemic corticosteroids to orally inhaled budesonide, asthma should be reasonably stable before initiating withdrawal from systemic corticosteroids.

• Initially, administer the oral inhalation therapy concurrently with the maintenance dosage of the systemic corticosteroid. After about 1 week, gradually withdraw systemic corticosteroid, followed by further reductions after an interval of 1 or 2 weeks.

• Usual decrements of ≤2.5 mg or ≤25% of prednisone dosage (or its equivalent) every 1–2 weeks used in patients receiving budesonide powder for inhalation or inhalation suspension, respectively. Once oral corticosteroids are discontinued and symptoms of asthma have been controlled, titrate the dosage to the lowest effective level.

• Death has occurred in some individuals due to adrenal insufficiency in whom systemic corticosteroids were withdrawn too rapidly. If evidence of adrenal insufficiency occurs, increase systemic corticosteroid dosage temporarily and then continue withdrawal from systemic corticosteroids more slowly. (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)

Administration

Administer orally as delayed-release capsules.

Administer by oral inhalation as an oral powder inhaler (Pulmicort Flexhaler), via nebulization (Pulmicort Respules), or as an oral aerosol inhaler (Symbicort).

Oral Administration

Administer orally once daily as delayed-release capsules containing enteric-coated granules.

Swallow the capsules intact; do not chew or break. However, limited data indicate that the release characteristics of capsules were not affected when unencapsulated granules were added to applesauce for 30 minutes.

Avoid concomitant use of the capsules and grapefruit juice. (See Specific Drugs or Food under Interactions.)

Manufacturer makes no specific recommendations regarding administration with meals; a high-fat meal may decrease the rate of absorption. (See Absorption under Pharmacokinetics.)

Oral Inhalation

Following each dose, rinse the mouth with water to remove residual drug and to minimize the development of fungal overgrowth and/or infection.

Inhalation Powder

Prime the oral inhaler prior to initial use.

Do not shake Pulmicort Flexhaler.

Place mouthpiece of the inhaler between the lips and inhale deeply and forcefully.

Do not use another dose even if the patient did not sense the presence of the drug entering their lungs.

Pulmicort Flexhaler cannot be refilled; discard when empty.

Inhalation Suspension

Do not administer the oral inhalation suspension parenterally or use with ultrasonic nebulizers.

Using in vitro testing at a flow rate of 5.5 L per minute for an average of 5 minutes, the Pari-LC-Jet Plus nebulizer delivered at the mouthpiece approximately 17% of the original dose.

Administer using a jet nebulizer (with face mask or mouthpiece) connected to a compressor that has an adequate air flow. To optimize delivery and to avoid exposure of the eyes to nebulized drug, adjust the face mask properly.

When a face mask is used for nebulization, wash the face after each use to avoid dermatologic corticosteroid effects (e.g., rash, contact dermatitis).

Safety and efficacy of budesonide inhalation suspension administered by a nebulizer other than the Pari-LC-Jet Plus Nebulizer or a compressor other than the Pari Master compressor not established.

Inhalation Aerosol

Administer budesonide in fixed combination with formoterol using an aerosol inhaler device. Administer twice daily (morning and evening).

Test spray 2 times before first use, if not used for >7 days, or if dropped.

Shake well for 5 seconds immediately prior to use.

Clean inhaler every 7 days by wiping mouthpiece with a dry cloth.

Use the actuator supplied with the product to administer budesonide in fixed combination with formoterol.

Symbicort cannot be refilled; discard when empty.

Dosage

Dosage of budesonide inhalation powder is expressed in mcg delivered from the mouthpiece. The amount of drug powder delivered to the lungs depends on factors such as the patient’s inspiratory flow.

Each actuation of the Pulmicort Flexhaler inhaler contains 90 or 180 mcg of budesonide inhalation powder and delivers approximately 80 or 160 mcg of budesonide, respectively, per activation from the mouthpiece.

