Expiration date: 03/2025

The composition and form of issue:

Capsules with powder for inhalations. 1 capsule contains:

formoterol fumarate 12.5 mg

excipients: lactose 

blistere in 10 PCs. in cardboard pack of 3 or 6 blisters in a kit with the device for inhalation (Aerolizer).

Description pharmaceutical form:

Clear, colourless capsules, size No. 3, with marking "CG" on the cap and "FXF" — or "CG" — on the body and "FXF" on the cap black ink.

The contents of the capsule: white color free flowing powder.

Pharmacokinetics:

The therapeutic dose range of formoterol is between 12 and 24 mcg 2 times a day. Data on the pharmacokinetics of formoterol obtained from healthy volunteers after inhalation of formoterol at doses above the recommended range and in patients with chronic obstructive pulmonary disease (COPD) after inhalation of formoterol at therapeutic doses.

Suction. After a single inhalation of formoterol fumarate in a dose of 120 mcg in healthy volunteers, formoterol was rapidly absorbirovanija in plasma, Cmax of formoterol in plasma were 266 pmol/l and was reached within 5 min after inhalation. In COPD patients treated with formoterol in a dose of 12 or 24 mcg 2 times a day for 12 weeks, the concentration of formoterol in plasma, measured after 10 min, 2 and 6 h after inhalation, were in the ranges of 11.5–25.7 and 23.3 and 50.3 per pmol/l, respectively.

In studies that have examined total urinary excretion of formoterol and its (R,R) and (S,S) enantiomers in the urine, it has been shown that the amount of formoterol in the systemic circulation increases in proportion to the magnitude ingaliruemogo dose (12-96 micrograms). After inhalation use formoterol in a dose of 12 or 24 mcg 2 times a day for 12 weeks excretion of unchanged formoterol urine in patients with bronchial asthma increased by 63-73%, and in patients with COPD — at 19-38%. This indicates some accumulation of formoterol in plasma after repeated inhalation. Thus there wasn't a greater accumulation of one enantiomer of formoterol compared to others after repeated inhalation.

Just as it was reported for other drugs used in the form of inhalation, a large part of formoterol used using inhaler, will proglatavetsa and then absorbed from the gastrointestinal tract. When assigning 80 micrograms of 3H-labelled formoterol inside 2 healthy volunteers were absorbiruyaci at least 65% of formoterol.

The plasma protein binding and blood distribution. The binding of formoterol plasma protein is 61 to 64%, and binding to serum albumin — 34%. The range of concentrations, observed after application of therapeutic doses of the drug, the saturation of the bonding is not achieved.

Metabolism. Major route of metabolism of formoterol is by direct conjugation with glucuronic acid. Another way of metabolism is O-demethylation followed by conjugation with glucuronic acid (glucuronidation).

Minor metabolic pathways include the conjugation of formoterol sulfate with subsequent deformirovanie. Many isoenzymes involved in the processes of glucuronidase (UGT1A1, 1??, 1?6, 1?7, 1?8, 1?9, 1?10, 2?7 and 2?15) and O-demethylation (CYP2D6, 2C19, 2C9 and 2A6) of formoterol, suggesting a low likelihood of drug interactions through the inhibition of any isozyme involved in the metabolism of formoterol. In therapeutic concentrations of formoterol does not inhibit isozymes of cytochrome P450.

Excretion. In patients with bronchial asthma and COPD are treated with formoterol fumarate in a dose of 12 or 24 mcg 2 times a day for 12 weeks, approximately 10 or 7% of the dose, respectively, was determined in the urine as unchanged formoterol. Calculated the shares of (R,R) and (S,S) enantiomers of unchanged formoterol in the urine are 40 and 60%, respectively, after a single dose of formoterol (12-120 ág) in healthy volunteers and after single and repeated doses of formoterol in patients with bronchial asthma. The active substance and its metabolites are completely eliminated from the body about 2/3 of the used inside of the dose is excreted in urine and 1/3 in feces. Renal clearance of formoterol is 150 ml/min.

In healthy volunteers, the final T1/2 of formoterol in plasma after a single inhalation of formoterol fumarate in a dose of 120 mcg is 10 h, the final T1/2 (R,R) and (S,S) enantiomers, calculated from urinary excretion, was 13.9 and 12.3 hours, respectively.

Pharmacokinetics in specific groups of patients

Paul. After adjustment for body weight pharmacokinetic parameters of formoterol in men and women have no significant differences.

