Budesonide / Formoterol Fumarate Dihydrate

Pronunciation: (bue-DES-oh-nide/for-MOE-ter-ol FUE-ma-rate DYE-hye-drate)Class: Respiratory inhalant combination

Trade Names:Symbicort 80/4.5- Inhalation aerosol budesonide 80 mcg and formoterol 4.5 mcg/actuation

Trade Names:Symbicort 160/4.5- Inhalation aerosol budesonide 160 mcg and formoterol 4.5 mcg/actuation

Pharmacology

Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity.

Formoterol fumarate is a long-acting selective beta-2 adrenergic agonist (beta-2 agonist) with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator.

Indications and Usage

Long-term maintenance treatment of asthma; maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema.

Contraindications

Primary treatment of status asthmaticus or other acute episodes of asthma in which intensive measures are required; hypersensitivity to any component of the product.

Dosage and Administration

AsthmaAdults and Children 12 yr of age and older

Oral Inhalation Recommended starting dose is 2 inhalations of budesonide/formoterol (80/4.5 or 160/4.5) twice daily approximately 12 h apart, depending upon asthma severity.

COPDAdults

Oral Inhalation Recommended dose is 2 inhalations of budesonide 160 mcg/formoterol 4.5 mcg twice daily. If shortness of breath occurs between doses, an inhaled short-acting beta-2 agonist should be taken for immediate relief.

General Advice

• Max daily recommended dosage is budesonide/formoterol (640/18 mcg) given as 2 inhalations of 160/4.5 mcg twice daily approximately 12 h apart.
• Do not use more than twice daily or for more than 2 inhalations.
• Rinse mouth with water without swallowing after inhalation.
• Titrate to the lowest effective strength after adequate asthma stability has been achieved.
• If symptoms arise in the period between doses, take an inhaled short-acting beta-2 agonist for immediate relief.
• Shake well for 5 min before using.
• Before using for the first time, prime the inhaler by releasing 2 test sprays into the air away from the face, shaking well for 5 sec before each spray. Prime the inhaler again by shaking well before each spray and releasing 2 test sprays if inhaler is not used for more than 7 days or if it is dropped.

Storage/Stability

Store at 68° to 77°F. Store with the mouthpiece down.

Drug Interactions

Beta-blockers (eg, propranolol)

If possible, avoid coadministration because beta-blockers may block the pulmonary effect of formoterol, in addition to producing severe bronchospasm in asthmatic patients.

Inhibitors of CYP3A4 (eg, ketoconazole)

Use with caution because budesonide plasma levels may be increased.

Loop diuretics (eg, furosemide), thiazide diuretics (eg, hydrochlorothiazide)

ECG changes and/or hypokalemia resulting from non–potassium-sparing diuretics can be worsened by formoterol.

MAOIs (eg, phenelzine), tricyclic antidepressants (eg, amitriptyline)

Use with caution in patients treated with MAOIs or tricyclic antidepressants, or within 2 wk of discontinuing these agents, because action of formoterol on the vascular system may be potentiated.

Salmeterol

Do not use in combination.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina pectoris, atrial fibrillation, atrial and ventricular tachyarrhythmias, extrasystoles, hypertension, hypotension, palpitations, tachycardia (postmarketing).

CNS

Headache (11%); agitation, behavior disturbances, depression, dizziness, nervousness, restlessness, sleep disturbances, tremor (postmarketing).

Dermatologic

Bruising (postmarketing).

EENT

Nasopharyngitis (11%); pharyngolaryngeal pain (9%); nasal congestion (3%); cataract, glaucoma, IOP (postmarketing).

GI

Stomach discomfort (7%); oral candidiasis (6%); vomiting (3%); nausea, oropharyngeal candidiasis (postmarketing).

Endocrine

Growth velocity reduction in children, hypercorticism (postmarketing).

Hypersensitivity

Delayed and immediate hypersensitivity reactions, including anaphylactic reaction, angioedema, bronchospasm, dermatitis, exanthema, pruritus, and urticaria (postmarketing).

Metabolic-Nutritional

Hyperglycemia, hypokalemia (postmarketing).

Musculoskeletal

Back pain (3%); muscle cramps (postmarketing).

