Brands, Medical Use, Clinical Data
- Bronchodilator Agents
- Metered-dose (aerosol)
Brands / Synonyms
Dulera; Foradil; Formoterol fumarate; Formoterol [Usan:Inn]; Formoterolum [Inn-Latin]; Oxeze; Oxeze Turbuhaler; Oxeze Turbuhaler Foradil
For use as long-term maintenance treatment of asthma in patients 6 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma, who are using optimal corticosteroid treatment and experiencing regular or frequent breakthrough symptoms requiring use of a short-acting bronchodilator.
Formoterol is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1- receptors. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10%-50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2- agonists may have cardiac effects.
Mechanism of Action
The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown.
Rapidly absorbed into plasma following administration by oral inhalation. It is likely that the majority of the inhaled formoterol delivered is swallowed and then absorbed from the gastrointestinal tract.
An overdosage is likely to lead to effects that are typical of ß2-adrenergic stimulants: nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia.
Biotrnasformation / Drug Metabolism
Metabolized primarily by direct glucuronidation at either the phenolic or aliphatic hydroxyl group and O-demethylation followed by glucuronide conjugation at either phenolic hydroxyl groups. Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation. The most prominent pathway involves direct conjugation at the phenolic hydroxyl group. The second major pathway involves O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group. Four cytochrome P450 isozymes (CYP2D6, CYP2C19, CYP2C9 and CYP2A6) are involved in the O-demethylation of formoterol.
FORADIL® (formoterol fumarate) is contraindicated in patients with cardiac tachyarrhythmias.
FORADIL contains lactose and is contraindicated in patients with an allergy to lactose, milk or in those who have
ever had any unusual or allergic reaction to formoterol fumarate.
Short-Acting ß2-agonists: Aerosol bronchodilators of the short-acting
adrenergic stimulant type may be used for relief of breakthrough symptoms while using formoterol. However, increasing
use of such preparations to control symptoms indicates deterioration of asthma control and the need to reassess the
Concomitant administration of other sympathomimetic agents may potentiate the undesirable effects of
Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: FORADIL should be administered
with extreme caution in patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants because
the action of formoterol on the cardiovascular system may be potentiated by these agents.
Corticosteroids, Methylxanthines and Diuretics: Concomitant treatment with xanthine
derivatives, steroids, or diuretics may potentiate a possible hypokalemic effect of ß2-agonists.
Hypokalemia may increase susceptibility to cardiac arrhythmias in patients treated with digitalis.
ß-adrenergic Blockers: ß-adrenergic blockers may weaken or antagonise the effect
of FORADIL. Therefore FORADIL should not be given together with ß-adrenergic blockers (including eye drops)
unless there are compelling reasons for their use.
Other Drugs:Drugs such as quinidine, disopyramide, procainamide, phenothiazines,
antihistamines, and tricyclic antidepressants may be associated with QT-interval prolongation and an increased risk
of ventricular arrhythmia.
INFORMATION TO BE PROVIDED TO THE PATIENT OR GUARDIAN
See illustrated Information For The Patient or Guardian section. It is
important that patients understand how to use FORADIL® (formoterol fumarate) capsules with the supplied
AerolizerTM inhalation device and how it should be used in relation to other asthma or COPD medications
they are taking. Patients/Guardians should be given the following information:
i. The recommended dosage (one or two capsules twice daily, morning and evening) should not be exceeded.
ii. FORADIL is not meant to relieve acute asthma or COPD symptoms and extra doses should not be used for that
purpose. Acute symptoms should be treated with a short-acting, inhaled ß2 -agonist such as
salbutamol (the physician should provide the patient with such medication and instruct the patient in how it should
iii. The physician should be notified immediately if any of the following situations occur, which may be a sign
of seriously worsening asthma:
ï Decreased effectiveness of short-acting, inhaled ß2- agonists;
ï Need for more inhalations than usual of short-acting, inhaled ß2 -agonists.
iv. FORADIL should not be used as a substitute for oral or inhaled corticosteroids. The dosage of these
medications should not be changed and they should not be stopped without consulting the physician, even if the
patient feels better after initiating treatment with FORADIL.
v. Patients should be cautioned regarding potential adverse cardiovascular effects, such as palpitations or
vi. In patients receiving FORADIL, other inhaled medications should be used only as directed by the
vii. Guardians of children who have been prescribed FORADIL should be alerted to the general concern regarding
asthma therapy compliance, especially neglect of anti-inflammatory therapy and overuse of short-acting