Dosing and uses of Symbicort (budesonide/formoterol)
Adult dosage forms and strengths
budesonide/formoteroL
aerosoL
- (80mcg/4.5mcg)/actuation
- (160mcg/4.5mcg)/actuation
Asthma
Treatment in patients whose disease is not adequately controlled by long-term medication or whose disease severity warrants treatment with long-acting beta agonist (LABA) and inhaled corticosteroid
160 mcg/9 mcg (2 actuations of 80 mcg/4.5 mcg) q12hr; for more severe asthma, 320 mcg/9 mcg (2 actuations of 160 mcg/4.5 mcg) q12hr; not to exceed 320 mcg/9 mcg q12hr
Chronic Obstructive Pulmonary Disease
Treatment of airflow obstruction
160 mcg/9 mcg (2 actuations of 80 mcg/4.5 mcg) q12hr; not to exceed 320 mcg/9 mcg q12hr
Dosing Considerations
Asthma: If response is inadequate after 1-2 weeks of therapy with 80 mcg/4.5 mcg, switching to 160 mcg/4.5 mcg may provide additional controL
Chronic obstructive pulmonary disease (COPD): 160 mcg/4.5 mcg is only approved treatment dose; if dyspnea occurs in period between doses, administer inhaled short-acting beta agonist (SABA) for immediate relief
Administration
Prime before first use by releasing 2 test sprays into air, shaking well for 5 seconds before each spray; repeat priming if inhaler is unused for >7 days or has been dropped
After inhalation, rinse mouth with water without swallowing
Pediatric dosage forms and strengths
budesonide/formoteroL
aerosoL
- (80mcg/4.5mcg)/actuation
- (160mcg/4.5mcg)/actuation
Asthma
<12 years: Safety and efficacy not established
>12 years: 160 mcg/9 mcg (2 actuations of 80 mcg/4.5 mcg) q12hr; for more severe asthma, 320 mcg/9 mcg (2 actuations of 160 mcg/4.5 mcg) q12hr; not to exceed 320 mcg/9 mcg q12hr
Dosing Considerations
If response is inadequate after 1-2 weeks of therapy with 80 mcg/4.5 mcg, switching to 160 mcg/4.5 mcg may provide additional controL
Symbicort (budesonide/formoterol) adverse (side) effects
>10%
Upper respiratory tract infection (URTI) (8-11%)
Headache (7-11%)
Nasopharyngitis (7-11%)
1-10%
Pharyngolaryngeal pain (6-9%)
Stomach discomfort (1-7%)
Sinusitis (5-6%)
Oral candidiasis (1-6%)
Bronchitis (5%)
Viral URTI (4%)
Backache (2-3%)
Influenza (2-3%)
Nasal congestion (2-3%)
Vomiting (1- 3%)
Postmarketing Reports
Cardiovascular: Angina pectoris, tachycardia, atrial and ventricular tachyarrhythmias, atrial fibrillation, extrasystoles, palpitations, hypotension, hypertension
Endocrine: Hypercorticism, growth velocity reduction (in children)
Sensory: Cataract, glaucoma, increased intraocular pressure (IOP), skin bruising
Gastrointestinal (GI): Oropharyngeal candidiasis, nausea
Immunologic: Immediate and delayed hypersensitivity reactions, such as anaphylactic reaction, angioedema, bronchospasm, urticaria, exanthema, dermatitis, pruritus
Metabolic: Hyperglycemia, hypokalemia
Musculoskeletal: Muscle cramps
Neurologic and psychiatric: Behavior disturbances, sleep disturbances, nervousness, agitation, depression, restlessness tremor, dizziness
Respiratory: Dysphonia, cough, throat irritation
Warnings
Black box warnings
LABAs, such as formoterol, may increase risk of asthma-related deaths; therefore, they should be used only as additional therapy for patients whose disease is not adequately controlled on other asthma-control medications (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including formoteroL
Because of risk, use of formoterol without concomitant long-term asthma-controlling medication (eg, inhaled corticosteroid) is contraindicated
Once asthma control is achieved or maintained, assess at regular intervals; step down therapy (eg, discontinue LABA) if doing so is possible without loss of asthma control, and maintain on long-term asthma-control medication (eg, inhaled corticosteroid)
Do not use formoterol if asthma is adequately controlled on low- or medium-dose inhaled corticosteroids
Controlled clinical trials suggest that LABAs increase risk of asthma-related hospitalization in pediatric and adolescent patients; if such patients require addition of LABA to inhaled corticosteroid, use fixed-dose combination product containing both inhaled corticosteroid and LABA to ensure adherence
Contraindications
Hypersensitivity
Primary treatment for acute bronchospasm, status asthmaticus, or exercise-induced bronchospasm
Cautions
Do not initiate in patients experiencing rapidly deteriorating or potentially life-threatening asthma or COPD episodes; additionally, increased inhaled SABA use is marker of deteriorating asthma
Do not use for relief of acute symptoms (rescue therapy)
Maximum dosage must not be exceeded, because of increased risk of serious cardiovascular effects
Localized infections with Candida albicans in mouth and pharynx occur in some patients; to reduce risk, mouth must be rinsed after inhalation
Monitor COPD patients for signs and symptoms of pneumonia and lung infections
Risk of more serious or fatal course of chickenpox or measles exists in susceptible patients (eg, unvaccinated or immunologically unexposed individuals); care must be taken to avoid exposure
Excessive use may suppress hypothalamic-pituitary-adrenal function; monitor closely, especially postoperatively or during periods of stress
Risk of paradoxical bronchospasm, which may be life-threatening; discontinue and treat immediately with inhaled SABA
Risk of immediate hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm)
Cardiovascular and central nervous system (CNS) effects due to excess beta-adrenergic stimulation; may result in asthma-related death; use with caution in patients with cardiovascular or convulsive disorders or thyrotoxicosis
Particular care is needed to transfer patients from systemic to inhaled corticosteroids; potentially fatal adrenal insufficiency may occur before or afterward; taper withdrawal gradually
During stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should resume PO corticosteroids immediately
Decrease in bone mineral density after long-term administration of corticosteroids; monitor patients at risk
May decrease growth velocity in children
Risk of cataracts, glaucoma, and increased IOp
Risk of systemic eosinophilic conditions, some consistent with Churg-Strauss syndrome
Risk of transient hypokalemia; may not warrant supplementation
Pregnancy and lactation
Pregnancy category: C
Lactation: No data; weigh risks of therapy against benefits, and either discontinue drug or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Symbicort (budesonide/formoterol)
Mechanism of action
Budesonide: Anti-inflammatory corticosteroid; has potent glucocorticoid activity and weak mineralocorticoid activity
Formoterol: Long-acting selective beta2-adrenergic agonist with rapid onset of action; acts locally as bronchodilator; stimulates intracellular adenyl cyclase, which results in increased cyclic adenosine monophosphate levels, causing relaxation of bronchial smooth muscle and inhibition of release of mast cell mediators
Absorption
Peak plasma time: Budesonide, 20 min; formoterol, 5-10 min
Peak plasma concentration: Budesonide, 0.6-1.6 nmol/L; formoterol, 136 pmol/L
Distribution
Protein bound: Budesonide, 85-90%; formoterol, 46-68%
Vd: Budesonide, 3 L/kg
Metabolism
Metabolized in liver by CYP3A4 (budesonide) or CYP2D6/CYP2C (formoterol; O-demethylation)
Elimination
Excretion (budesonide): Urine (60%), feces
Excretion (formoterol): Urine (62%), feces (24%)
