Formoterol indications. Medicinal reference book geotar

Lung problems are no joke. They not only cause discomfort and make you feel worse, but can also cause various complications. For example, asthma can even lead to The drug "Formoterol", instructions for use of which will be presented below, is precisely intended for the treatment of pathologies of the respiratory system. However, keep in mind that it is used to combat a narrow range of diseases.

Features of the drug's action

The drug is capable of expanding the bronchial lumens. At the same time, it significantly slows down the release of leukotrines and histamine from lung tissue. The main active ingredient is fumartate dihydrate.

The drug acts within 5 minutes, and its maximum effect is achieved after 2 hours. If bronchial obstruction is impaired, the medicine can remain effective for about 10 hours. This makes it possible to alleviate the patient’s condition for a long time.

A significant part of the drug after inhalation enters the stomach. There the components are absorbed. The half-life of the drug is approximately 13 hours. Its components accumulate and are metabolized in the liver. The drug is excreted in the urine. Its bioavailability is more than 40%. And it binds to blood plasma by 68%.

The most basic document that you should read before using Formoterol is the instructions for use. There is not one form of release of the drug, there are several of them: capsules with powder, dosed powder in a bottle, dosed aerosol. Regardless of which one you purchased, the medicine is for inhalation only. The product is sold in cardboard packaging.

What indications for use are there?

If you have already used Formoterol, the instructions for use (we will look at synonyms for the drug later) indicate a fairly narrow range of use. The following indications for use can be distinguished:

Treatment and prevention of sharp narrowing of the bronchial lumens - spasm.
Asthma. In this case, the drug is not the main one, but is used only to support the body.
Chronic bronchitis.
Pulmonary emphysema.
Allergic bronchial spasm. The fact is that the medicine can inhibit the release of histamine.
Obstructive inflammation of the upper respiratory tract, which is accompanied by impaired air flow through it.

In what cases is taking the drug prohibited?

Not everyone can take Formoterol. Instructions for use indicate the following contraindications:

Too high sensitivity to the main or additional components of the drug, which can cause a worsening of the condition.
Excessive production of thyroid hormones - thyrotoxicosis.
Sustained increase in blood pressure.
Pregnancy and lactation period. The fact is that no research has been conducted in this area. That is, it is unknown whether the main component will be excreted in milk. Therefore, if the drug still needs to be taken, then it is better to stop feeding. As for pregnancy, everything is decided by the attending doctor.
Heart rhythm disorder: arrhythmia, tachycardia.
Coronary heart disease. Some drug interactions can cause problems with the ventricles.
Age up to 5 years. For small children, the drug presented is very difficult.

Possible side effects

"Formoterol" (instructions for use are in each package) can provoke some unwanted reactions, although their likelihood is low if the rules for taking the drug are followed. The following side effects may occur:

From the nervous system: pain and dizziness, convulsions, sleep disturbance, nervousness, increased anxiety.
From the cardiovascular system: increased or irregular heartbeat, angina pectoris, persistent decrease or increase in blood pressure.
From the gastrointestinal tract: nausea and vomiting, dry oral mucosa, abdominal pain, gastroenteritis (inflammation of the stomach), dyspepsia (difficulty in digestion, which may be accompanied by pain).
From the respiratory system: infectious pathologies of the bronchi, sinusitis, pharyngitis, tonsillitis, exacerbation of asthma, voice disturbance.
Others: chest pain, allergic reaction in the form of a rash, itching, anaphylactic shock.

Features of the use of the medicine

If you need to take Formoterol, the instructions for use tell you about the following dosages:

For bronchial asthma, you need to take 12 mcg inhalations every 12 hours. Just 1-2 breaths are enough. In this way, the body is supported. If an attack can be triggered by physical activity, then it is better to take the drug 15 minutes before the start of the intended work, and the dosage is the same.
To support obstructive pulmonary disease, inhalations of 12 mcg should be taken twice a day.

It should be borne in mind that the presented medicine can be used no more than once every 12 hours. That is, the maximum daily dose should not exceed 24 mcg. The product is intended for inhalation only. If the doctor has prescribed the drug "Formoterol", the instructions for use (aerosol is used most often) prohibit taking it intravenously, intramuscularly or orally.

If an overdose occurs

Are you forced to take Formoterol? Instructions for use can be purchased at a pharmacy only with special permission from a doctor) is in the box for a reason. It clearly indicates the dosage of the medicine. But if for some reason you violate these instructions, an overdose may occur. It is determined by the following symptoms: tachycardia, dry mouth, headache, nausea. If the situation is not corrected in time, even death is quite possible.

In case of overdose, you must urgently call an ambulance. Treatment should be symptomatic. In this case, further use of the medicine is stopped. During treatment, it is necessary to monitor heart function using electrocardiography. During the recovery period after an overdose, the patient should be under constant supervision of specialists.

Features of drug interaction with other drugs

Are you taking Formoterol? Instructions for use (analogues have a similar composition) contain information about the features of its combination with other medications. For example, caution should be exercised when using it simultaneously with adrenergic drugs.

A pathological decrease in potassium levels in the body can be provoked by a combination of Formoterol with diuretics, steroids, and xanthine derivatives. However, kalemia is not a permanent condition. Moreover, no external replenishment of the amount of this element in the body is required.

