Instructions Nebufluzon suspension for inhalation 1 mg/ml single-dose container 2 ml No. 10
Composition
active ingredient: fluticasone propionate;
1 ml of suspension contains fluticasone propionate 1 mg;
Excipients: decamethoxine; polysorbate-80; sodium dihydrogen phosphate dihydrate; sodium hydrogen phosphate anhydrous; sodium chloride; water for injections.
Dosage form
Suspension for inhalation.
Main physicochemical properties: white opaque suspension that disperses easily.
Pharmacotherapeutic group
Antiasthmatic agents for inhalation use. Glucocorticoids. ATX code R03B A05.
Pharmacological properties
Pharmacodynamics
The glucocorticosteroid fluticasone propionate at recommended doses for inhalation has a powerful anti-inflammatory effect on the lungs, which leads to a reduction in the symptoms and frequency of asthma attacks.
Pharmacokinetics
Following inhalation, the systemic availability of nebulised fluticasone propionate in healthy volunteers is expected to be 8% compared to 26% for the metered dose inhaler. Systemic absorption occurs primarily via the respiratory tract, initially rapidly and then over a prolonged period. Any remaining inhaled dose in the mouth may be swallowed.
Absolute oral bioavailability is very low (< 1%) due to a combination of incomplete absorption from the gastrointestinal tract and extensive first-pass metabolism. 87–100% of an oral dose is excreted in the feces, up to 75% as the parent compound and the inactive major metabolite.
Drug safety data
Toxicological studies have shown only the effects typical of strong corticosteroids, but in doses that are many times higher than those indicated for therapeutic use. Studies on the effects of the drug on reproductive function and the presence of teratogenic properties of the drug have not revealed any new data. Fluticasone propionate does not have mutagenic activity in vitro and in vivo. Animal experiments have shown the absence of carcinogenic potential in the drug, as well as irritant and sensitizing properties.
Indication
Adults and adolescents aged 16 and over
Prophylactic use in severe asthma in patients requiring high doses of inhaled or oral corticosteroids. In patients treated with high doses of oral corticosteroids, to reduce or eliminate the use of oral corticosteroids.
Children and adolescents aged 4 to 16 years
Treatment of asthma exacerbations: Appropriate maintenance therapy can be supplemented by the use of a metered dose aerosol or dry powder inhaler.
Inhaled fluticasone propionate has a potent glucocorticoid anti-inflammatory effect in the lung. It reduces symptoms and exacerbations of asthma in patients previously treated with bronchodilators alone or in combination with other prophylactic agents. Short-term symptomatic exacerbations can generally be relieved with rapid-acting bronchodilators, but longer exacerbations require additional corticosteroid therapy as early as possible to control inflammation.
Contraindication
History of hypersensitivity to any of the components of the drug.
Interaction with other medicinal products and other types of interactions
Under normal conditions, low plasma concentrations of fluticasone propionate are achieved after inhalation administration due to extensive first-pass metabolism and high systemic clearance of the drug mediated by cytochrome P450 3A4 in the liver and intestine. Therefore, the likelihood of clinically significant drug interactions mediated by fluticasone propionate is very low.
Drug interaction studies with intranasal fluticasone propionate in healthy volunteers have shown that ritonavir (a potent inhibitor of cytochrome P450 3A4) 100 mcg twice daily can increase the plasma concentration of fluticasone propionate by hundreds of times, resulting in a significant decrease in serum cortisol concentration. There is limited information on this interaction with inhaled fluticasone propionate, but this increase in plasma fluticasone propionate concentration may occur. Cushing's syndrome and adrenal suppression have also been reported. Concomitant use of fluticasone propionate and ritonavir should be avoided unless the benefit outweighs the risk of systemic corticosteroid exposure.
Concomitant use of fluticasone propionate with other strong CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic adverse reactions.
Other CYP3A4 inhibitors cause a very small (erythromycin) and small (ketoconazole) increase in systemic exposure to fluticasone propionate without a significant decrease in serum cortisol concentrations. Such combinations should be avoided unless the expected benefit outweighs the potential increased risk of systemic corticosteroid adverse reactions, in which case patients should be monitored for systemic adverse events.
