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

Active substanceFormoterolFormoterol

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Formoterol-native

capsules d / inhal.

NATIVA, LLC Russia

Dosage form: & nbspcapsules with powder for inhalation

Composition:

Active substance:

Formoterol fumarate dihydrate 12 μg

Excipients:

Sodium benzoate 0.02 mg

Lactose Monohydrate up to 12 mg

Capsule

Caramel dye (E 150s) 1,4388 %

Hypromellose up to 100%

Description:

Solid capsules № 3, transparent, light brown in color. The contents of capsules are white or almost white powder.

Pharmacotherapeutic group: bronchodilator - β2 adrenergic selective

ATX: & nbsp

R.03.A.C Selective beta-2-adrenomimetics

R.03.A.C.13 Formoterol

Pharmacodynamics:

Formoterol is a selective agonist of beta2-adrenoreceptors (beta2-adrenomimetic). It has a bronchodilator effect in patients with reversible airway obstruction. The effect of the drug occurs quickly (within 1-3 minutes) and persists for 12 hours after inhalation. When using therapeutic doses the effect on the cardiovascular system is minimal and is noted only in rare cases.

Formoterol inhibits the release of histamine and leukotri- ses from mast cells. In animal experiments, some of the anti-inflammatory properties of formoterol have been shown, such as the ability to inhibit the development of edema and the accumulation of inflammatory cells.

In experimental studies on animals in vitro it was shown that racemic formoterol and his (R.R) and (S.S.) enantiomers are highly selective β2 receptor agonists. (S.S.) enantiomer was 800-1000 times less active than (R, R) enantiomer and did not adversely affect activity (R.R) enantiomer with respect to the effect on the smooth muscle of the trachea. No pharmacological evidence has been obtained for the advantages of using one of these two enantiomers, but compared with the racemic mixture.

In studies conducted in humans, it was shown that formoterol effectively prevents bronchospasm caused by inhaled allergens, physical exertion, cold air, histamine or methacholine. As the bronchodilating effect of formoterol remains pronounced within 12 hours after inhalation,administration of the drug 2 times a day for prolonged maintenance therapy allows in most cases to provide the necessary control of bronchospasm in chronic lung diseases, both during the day and at night.

In patients with chronic obstructive pulmonary disease (COPD) of stable course formoterol, used in the form of inhalations in doses of 12 or 24 μg 2 times a day is accompanied by an improvement in the quality of life parameters.

Pharmacokinetics:

The therapeutic dosage range of formoterol is from 12 μg to 24 μg 2 times a day. Data on pharmacokinetics of formoterol were obtained in healthy volunteers after inhalation of formoterol in doses above the recommended range and in COPD patients after inhalation of formoterol in therapeutic doses.

Suction

After a single inhalation of formoterol in a dose of 120 μg to healthy volunteers formoterol quickly absorbed into the blood plasma, the maximum concentration of formoterol in the blood plasma (Cmax) is 266 pmol / l and is reached within 5 minutes after inhalation. In patients with COPD. who received formoterol in a dose of 12 or 24 μg twice a day for 12 weeks, the concentration of formoterol in the blood plasma, measured after 10 minutes, 2 hours and 6 hours after inhalation, were in the ranges 11.5-25.7 lmol / l and 23.3-50.3 pmol / l, respectively.

AT studies in which the total excretion of formoterol and its (R.R) and (S.S) enantiomers with urine, it was shown that the amount of formoterol in the systemic blood flow increases in proportion to the amount of inhaled dose (12-96 μg).

After the inhalation of formoterol 12 or 24 μg twice a day for 12 weeks, the excretion of unchanged formoterol with urine in patients with bronchial asthma (BA) increased by 63-73%, and in COPD patients by 19-38%. This indicates a certain cumulation of formoterol in the blood plasma after multiple inhalations. In this case, there was no greater accumulation of one of the enantiomers of formoterol compared to another after repeated inhalations.