Try not to take this drug together with tricyclic antidepressants. Combining it with beta-blockers leads to mutual blocking of the action of these drugs. That is, there will be no benefit from them, but the harm can be serious.

Combined use with drugs such as Quinidine and Disopyramide can be dangerous, as it provokes the development of cardiac ventricular arrhythmias. If there is a cardiac reaction to the medication, it must be discontinued immediately.

Special instructions

"Formoterol" (you already know the instructions) has some features of use:

You should not use the drug to relieve an asthma attack. There are other means for this. If Formoterol is needed, the instructions for use (reviews about it are mostly good) indicate that it is only an addition to the main therapy. If during treatment you feel that your condition is worsening, you should immediately consult a doctor.
This medicine should not be taken in place of corticosteroids. "Formoterol" does not have a pronounced anti-inflammatory function. In this case, taking corticosteroids should be continued without reducing the dose prescribed by the doctor.
Women who have been diagnosed with uterine fibroids, as well as people with diabetes, should be very careful when using this product.
You should not immediately drive or engage in activities that require increased attention immediately after taking it.
Do not use the product during childbirth. The fact is that the main active ingredient can negatively affect uterine contractions.

Analogues and storage features

Most often, patients prefer an inhaler that contains 100 single doses. The product should be stored in a cool and dark place, but it is not advisable to freeze it. Direct sunlight should not fall on the bottle. Do not place the medicine near a heat source.

If this drug is not suitable for you, you can consult your doctor about analogues. Among them are the following: “Atimos”, “Oxis”, “Foradil”, “Bronkhoril”, “Shadrin”. Please note that you cannot buy or take any other medications yourself.

Active ingredient(INN) Formoterol (Formoterol)

Synonyms:

Zafiron, Athimos; Oxis; Oxis Turbuhaler; Foradil; Foradil Aerolyzer; Formoterol; Formoterol Easyhaler; Formoterol fumarate.

Rice. Fomroterol ( Foradil)

Pharmacokinetics:
Absorption:
Formoterol, when administered orally in a single dose of up to 300 mcg, is quickly absorbed from the gastrointestinal tract. As has been reported for other inhaled medicinal products, it is estimated that approximately 90% of formoterol administered by inhaler will be swallowed and subsequently absorbed from the gastrointestinal tract. This means that the pharmacokinetic characteristics of dosage forms administered orally are largely applicable to inhaled dosage forms. When an 80 mcg dose is taken orally, absorption is approximately 65%.
Maximum concentrations of unchanged active substance are achieved 15 minutes - 1 hour after administration.
In the studied dose range (20-300 mcg) administered orally, the pharmacokinetics of formoterol are linear. Repeated oral administration in doses of 40-160 mcg per day did not lead to significant accumulation of the drug.
Distribution and metabolism:
Protein binding in plasma is approximately 50% - 65% (primarily binding to albumin - 34%).
In the concentration range observed after the use of therapeutic doses of the drug, saturation of binding sites is not achieved.
The drug is metabolized by direct glucuronidation (addition of a glucuronic acid residue) and o-demethylation followed by glucuronidation.
Excretion from the body:
The elimination of formoterol from the bloodstream appears to be polyphasic. The half-life in plasma is 8 hours. The active substance and its metabolites are completely eliminated from the body; about 2/3 of the dose administered orally is excreted in the urine (6-10% unchanged), and 1/3 in feces. The maximum excretion rate is achieved within 1-2 hours. The half-life of formoterol, calculated from urinary excretion rates observed between 3 and 16 hours after inhalation of the drug, was approximately 5 hours. The renal clearance of formoterol is 150 ml/min.

Application Formoterol: According to the Physician Desk Reference (2003), formoterol fumarate is indicated for long-term (twice daily - morning and evening) maintenance therapy for bronchial asthma and prevention (in adults and children 5 years and older) of bronchospasm in reversible obstructive diseases respiratory tract, incl. in patients with symptoms of nocturnal asthma who require regular inhalation of short-acting beta2-agonists.
Can be used for bronchial asthma in conjunction with short-acting beta2-agonists, corticosteroids (systemic or inhaled) and theophylline.
The use of Formoterol formoterol fumarate "on demand" (if necessary) is indicated for adults and children 12 years of age and older for the rapid prevention of bronchospasm caused by exercise.
Formoterol fumarate is used in patients with COPD, including chronic bronchitis and emphysema, for long-term maintenance therapy.

Contraindications Formoterol: Hypersensitivity.

Restrictions on use: Cardiovascular disorders, incl. coronary insufficiency, arrhythmias, arterial hypertension, convulsive disorders, thyrotoxicosis, unusual response to sympathomimetics, pregnancy, breastfeeding, age under 5 years (safety and effectiveness have not been established).
Formoterol fumarate is not recommended for patients whose asthma can only be controlled by non-systematic inhalation of short-acting beta2-adrenergic agonists.

Use of Formoterol during pregnancy and lactation: Adequate controlled studies of formoterol fumarate in pregnant women, incl. during childbirth, was not carried out. Formoterol fumarate should be used during pregnancy and childbirth (as beta-agonists may adversely affect uterine contractility) only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. Formoterol fumarate is excreted in rat milk. It is not known whether it is excreted in breast milk in women, but since many drugs are excreted in human milk, formoterol fumarate should be administered with caution to nursing women (well-controlled studies have not been conducted in nursing women).