Application features
Treatment of bronchial asthma should be carried out according to a phased program, the patient's condition should be regularly monitored both clinically and by determining indicators of external respiratory function.
Sudden and progressive deterioration of asthma control is a potentially life-threatening condition and the need for increased corticosteroid dosage should be considered. If this risk arises, the patient should have daily peak flow measurements.
Nebufluzon is not intended for the relief of acute asthma attacks when rapid-acting and short-acting inhaled bronchodilators are required. Patients should be advised to carry such medications with them. Nebufluzon should be used for long-term preventive treatment.
Nebufluzon is not a drug that can replace injectable or oral corticosteroids in emergency conditions (for example, in severe, life-threatening asthma exacerbations).
Severe asthma requires constant medical monitoring, including determination of respiratory function indicators, as there is a risk of acute asthma attacks and even death in such patients.
Increasing the frequency and dose of short-acting inhaled beta-2-agonists indicates a gradual loss of asthma control. If the effectiveness of short-acting bronchodilators decreases or if more frequent use is required, the patient should consult a doctor. In such situations, patients should undergo additional evaluation to determine the need for increased anti-inflammatory therapy (e.g., increasing the dose of inhaled corticosteroids or prescribing a course of oral corticosteroids). In severe exacerbations of asthma, the usual therapy for this condition should be prescribed.
There have been isolated reports of increased blood glucose levels in both diabetic and non-diabetic patients (see section 4.8). This should be taken into account when prescribing Nebufluzon to diabetic patients.
As with other inhaled medications, paradoxical bronchospasm with rapidly increasing dyspnea after inhalation may occur. In this case, Nebufluzon inhalation should be discontinued immediately, the patient should be examined and, if necessary, alternative therapy should be prescribed.
Systemic effects may occur with high doses of inhaled corticosteroids over long periods of time, but are less likely than with oral steroids. Systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineralization, and, in rare cases, psychiatric disorders, behavioral changes including psychomotor hyperactivity, sleep disorders, restlessness, depression, and aggression (mainly in children). It is therefore important that the dose of inhaled corticosteroids is regularly reviewed and titrated to the lowest dose at which effective control of asthma symptoms is maintained.
Prolonged use of high doses of inhaled corticosteroids may cause adrenal suppression and acute adrenal crisis. Children under 16 years of age are at particular risk when using fluticasone doses exceeding those approved (usually ≥ 1000 mcg/day). Acute adrenal crisis may be precipitated by trauma, surgery, infection, or abrupt reduction in the dose of the drug. Symptoms are usually vague and may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased level of consciousness, hypoglycemia, and seizures. In case of stress or surgery, additional use of systemic corticosteroids may be necessary.
It is recommended that the growth of children receiving long-term treatment with inhaled corticosteroids be monitored regularly. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroids, if possible to the lowest dose that maintains effective control of asthma symptoms. In addition, the child should be consulted by a pediatric pulmonologist.
The effect of inhaled fluticasone propionate should reduce the need for oral steroids. However, when switching from oral steroids to inhaled fluticasone propionate, patients remain at risk of adrenal suppression. The potential for adverse reactions persists for some time. Such patients may require specialist advice to determine the extent of adrenal suppression before certain procedures. The possibility of residual adrenal suppression should be considered in emergency situations, including surgery and other stressful situations, and appropriate corticosteroid treatment should be considered.
Patients should receive doses of inhaled fluticasone propionate appropriate to the severity of their disease. The dosage should be reduced to the lowest effective dose that maintains effective disease control. Systemic steroids and/or antibiotics may be necessary if effective disease control is not achieved.
Switching from systemic steroid therapy to inhaled steroid therapy may sometimes unmask allergic conditions, such as allergic rhinitis or eczema, that were previously controlled by systemic steroids. These allergic manifestations should be treated symptomatically with antihistamines and/or topical agents, including topical corticosteroids.
As with all inhaled corticosteroids, special care is required in patients with active or latent pulmonary tuberculosis.
Treatment with Nebufluzon should not be stopped suddenly.
Switching patients treated with oral corticosteroids to inhaled use.
The transfer of patients treated with oral steroids to inhaled Nebufluzon and their subsequent treatment requires special attention, since the restoration of adrenal function weakened by prolonged systemic steroid therapy may require a long time.