Delivery of oral inhalation suspension (Pulmicort Respules) to the lungs depends on the type of jet nebulizers used, performance of the compressor, and on factors such as the patient’s inspiratory flow.

Dosage of budesonide in fixed combination with formoterol fumarate dihydrate (Symbicort) inhalation aerosol is expressed in mcg delivered from the mouthpiece. Each actuation of the Symbicort inhalation aerosol delivers 91 or 181 mcg of budesonide and 5.1 mcg of formoterol fumarate dihydrate from the valve, and 80 or 160 mcg of budesonide and 4.5 mcg of formoterol fumarate dihydrate from the actuator per metered spray. The amount of drug delivered to the lungs depends on factors such as the patient’s inspiratory flow. The aerosol inhaler delivers 60 metered sprays per 6- or 6.9-g canister, and 120 metered sprays per 10.2-g canister.

Pediatric Patients

Asthma

Maintenance Monotherapy

Children and adolescents 6–17 years of age: Initially, 160 mcg (labeled 180 mcg) twice daily. If required, may increase dosage to a maximum of 320 mcg (labeled 360 mcg) twice daily. In some patients, an initial dosage of 320 mcg (labeled 360 mcg) twice daily may be appropriate.

Oral Inhalation Suspension

Children 1–8 years of age inadequately controlled with nonsteroidal (e.g., bronchodilator, mast-cell stabilizer) therapy: Initially, 0.25 mg once daily. If the response is inadequate, increase the total daily dosage and/or administer in divided doses.

Children 1–8 years of age previously receiving bronchodilators alone: 0.5 mg daily, given in 1 or 2 divided doses.

Children 1–8 years of age previously receiving inhaled corticosteroids: Initially, 0.5 mg daily, given in 1 or 2 divided doses. If response is inadequate, dosage may be increased to a maximum of 1 mg daily and/or administered in divided doses.

Children 1–8 years of age previously receiving oral corticosteroids: 1 mg daily, given in 1 or 2 divided doses.

Budesonide/Formoterol Fixed-combination Therapy

Adolescents ≥12 years of age: Initially, 160 or 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily, depending on asthma severity, level of control of asthma symptoms, and/or risk of asthma exacerbations during current therapy with inhaled corticosteroids.

If control of asthma is inadequate after 1–2 weeks of therapy at the lower dosage, a higher strength (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.

Children 6 to <12 years of age: 160 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Adults

Crohn’s Disease

Management of Mild to Moderately Active Crohn’s Disease

Initially, 9 mg daily in the morning for 8 weeks.

In patients who have not experienced remission during the initial 8-week course, a second 8-week course (16 weeks of continuous therapy) may be used.

Maintenance of Remission

6 mg once daily for up to 3 months. If symptom control is maintained at 3 months, attempt to taper dosage to complete cessation. The manufacturer states that continued therapy beyond 3 months has not been shown to provide substantial clinical benefit.

Asthma

Maintenance Monotherapy

Usual initial dosage is 320 mcg (labeled 360 mcg) twice daily. In some patients, an initial dosage of 160 mcg (labeled 180 mcg) twice daily may be adequate. If required, may increase dosage to a maximum of 640 mcg (labeled 720 mcg) twice daily.

Budesonide/Formoterol Fixed-combination Therapy

Patients not currently receiving an orally inhaled corticosteroid: Initially, 160 or 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily, depending on asthma severity.

Patients inadequately controlled with low-to-medium dosages of an inhaled corticosteroid: Initially, 160 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Patients inadequately controlled with medium-to-high dosages of an inhaled corticosteroid: Initially, 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

If control of asthma is inadequate after 1–2 weeks of therapy at the lower dosage, a higher strength (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.

Prescribing Limits

Pediatric Patients

Asthma

Maintenance Monotherapy

Pulmicort Flexhaler in children and adolescents 6–17 years of age: Maximum 320 mcg (labeled 360 mcg) twice daily.

Children 1–8 years of age, previously receiving bronchodilators alone: Maximum 0.5 mg daily.

