Instructions Freeway inhalation solution 0.25 mg/ml bottle 25 ml No. 1
Composition
active ingredient: ipratropium bromide;
1 ml of solution contains ipratropium bromide - 0.261 mg, which is equivalent to ipratropium bromide anhydrous - 0.25 mg;
Excipients: benzalkonium chloride, disodium edetate, sodium chloride, 1 M hydrochloric acid prepared from concentrated hydrochloric acid, purified water.
Dosage form
Solution for inhalation.
Main physicochemical properties: clear colorless liquid.
Pharmacotherapeutic group
Anticholinergics. ATX code R03BB01.
Pharmacological properties
Pharmacodynamics.
Freeway® is a quaternary ammonium compound with anticholinergic (parasympatholytic) properties. Preclinical studies have shown that ipratropium bromide inhibits vagal reflexes through an antagonistic interaction with acetylcholine, a neurotransmitter that provides vagal nerve impulse transmission. Anticholinergics prevent the increase in intracellular calcium ion concentration Ca++. The effect of acetylcholine on muscarinic receptors of smooth muscle is achieved through another system of mediators, which consists of inositol triphosphate (ITP) and diacylglycerol (DAG).
Bronchodilation after inhalation of ipratropium bromide is mainly due to the local, rather than systemic, action of the drug.
There are no preclinical or clinical data on the negative effects of ipratropium bromide on respiratory mucus secretion, mucociliary clearance, or gas exchange.
Clinical trials
In controlled 85-90-day studies conducted in patients with bronchospasm due to chronic obstructive pulmonary disease (chronic bronchitis and emphysema), significant improvement in lung function was observed within 15 minutes, with maximal improvement occurring after 1-2 hours, and the effect persisting for 4-6 hours.
Studies conducted in adults and children aged 6 years and older have demonstrated the bronchodilator effect of ipratropium bromide in the treatment of severe bronchospasm associated with asthma. In most of these studies, ipratropium bromide was administered in combination with inhaled beta-agonists.
Despite the small amount of data, the therapeutic effect of the drug was found in the treatment of bronchospasm caused by infectious inflammation of the bronchioles and bronchopulmonary dysplasia in infants and young children.
Pharmacokinetics.
Absorption.
The therapeutic effect of the drug is manifested by its local effect on the respiratory tract. The duration of the therapeutic effect (bronchodilation) is not related to the pharmacokinetics of the active ingredients of the drug.
After inhalation, approximately 10-30% of the drug dose, depending on its composition and inhalation technique, is mainly deposited in the respiratory tract. The majority of the drug dose is swallowed and passes through the gastrointestinal tract.
The portion of the dose that reaches the lungs is rapidly absorbed into the bloodstream (within minutes). Total renal excretion (0-24 hours) of unchanged active substance was 46% of the dose after intravenous administration, less than 1% after oral administration and approximately 3 to 13% after inhalation. Based on these data, the total systemic bioavailability of ipratropium bromide after oral administration and inhalation is 2%, 7 to 28%, respectively. Thus, the swallowed portion of the dose has no significant effect on the plasma concentration of the active substance.
Distribution.
Pharmacokinetic parameters characterizing the disposition of ipratropium were calculated based on its plasma concentration after intravenous administration. A rapid biphasic decline in plasma concentration is observed. The apparent volume of distribution at steady state (Vdss) is approximately 176 L (approximately 2.4 L/kg). The drug is poorly bound to plasma proteins (less than 20%). Preclinical data suggest that the quaternary amine ipratropium does not cross the placental or blood-brain barrier.
Metabolism.
After intravenous administration, approximately 60% of the dose is metabolized, probably in the liver by oxidation. The identified metabolites, which are formed by hydrolysis, dehydration or separation of the hydroxymethyl group from the tropic acid, show weak affinity for muscarinic receptors and are considered inactive.
Elimination.
The terminal elimination half-life is approximately 1.6 hours.
In a 6-day excretion balance study using radiolabeled drug, 72.1%, 9.3% and 3.2% of the dose of the labeled product (both unchanged and as metabolites) were recovered in the urine after intravenous, oral and inhalation administration, respectively. The faecal excretion rate was 6.3% after intravenous administration, 88.5% after oral administration and 69.4% after inhalation. Elimination of the drug after intravenous administration, as determined by radiolabeled drug, is mainly renal. The elimination half-life, as measured by radiolabeled drug (measured for parent compound and metabolites), is 3.6 hours.