Prolonged use of high doses of inhaled corticosteroids may cause adrenal suppression. Adrenal function should be monitored regularly in such patients. Doses of systemic steroids should be reduced with caution (see section 4.2).
Some patients experience nonspecific deterioration during the transition period, despite maintenance or even improvement in respiratory function. They should continue to switch from systemic steroids to inhaled fluticasone propionate treatment unless objective symptoms of adrenal insufficiency develop.
Patients who have discontinued oral steroid treatment but whose adrenal function remains impaired should carry a special card warning of the need for additional systemic steroid administration in stressful situations, such as acute asthma attacks, respiratory tract infections, significant intercurrent illnesses, surgery, and trauma.
Ritonavir may significantly increase the plasma concentrations of fluticasone propionate. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the benefit outweighs the risk of systemic corticosteroid exposure. There is also an increased risk of systemic exposure to fluticasone propionate when used concomitantly with CYP3A4 inhibitors (see section 4.5).
Vision impairment
Visual impairment may occur with systemic and topical corticosteroids. If a patient presents with symptoms such as blurred vision or other visual disturbances, they should be referred to an ophthalmologist for evaluation of possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported with systemic and topical corticosteroids.
Use during pregnancy or breastfeeding
Fertility
There are no data on the effect on human fertility. Animal studies have not shown any effect of fluticasone propionate on fertility.
Pregnancy
Experience with use during pregnancy in humans is limited.
When deciding whether to prescribe the drug during this period, the expected benefit to the mother should be weighed against the potential risk to the fetus. The results of a retrospective epidemiological study did not reveal an increased risk of major congenital malformations after exposure to fluticasone propionate during the first trimester of pregnancy compared with other inhaled corticosteroids.
Breast-feeding
It is currently not known whether fluticasone propionate is excreted in human milk, but based on the pharmacological profile of the drug, this is unlikely. The drug should be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus.
Ability to influence reaction speed when driving vehicles or other mechanisms
Any impact is unlikely.
Method of administration and doses
The drug is intended for inhalation use only.
Nebufluzon should be administered as an aerosol from a jet nebulizer. Since the delivery of the drug is affected by numerous factors, the recommendations of the nebulizer manufacturer should be followed.
It is generally not recommended to use Nebufluzon using ultrasonic nebulizers.
Patients should be advised that treatment with inhaled fluticasone propionate is prophylactic and therefore should be used regularly even in the absence of symptoms.
If the effectiveness of short-acting bronchodilators decreases or if they need to be used more frequently, the patient should consult a doctor.
The initial dose should be appropriate for the severity of the disease. The dosage may be increased until control is achieved or reduced to the minimum effective dose that allows effective control of the disease.
Adults and adolescents aged 16 years and over: 0.5–2 mg of suspension twice daily.
Fluticasone propionate is effective at a dose that is half the dose of other inhaled corticosteroids. For example, 100 mcg of fluticasone propionate is approximately equivalent to a 200 mcg dose of beclomethasone dipropionate (containing freon) or budesonide.
There is always a risk of systemic effects when using high doses of corticosteroids (see sections "Special warnings and precautions for use" and "Adverse reactions").
The initial dose of inhaled fluticasone propionate should be appropriate for the severity of the patient's disease.
The dosage should be reduced to the minimum effective dose that allows effective control of the disease.
Children and adolescents aged 4–16 years: 1 mg of suspension twice daily.
The dosage should be reduced to the minimum effective dose that allows effective control of the disease.
Certain groups of patients.
There is no need to change the dose for elderly patients or those with impaired liver and kidney function.
Switching patients treated with oral corticosteroids to inhaled use.
Gradual withdrawal of systemic steroids begins after about a week. Dose reductions should be consistent with the maintenance level of systemic steroids and occur at intervals of at least one week. In general, for a maintenance dose of prednisolone (or analogue) of 10 mg per day or less, dose reductions should not be greater than 1 mg per day at intervals of at least one week. For maintenance doses of prednisolone exceeding 10 mg per day, dose reductions of more than 1 mg per day at intervals of at least one week are permissible, with extreme caution.
Nebufluzon should not be administered as an injection.