Elderly patients. The pharmacokinetics of formoterol in elderly patients has not been studied.

Pediatrics. In a clinical study in children aged 5-12 years with asthma treated with formoterol fumarate in a dose of 12 or 24 mcg 2 times a day for 12 weeks, urinary excretion of unchanged formoterol urine increased by 18-84% in comparison with the corresponding value measured after the first dose. In clinical studies in children in the urine was determined about 6% of unchanged formoterol.

Patients with impaired liver and/or kidneys. The pharmacokinetics of formoterol in patients with impaired liver and/or kidney disease has not been studied.

Description pharmacological action:

Formoterol is a selective agonist of &beta2 receptors. It has a bronchodilator effect in patients with reversible airway obstruction. The effect of the drug occurs quickly (within 1-3 min) and persisted for 12 h after inhalation. When using therapeutic doses, the effects on the cardiovascular system is minimal and occurs only in rare cases.

The drug was Foradil inhibits the release of histamine and leukotriene from mast cells. In animal experiments was shown some anti-inflammatory properties of formoterol, such as the ability to inhibit the development of edema and accumulation of cell inflammation.

In experimental animal studies in vitro it was shown that racemic formoterol and its (R,R) and (S,S) enantiomers are highly selective agonists &beta2 receptors. (S,S) enantiomer was 800 to 1,000 times less active than (R,R) enantiomer and not have a negative impact on the activity of (R,R) enantiomer in respect to the influence on smooth muscles of the trachea. Was not obtained pharmacological evidence of the benefits of using one of these 2 enantiomers compared to the racemic mixture.

In studies conducted in humans showing that the drug was Foradil effectively prevents bronchoconstriction caused by inhaled allergens, exercise, cold air, histamine or methacholine. Since the bronchodilator effect of the drug was Foradil remains strong within 12 hours after inhalation, the drug 2 times a day for long-term maintenance therapy allows in most cases to provide the necessary control of bronchospasm in chronic lung diseases during the day and night.

In COPD patients, a stable flow formoterol used in the form of inhalations from Aerolizer in doses of 12 or 24 mcg 2 times per day, causes a rapid onset of bronchodilator effect, which lasts for a minimum of 12 hours and is accompanied by improvement of parameters of quality of life.

Indications:

• prevention and treatment of bronchospasm in patients with bronchial asthma as add-on therapy to inhaled corticosteroids
  
• prevention of bronchospasm caused by physical activity, cold air or inhaled allergens, as a complement to therapy with inhaled corticosteroids
  
• prevention and treatment of bronchial obstruction in patients with COPD, in the presence of both reversible and irreversible bronchial obstruction, chronic bronchitis and emphysema.
  

Contraindications:

• hypersensitivity to any component of the drug
  
• children up to age 5 years
  
• breast-feeding.
  

With caution:

Compliance with special caution in the use of the drug was Foradil (especially from the viewpoint of lowering the dose) and careful monitoring of patients is required in the presence of the following comorbidities:

• coronary heart disease
  
• cardiac rhythm and conduction, especially AV blockade III degree
  
• severe heart failure
  
• idiopathic subvalvular aortic stenosis
  
• hypertrophic obstructive cardiomyopathy
  
• thyrotoxicosis
  
• known or suspected prolonged QT interval (corrected QT >0,44 sec)
  
• diabetes mellitus (hyperglycemic effect of a given characteristic of beta2-adrenergic agonists, including the drug was Foradil, it is recommended that regular monitoring of the concentration of glucose in the blood).
  

Application of pregnancy and breast-feeding:

The safety of the drug was Foradil during pregnancy and lactation has so far not been established.

The use of the drug during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Formoterol, like other beta2 - agonists, can slow down the process of childbirth due to tocolytic action (relaxing action on the smooth muscles of the uterus).

It is unknown whether formoterol penetrates into human breast milk. Mothers receiving the drug was Foradil should not breast-feed.

Side effects:

Adverse reactions are distributed in accordance with the frequency of occurrence. To assess the frequency used the following criteria: very common (&ge1/10) frequently (&GE. 1/100, <1/10), sometimes (&ge1/1000, <1/100) rare (&ge1/10000, <1/1000) very rare (<1/10000), including individual messages.

The immune system: very rarely — hypersensitivity reactions such as hypotension, urticaria, angioneurotic edema, pruritus, rash.