Indication
Freeway® inhalation solution is intended for use as a bronchodilator in the maintenance therapy of bronchospasm, chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, as well as in bronchial asthma.
Contraindication
Hypersensitivity to atropine and its derivatives (such as ipratropium bromide), or to any of the excipients.
Interaction with other medicinal products and other types of interactions
Long-term use of Freeway® with other anticholinergics has not been studied. Therefore, long-term use of Freeway® with these drugs is not recommended.
Drugs that affect beta-adrenergic receptors and xanthine derivatives may enhance the bronchodilator effect.
Concomitant use of inhaled ipratropium bromide and beta-agonists may increase the risk of developing acute glaucoma in patients with a history of angle-closure glaucoma.
Application features
Hypersensitivity
Immediate hypersensitivity reactions may occur after administration of the medicinal product, as evidenced by rare cases of rash, urticaria, angioedema, swelling of the mucous membrane of the mouth and throat, bronchospasm and anaphylaxis.
Paradoxical bronchospasm
Like other inhaled medications, Freeway® may cause paradoxical bronchospasm, which may be life-threatening. In the event of paradoxical bronchospasm, discontinue use of the medication immediately and use alternative treatment.
Complications from the organs of vision
It is recommended to use the drug with caution in patients with a predisposition to the development of angle-closure glaucoma.
There have been a few reports of eye complications (such as mydriasis, increased intraocular pressure, angle-closure glaucoma, eye pain) resulting from ocular exposure to aerosol containing ipratropium bromide alone or in combination with beta2-agonists.
Eye pain or discomfort, blurred vision, halos around lights or colored spots in front of the eyes, in the presence of red eyes caused by conjunctival hyperemia and corneal edema, may be symptoms of acute angle-closure glaucoma. If any of the above symptoms occur in any combination, treatment with miotics should be initiated and a doctor should be consulted immediately.
Patients should be instructed on the correct use of Freeway®.
Do not allow the solution or the drug sprayed during inhalation to get into the eyes. It is recommended to inhale the drug sprayed using a nebulizer through the mouthpiece. In the absence of a mouthpiece, the drug can be inhaled through an inhalation mask, but it must fit tightly to the face. Patients with a tendency to develop glaucoma should take special care to protect their eyes.
Effects on the kidneys and urinary system.
Caution is recommended when using the drug in patients with urinary tract obstruction (e.g., prostatic hyperplasia or bladder neck stenosis).
Gastrointestinal motility disorders
Patients with cystic fibrosis may be more susceptible to gastrointestinal motility disorders.
Local action
The drug contains a preservative - benzalkonium chloride and a stabilizer - disodium edetate. In patients with respiratory hypersensitivity, these components may cause bronchospasm during inhalation.
Use during pregnancy or breastfeeding
Pregnancy
The safety of ipratropium bromide during pregnancy has not been established. The drug can be used during confirmed or suspected pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. Preclinical studies have not revealed any embryotoxic or teratogenic effects of ipratropium bromide when administered by oral or intranasal inhalation at doses significantly exceeding those recommended for human use.
Breast-feeding
It is not known whether the drug passes into breast milk. It is unlikely that a drug administered by inhalation would reach the infant in significant amounts. Caution should be exercised when Freeway® is administered to breastfeeding women.
There are no clinical data on the effect of ipratropium bromide on fertility. Preclinical studies conducted with ipratropium bromide did not reveal any negative effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies to determine the effect of the drug on the ability to drive a car and other mechanical devices have not been conducted. However, patients should be warned that during therapy with the drug Freeway®, side effects such as dizziness, accommodation disorders, mydriasis and blurred vision may occur. Caution should be exercised when driving or operating machinery. In the event of any of the adverse reactions, the patient should avoid performing potentially hazardous activities, such as driving or operating machinery.
Method of administration and doses
Doses
The dose should be selected individually for each patient. During treatment, patients should be under the supervision of a physician. The recommended daily dose should not be exceeded.
The patient should be informed that in the absence of a therapeutic effect from the use of the drug or in case of deterioration of the condition, he should consult a doctor who will prescribe a new treatment regimen. Urgent consultation of a doctor is necessary in case of sudden onset or increase in shortness of breath (dyspnea).