Most of the formoterol used with the inhaler is swallowed and then absorbed from the gastrointestinal tract (GIT). When 80 μg of 3H-labeled formoterol was administered, at least 65% of formoterol was absorbed into two healthy volunteers.

Distribution

The binding of formoterol to plasma proteins is 61-64%, binding to serum albumin is 34%.13 the concentration range observed after the application of therapeutic doses of the preparation, saturation of binding sites is not achieved.

Metabolism

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

Low-value metabolic pathways include conjugation of formoterol with sulfate, followed by deforming. A variety of isoenzymes are involved in glucuronidation processes (UGT1A1, 1AS, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7 and 2B15) and O-demethylation (CYP2D6, 209, 2C9 and 2A6) of formoterol, which implies a low probability of drug interaction by inhibiting any isoenzyme involved in the metabolism of formoterol. In therapeutic concentrations formoterol It does not inhibit the isoenzymes of the cytochrome P450 system.

Excretion

When taking formoterol in a dose of 12 or 24 mcg twice a day for 12 weeks, unchanged in the urine is released 10% and 15-18% of the total dose in patients with asthma; 7% and 6-9% of the total dose, respectively, in patients with COPD.

The calculated fractions of (R, R) and (S, S) enantiomers of unchanged formoterol in urine are 40% and 60%, respectively,after a single dose of formoterol (12-120> 1 kg) in healthy volunteers and after single and repeated doses of formoterol in patients with asthma.

The active substance and its metabolites are completely eliminated from the body; about 2/3 of the applied dose is excreted in the urine, 1/3 - with feces. The renal clearance of formoterol is 150 ml / min.

In healthy volunteers, the final half-life of formoterol from the plasma after a single inhalation of a formoterol preparation at a dose of 120 μg is 10 hours; terminal half-lives (R, R) and (S, S) Enantiomers, calculated by urinary excretion, are 13.9 and 12.3 hours, respectively.

Pharmacokinetics in selected patient groups

Floor

After adjusting for body weight, pharmacokinetic parameters of formoterol in men and women do not differ significantly.

Elderly patients (over 65 years of age)

Data in favor of the need to change the dosage of formoterol in patients older than 65 years but compared with younger patients is not obtained.

Patients with impaired hepatic and / or renal function

The pharmacokinetics of formoterol in patients with impaired hepatic and / or renal function have not been studied.

Indications:

Prevention and treatment of bronchial obstruction in patients with bronchial asthma (BA) as an adjunct to therapy with inhaled glucocorticosteroids.
Prevention of bronchospasm induced by inhalation of allergens, cold air or exercise as an adjunct to therapy with inhaled glucocorticosteroids.
Prevention and treatment of bronchial obstruction disorders in patients with chronic obstructive pulmonary disease (COPD), in the presence of both reversible and irreversible airflow obstruction, chronic bronchitis and pulmonary emphysema.

Contraindications:

Hypersensitivity and / or intolerance to any of the components of the drug.
Age to 18 years.
Lactation.
Rare genetic diseases, such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

If you have one of these diseases, always consult a doctor before using the drug.

Exercise caution when using the drug Formoterol-native (especially in terms of dose reduction) and careful monitoring of patients is requiredin the presence of the following concomitant diseases: coronary heart disease; disorders of the heart rhythm and conductivity, especially atrioventricular blockade III degree; severe heart failure; idiomatic hypertrophic subaortic stenosis; severe degree of arterial hypertension; aneurysm of any localization; fosochromocytoma; ketoacidosis; hypertrophic obstructive cardiomyopathy; thyrotoxicosis; known or suspected lengthening interval QTc (QT Corrected> 0.44 seconds);

Considering the hyperglycemic effect characteristic of β₂-adrenomimetics, in patients with diabetes mellitus receiving Formoterol-native, additional regular monitoring of blood glucose concentration is recommended.

Pregnancy and lactation:

The safety of the use of formoterol in pregnancy and during breastfeeding has not been established to date.

Use during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. Formoterol, as well as other beta2-adrenomimetics, can slow the process of labor due to tocolytic action (a relaxing effect on the smooth muscles of the uterus).