Mental disorders: rarely — agitation, anxiety, irritability, and insomnia.

From the nervous system: often — headache, tremor sometimes — dizziness very rare — disorders of taste.

Of the cardiovascular system: often- palpitations sometimes — tachycardia, very rarely — peripheral edema.

The respiratory system: sometimes — bronchospasm, including paradoxical.

Local reactions: sometimes — irritation of the mucous membrane of the pharynx and larynx.

From the digestive system: very rarely — nausea.

From the side of musculoskeletal system: sometimes — cramps in the muscles, myalgia.

Other: distortion of taste sensations.

In applying the drug was Foradil in clinical practice noted the following changes laboratory findings: hypokalemia, hyperglycemia, QT prolongation (with ECG). In clinical trials using the drug have Foradil has been a slight increase in the incidence of severe exacerbations of asthma compared to placebo. However, the results of the above clinical studies do not allow to quantify the incidence of serious exacerbations of asthma in different groups.

Drug interactions:

The drug was Foradil, like other beta2-agonists, should be used with caution in patients receiving such drugs as quinidine, disopyramide, procainamide, phenothiazines, antihistamines, MAO inhibitors, tricyclic antidepressants, and other drugs which are known that they lengthen the QT interval, as in these cases the action of the agonists on the cardiovascular system may increase. When using drugs that can prolong the QT interval, increased risk of ventricular arrhythmias. The simultaneous use of other sympathomimetic agents may lead to worsening side effects of the drug were Foradil.

Beta-blockers may weaken the effect of the drug was Foradil. In this regard, it should not be used the drug was Foradil in conjunction with beta-adrenoblokatorami (including eye drops) unless the use of such combinations of drugs do not require any extraordinary reason.

Method of application and dose:

Inhalation.

Intended for inhalation use in adults and children 5 years and older.

Dose selected individually depending on the needs of the patient. You should use the lowest dose that provides therapeutic zffekt. When achieving control of symptoms of asthma on the background of drug therapy was Foradil, you should consider gradually reducing the dose. Dose reduction is carried out under regular medical control of the patient.

The drug is a powder for inhalation, which should be used only with a special device Aerolizer, which is included in the package.

Adults

In bronchial asthma, the dose for regular maintenance therapy is 12-24 mcg (contents of 1-2 caps.) 2 times a day.

Do not exceed the maximum recommended dose for adults (48 micrograms/day). Given that the maximum daily dose of the drug was Foradil — 48 mcg, optionally can be applied 12-24 micrograms per day for relief of symptoms of bronchial asthma.

If need to use additional doses of the drug ceases to be episodic (for example is becoming more often than 2 days a week), should recommend the patient to consult a doctor for review of treatment, because it may indicate the worsening of asthma.

On the background of aggravation of asthma, you should not start treatment with medication was Foradil or change the dosage. The drug was Foradil should not be used for relief of acute asthma attacks.

To prevent bronchospasm caused by exercise or unavoidable exposure to known allergen for 15 min prior to expected exposure to the allergen or until the load is inhaled 12 mg of the drug (content of 1 caps.).

Patients with severe bronchospasm in anamnesis for prevention may require inhalation of contents 2 caps. (24 µg).

With COPD, the dose for regular maintenance therapy for 12 to 24 g (contents of 1-2 caps.) 2 times a day.

Children under the age of 5 years and older

The maximum recommended dose is 24 micrograms per day.

In bronchial asthma, the dose for regular maintenance therapy — 12 mcg 2 times per day.

To prevent bronchospasm caused by exercise or unavoidable exposure to known allergen for 15 min prior to expected exposure to the allergen or until the load is inhaled 12 mg of the drug (content of 1 caps.).

Guidance for conducting inhalation

In order to ensure proper use of the drug, a doctor or other health professional should show the patient how to use the inhaler, to explain to the patient that the use the capsules with powder for inhalation should only be through Aerolizer, warn the patient that the capsules are intended only for inhalation use and not intended for ingestion.

It is important that the patient understand that due to destruction of the gelatin capsules are small pieces of gelatin as a result of the inhalation can get in the mouth or throat. In order to reduce this phenomenon to a minimum, you should not pierce the capsule more than 1 times. Remove the capsule from the blister packaging immediately before use. (see "Instruction for use of Aerolizer").

