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Foradil®; Oxeze® Turbuhaler®
Maintenance treatment of asthma and prevention of bronchospasm in patients 5 years of age with reversible obstructive airway disease, including patients with symptoms of nocturnal asthma, who require regular treatment with inhaled, short-acting beta2 agonists; maintenance treatment of bronchoconstriction in patients with COPD; prevention of exercise-induced bronchospasm in patients 5 years of age
Note: Oxeze® is also approved in Canada for acute relief of symptoms ("on demand" treatment) in patients
When given orally to rats throughout organogenesis, formoterol caused delayed ossification and decreased fetal weight, but no malformations. There were no adverse events when given to pregnant rats in late pregnancy. Doses used were 70 times the recommended daily inhalation dose in humans. There are no adequate and well-controlled studies in pregnant women. Use only if benefit outweighs risk to the fetus. Beta agonists interfere with uterine contractility so use during labor only if benefit outweighs risk to the fetus.
Excretion in breast milk unknown/use caution
Hypersensitivity to adrenergic amines, formoterol, or any component of the formulation
Note: The approved U.S. labeling lists the need for acute bronchodilation as a contraindication; however, a formulation (Oxeze®) is approved for acute treatment in other countries (ie, Canada).
Optimize anti-inflammatory treatment before initiating maintenance treatment with formoterol. Do not use as a component of chronic therapy without an anti-inflammatory agent. Patient must be instructed to seek medical attention in cases where acute symptoms are not relieved by rapid-onset beta-agonist or when a previous level of response is diminished. Treatment must not be delayed. Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.
Acute episodes should be treated with rapid-onset beta2 agonist. The approved U.S. labeling states that formoterol is not meant to relieve acute asthmatic symptoms. Although, a formulation of formoterol (Oxeze®) is approved for acute treatment outside the U.S. (ie, Canada).
Do not exceed recommended dose; serious adverse events (including fatalities) have been associated with excessive use of inhaled sympathomimetics. Beta2 agonists may increase risk of arrhythmias, decrease serum potassium, prolong QTc interval, or increase serum glucose. These effects may be exacerbated in hypoxemia. Use caution in patients with cardiovascular disease (arrhythmia or hypertension or CHF), convulsive disorders, diabetes, glaucoma, hyperthyroidism, or hypokalemia. Beta agonists may cause elevation in blood pressure, heart rate, and result in CNS stimulation/excitation. Safety and efficacy have not been established in children <5 years of age.
Children are more likely to have infection, inflammation, abdominal pain, nausea, and dyspepsia.
Endocrine & metabolic: Serum glucose increased, serum potassium decreased
Miscellaneous: Viral infection (17%)
1% to 10%:
Cardiovascular: Chest pain (2%)
Central nervous system: Tremor (2%), dizziness (2%), insomnia (2%), dysphonia (1%)
Dermatologic: Rash (1%)
Respiratory: Bronchitis (5%), infection (3%), dyspnea (2%), tonsillitis (1%)
<1%: Anaphylactic reactions (severe hypotension, angioedema), asthma exacerbation, cramps, hypokalemia, increase in plasma glucose, tachycardia
Symptoms of overdose include tachycardia, tremor, hypertension, angina, and seizures. Hypokalemia also may occur. Cardiac arrest and death may be associated with abuse of beta-agonist bronchodilators. Treatment includes immediate discontinuation and symptomatic and supportive therapies. Cautious use of beta-adrenergic blocking agents may be considered in severe cases.
(minor) of CYP2A6, 2C8/9, 2C19, 2D6Substrate
Adrenergic agonist: Additive adrenergic stimulation may occur with concurrent use
Antidepressants, tricyclic: Concurrent use may potentiate cardiovascular side effects
Beta blockers: May block therapeutic effects of formoterol; may produce bronchospasm. If use is necessary, cautiously consider a cardioselective beta-blocker. Monitor closely.
Corticosteroids: May potentiate hypokalemia
Diuretics (thiazide or loops): May potentiate hypokalemia
MAO inhibitors: Concurrent use may potentiate cardiovascular side effects.
QTc-prolonging agents: Concurrent use may potentiate cardiovascular side effects; includes dofetilide, type Ia antiarrhythmics (quinidine, procainamide), pimozide, some quinolone antibiotics (moxifloxacin, sparfloxacin, gatifloxacin), sotalol, mesoridazine, and thioridazine
Theophylline derivatives: May potentiate hypokalemia
Prior to dispensing, store in refrigerator at 2°C to 8°C (36°F to 46°F); after dispensing, store at room temperature at 20°C to 25°C (68°F to 77°F). Protect from heat and moisture. Capsules should always be stored in the blister and only removed immediately before use. Always check expiration date. Use within 4 months of purchase date or product expiration date, whichever comes first.