Side effects: Side effects of formoterol fumarate are similar to the side effects of other selective beta2-agonists and include angina, arterial hypo- or hypertension, tachycardia, arrhythmia, nervousness, headache, tremor, dry mouth, palpitations, dizziness, convulsions, nausea, fatigue, weakness , hypokalemia, hyperglycemia, metabolic acidosis and insomnia.
Bronchial asthma
During controlled clinical trials, formoterol fumarate (12 mcg 2 times a day) was administered to 1985 patients (children 5 years and older, adolescents and adults) with bronchial asthma. Among the identified side effects of formoterol fumarate with a frequency of 1% or more, exceeding the frequency of side effects in the placebo group, the following were noted (next to the name is the percentage of occurrence of this side effect in the formoterol fumarate group, in parentheses - in the placebo group):
From the nervous system and sensory organs: tremor 1.9% (0.4%), dizziness 1.6% (1.5%), insomnia 1.5% (0.8%).
From the respiratory system: bronchitis 4.6% (4.3%), chest infections 2.7% (0.4%), dyspnea 2.1% (1.7%), tonsillitis 1.2% ( 0.7%), dysphonia 1.0% (0.9%).
Other: viral infections 17.2% (17.1%), chest pain 1.9% (1.3%), rash 1.1% (0.7%).
Three side effects - tremor, dizziness and dysphonia - were dose-dependent (doses of 6, 12 and 24 mcg were studied when taken twice a day).
The safety of formoterol fumarate compared with placebo was studied in a multicenter, randomized, double-blind clinical trial in 518 children aged 5–12 years with asthma who required daily bronchodilators and anti-inflammatory drugs. When taking 12 mcg of formoterol fumarate 2 times a day, the frequency of side effects was comparable to that in the placebo group. The nature of the side effects detected in children differed from the side effects of formoterol fumarate noted in adults. Side effects in the formoterol fumarate group in children that exceeded the incidence of side effects in the placebo group included infections/inflammation (viral infections, rhinitis, tonsillitis, gastroenteritis) or gastrointestinal complaints (abdominal pain, nausea, dyspepsia).
COPD
In two controlled studies, 405 patients with COPD received formoterol fumarate (12 mcg twice daily). The incidence of adverse events was comparable in the formoterol fumarate and placebo groups. Among the side effects in the formoterol fumarate group with a frequency equal to or exceeding 1% and exceeding that in the placebo group, the following were noted (the percentage of occurrence in the formoterol fumarate group is indicated next to the name, in parentheses - in the placebo group):
From the nervous system and sensory organs: cramps 1.7% (0%), cramps of the calf muscles 1.7% (0.5%), anxiety 1.5% (1.2%).
From the respiratory system: upper respiratory tract infections 7.4% (5.7%), pharyngitis 3.5% (2.4%), sinusitis 2.7% (1.7%), increased sputum 1.5 % (1.2%).
Other: back pain 4.2% (4.0%), chest pain 3.2% (2.1%), fever 2.2% (1.4%), itching 1.5% (1. 0%), dry mouth 1.2% (1.0%), trauma 1.2% (0%).
Overall, the incidence of all cardiovascular adverse events in the two main studies was low and comparable to placebo (6.4% in patients taking formoterol fumarate 12 mcg twice daily and 6.0% in the placebo group). No specific cardiovascular side effects were observed in the formoterol fumarate group, which occurred with a frequency of 1% or more and exceeded the frequency of occurrence in the placebo group.
In two studies in patients taking 12 mcg and 24 mcg of formoterol fumarate twice daily, seven side effects (pharyngitis, fever, convulsions, increased sputum production, dysphonia, myalgia and tremor) were noted to be dose-dependent.
Post-marketing studies
During widespread post-marketing use of formoterol fumarate, there have been reports of severe exacerbations of asthma, some of which have been fatal. Although most of these cases were observed in patients with severe bronchial asthma or acute decompensation of the condition, a few cases were observed in patients with less severe bronchial asthma. The relationship of these cases to the use of formoterol fumarate has not been determined. There are rare reports of anaphylactic reactions, including severe hypotension and angioedema, associated with inhaled formoterol fumarate. Allergic reactions can manifest as urticaria and bronchospasm. There was no evidence of the development of drug dependence with the use of formoterol fumarate in clinical trials.

Interaction: Other adrenergic agents should be used with caution while taking formoterol, as there is a risk of potentiating the predictable sympathomimetic effects of formoterol. When taking xanthine derivatives, steroids or diuretics simultaneously, the hypokalemic effect of adrenergic receptor agonists may be enhanced. ECG changes and/or hypokalemia caused by non-potassium sparing diuretics, such as loop or thiazide diuretics, may be suddenly exacerbated by beta-agonists, especially when the dose is exceeded (although the clinical significance of these effects is unclear, caution is required when co-administering drugs of these groups ). Formoterol, like other beta2-agonists, should be prescribed with special care when taking MAO inhibitors, tricyclic antidepressants or other drugs that can prolong the QTc interval, as this may potentiate the effect of adrenergic agonists on the cardiovascular system (increases the risk of developing ventricular arrhythmias) . Formoterol and beta-blockers may mutually suppress each other's effects when administered simultaneously. Beta blockers may not only antagonize the pharmacological action of beta agonists, but may also cause severe bronchospasm in patients with asthma.

