formoterol/budesonide inhaled (Rx)

>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

Contraindications

Hypersensitivity

Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures

Cautions

Risk of LABAs used as monotherapy

• Use of LABAs as monotherapy (without inhaled corticosteroids) for asthma is associated with an increased risk of asthma-related death
• Data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patient
• These findings are considered a class effect of LABA monotherapy
• When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone

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

During periods of stress, a severe asthma attack or a severe COPD exacerbation, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction

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

Decrease in bone mineral density after long-term administration of corticosteroids; monitor patients at risk; assess bone mineral density initially and periodically thereafter

May decrease growth velocity in children; monitor

Risk of cataracts, glaucoma, and increased IOP; monitor

Risk of systemic eosinophilic conditions, some consistent with Churg-Strauss syndrome

Risk of transient hypokalemia; may not warrant supplementation

Risk of overdose if used with additional long-acting beta2-agonist in other combination products

Hypercorticism and adrenal suppression; may occur with very high dosages or at regular dosage in susceptible individuals; discontinue therapy if such changes occur

Pregnancy

In women with poorly or moderately controlled asthma, there is increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in neonate; pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control

There are no well-controlled human studies that have investigated the effects of therapy during labor and delivery; because of potential for beta-agonist interference with uterine contractility, use of therapy during labor should be restricted to those patients in whom the benefits clearly outweigh risk

Lactation

There are no available data on the breastfed child or on milk production; budesonide, like other inhaled corticosteroids, is present in human milk; there are no available data on the presence of formoterol fumarate in human milk; formoterol fumarate is present in rat milk; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from therapy or from underlying maternal condition

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.

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%)

Oral Inhalation 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