Formoterol - instructions for use, dose, side effects, contraindications

Formoterol fumarate is a selective agonist of long-acting adrenergic beta 2 -receptors. When inhaled formoterol fumarate locally acts on the bronchi, causing bronchodilation. In vitro studies have shown that its activity against beta2-adrenoreceptors, located mainly in the smooth muscles of the bronchi, is more than 200 times higher than that for beta 1-adrenergic receptors located mainly in the myocardium. In the myocardium, beta-2-adrenergic receptors, which constitute up to 10-50% of the total number of beta-adrenergic receptors, have also been detected. The exact function of these receptors is not established, but they increase the possibility of developing cardiac effects even of highly selective beta 2-adrenomimetics.Formoterol fumarate stimulates intracellular adenylate cyclase catalyzing the transformation of ATP into cAMP. An increase in cAMP levels causes relaxation of the smooth muscles of the bronchi and inhibits the release of immediate-type hypersensitivity mediators from cells, especially from obese. In vitro studies have shown that formoterol fumarate inhibits the release of mediators (histamine and leukotrienes) from mast cells in the human lungs. In animal studies, it has been found that formoterol fumarate inhibits histamine-induced extravasation of plasma albumin in guinea pigs under anesthesia and an allergen-induced influx of eosinophils in dogs with airway hyperresponsiveness. The importance of these facts, obtained in animal studies and in vitro, is unclear for humans.

Pharmacokinetics:

With inhalation, about 90% of the active substance can be swallowed. When ingested quickly absorbed from the digestive tract. Absorption is 65%. The maximum concentration is achieved after 0.5-1 h. Binding to plasma proteins - 61-64%. The half-life is 2-3 hours. It is metabolized mainly by glucuronization.It is excreted by the kidneys (70%) and through the intestine (30%). Kidney clearance - 150 ml / min.

When inhaled, it is rapidly absorbed, the maximum concentration is reached after 15 minutes, the concentration of the active substance in the lungs after inhalation with a turbuhaler is 21-37%. Bioavailability - 46%. Binding to plasma proteins - 50%. The half-life is 8 hours.

Indications:Treatment and prevention of bronchial obstructiona syndrome: bronchial asthma, chronic obstructive pulmonary disease ..

ICD-10

X.J40-J47.J42 Chronic bronchitis, unspecified

X.J40-J47.J43 Emphysema

X.J40-J47.J44 Other chronic obstructive pulmonary disease

X.J40-J47.J45 Asthma

Contraindications:Hypersensitivitychildren's age (up to 5 years).

Carefully:Diabetes mellitus, severe chronic heart failure, IHD, heart rhythm disturbances, atrioventricularth blockade of the third degree, extension of the QT-interval (QT correctedth more than 0.44 s), hypertrophic obstructive cardiomyopathy, thyrotoxicosis, pregnancy, breast-feeding.

Pregnancy and lactation:

During pregnancy and lactation formoterol apply with caution, only in cases,when the expected therapeutic effect for the mother exceeds the potential risk of side effects to the fetus or the child.

Action category for the fetus by FDA - C.

Dosing and Administration:Inhalation. Bronchial asthma (maintenance therapy): adults and children 5 years and older - 12 μg every 12 hours. Prevention of asthma attacks caused by physical activity: adults and children 5 years and older - 12 μg 15 minutes before the estimated load. Repeated administration is possible no earlier than 12 hours after the previous inhalation. Chronic obstructive pulmonary disease (maintenance therapy): 12 μg every 12 hours. The maximum recommended dose is 24 μg per day.

Side effects:Upper respiratory tract infections, viral infections, headache, pharyngitis, sinusitis, tonsillitis, bronchitis, discomfort or pain in the chest, dyspnoea, dysphonia, fever, back pain, agitation, anxiety, tremor, cramps, dizziness, insomnia, dry mouth, increased mucus formation in the pharynx, dermal rash, itching, urticaria, tachycardia, palpitation, bronchospasm, hypokalemia.

Overdose:

Symptoms: tachycardia, anginal pain, arrhythmia, cardiac arrest, hypertension or hypotension, dizziness, insomnia, headache, tremor, nervousness, weakness, fatigue, muscle spasms, convulsions, hyperglycemia, hypokalemia, metabolic acidosis, nausea, dry mouth.

Treatment: symptomatic.