Overdose: Symptoms: angina attack, arterial hyper- or hypotension, tachycardia (more than 200 beats/min), arrhythmia, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, palpitations, nausea, dizziness, fatigue, weakness , hypokalemia, hyperglycemia, insomnia, metabolic acidosis. Cardiac arrest and death are possible (as with all inhaled sympathomimetics). The minimum lethal dose for rats receiving inhaled formoterol fumarate was 156 mg/kg (approximately 53,000 and 25,000 times the inhaled MDV for adults and children, respectively, based on body surface area in mg/m2).
Treatment: discontinuation of formoterol fumarate, symptomatic and supportive therapy, ECG monitoring. The use of cardioselective beta-blockers should take into account the possible risk of bronchospasm. Data on the effectiveness of dialysis for formoterol fumarate overdose are insufficient.

Directions for use and doses: Inhalation. Bronchial asthma (maintenance therapy): adults and children 5 years of age and older - 12 mcg every 12 hours. If symptoms of bronchial asthma occur during the period between inhalations, short-acting beta2-agonists should be used. Prevention of bronchial asthma attacks caused by physical activity: adults and adolescents 12 years of age and older - 12 mcg 15 minutes before the expected exercise. Repeated administration is possible no earlier than 12 hours after the previous inhalation. COPD (maintenance therapy): 12 mcg every 12 hours. The maximum recommended dose is 24 mcg/day.

Precautions: Formoterol fumarate is not intended to relieve an attack of bronchial asthma. If, while taking formoterol fumarate at a previously effective dosage, attacks of bronchial asthma begin to occur or the patient requires a greater than usual number of inhalations of short-acting beta2-agonists, urgent consultation with a doctor is necessary, since these are frequent signs of destabilization of the condition. In this case, therapy should be reviewed and additional treatments prescribed (anti-inflammatory therapy, such as corticosteroids); An increase in the daily dose of formoterol fumarate is unacceptable. The frequency of inhalations should not be increased (more than 2 times a day). Formoterol fumarate should not be used in patients with visible worsening or acute decompensation of asthma as this may be a life-threatening situation.
When prescribing formoterol fumarate to patients who have previously taken short-acting beta2-agonists as background therapy (for example, 4 times a day), patients should be warned to discontinue regular use of these drugs and to use them only as symptomatic therapy for exacerbation of asthma symptoms. Like other inhaled beta2-agonists, formoterol fumarate may cause paradoxical bronchospasm; in this case, formoterol fumarate should be discontinued immediately and alternative treatment should be prescribed. In many patients, monotherapy with beta2-agonists does not provide adequate control of asthma symptoms; such patients require early administration of anti-inflammatory drugs, such as corticosteroids.
There is no evidence of clinically significant anti-inflammatory activity of formoterol fumarate; therefore, it cannot be considered as an alternative to corticosteroids. Formoterol fumarate is not intended to replace corticosteroids taken by inhalation or by mouth; You should not stop taking or reduce the dose of corticosteroids. Treatment with corticosteroids in patients who have previously taken these drugs orally or inhaled should be continued, even if the patient's well-being has improved as a result of taking formoterol fumarate. Any changes in the dose of corticosteroids, in particular reductions, should be based only on clinical assessment of the patient's condition.
Like other beta2-adrenergic receptor agonists, formoterol fumarate can cause clinically significant cardiovascular effects (increased heart rate, increased blood pressure, etc.) in some patients; in such cases, formoterol fumarate should be discontinued. Similar to other beta2-agonists, formoterol can cause clinically significant hypokalemia (possibly due to intracellular ion redistribution), which contributes to the development of cardiovascular side effects. Decreases in serum potassium levels are usually transient and do not require replacement.
In patients with bronchial asthma, the use of beta-blockers, incl. for secondary prevention of myocardial infarction, is undesirable. In such cases, the use of cardioselective beta-blockers should be considered, although they should be used with caution.

Special instructions: Capsules containing formoterol fumarate should not be taken orally; they should only be used by inhalation through a special device. Do not exhale into the inhalation device.

Atimos, Oxisturbuhaler, Foradil.

Composition and release form

Formoterol fumarate.
Capsules complete with aerolizer (12 mcg); Formoterol fumarate microionized. Metered aerosol for inhalation (1 dose - 12 mcg); dosed powder for inhalation (1 dose - 4.5 mcg, 9 mcg).
Formoterol fumarate dihydrate.
Capsules with powder for inhalation (12 mcg).

Pharmacological action

Beta adrenergic agonist. Acts primarily on beta2-adrenergic receptors. It has a bronchodilator effect, relieves and prevents bronchospasm. Inhibits the release of histamine, leukotrienes and prostaglandin D2 from mast cells, basophilic granulocytes and sensitized cells of the bronchoalveolar tree.