Relaxes bronchial smooth muscle by selective action on beta2 receptors with little effect on heart rate. Formoterol has a long-acting effect.
Onset: Within 3 minutes
Peak effect: 80% of peak effect within 15 minutes
Duration: Improvement in FEV1 observed for 12 hours in most patients
Absorption: Rapidly into plasma
Protein binding: 61% to 64% in vitro at higher concentrations than achieved with usual dosing
Metabolism: Hepatic via direct glucuronidation and O-demethylation; CYP2D6, CYP2C8/9, CYP2C19, CYP2A6 involved in O-demethylation
Half-life elimination: ~10-14 hours
Time to peak: Maximum improvement in FEV1 in 1-3 hours
Children 5-12 years: Urine (7% to 9% as direct glucuronide metabolites, 6% as unchanged drug)
Adults: Urine (15% to 18% as direct glucuronide metabolites, 10% as unchanged drug)
Asthma maintenance treatment: Children
Oxeze® (CAN): Note: Not labeled for use in the U.S.: Children
Prevention of exercise-induced bronchospasm: Children
Oxeze® (CAN): Note: Not labeled for use in the U.S.: Children
COPD maintenance treatment: Adults: Inhalation: 12 mcg capsule every 12 hours
Additional indication for Oxeze® (approved in Canada): Acute ("on demand") relief of bronchoconstriction: Children
Remove capsule from foil blister before use. Place capsule in the capsule-chamber in the base of the Aerolizer™ Inhaler. Must only use the Aerolizer™ Inhaler. Press both buttons and then release. Keep inhaler in a level, horizontal position. Exhale fully. Do not exhale into inhaler. Tilt head slightly back and inhale (rapidly, steadily, and deeply). Hold breath as long as possible. If any powder remains in capsule, exhale and inhale again. Repeat until capsule is empty. Throw away empty capsule; do not leave in inhaler. Do not use a spacer with the Aerolizer™ Inhaler. Always keep capsules and inhaler dry.immediatelyonce only
FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium
Do not swallow capsules; this medication can only be used in the Aerolizer™ Inhaler. Use exactly as directed and do not use more often than recommended. Store capsules in blister and do not remove from blister until ready for treatment. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. It is recommended that you wear identification (Med-Alert bracelet) if you have an asthmatic condition. You may experience nervousness, dizziness, or insomnia (use caution when driving or engaging in hazardous activities until response to medication is known); dry mouth, nausea, or GI discomfort (small, frequent meals, good mouth care, sucking lozenges, or chewing gum may help); or difficulty voiding (always void before treatment). Report any unresolved GI upset, nervousness or dizziness, muscle cramping, chest pain or palpitations, skin rash, signs of infection, unusual cough, or worsening of condition. Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.Pregnancy/breast-feeding precautions:
Administration: Follow directions for use and storage of inhaler exactly. Wash hands prior to treatment and sit in comfortable position for treatment. Remove capsule from foil blister immediately before treatment and place capsule in the capsule-chamber in the base of the Aerolizer™ Inhaler. Press both buttons once only and then release. Hold inhaler in a level, horizontal position, exhale fully (do not exhale into inhaler). Tilt head slightly back and inhale from inhaler rapidly, steadily, and deeply. Hold breath as long as possible. If any powder remains in capsule, exhale and inhale again. Repeat until capsule is empty. Throw away empty capsule. Do not use a spacer with aerolizer. Do not wash inhaler; store in dry place.
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
No information available to require special precautions
May cause dizziness or insomnia
Concurrent use with MAO inhibitors, TCAs, thioridazine, or mesoridazine may potentiate cardiovascular effects
[CAN] = Canadian brand name
Aerosol, oral (Oxeze® [CAN]): 6 mcg/dose (60 doses), 12 mcg/dose (60 doses) [contains lactose 600 mcg/dose]
Powder for oral inhalation, as fumarate [capsule]: 12 mcg (12s, 60s) [contains lactose 25 mg]
Cazzola M, Centanni S, Regorda C, et al, "Onset of Action of Single Doses of Formoterol Administered Via Turbuhaler in Patients With Stable COPD,"Pulm Pharmacol Ther, 2001, 14:41-45.
Cazzola M and Donner CF, "Long-acting Beta2 Agonists in the Management of Stable Chronic Obstructive Pulmonary Disease,"Drugs, 2000, 60:307-20.
National Asthma Education and Prevention Program, "Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma," Bethesda, MD, National Institutes of Health, 1997. NIH publication 97-4051.
National Asthma Education and Prevention Program, "Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics - 2002,"J Allergy Clin Immunol, 2002, 110(5 Suppl):141-219.
Foradil® (CA); Oxeze® Turbuhaler® (CA); Oxis® (AT, BE, DK, GR, IE)