Unless otherwise prescribed by the doctor, it is recommended to use the drug in the following doses (20 drops = approximately 1 ml; 1 drop = 0.0125 ipratropium bromide anhydrous).
Supportive therapy:
Adults (including the elderly) and children aged 14 and over:
2.0 ml (40 drops = 0.5 mg) 3 - 4 times a day
Children aged 6 to 14 years:
Due to the lack of sufficient information on the use of the drug in this age group, inhalations at the dose indicated below should be carried out under the supervision of a physician:
1.0 ml (20 drops = 0.25 mg) 3 - 4 times a day
Children under 6 years of age:
Due to the lack of sufficient information on the use of the drug in this age group, inhalations at the dose indicated below should be carried out under the supervision of a physician:
0.4 - 1.0 ml (8 - 20 drops = 0.1 - 0.25 mg) 3 - 4 times a day.
Administration of the drug in a daily dose exceeding 2 mg for adults and children over 14 years of age, as well as 1 mg for children under 14 years of age, must be carried out under the supervision of a physician.
Method of application
The recommended dose of the drug should be diluted with 0.9% sodium chloride solution to a volume of 3-4 ml, poured into a nebulizer and inhaled until the solution is used up. The solution should be prepared immediately before each use; unused diluted solution should be discarded.
The dosage regimen may depend on the method of inhalation and the characteristics of the nebulizer. The duration of inhalation can be controlled by the volume of dilution of the solution.
Inhalations with Freeway® solution can be performed using various models of nebulizers available on the market. When using a centralized oxygen machine, inhalation is best performed with a solution flow rate of 6–8 liters per minute.
The drug can be used in combination with medications that thin phlegm and facilitate its excretion.
Freeway® and disodium cromoglicate should not be used simultaneously in the same nebulizer, as this may result in precipitation.
Children
The drug is used in pediatric practice. Children under 6 years of age should use it under the supervision of a physician.
Overdose
No symptoms characteristic of overdose have been observed. Given the wide therapeutic range and local administration of the drug, the occurrence of serious anticholinergic symptoms is unlikely. As with other anticholinergic drugs, the expected symptoms of overdose are: dry mouth, accommodation disorders and tachycardia.
Adverse reactions
Many of the adverse reactions listed below can be attributed to the anticholinergic properties of ipratropium bromide. Like all inhaled drugs, Freeway® may cause local irritation. Adverse reaction data were obtained from clinical trials and post-marketing surveillance.
The most common adverse reactions reported during clinical trials were: headache, throat irritation, cough, dry mouth, pharyngitis, gastrointestinal motility disorders (including constipation, diarrhea, and vomiting), nausea, and dizziness.
The frequency of adverse reactions is indicated according to the MedDRA classification: very common (> 1/10); common (> 1/100 to <1/10); uncommon (> 1/1000 to <1/100); rare (> 1/10,000 to <1/1,000); very rare (<1/10,000); unknown (frequency cannot be estimated from the available data).
Cardiovascular system
Uncommon: palpitations, supraventricular tachycardia.
Rare: atrial fibrillation, increased heart rate.
From the nervous system
Common: headache, dizziness.
From the organs of vision
Uncommon: blurred vision, mydriasis, increased intraocular pressure, glaucoma, eye pain, halos around light sources, conjunctival hyperemia, corneal edema.
Rare: accommodation disorders.
Common: throat irritation, cough.
Uncommon: bronchospasm, paradoxical bronchospasm, laryngospasm, laryngeal edema, dry throat.
Gastrointestinal tract
Common: dry mouth, nausea, gastrointestinal motility disorders.
Uncommon: diarrhoea, constipation, vomiting, inflammation of the oral mucosa, swelling of the oral cavity.
From the urinary system
Uncommon: urinary retention.
Skin and subcutaneous tissue disorders
Uncommon: skin rash, pruritus, angioedema.
Rare: urticaria.
On the part of the immune system
Uncommon: hypersensitivity, anaphylactic reactions.
Expiration date
2 years.
The shelf life after first opening the bottle is 6 months.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 30℃.
Keep out of reach of children.
Packaging
25 ml in a bottle with a dropper. 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