Pharmacokinetics

It is expected that after inhalation, most of the fumarate will be swallowed and then absorbed from the gastrointestinal tract. Binding to blood plasma proteins (albumin) - 31-38%. T1/2 of various metabolites - 13.9 and 12.3 hours. Metabolized in the liver. It is excreted in the urine unchanged and in the form of metabolites.

Indications

Prevention and treatment of bronchospasm in patients with obstructive .

Application

The drug is administered by inhalation. To relieve acute bronchospasm, you should take a single inhalation (12 mcg) of the drug, and, if necessary, inhale again after 1 minute. If the therapeutic effect is weak, you can take 2 more breaths after 30 minutes. The maximum daily dose is 96 mcg (8 breaths).

To prevent asthma attacks, take one breath (12 mcg) in the morning and evening, and in severe cases, take two breaths (24 mcg) 2 times a day. The interval between administrations should be at least 8 hours.

The drug is prescribed with caution to patients suffering from diabetes mellitus, as well as uterine fibroids. When using the drug, patients are not recommended to engage in potentially hazardous activities that require increased attention and rapid mental and motor reactions. The use of the aerosol in young children should only be carried out under the supervision of adults.

Side effect

Headache, nausea, dizziness, dry mouth, nervousness, tremor, convulsions, tachycardia and tachyarrhythmia.

Contraindications

Hypersensitivity to the drug or other beta-agonists, thyrotoxicosis, tachyarrhythmias, pregnancy and lactation.

Pharmacological action

Beta adrenergic agonist. Acts primarily on β 2 -adrenergic receptors. It has a bronchodilator effect, relieves and prevents bronchospasm. Inhibits the release of histamine, leukotrienes and prostaglandin D 2 from mast cells, basophils and sensitized cells of the bronchoalveolar tree.

Pharmacokinetics

When administered by inhalation, about 90% of the active substance can be swallowed. When taken orally, it is quickly absorbed from the gastrointestinal tract. Absorption is 65%. Cmax is reached within 0.5-1 hour. Plasma protein binding is 61-64%. T 1/2 - 2-3 hours. Metabolized mainly by glucuronidation. Excreted by the kidneys (70%) and through the intestines (30%). Renal clearance – 150 ml/min.

When used by inhalation, it is quickly absorbed, Cmax is achieved after 15 minutes, the concentration of the active substance in the lungs after inhalation with a turbuhaler is 21-37%. Bioavailability – 46%. Plasma protein binding – 50%. T 1/2 – 8 hours.

Indications

Prevention and treatment of bronchospasm in patients with obstructive bronchitis and bronchial asthma.

Dosage regimen

Used in the form of inhalations. The dose depends on the dosage form used and the age of the patient.

Side effect

Maybe: headache, nausea, dry mouth, tremor.

Rarely: muscle cramps, myalgia, tachycardia, dizziness, agitation, anxiety, sleep disturbances, nervousness, increased bronchospasm.

In some cases: hypersensitivity reactions (severe arterial hypotension, urticaria, angioedema, itching, exanthema), peripheral edema, changes in taste.

Contraindications for use

Hypersensitivity to formoterol or other beta-agonists, children under 5 years of age.

Use during pregnancy and breastfeeding

During pregnancy and lactation, formoterol is used with caution, only in cases where the expected therapeutic effect for the mother outweighs the potential risk of side effects for the fetus or child.

Use in children

Contraindicated in children under 5 years of age.

Drug interactions

You should not combine formoterol with adrenomimetic drugs, MAO inhibitors, tricyclic antidepressants (the risk of side effects from the cardiovascular system increases).

With simultaneous use, xanthine derivatives, corticosteroids, and diuretics increase the likelihood of a hypokalemic effect of the drug.

With simultaneous use of quinidine, disopyramide, procainamide, phenothiazines, antihistamines, tricyclic antidepressants, they increase the risk of developing ventricular arrhythmias.

Beta blockers (including in the form of eye drops) partially or completely block the effect of formoterol.

Special instructions

Particular caution and close monitoring are required if it is necessary to use formoterol in patients with the following concomitant diseases: coronary artery disease; disturbances of heart rhythm and conduction, especially AV blockade of the third degree; severe heart failure; idiopathic subvalvular aortic stenosis; hypertrophic obstructive cardiomyopathy; thyrotoxicosis; known or suspected prolongation of the QT interval (QT corrected >0.44 sec).

Use with caution in patients with diabetes mellitus and uterine fibroids.

Impact on the ability to drive vehicles and operate machinery

Tremor or anxiety that occurs during treatment with beta-agonists may affect the patient's ability to drive, therefore, when using formoterol, it is not recommended to engage in potentially hazardous activities that require increased attention and rapid psychomotor reactions.

Formoterol-native: instructions for use and reviews

Formoterol native is a bronchodilator.

Release form and composition

Dosage form – capsules with powder for inhalation: hard, size No. 3, transparent, light brown; contents – almost white or white powder (in blister packs of 10 pcs., in a cardboard pack 3 or 6 packs with or without an inhalation device, as well as instructions for use of Formoterol-native).

Composition of 1 capsule:

active substance: formoterol fumarate dihydrate – 12 mcg;
auxiliary components: lactose monohydrate, sodium benzoate;
capsule shell: hypromellose, caramel coloring (E150c).