Children 1–8 years of age, previously receiving inhaled corticosteroids: Maximum 1 mg daily.

Children 1–8 years of age, previously receiving oral corticosteroids: Maximum 1 mg daily.

Budesonide/Formoterol Fixed-combination Therapy

Adolescents ≥12 years of age: Maximum 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Adults

Asthma

Maintenance Monotherapy

Pulmicort Flexhaler in patients ≥18 years of age: Maximum 640 mcg (labeled 720 mcg) twice daily.

Budesonide/Formoterol Fixed-combination Therapy

Maximum 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Special Populations

Hepatic Impairment

Crohn’s Disease

Consider dosage reduction in moderate to severe hepatic impairment. (See Special Populations under Absorption in Pharmacokinetics.)

Asthma

No specific dosage recommendations at this time.

Renal Impairment

Asthma

No specific dosage recommendations at this time.

Geriatric Patients

Oral monotherapy: Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Oral inhalation powder (Pulmicort Flexhaler): Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Fixed combination of budesonide and formoterol fumarate dihydrate: No dosage adjustment required. (See Geriatric Use under Cautions.)

Contraindications

• Known hypersensitivity to budesonide or any ingredient in the formulation.

• Orally inhaled budesonide for primary treatment of acute asthmatic attacks or status asthmaticus when intensive measures (e.g., an orally inhaled β₂-adrenergic agonist, an orally inhaled anticholinergic agent, subcutaneous epinephrine, IV aminophylline, and/or an oral/IV glucocorticoid) are required.

• Oral inhalation powder: Known severe hypersensitivity to milk proteins.

• When budesonide is used in fixed combination with formoterol fumarate, contraindications associated with formoterol should be considered.

Warnings/Precautions

Warnings

Serious Asthma-related Events

Long-acting β₂-adrenergic agonists, such as formoterol, a component of Symbicort, increase the risk of asthma-related death when used as monotherapy. Data from clinical trials suggest that monotherapy with long-acting β₂-adrenergic agonists also increases the risk of asthma-related hospitalization in children and adolescents.

Use the fixed combination of budesonide and formoterol only in patients with asthma who have not responded adequately to long-term asthma controller therapy (e.g., inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a long-acting β₂-adrenergic agonist. (See Asthma under Uses.)

Based on review of 4 clinical trials (3 in adults and adolescents and 1 in children), FDA concluded there is no clinically important increased risk of serious asthma-related events associated with concomitant use of long-acting β₂-adrenergic agonists and inhaled corticosteroids compared with inhaled corticosteroids alone for the treatment of asthma. Results of these studies showed no evidence of a clinically important increased risk of asthma-related hospitalization, intubation, or death with such combination therapy compared with inhaled corticosteroids alone. These studies also showed that combination therapy with long-acting β₂-adrenergic agonists and inhaled corticosteroids reduced the incidence of asthma exacerbations compared with use of inhaled corticosteroids alone.

Withdrawal of Systemic Corticosteroid Therapy

Possible life-threatening adrenal insufficiency in patients being switched from systemic corticosteroids to orally inhaled budesonide.

Withdraw systemic corticosteroid therapy gradually. In general, the greater the dosage and duration of systemic corticosteroid therapy, the greater the time required for withdrawal of systemic corticosteroids and replacement by orally inhaled corticosteroids.

Monitor carefully for objective signs of adrenal insufficiency (e.g., fatigue, lassitude, weakness, nausea, vomiting, hypotension) and asthma instability (e.g., airway function) during withdrawal of systemic therapy. Carefully monitor lung function (forced expiratory volume in 1 second [FEV₁], morning peak expiratory flow [PEF]), adjunctive β₂-adrenergic agonist use, and asthma symptoms. Patients who have been maintained on ≥20 mg of prednisone (or its equivalent) daily may be most susceptible to such adverse events, particularly during latter part of the transfer. (See Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids under Dosage and Administration.)

Corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression) may occur.

Adrenal insufficiency may occur during exposure to trauma, surgery, infection (particularly gastroenteritis), or other conditions associated with acute electrolyte loss.