It is not known whether the formoterol in breast milk.Therefore, if it is necessary to use formoterol, breastfeeding should be stopped.

There are no data on the effect of the drug on fertility. Studies on experimental animals showed no effect on fertility with oral administration of formoterol.

Dosing and Administration:

Formoterol-native is intended for inhalation in patients over 18 years of age. The drug is not intended for oral administration.

Dose of the drug Formoterol-native is selected individually depending on the needs of the patient. Use the smallest dose that provides a therapeutic effect. At achievement of the control of symptoms of a bronchial asthma on a background of therapy by a preparation Formoterol-native, it is necessary to consider the possibility of gradually reducing the dose of the drug. Dose reduction Formoterol-nativeThe patient is under regular medical supervision.

A drug is a capsule with a powder for inhalation, which should be used only with a special device - inhaler "Inhaler CDM ", towhich is included in the package.

Bronchial asthma

Dose of the drug Formoterol-native for regular maintenance therapy (12-24 μg (1-2 capsules) 2 times a day.

Formoterol-native should be used only as an additional therapy for inhaled glucocorticosteroids (GCS). Do not exceed the maximum recommended dose of the drug 48 μg (content of 4 capsules) per day.

Given that the maximum daily dose of the drug Formoterol-native is 48 μg, if necessary, you can additionally apply 12-24 μg per day to relieve symptoms of bronchial asthma.

If the need for additional doses of the drug Formoterol-native ceases to be episodic (for example, it becomes more frequent than 2 days a week), it may indicate a worsening of the course of bronchial asthma, you should consult your doctor. Against the background of exacerbation of bronchial asthma should not begin treatment with the drug Formoterol-native or change the dosage of the drug.

Formoterol-native It should not be used to stop acute attacks of bronchial asthma.

Prevention of bronchospasm caused by physical exertion or the inevitable effects of a known allergen

It should be applied Formoterol-native in a dose of 12 μg (the contents of 1 capsule) 15 minutes before the alleged contact with the allergen or before the load. Additional inhalations of the drug ns should be performed within the next 12 hours.

Prevention of severe bronchospasm

Patients with severe bronchospasm in the anamnesis may require a single inhalation in a dose of 24 mcg (the contents of 2 capsules).

COPD

The dose of the drug Formotrol-napsh for regular maintenance therapy of COPD is 12-24 μg (1-2 capsules) twice a day.

Instructions for inhalation

In order to ensure the correct use of the drug, a doctor or other health care provider should:

1. warn the patient that the capsules are for inhalation use only and are not intended for ingestion;

2. Explain to the patient that capsules with powder for inhalation should only be taken with Inhaler CDM;

3. show the patient how to use the inhaler.

Remove the capsule from the cell pack immediately before use.

Instructions for the use of the inhaler "Inhaler CDM"

Inhaler powder "Inhaler CDM" - a plastic device with a movable top and with a retractable compartment for the capsule, about 6 cm high.

"Iphalera CDM" is a single-dose inhaler that allows you to dose and inhale the drug in very small doses. The formoterol-native drug enters the patient's airway along with the air streams when performing an active inspiration through the mouthpiece of the device.

Inhaler CDM® is very simple to use. Follow the step-by-step instructions below:

Step 1. Remove the transparent cap from the device "Inhaler CDM", as shown in Fig.1.

Step 2. Hold the device firmly with one hand, with the index finger and the thumb of the other hand, open the capsule compartment, as shown in Fig. To do this, press the index finger on the PUSH in the moving part of the Inhaler CDM, sliding the compartment in the opposite direction.

Step 3. While holding the device with one hand, insert the capsule with the drug into the compartment of the compartment (Fig. 3).

Step 4. Make sure that the capsule is correctly inserted into the socket (Fig. 4).

Step 5. While holding the Inhaler CDM in the upright position, close the compartment by pressing the thumb in the opposite direction until it stops, until a click is heard (Fig. 5).

Step 6. Hold the device "Inhaler CDM" strictly vertically (Fig. 6).