Pharmacological properties

Pharmacodynamics

Formoterol is a selective β 2 -adrenergic receptor agonist (β 2 -adrenergic agonist), which has a bronchodilator effect in case of reversible airway obstruction. The effect develops quickly (within 1–3 minutes) and lasts up to 12 hours after inhalation. The drug in therapeutic doses has minimal effects on the cardiovascular system and in rare cases.

Native formoterol inhibits the release of leukotrienes and histamine from mast cells. Experimental studies on animals revealed some anti-inflammatory activity of the drug, in particular the ability to prevent the accumulation of inflammatory cells and the development of edema.

In vitro animal studies have shown that racemic formoterol and its (R,R) and (S,S) enantiomers are highly selective β 2 receptor agonists. The (S,S) enantiomer demonstrated 800 to 1000 times less activity than the (R,R) enantiomer and did not adversely affect the potency of the (R,R) enantiomer on tracheal smooth muscle. No pharmacological evidence has been obtained to demonstrate the superiority of using one of these two enantiomers over the use of the racemic mixture.

In humans, studies of formoterol have shown its high effectiveness in preventing bronchospasm associated with exposure to inhaled allergens, cold air, exercise, methacholine and histamine. After inhalation, the bronchodilator effect persists for 12 hours, therefore, with long-term maintenance therapy, twice daily use of the drug in most patients allows for adequate control of chronic lung diseases around the clock (both day and night).

In stable cases of chronic obstructive pulmonary disease (COPD), inhalation of Formoterol-native 12 or 24 mcg twice a day significantly improves quality of life parameters.

Pharmacokinetics

Formoterol is used 2 times a day in a therapeutic dose of 12–24 mcg. The pharmacokinetic parameters of the drug were studied in healthy volunteers who received inhalations at higher doses than recommended, and in patients with COPD who received the drug in therapeutic doses.

After a single dose of 120 mcg in healthy volunteers, formoterol was rapidly absorbed into the blood plasma. The maximum plasma concentration (C max) of 266 pmol/l was reached within 5 minutes after inhalation.

When using formoterol 12 or 24 mcg 2 times a day for 12 weeks in patients with COPD, concentrations of the active substance measured after 10 minutes, 2 hours and 6 hours from the moment of inhalation were in the ranges of 11.5–25.7 or 23 .3–50.3 pmol/l, respectively.

When studying the total excretion of formoterol and its enantiomers in urine, it was revealed that the content of formoterol in the systemic circulation is proportional to the dose administered (ranging from 12 to 96 mcg).

When using formoterol 12 or 24 mcg 2 times a day for 12 weeks in patients with bronchial asthma, the excretion of unchanged formoterol in urine increased by 63–73%, and in patients with COPD – by 19–38%. This indicates some accumulation of the drug in the body with repeated use of Formoterol-native. However, there was no greater accumulation of one of the enantiomers compared to the other during repeated inhalations.

A larger amount of the inhaled drug is swallowed, after which it is absorbed from the gastrointestinal tract (GIT). After oral administration of 3H-labeled formoterol at a dose of 80 mcg in healthy volunteers, at least 65% of the dose was absorbed.

Formoterol binds to plasma proteins by 61–64%, including 34% to serum albumin. In the range of concentrations that are observed after the use of Formoterol-native in therapeutic doses, saturation of binding sites is not achieved.

Formoterol is metabolized primarily by direct conjugation with glucuronic acid, as well as by O-demethylation followed by conjugation with glucuronic acid (glucuronidation). Other minor metabolic pathways include conjugation of formoterol with sulfate and subsequent deformylation. Many isoenzymes are involved in the processes of glucuronidation (1A6, 1A9, 1A3, 1A8, 1A7, 1A10, 2B7, 2B15, UGT1A1) and O-demethylation (2C9, 2A6, 209, CYP2D6) of formoterol. This suggests a low likelihood of developing drug interactions through inhibition of any isoenzyme involved in the metabolism of formoterol. The drug, used in therapeutic doses, does not suppress isoenzymes of the cytochrome P 450 system.

When using formoterol 12 or 24 mcg 2 times a day for 12 weeks in patients with bronchial asthma, 10 and 15–18% of the total dose are excreted unchanged in the urine, respectively, in patients with COPD – 7 and 6–9%, respectively. .

The share of (R,R) and (S,S) enantiomers of unchanged formoterol in urine accounts for 40 and 60%, respectively, after a single dose of the drug in healthy volunteers and after single and multiple doses in patients with bronchial asthma.

Formoterol and its metabolites are completely excreted from the body. Approximately ⅔ of the dose taken orally is excreted in the urine, ⅓ in feces. Renal clearance is 150 ml/min.

The terminal half-life (T ½) of formoterol from plasma in healthy volunteers after a single inhalation of a dose of 120 mcg is 10 hours. The terminal T ½ (R, R) and (S, S) enantiomers, calculated from urinary excretion, are 13.9, respectively. and 12.3 hours.

Pharmacokinetics in selected cases:

gender: in women and men, the pharmacokinetic characteristics of the drug do not differ significantly;
age: in patients over 65 years of age, no significant differences in formoterol parameters were identified, so dose adjustment is not required;
renal/liver function: the pharmacokinetics of the drug have not been studied in patients with functional impairment of the kidneys/liver.