Respiratory

Upper respiratory tract infection (11%); sinusitis (6%); bronchitis (5%); cough, dysphonia, throat irritation (postmarketing).

Miscellaneous

Influenza (3%).

Precautions

Warnings Long-acting beta-2 adrenergic agonists, such as formoterol, may increase the risk of asthma-related death. Therefore, only use for patients not adequately managed on other asthma-controller medications or whose disease severity warrants treatment with 2 maintenance agents.

Monitor Monitor for increasing use of inhaled short-acting beta-2 agonist, which may indicate deterioration of asthma. Observe patients for evidence of systemic corticosteroid effects. Closely monitor patients with a change in vision or with a history of increased IOP, glaucoma, and/or cataracts. Closely monitor use in patients with hepatic disease.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in asthmatic children younger than 12 yr of age. May cause reduction in growth velocity when administered to children.

Elderly

Use with caution in elderly patients who have concomitant CV disease that could be adversely affected by beta-2 agonists.

Hypersensitivity

Immediate hypersensitivity reactions, such as urticaria, angioedema, rash, and bronchospasm, may occur.

Hepatic Function

Use with caution and closely monitor patients.

Special Risk Patients

Use with caution in patients with CV disorders, especially coronary insufficiency, cardiac arrhythmias, hypertension, convulsive disorders, untreated hypokalemia, thyrotoxicosis, active or quiescent tuberculosis of the respiratory tract, untreated systemic fungal, bacterial, viral, or parasitic infection, or ocular herpes simplex, and in patients taking daily or alternate-day steroid therapy because of increased likelihood of hypothalmic-pituitary axis suppression.

Acute bronchospasm

Not indicated for the relief of acute bronchospasm.

Adrenal suppression

Adrenal suppression (including adrenal crisis) and hypercorticism may appear in a small number of patients.

Deteriorations of disease

Do not initiate treatment in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD. Do not use as rescue treatment of acute episodes of bronchospasm.

Eosinophilic conditions

In rare cases, systemic eosinophilic conditions may occur in patients receiving inhaled corticosteroids.

Excessive use

CV effects and fatalities have been reported with excessive use of inhaled sympathomimetic agents.

Hyperglycemia and hypokalemia

Changes in blood glucose and/or serum potassium may occur.

Immunosuppression

Patients receiving immunosuppressive agents are more susceptible to infections than healthy individuals. If patient is exposed to measles or chickenpox, appropriate prophylaxis and treatment may be warranted.

Infections

Lower respiratory tract infections, including pneumonia, have been reported following inhaled administration of corticosteroids. Localized Candida albicans infections occurred in the mouth and pharynx.

Metabolic effects

Long-term use of orally inhaled corticosteroids may affect normal bone metabolism, resulting in loss of bone mineral density.

Ocular effects

Glaucoma, increased IOP, and cataracts have been reported with following the long-term use of corticosteroids, including budesonide.

Paradoxical bronchospasm

Life-threatening paradoxical bronchospasm may occur.

Systemic corticosteroids

Transferring patients from systemic corticosteroid therapy to inhaled corticosteroids may unmask conditions previously suppressed by systemic corticosteroid therapy (eg, arthritis, eczema). Budesonide/formoterol should not be used for transferring patients from systemic corticosteroids.

Overdosage

Symptoms

Budesonide

Adrenal suppression, hypercorticism.

Formoterol

Angina, arrhythmias, cardiac arrest, death, dizziness, dry mouth, fatigue, headache, hyperglycemia, hypertension, hypokalemia, hypotension, insomnia, malaise, metabolic acidosis, muscle cramps, nausea, nervousness, palpitation, prolonged QTc interval, seizures, tachycardia, tremor, vomiting.

Patient Information

• Advise patient to read the patient information leaflet material before using product the first time and with each refill.
• Explain name, dose, action, how to use the inhaler, possible drug interactions, and potential adverse reactions of drug.
• Instruct patient to notify health care provider immediately if they experience decreasing effectiveness, need for more inhalations than usual, a decrease in lung function as outlined by the health care provider, or a marked change in symptoms.
• Instruct patient to use exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
• Warn patient to avoid exposure to chickenpox or measles and to notify health care provider immediately if exposed.
• Instruct patient regarding how to store, administer, and dispose of outdated medication.

Copyright © 2009 Wolters Kluwer Health.