Interaction:

β2-Adrenoblockers, including those used in ophthalmology - mutual weakening of therapeutic effects.

Alcohol, levodopa, levothyroxine sodium, oxytocin increase the sensitivity of the myocardium to the action of formoterol.

Glucocorticoids, diuretics, methylxanthines, cardiac glycosides potentiate the hypokalemic effect of formoterol and increase the risk of rhythm disturbances.

Dysopyramide, MAO inhibitors (including furazolidone and procarbazine) and tricyclic antidepressants, procainamide, phenothiazines, quinidine - prolongation of the QT-interval and increased risk of ventricular arrhythmias, as well as an increase in the likelihood of hypertension when used simultaneously with MAO inhibitors.

Special instructions:

Formoterol fumarate is not recommended for patients,who manage to control bronchial asthma only with non-systematic inhalations of short-acting beta 2-adrenergic agonists, as well as patients for whom inhaled corticosteroids or other drugs are fully adequate, one of which is from time to time inhaled short-acting beta 2-adrenomimetic.

Long-acting beta 2-adrenergic agonists may increase the risk of death from asthma. In this regard, in the therapy of bronchial asthma formoterol fumarate should be used only in addition to treatment in patients who do not achieve an adequate effect in the appointment of other agents for the treatment of bronchial asthma (for example, with the appointment of low or moderate doses of inhaled glucocorticoids) when the severity of the disease requires the use of two types of therapy, including formoterol fumarate. A large, placebo-controlled study in the United States compared the safety of another long-acting beta 2-adrenergic agonist (salmeterol) and placebo when added to conventional asthma therapy, showed that salmeterol led to an increased risk of death compared with placebo.These findings can extend to formoterol fumarate, which is a beta-2-adrenoreceptor agonist prolonged action.

Formoterol fumarate is not intended for arresting an attack of bronchial asthma. If, against the background of taking formoterol fumarate in a previously effective dosage, asthma attacks occur or the patient needs more than usual number of short-acting beta-2 -agonists for inhalation, urgent medical consultation is needed, since these are frequent signs of destabilization of the condition. In this case, therapy should be reviewed and additional treatment methods prescribed (anti-inflammatory therapy, for example, corticosteroids); an increase in the daily dose of formoterol fumarate is unacceptable. Do not increase the frequency of inhalation (more than 2 times a day). Do not use formoterol fumarate in patients with apparent worsening or acute decompensation of bronchial asthma, as these can be life threatening situations.

Like other inhaled beta 2-adrenomimetics, formoterol fumarate can cause paradoxical bronchospasm; in this case, taking formoterol fumarate should be immediately discontinued, and an alternative treatment is prescribed.In many patients, monotherapy with beta 2-adrenomimetics does not adequately control the symptoms of bronchial asthma; such patients require early administration of anti-inflammatory drugs, for example, corticosteroids.

No data have been obtained on the clinically significant anti-inflammatory activity of formoterol fumarate, therefore, it can not be considered an alternative to corticosteroids. Formoterol fumarate is not intended to replace corticosteroids taken by inhalation or by mouth; stop taking or reduce the dose of corticosteroids should not be. Treatment with corticosteroids in patients who have previously taken these drugs orally or inhaled, should be continued, even if the patient's health as a result of taking formoterol fumarate has improved. Any changes in the dose of corticosteroids, in particular, the reduction should be based only on the clinical assessment of the patient's condition.

Like other beta 2-adrenoreceptor agonists, formoterol fumarate in some patients can cause clinically significant cardiovascular effects (increased heart rate, increased blood pressure, and others); in such cases, taking formoterol fumarate should be discontinued. Similarly to other beta 2-adrenomimetics, formoterol can cause clinically significant hypokalemia (possibly due to intracellular ion redistribution), which contributes to the development of adverse cardiovascular effects. Lowering the serum potassium level is usually of a transient nature and does not require replenishment.

In patients with bronchial asthma, the use of beta-blockers, including for the secondary prevention of myocardial infarction, is undesirable. In such cases, the appointment of cardioselective beta-blockers should be considered, although they should be used with caution.

Impact on the ability to drive vehicles and manage mechanisms.

Tremor, or anxiety that occur during treatment with beta-agonists, may affect the patient's ability to drive a car, so the application of formoterol is not recommended to engage in potentially hazardous activities that require attention, rapid psychomotor reactions.

Instructions

Formoterol (Formoterolum)