Active ingredient: Formoterol - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Bronchodilator Agents
• Sympathomimetic

Dosage Forms

• Metered-dose (aerosol)
• Powder

Brands / Synonyms

Dulera; Foradil; Formoterol fumarate; Formoterol [Usan:Inn]; Formoterolum [Inn-Latin]; Oxeze; Oxeze Turbuhaler; Oxeze Turbuhaler Foradil

Indications

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.

Pharmacology

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.

Absorption

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.

Toxicity

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.

Contraindications

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.

Drug Interactions

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 patientís therapy.

Concomitant administration of other sympathomimetic agents may potentiate the undesirable effects of FORADIL.

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 Aerolizer^TM 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 be used).

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 chest pain.

vi. In patients receiving FORADIL, other inhaled medications should be used only as directed by the physician.

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 ß₂-agonists.