Step 7. Bring it to the working state, as shown in Fig. 7.To do this, press firmly onto the mouthpiece so that the arrow on the body disappears from the bottom of the device to the top line. Then release the mouthpiece to return it to its original position. Thus, you will pierce the capsule, opening access to the drug in the lumen of the mouthpiece.

Attention: due to the destruction of the gelatin capsule, small pieces of gelatin can be inhaled into the mouth or throat. In order to reduce this phenomenon to a minimum, do not pierce the capsule more than 1 time.

Step 8. Attention: Before inhalation, exhale (Fig. 8). Do not exhale through the mouthpiece!

Step 9. Gently squeeze the mouthpiece "Inhaler CDM" with your teeth, tightly grasp it with your lips and take a deep and strong breath through your mouth (Fig. 9). You will hear a vibrating sound inside the capsule compartment, emitted by the capsule while rotating and dispersing the drug. Attention: the mouthpiece can not be chewed and hard to hear with your teeth! Do not press on the mouthpiece when inhaled. This can block the movement of the capsule. Hold your breath for about 10 seconds or longer, as far as possible.

Remove the inhaler from the mouth. Make a slow exhalation.Then breathe normally.

Repeat steps 8-9 again, to ensure that the dose of the drug is inhaled.

Step 10. After the inhalation, open the capsule compartment, remove the empty capsule and then close it, as shown in Fig. 5.

Attention: When carrying out inhalation, try not to cover the holes located on the sides of the mouthpiece. This can interfere with the free movement of air within the inhaler, thereby reducing the dispersion of the contents of the capsule.

Always close the "Inhaler CDM" cap after use, this will keep the mouthpiece clean.

Regularly (once a week), you should clean the mouthpiece from the outside with a dry cloth.

There are separate reports of accidental ingestion of whole capsules by the patients, without using an inhalation device. Most of these cases are not associated with the development of adverse events. The health worker should explain to the patient how to correctly apply the medication, especially if after inhalation the patient does not have an improvement in breathing.

Side effects:

Undesired reactions are distributed according to the frequency of occurrence.The following criteria were used to estimate the frequency: very often (> 1/10), often (from 1/100 to 1/10), infrequently (from 1/1000 to 1/100), rarely (from 1/10000 to 1/1000), very rarely (< 1/10000), (including individual messages).

Infectious and parasitic diseases: often - pharyngitis, acute respiratory viral infection.

Immune system disorders: very rare - anaphylactic reactions, urticaria, angioedema (Quincke's edema), itching, rash.

Disorders from the metabolism and nutrition: very rare - metabolic acidosis. Disorders of the psyche: infrequently - agitation, anxiety, increased excitability, insomnia; rarely - increased fatigue.

Disorders from the nervous system: often - headache, tremor; infrequently- dizziness; rarely - change in taste.

Heart Disease: Frequent - heart palpitations, chest pain; infrequently - tachycardia; rarely - peripheral edema; stenocardia, disturbance of the heart rhythm (including atrial fibrillation, ventricular extrasystoles, tachyarrhythmia).

Vascular disorders: very rare - lowering blood pressure (hypotension), increasing blood pressure (hypertension).

Disturbances from the respiratory system, chest and mediastinal organs: often - sinusitis, increased production of phlegm; infrequently - bronchospasm, including paradoxical, dysphonia; rarely - cough.

Disorders from the gastrointestinal tract: infrequently - dryness of the oral mucosa; rarely - nausea.

Disturbances from the musculoskeletal and connective tissue: often - pain in the back, leg cramps; infrequently - Muscle spasm, myalgia.

General disorders and disorders at the site of administration: often - fever; infrequently - irritation of the mucous membrane of the pharynx and larynx.

Laboratory and instrumental data: infrequently - flattening or inversion of the T wave, segment depression ST, interval lengthening QT on the electrocardiogram; rarely - hypokalemia, hyperglycemia.

If any of the side effects indicated in the manual are aggravated, or if you notice any other adverse reactions not listed in the instructions, tell your doctor.