It is useful to administer the drug through a mouthpiece in order to avoid the development of atrophic changes in the facial skin, which can occur with prolonged use of a face mask.
When using a mask, the skin of the face exposed to the drug must be protected with a protective cream or by washing thoroughly after use.
Instructions for use of Nebufluzon
You should read the instructions from the nebulizer manufacturer.
Before use, make sure that the contents of the container are well mixed. Holding the container horizontally by the edge on which the marking is located, shake it several times from the other edge. Repeat this process several times until the contents are completely mixed. To open the container, turn the cap located on its top.
If necessary, the drug can be diluted with sodium chloride solution. Unused solution from the nebulizer container cannot be reused. It should be destroyed.
Children
Use for children aged 4 and over.
Overdose
When using Nebufluzon in doses exceeding the recommended, acute overdose may occur, manifested by temporary suppression of adrenal function. This does not require emergency care, since adrenal cortex function is restored after a few days, as confirmed by measuring the level of cortisol in the blood plasma.
However, when doses higher than recommended are used for prolonged periods, some suppression of adrenal function may occur, and adrenal reserve may need to be checked.
In case of overdose, therapy can be continued at doses necessary to control asthma symptoms. Patients treated with doses higher than recommended should be under special medical supervision and the dose of the drug should be reduced gradually (see section "Special instructions").
Side effects
The following adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1,000 and < 1/100), rare (≥ 1/10,000 and < 1/1,000), very rare (< 1/10,000) and not known (frequency cannot be estimated from the available data), including isolated reports. Very common, common and uncommon adverse reactions are mainly based on clinical trials. Rare and very rare adverse reactions are mainly collected spontaneously.
Infections and infestations
Some patients may develop oral and pharyngeal candidiasis (thrush). To prevent this, rinse your mouth after using Nebufluzon in the form of inhalation through a nebulizer. If necessary, prescribe an antifungal drug topically throughout the entire treatment period, while continuing to use Nebufluzon.
Common: Pneumonia may develop in patients with COPD (chronic obstructive pulmonary disease).
In clinical trials of patients with COPD treated with fluticasone propionate 500 mcg, an increased incidence of pneumonia was reported. Physicians should be alert to the possible development of pneumonia in patients with COPD, as the clinical symptoms of pneumonia and COPD exacerbations often overlap.
Rare: esophageal candidiasis.
On the part of the immune system
Hypersensitivity reactions with the following manifestations have been reported.
Uncommon: cutaneous hypersensitivity reactions.
Very rare: angioedema (mainly of the face and oropharynx), respiratory symptoms (dyspnea and/or bronchospasm) and anaphylactic reaction.
Organs of vision
Frequency unknown: blurred vision.
From the endocrine system
Systemic effects are possible, which very rarely include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineralization, cataracts and glaucoma (see section "Special warnings and precautions for use").
Metabolic disorders, metabolism
Very rare: hyperglycemia (see section "Special warnings and precautions for use").
From the digestive system
Very rare: dyspepsia.
Musculoskeletal and connective tissue disorders
Very rare: arthralgia.
Mental disorders
Very rare: restlessness, sleep disorders, behavioral changes, including hyperactivity and agitation (mainly in children).
Frequency unknown: depression, aggression (mainly in children).
Respiratory and thoracic disorders
Common: hoarseness of voice.
In some patients, inhaled fluticasone propionate may cause hoarseness, in which case gargling with water immediately after inhalation may be helpful.
Very rare: paradoxical bronchospasm (see section "Special warnings and precautions for use").
Frequency unknown: nosebleeds.
Skin and subcutaneous tissue disorders
Common: bruising.
Expiration date
3 years.
Storage conditions
Store out of the reach of children at a temperature not exceeding 25 ° C. Do not allow freezing and exposure to direct sunlight.
Opened containers should be stored in the refrigerator and used within 12 hours of opening.
Store in an upright position.
Packaging
2 ml in a single-dose container; 10 containers in a package; 1 package in a cardboard pack.
Vacation category
According to the recipe.
Producer
LLC "Yuria-Pharm".
Location of the manufacturer and address of its place of business
Ukraine, 18030, Cherkasy region, Cherkasy city, Kobzarska st., 108. Tel.: (044) 281-01-01.