Indications for use

prevention of bronchospasm caused by physical activity, cold air or inhalation of allergens [as part of complex therapy with inhaled glucocorticosteroids (GCS)];
treatment and prevention of bronchial obstruction in COPD (with reversible and irreversible bronchial obstruction), chronic bronchitis and emphysema;
treatment and prevention of bronchial obstruction in bronchial asthma (as part of complex therapy with inhaled corticosteroids).

Contraindications

Absolute:

lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
age under 18 years;
lactation period;
hypersensitivity to any component of the drug.

Formoterol-native should be used with extreme caution and under close medical supervision, after assessing the benefits and risks, in patients with coronary heart disease, heart rhythm and conduction disorders (especially with third degree atrioventricular block), severe heart failure, severe arterial hypertension, idiomatic hypertrophic subaortic stenosis, aneurysm of any location, hypertrophic obstructive cardiomyopathy, known or suspected prolongation of the QTc interval (QT corrected > 0.44 sec), ketoacidosis, pheochromocytoma, thyrotoxicosis, diabetes mellitus, as well as pregnant women.

Formoterol-native, instructions for use: method and dosage

Formoterol native is used only by inhalation using the Inhaler CDM inhaler included in the kit. Taking capsules orally is prohibited!

The doctor selects the optimal dose individually, based on the characteristics of each patient’s disease. Formoterol native is recommended to be prescribed in the smallest doses that provide a sufficient therapeutic effect. After achieving stable control of asthma symptoms, a gradual dose reduction should be considered. Dosage reduction is carried out under close medical supervision.

bronchial asthma: for regular maintenance therapy, a dose of 12–24 mcg (1–2 capsules) 2 times a day is indicated. The maximum permissible daily dose is 48 mcg (4 capsules). For this disease, Formoterol-native is prescribed in addition to inhaled corticosteroids. Considering the maximum permitted daily dose, if necessary and depending on the initial dose, an additional occasional dose of 12–24 mcg per day is possible to relieve the symptoms of bronchial asthma. If the need to take additional doses ceases to be episodic (for example, becomes more often than twice a week), this may indicate a worsening of the disease, in which case a doctor's consultation is required. You should not start using Formoterol-native or change its dose during an exacerbation of the disease. The drug is not intended for the relief of acute attacks of bronchial asthma;
COPD: for regular maintenance therapy, a dose of 12–24 mcg 2 times a day is indicated;
prevention of bronchospasm during physical activity or exposure to a known allergen: the recommended dose is 12 mcg 15 minutes before exercise or expected contact with the allergen. Additional doses should not be inhaled within 12 hours. Patients with a history of severe bronchospasm may require an increase in the single dose to 24 mcg.

Proper inhalation

To ensure proper use of Formoterol-native capsules, a healthcare professional should:

warn patients that the capsules should not be swallowed, they are only allowed to be used for inhalation, removing them from the package immediately before use;
explain to patients that capsules can only be used with the Inhaler CDM inhaler;
train patients to use the inhaler.

The Inhaler CDM is a plastic device about 6 cm high with a movable top and a retractable compartment for the capsule. This is a single-dose inhaler that allows you to inhale medication in very small doses.

Step-by-step instructions for using the inhaler:

Remove the transparent cap from the inhaler.
Holding the device firmly with one hand, use the thumb and forefinger of the other hand to open the capsule compartment, pressing PUSH on the moving part of the inhaler with your index finger and sliding the compartment in the opposite direction.
Hold the device with one hand and insert the capsule into the compartment slot with the other.
Make sure the capsule is installed correctly.
Holding the inhaler strictly in a vertical position, close the compartment by pressing PUSH with your thumb in the opposite direction until it stops until you hear a click.
To bring the device into working condition: press firmly on the mouthpiece so that the arrow printed on the body disappears beyond the boundaries of the lower part of the inhaler to the top line, then release the mouthpiece to return to its original position (this manipulation allows you to puncture the capsule and open access to the powder contained in the capsule , into the lumen of the mouthpiece). The capsule should be pierced only once, this minimizes the entry of pieces of gelatin from the destroyed capsule shell into the mouth and/or throat during inhalation.
Exhale deeply (not through the mouthpiece).
Gently squeeze the mouthpiece with your teeth and wrap your lips tightly around it. Take a deep and strong breath through your mouth. At this point, a vibrating sound will be heard inside the capsule compartment due to the rotation of the capsule and dispersion of the drug. There is no need to squeeze or chew the mouthpiece with your teeth; you do not need to press on it when inhaling, otherwise the movement of the capsule may be blocked. The holes located on the sides of the mouthpiece should not be closed, otherwise the free movement of air inside the inhaler will be impaired and, as a result, the dispersion of the powder will be reduced.
Hold your breath for at least 10 seconds (longer if possible). Remove the inhaler from your mouth. Exhale slowly. You can then breathe normally.
To ensure that the full dose is inhaled, steps 7–9 should be repeated.
Open the compartment, remove the empty capsule, close the compartment.
Close the mouthpiece tightly with the cap.

The outside of the mouthpiece should be cleaned with a dry cloth at least once a week.