Overdose:

Symptoms. An overdose of formoterol can probably lead to the development of phenomena characteristic of an overdose of beta2-adrenomimetics or increased side effects: chest pain, palpitation, tachycardia up to 200 beats / min,ventricular arrhythmias, increase or decrease in blood pressure, dry mouth, nausea, vomiting, headache, dizziness, tremors, nervousness, weakness, anxiety, drowsiness, metabolic acidosis, hypokalemia, hyperglycemia, seizures. As with all inhaled beta2-agonists, formoterol overdose, possible cardiac arrest and death.

Treatment. Supportive and symptomatic therapy is indicated. Serious cases require hospitalization.

The use of cardioselective beta2-adrenoblockers can be considered. but only under close medical supervision, subject to extreme caution since the use of such tools can cause bronchospasm. It is recommended to monitor cardiac activity.

Interaction:

A drug Formoterol-native, as well as other beta2-agonists, should be used with caution in patients taking drugs such as: quinidine, disopyramide, procainamide, Phenothiazines, macrolides, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, antihistamines, and other drugs which are known to lengthen the interval QT, since in these cases, the action of adrestrostimulators on the cardiovascular system may increase and the risk of ventricular arrhythmia increases. Simultaneous use of other sympathomimetic agents can lead to aggravation of adverse drug reactions Formoterol-native.

The simultaneous use of xanthine derivatives, glucocorticosteroids or diuretics can enhance the potential hypokalemic effect of the drug Formoterol-native.

In patients receiving anesthesia using halogenated hydrocarbons, the risk of arrhythmia increases.

Drugs related to beta2-adrenoblockers can weaken the effect of the drug Formoterol-native and lead to severe bronchospasm in patients with bronchial asthma. In this regard, do not use the drug Formoterol-native together with beta2-adrenoblockers (including eye drops), unless the use of such a combination of drugs is caused for any extraordinary reasons.

Special instructions:

Anti-inflammatory therapy In patients with bronchial asthma Formoterol-native should be used only as an additional treatment with insufficient control of symptoms against the background of monotherapy with inhaled glucocorticosteroids or in severe form of the disease requiring the use of a combination of inhaled GCS and a long-acting beta2-addressoperator agonist. You can not use Formoterol-native with other long-acting beta2-adrenergic agonists.

When the drug is prescribed Formoterol-native It is necessary to assess the condition of patients with regard to the adequacy of the anti-inflammatory therapy that they receive. After the beginning of treatment with the drug Formoterol-native patients should be advised to continue anti-inflammatory therapy without changes, even if improvement is noted.

For relief of an acute attack of bronchial asthma, agonists of beta2-adrenergic receptors should be used. In case of sudden deterioration of the condition, patients should immediately seek medical help.

Hypokalemia

The consequence of therapy with beta2-adrenomimetics, including Formoterol-native, there may be a development of potentially serious hypokalemia. Hypokalemia may increase the risk of arrhythmias.Since this action of the drug Formoterol-native can be intensified by hypoxia and concomitant treatment, special care should be taken in patients with severe bronchial asthma. In these cases, regular monitoring of potassium concentration in the blood serum is recommended.

Paradoxical bronchospasm

Like other inhaled drugs, Formoterol-native can cause a paradoxical bronchospasm. In this case, immediately cancel the drug and prescribe an alternative treatment.

The use of formoterol in a dose exceeding 54 μg / day (more than 4 inhalations) can lead to positive results of doping tests.

Effect on the ability to drive transp. cf. and fur:

Data on the effect of the drug Formoterol-pativ there is no ability to drive vehicles and manage mechanisms. In case of development of such adverse reactions as dizziness, tremor, convulsions or muscle spasms, it is necessary to refrain from driving vehicles and controlling mechanisms, as well as from engaging in other potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Capsules with powder for inhalation, 12 mcg.

Packaging:

10 capsules per circuit cell packaging made of aluminum foil and laminated aluminum foil.

For 3 or 6 contour packagings with or without an inhalation device, the instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not apply but the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003180