Possible unmasking of allergic conditions previously controlled by systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).

Do not use the fixed combination of budesonide and formoterol fumarate dihydrate for transferring therapy from systemic to inhaled corticosteroids.

Immunosuppressed Patients

Increased susceptibility to infections in patients taking immunosuppressant drugs compared with healthy individuals. Certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients, particularly in children.

Take particular care to avoid exposure in susceptible patients. If exposure to varicella or measles occurs in susceptible patients, consider administering varicella zoster immune globulin (VZIG) or pooled immune globulin (IG), respectively. Consider treatment with an antiviral agent if varicella develops.

Paradoxical Bronchospasm

Possible life-threatening, acute, paradoxical bronchospasm and/or wheezing. If bronchospasm occurs, treat immediately with a short-acting bronchodilator, discontinue treatment with budesonide, and institute alternative therapy.

General Precautions

Ocular Effects

Glaucoma, increased IOP, and cataracts reported rarely in patients receiving orally inhaled corticosteroids.

Use delayed-release capsules with caution in patients with glaucoma, cataracts, or a family history of glaucoma.

Consider regular eye examinations.

Systemic Corticosteroid Effects

Administration of higher than recommended dosages of orally inhaled budesonide or prolonged oral administration of budesonide capsules may result in manifestations of hypercorticism and suppression of HPA function. To minimize potential for such changes, do not exceed recommended dosages of orally inhaled budesonide-containing therapy.

Monitor patients receiving orally inhaled budesonide-containing therapy for any evidence of systemic corticosteroid effects. If systemic corticosteroid effects occur, reduce the dosage of budesonide-containing therapy slowly, consistent with accepted procedures for reducing corticosteroid dosage and management of asthma symptoms.

Take particular care in monitoring patients postoperatively or during periods of stress for evidence of inadequate adrenal response. Supplemental therapy with a systemic corticosteroid required during stress or severe asthma attacks.

Musculoskeletal Effects

Long-term use may affect normal bone metabolism, resulting in a loss of bone mineral density (BMD).

Use of orally inhaled corticosteroids can pose additional risks in patients with major risk factors for decreased BMD, such as tobacco use, advanced age, sedentary lifestyle, poor nutrition, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, additional corticosteroids).

Use delayed-release capsules with caution in patients with osteoporosis.

Possible growth suppression in pediatric patients. (See Pediatric Use under Cautions.)

Concomitant Disease States

Use delayed-release capsules with caution in patients with hypertension, diabetes mellitus, peptic ulcer, a family history of diabetes, or any other condition in which glucocorticoids may be associated with adverse effects.

Infection

Localized candidal infections of the mouth and/or pharynx reported with oral inhalation therapy.

If infection occurs, initiate appropriate local or systemic antifungal treatment while still continuing with inhaled budesonide therapy. May require discontinuance of budesonide therapy (under close medical supervision) in some patients.

Lower respiratory tract infections, including pneumonia, reported with orally inhaled corticosteroid therapy. Use oral inhalation therapy with extreme caution, if at all, in patients with clinical tuberculosis or latent M. tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Use delayed-release capsules with caution in patients with tuberculosis.

Other Effects

Unknown long-term local and systemic effects of the drug in humans, particularly local effects on developmental or immunologic processes in the mouth, pharynx, trachea, and lung.

Use of Fixed Combinations

When used in fixed combination with formoterol fumarate dihydrate, consider the cautions, precautions, and contraindications associated with formoterol.

Specific Populations

Pregnancy

Category B (orally inhaled powder and inhalation suspension); category C (oral capsules, inhalation aerosol).

Hypoadrenalism may occur in infants of women receiving corticosteroid therapy during pregnancy; monitor these infants carefully.

Lactation

Distributed into milk; data not available on effects of the drug on the breast-fed child or milk production.

Consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Manufacturer of oral inhalation powder (Pulmicort Flexhaler) states drug should be used only if clinically appropriate; titrate to lowest effective dosage and use inhaler immediately after nursing to minimize infant exposure.