Side effects

Formoterol native can cause the following side effects (estimated frequency of their occurrence: very often - > 1/10 of prescriptions, often - from 1/100 to 1/10, infrequently - from 1/1000 to 1/100, rarely - from 1/10 10,000 to 1/1000, very rarely –< 1/10 000, в том числе отдельные сообщения):

Cases of overdose of Formoterol-native have not been recorded. Presumably, it is possible to develop phenomena characteristic of an overdose of other β 2 -adrenergic agonists, or to intensify existing adverse reactions: dry mouth, nausea, vomiting, metabolic acidosis, hyperglycemia, hypokalemia, dizziness, headache, drowsiness, weakness, nervousness, anxiety, tremor, increased or decreased blood pressure, palpitations, chest pain, ventricular arrhythmias, tachycardia up to 200 beats/min, convulsions, cardiac arrest.

Symptomatic and supportive therapy is required. In serious cases, the patient is hospitalized. Cardiac indicators should be monitored. If necessary, it is possible to use cardioselective β 2 -blockers, but under strict medical supervision and subject to extreme caution, since there is a risk of developing bronchospasm.

Special instructions

For bronchial asthma, Formoterol native is prescribed only in addition to the main therapy in case of insufficient control of symptoms during monotherapy with inhaled GCS or severe forms of the disease requiring the use of a combination of inhaled GCS and a long-acting β 2 -adreceptor agonist. Native formoterol should not be prescribed concomitantly with other long-acting β 2 -adrenergic receptor agonists. When prescribing the drug, the physician must assess the patient's condition regarding the adequacy of the anti-inflammatory therapy they are receiving. It should be continued without changes while using formoterol, even if the condition improves significantly.

To relieve an acute attack of bronchial asthma, the use of β 2 -adrenergic receptor agonists is indicated. If your condition suddenly worsens, you should immediately consult a doctor.

Native formoterol in rare cases causes the development of hypokalemia, which increases the risk of arrhythmias and can be potentially dangerous. This effect of the drug can be enhanced by hypoxia and under the influence of concomitant treatment, so special care should be taken in patients with severe bronchial asthma. It is recommended to regularly monitor serum potassium levels.

Like other inhaled drugs, native Formoterol can cause the development of paradoxical bronchospasm. In this case, the drug is discontinued and alternative treatment is carried out.

At a daily dose exceeding 54 mcg (more than 4 inhalations), formoterol may cause false positive drug test results.

There have been isolated reports of accidental ingestion of Formoterol-native capsules. In most cases, no adverse events were observed.

The medical professional should explain to the patient how to use the drug correctly, especially if his breathing does not improve after inhalation.

Impact on the ability to drive vehicles and complex mechanisms

There is no information on the effect of formoterol on human cognitive and psychophysical functions. Patients in whom Formoterol native causes undesirable reactions in the form of dizziness, tremor, muscle spasms, etc., should refrain from driving a car and potentially dangerous types of work that require quick reactions and/or increased attention.

Use during pregnancy and lactation

The safety of formoterol when used during pregnancy and lactation has not been established.

Pregnant women can only be prescribed Formoterol-native by a doctor if the expected benefit from the upcoming therapy for the mother outweighs the possible risks for the fetus. It should be borne in mind that beta 2 adrenergic agonists (including formoterol) can slow down the process of labor due to their relaxing effect on the smooth muscles of the uterus.

It is unknown whether the drug passes into mother's milk. If treatment is required during this period, breastfeeding should be discontinued.

In experimental studies in animals, oral administration of formoterol did not reveal a negative effect on fertility. The effect of Formoterol-native on the human reproductive system has not been established.

Use in childhood

The use of Formoterol-native is contraindicated for children and adolescents under 18 years of age.

For impaired renal function

In patients with functional renal impairment, the pharmacokinetic parameters of the drug have not been studied.

For liver dysfunction

The pharmacokinetics of the drug has not been studied in patients with functional liver disorders.

Use in old age

There are no special dosage instructions for elderly patients.

Drug interactions

Formoterol native should be used with caution in combination with the following drugs: tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), macrolides, antihistamines, phenothiazines, procainamide, disopyramide, quinidine and other drugs that can prolong the QT interval. With this combination, it is possible to enhance the effect of adrenergic stimulants on the cardiovascular system and increase the risk of developing ventricular arrhythmias. Concomitant use of other sympathomimetics may exacerbate the side effects of Formoterol native.

Glucocorticosteroids, diuretics and xanthine derivatives may enhance the potential hypokalemic effects of formoterol.

In patients with bronchial asthma, simultaneous use of β 2 -blockers may weaken the effect of formoterol and lead to serious bronchospasm. Therefore, in case of bronchial asthma, Formoterol-native is contraindicated for use with β 2 -blockers (including eye drops), except in cases of urgent need.

Anesthesia using halogenated hydrocarbons during formoterol therapy increases the risk of developing arrhythmias.

Analogs

Analogs of Formoterol-native are: Astalin, Atimos, Berotek, Ventolin, Vertasort, Clenbuterol, Kombipek, Oxis Turbuhaler, Salamol Steri-Neb, Salamol Eco Easy Breathing, Salbutamol, Salgim, Foradil, Cibutol Cyclocaps, etc.

Terms and conditions of storage

Store at a temperature of no more than 25 ° C, out of the reach of children, protected from light.

Shelf life – 2 years.