The instruction on the application of Aerolizer

1. It is necessary to remove the cap from Aerolizer.

2. It is hard to keep Aerolizer the base and turn mouthpiece in direction of arrow.

3. Place the capsule in the cell, located at the base of Aerolizer (it has the form of a capsule). It must be remembered that to take the capsule out of the blister pack need, immediately prior to inhalation.

4. Turning the mouthpiece, you should close Aerolizer.

5. Holding Aerolizer in a strictly vertical position, 1 time should be pressed until the end of the blue buttons available on the sides of Aerolizer. Then let them go.

Note. At this stage in the piercing of the capsule she can break, resulting in small pieces of gelatin might reach the mouth or in the throat. Since gelatin is edible, it won't cause any harm. In order for the capsule not destroyed fully, you must fulfill the following requirements: do not pierce the capsule more than 1 times to observe the rules of storage to remove the capsule from the blister only directly prior to the inhalation.

6. Make a full exhalation.

7. You should take the mouthpiece in your mouth and gently tilt your head back. Firmly grasp the mouthpiece with your lips and make rapid, consistent, maximally deep breath. You should experience a characteristic rattling sound generated by the rotation of the capsule and atomization of the powder. If there is no sound, then you should open Aerolizer and see what happened with the capsule. Perhaps she is stuck in the cell. In this case, you need to carefully extract the capsule. In any case you should not attempt to release the capsule by repeated clicks on the buttons on the sides of Aerolizer.

8. If inhalation emerged a distinctive sound, you need to hold your breath as long as possible. At the same time, we need to remove the mouth the mouthpiece. Then to breathe out. Open Aerolizer and see if there are any in the capsule powder. If the capsule remained in the powder, re-do the steps described in paragraphs 6-8.

9. After inhalation it is necessary to open Aerolizer, remove the empty capsule, close mouthpiece and cap Aerolizer.

Care Analisaram: to remove powder residue should be wiped off the mouthpiece and the cell with dry cloth. You can also use a soft brush.

Overdose:

Symptoms: overdose of the drug was Foradil is likely to lead to the development of phenomena that are typical for beta2-agonists are nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia.

Treatment: shown holding a supportive and symptomatic therapy. In serious cases, hospitalization is required.

Can be considered the use of cardioselective beta-blockers, but only under careful medical supervision, subject to extreme caution since the use of these agents can cause bronchospasm.

Special instructions:

Formoterol belongs to the class of agonists &beta2-adrenergic long-acting On the background of the application of the other agonist &beta2-adrenergic long-acting salmeterol, there was an increase in the frequency of deaths, associated with bronchial asthma (13 of 13176 patients) compared with placebo (3 of 13179 patients). Clinical studies evaluating the incidence of deaths associated with asthma, on the background of the drug was Foradil was conducted.

It is shown that the use of the drug was Foradil improves the quality of life for COPD patients.

Anti-inflammatory therapy. In patients with bronchial asthma, the drug was Foradil should only be used as a complementary treatment for lack of effectiveness of other, controlling the disease drugs, such as inhaled corticosteroids (medium and low doses) or a severe form of the disease, requiring the use of 2 maintenance therapies, including the drug was Foradil. In appointing the drug to patients, not receiving anti-inflammatory therapy should be started simultaneously with drug application were Foradil. In appointing the drug was Foradil, it is necessary to assess the condition of patients in relation to the adequacy of the anti-inflammatory therapy they receive. After the start of treatment, the drug was Foradil patients should be advised to continue anti-inflammatory therapy unchanged, even if it was an improvement.

For the relief of acute attack of asthma should be applied agonists of beta2-adrenoceptor short-acting. The sudden deterioration of the patients should immediately seek medical help.

Hypokalemia. The consequence of therapy &beta2-agonists, including the drug was Foradil, may be the development of potentially serious hypokalemia. Hypokalemia may increase susceptibility to develop arrhythmias.

Because of this drug action may be increased by hypoxia and concomitant treatment particular caution should be exercised in patients with bronchial asthma heavy currents. In these cases, regular monitoring of the concentration of potassium in the blood serum.

Paradoxical bronchospasm. As with other inhalation therapy, one should consider the possibility of paradoxical bronchospasm. If it occurs, should immediately stop the drug and prescribe an alternative treatment.

Effects on ability to drive vehicles and operate machinery. Patients on the background of the drug was Foradil occurs dizziness or other disorders of the Central nervous system, should refrain from driving vehicles or work with machinery during the period of use of the drug.