Pediatric Use

Safety and efficacy of oral budesonide delayed-release capsules not established in pediatric patients <18 years of age with Crohn’s disease.

Safety and efficacy of budesonide inhalation powder not established in children <6 years of age.

Efficacy of budesonide inhalation suspension not established in children <1 year of age, while safety of the suspension not evaluated in children <6 months of age.

Efficacy of inhalation aerosol containing budesonide in fixed combination with formoterol fumarate dihydrate not established in children <6 years of age. Safety of combination therapy in children 6 to <12 years of age similar to that in adolescents and adults.

With long-term use, slows growth rate in children and adolescents. Monitor routinely (e.g., via stadiometry) growth and development of pediatric patients receiving orally inhaled corticosteroid therapy. Weigh benefits of orally inhaled corticosteroid therapy versus possibility of growth suppression. Use the lowest possible dosage that effectively controls asthma.

Geriatric Use

Insufficient experience with oral drug and inhalation powder in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. (See Geriatric Patients under Dosage and Administration.)

Safety of inhalation powder in patients ≥65 years of age similar to that in younger adults.

Safety and efficacy of inhalation suspension or inhalation aerosol in patients ≥65 years of age similar to that in younger adults.

Hepatic Impairment

Monitor patients with Crohn’s disease and moderate to severe hepatic impairment for increased signs and symptoms of hypercorticism. (See Hepatic Impairment under Dosage and Administration.)

Common Adverse Effects

With oral capsules, headache, dizziness, nausea, vomiting, dyspepsia, diarrhea, sinusitis, symptoms of hypercorticism, respiratory infection, viral infection, pain (including back pain), arthralgia, fatigue. Adverse effect profile in long-term treatment similar to short-term treatment.

With oral inhalation, respiratory infection, nasopharyngitis, nasal congestion, pharyngitis, allergic rhinitis, sinusitis, cough, nausea, gastroenteritis, otitis (media or externa), oral candidiasis, flu or flu-like syndrome, headache, pain (e.g., back pain).

General

Asthma

• Individualize dosage carefully according to disease severity.

• Base initial and maximum dosages of oral inhalation on previous asthma therapy.

• After a satisfactory response is obtained, decrease dosage gradually to the lowest dosage that maintains an adequate clinical response. Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth. (See Pediatric Use under Cautions.)

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

• When switching from systemic corticosteroids to orally inhaled budesonide, asthma should be reasonably stable before initiating withdrawal from systemic corticosteroids.

• Initially, administer the oral inhalation therapy concurrently with the maintenance dosage of the systemic corticosteroid. After about 1 week, gradually withdraw systemic corticosteroid, followed by further reductions after an interval of 1 or 2 weeks.

• Usual decrements of ≤2.5 mg or ≤25% of prednisone dosage (or its equivalent) every 1–2 weeks used in patients receiving budesonide powder for inhalation or inhalation suspension, respectively. Once oral corticosteroids are discontinued and symptoms of asthma have been controlled, titrate the dosage to the lowest effective level.

• Death has occurred in some individuals due to adrenal insufficiency in whom systemic corticosteroids were withdrawn too rapidly. If evidence of adrenal insufficiency occurs, increase systemic corticosteroid dosage temporarily and then continue withdrawal from systemic corticosteroids more slowly. (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)

Administration

Administer orally as delayed-release capsules.

Administer by oral inhalation as an oral powder inhaler (Pulmicort Flexhaler), via nebulization (Pulmicort Respules), or as an oral aerosol inhaler (Symbicort).

Oral Administration

Administer orally once daily as delayed-release capsules containing enteric-coated granules.

Swallow the capsules intact; do not chew or break. However, limited data indicate that the release characteristics of capsules were not affected when unencapsulated granules were added to applesauce for 30 minutes.

Avoid concomitant use of the capsules and grapefruit juice. (See Specific Drugs or Food under Interactions.)

Manufacturer makes no specific recommendations regarding administration with meals; a high-fat meal may decrease the rate of absorption. (See Absorption under Pharmacokinetics.)

Oral Inhalation

Following each dose, rinse the mouth with water to remove residual drug and to minimize the development of fungal overgrowth and/or infection.

Inhalation Powder

Prime the oral inhaler prior to initial use.

Do not shake Pulmicort Flexhaler.

Place mouthpiece of the inhaler between the lips and inhale deeply and forcefully.

Do not use another dose even if the patient did not sense the presence of the drug entering their lungs.

Pulmicort Flexhaler cannot be refilled; discard when empty.

Inhalation Suspension

Do not administer the oral inhalation suspension parenterally or use with ultrasonic nebulizers.

Using in vitro testing at a flow rate of 5.5 L per minute for an average of 5 minutes, the Pari-LC-Jet Plus nebulizer delivered at the mouthpiece approximately 17% of the original dose.

Administer using a jet nebulizer (with face mask or mouthpiece) connected to a compressor that has an adequate air flow. To optimize delivery and to avoid exposure of the eyes to nebulized drug, adjust the face mask properly.

When a face mask is used for nebulization, wash the face after each use to avoid dermatologic corticosteroid effects (e.g., rash, contact dermatitis).

Safety and efficacy of budesonide inhalation suspension administered by a nebulizer other than the Pari-LC-Jet Plus Nebulizer or a compressor other than the Pari Master compressor not established.

Inhalation Aerosol

Administer budesonide in fixed combination with formoterol using an aerosol inhaler device. Administer twice daily (morning and evening).

Test spray 2 times before first use, if not used for >7 days, or if dropped.

Shake well for 5 seconds immediately prior to use.

Clean inhaler every 7 days by wiping mouthpiece with a dry cloth.

Use the actuator supplied with the product to administer budesonide in fixed combination with formoterol.

Symbicort cannot be refilled; discard when empty.

Dosage

Dosage of budesonide inhalation powder is expressed in mcg delivered from the mouthpiece. The amount of drug powder delivered to the lungs depends on factors such as the patient’s inspiratory flow.

Each actuation of the Pulmicort Flexhaler inhaler contains 90 or 180 mcg of budesonide inhalation powder and delivers approximately 80 or 160 mcg of budesonide, respectively, per activation from the mouthpiece.

Delivery of oral inhalation suspension (Pulmicort Respules) to the lungs depends on the type of jet nebulizers used, performance of the compressor, and on factors such as the patient’s inspiratory flow.

Dosage of budesonide in fixed combination with formoterol fumarate dihydrate (Symbicort) inhalation aerosol is expressed in mcg delivered from the mouthpiece. Each actuation of the Symbicort inhalation aerosol delivers 91 or 181 mcg of budesonide and 5.1 mcg of formoterol fumarate dihydrate from the valve, and 80 or 160 mcg of budesonide and 4.5 mcg of formoterol fumarate dihydrate from the actuator per metered spray. The amount of drug delivered to the lungs depends on factors such as the patient’s inspiratory flow. The aerosol inhaler delivers 60 metered sprays per 6- or 6.9-g canister, and 120 metered sprays per 10.2-g canister.

Pediatric Patients

Asthma

Maintenance Monotherapy

Children and adolescents 6–17 years of age: Initially, 160 mcg (labeled 180 mcg) twice daily. If required, may increase dosage to a maximum of 320 mcg (labeled 360 mcg) twice daily. In some patients, an initial dosage of 320 mcg (labeled 360 mcg) twice daily may be appropriate.

Oral Inhalation Suspension

Children 1–8 years of age inadequately controlled with nonsteroidal (e.g., bronchodilator, mast-cell stabilizer) therapy: Initially, 0.25 mg once daily. If the response is inadequate, increase the total daily dosage and/or administer in divided doses.

Children 1–8 years of age previously receiving bronchodilators alone: 0.5 mg daily, given in 1 or 2 divided doses.

Children 1–8 years of age previously receiving inhaled corticosteroids: Initially, 0.5 mg daily, given in 1 or 2 divided doses. If response is inadequate, dosage may be increased to a maximum of 1 mg daily and/or administered in divided doses.

Children 1–8 years of age previously receiving oral corticosteroids: 1 mg daily, given in 1 or 2 divided doses.

Budesonide/Formoterol Fixed-combination Therapy

Adolescents ≥12 years of age: Initially, 160 or 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily, depending on asthma severity, level of control of asthma symptoms, and/or risk of asthma exacerbations during current therapy with inhaled corticosteroids.

If control of asthma is inadequate after 1–2 weeks of therapy at the lower dosage, a higher strength (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.

Children 6 to <12 years of age: 160 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Adults

Crohn’s Disease

Management of Mild to Moderately Active Crohn’s Disease

Initially, 9 mg daily in the morning for 8 weeks.

In patients who have not experienced remission during the initial 8-week course, a second 8-week course (16 weeks of continuous therapy) may be used.

Maintenance of Remission

6 mg once daily for up to 3 months. If symptom control is maintained at 3 months, attempt to taper dosage to complete cessation. The manufacturer states that continued therapy beyond 3 months has not been shown to provide substantial clinical benefit.

Asthma

Maintenance Monotherapy

Usual initial dosage is 320 mcg (labeled 360 mcg) twice daily. In some patients, an initial dosage of 160 mcg (labeled 180 mcg) twice daily may be adequate. If required, may increase dosage to a maximum of 640 mcg (labeled 720 mcg) twice daily.

Budesonide/Formoterol Fixed-combination Therapy

Patients not currently receiving an orally inhaled corticosteroid: Initially, 160 or 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily, depending on asthma severity.

Patients inadequately controlled with low-to-medium dosages of an inhaled corticosteroid: Initially, 160 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Patients inadequately controlled with medium-to-high dosages of an inhaled corticosteroid: Initially, 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

If control of asthma is inadequate after 1–2 weeks of therapy at the lower dosage, a higher strength (higher strengths contain higher dosages of budesonide only) may provide additional asthma control.

Prescribing Limits

Pediatric Patients

Asthma

Maintenance Monotherapy

Pulmicort Flexhaler in children and adolescents 6–17 years of age: Maximum 320 mcg (labeled 360 mcg) twice daily.

Children 1–8 years of age, previously receiving bronchodilators alone: Maximum 0.5 mg daily.

Children 1–8 years of age, previously receiving inhaled corticosteroids: Maximum 1 mg daily.

Children 1–8 years of age, previously receiving oral corticosteroids: Maximum 1 mg daily.

Budesonide/Formoterol Fixed-combination Therapy

Adolescents ≥12 years of age: Maximum 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Adults

Asthma

Maintenance Monotherapy

Pulmicort Flexhaler in patients ≥18 years of age: Maximum 640 mcg (labeled 720 mcg) twice daily.

Budesonide/Formoterol Fixed-combination Therapy

Maximum 320 mcg of budesonide and 9 mcg of formoterol fumarate dihydrate twice daily.

Special Populations

Hepatic Impairment

Crohn’s Disease

Consider dosage reduction in moderate to severe hepatic impairment. (See Special Populations under Absorption in Pharmacokinetics.)

Asthma

No specific dosage recommendations at this time.

Renal Impairment

Asthma

No specific dosage recommendations at this time.

Geriatric Patients

Oral monotherapy: Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Oral inhalation powder (Pulmicort Flexhaler): Careful dosage selection recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Fixed combination of budesonide and formoterol fumarate dihydrate: No dosage adjustment required. (See Geriatric Use under Cautions.)

Metabolized by the CYP3A4 isoenzyme.

Drugs or Foods Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma budesonide concentrations).

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma budesonide concentrations).

Drugs Affecting GI pH

Potential pharmacokinetic interaction (may affect release properties and systemic absorption of enteric coated budesonide capsules).

Specific Drugs or Food