Instructions Flixotide Evohaler aerosol for inhalation dosed 50 mcg/dose canister 120 doses No. 1
Composition
active ingredient: fluticasone propionate;
1 dose contains fluticasone propionate 50 mcg or 125 mcg;
excipient: propellant HFA 134a.
Dosage form
Inhalation aerosol, metered.
Main physicochemical properties: white or almost white suspension.
Pharmacotherapeutic group
Antiasthmatic agents for inhalation use. Glucocorticoids. ATX code R03B A05.
Pharmacological properties
Pharmacodynamics.
Fluticasone propionate, when administered by inhalation at recommended doses, has a pronounced glucocorticoid anti-inflammatory effect in the lungs. This is manifested in a reduction in both symptoms and exacerbations of asthma with a decrease in the number and intensity of adverse reactions compared with systemic use of corticosteroids.
Pharmacokinetics.
The mean systemic bioavailability of Flixotide Evohaler in healthy volunteers was 28.6%. Systemic absorption occurs primarily through the respiratory system, initially rapidly and then over a prolonged period. The remainder of the inhaled dose may be swallowed.
Absolute oral bioavailability is very low (< 1%) due to 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
Preventive treatment of bronchial asthma
Adults
Mild asthma: patients who require intermittent symptomatic treatment with daily bronchodilators.
Moderate asthma: patients with unstable asthma or with worsening asthma on existing preventive therapy or bronchodilator therapy alone.
Severe asthma: Patients with severe chronic asthma and patients dependent on systemic corticosteroids for adequate control of symptoms. After initiation of inhaled fluticasone propionate, many such patients will be able to significantly reduce or completely discontinue oral corticosteroids.
Children
Prophylactic anti-asthma treatment, including when asthma symptoms are not controlled despite previous treatment with other anti-asthma drugs.
Contraindication
Hypersensitivity to any component 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.
In drug interaction studies with intranasal fluticasone propionate in healthy volunteers, ritonavir (a potent inhibitor of cytochrome P450 3A4) 100 mg twice daily was shown to increase plasma fluticasone propionate concentrations hundreds of times, resulting in significant decreases in serum cortisol concentrations. There is limited information on this interaction with inhaled fluticasone propionate, but this increase in plasma fluticasone propionate concentrations 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.
In a small study in healthy volunteers, the less potent CYP3A inhibitor ketoconazole increased fluticasone propionate concentrations after a single inhalation by up to 150%, resulting in a significant reduction in serum cortisol concentrations compared with fluticasone propionate alone. Concomitant use with other potent CYP3A inhibitors, such as itraconazole, is also expected to increase systemic fluticasone propionate concentrations and the risk of systemic effects. Caution should be exercised and prolonged use of this combination should be avoided if possible.
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.
It is necessary to periodically check the inhalation technique to ensure that pressing the valve coincides with inhalation for optimal delivery of the drug to the lungs.
During inhalation, it is advisable for the patient to sit or stand, as the inhaler is designed to be used in an upright position.
Sudden and progressive deterioration of asthma control is life-threatening and the need for increased corticosteroid dosage should be considered. If this risk arises, the patient should have daily peak flow measurements.
Flixotide Evohaler is not intended for the relief of acute symptoms when short-acting bronchodilators are required. Patients should be advised to carry their own reliever medication for acute asthma attacks.
Severe asthma requires constant medical monitoring, including determination of indicators of external respiratory function, since there is a risk of acute asthma attacks and even death in such patients. An increase in the frequency and dose of short-acting inhaled beta-2-agonists signals a gradual loss of asthma control. In case of a decrease in the effectiveness of short-acting bronchodilators or the need for their more frequent use, the patient should consult a doctor. In such situations, patients should undergo additional examination to determine the need for increased anti-inflammatory therapy (for example, increasing the dose of inhaled corticosteroids or prescribing a course of oral corticosteroids). In severe exacerbations of asthma, the usual therapy for this condition is 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 Flixotide to diabetic patients.
As with other inhaled medications, paradoxical bronchospasm with rapidly increasing dyspnea after inhalation may occur. In this case, Flixotide Evohaler should be discontinued, the patient should be evaluated, and alternative therapy should be instituted if necessary.
Systemic effects may occur with inhaled corticosteroids, particularly at high doses and 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 be reduced to the lowest possible 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 dose reduction. Symptoms are usually vague and may include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased level of consciousness, hypoglycemia, and seizures. Additional systemic corticosteroids may be required in the event of stress or surgery.
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, a pulmonologist should be consulted.
It is recommended that doses of more than 1000 mcg/day be delivered using a spacer device to reduce the risk of oral and throat side effects. However, since the drug is mainly absorbed through the lungs, the use of a spacer device in addition to an inhaler may increase the level of drug delivery to the lungs. This should be considered as it may potentially increase the risk of systemic side effects. A dose reduction may be necessary (see section 4.2).
The effect of inhaled fluticasone propionate is to minimise the need for oral steroids. However, after switching a patient from oral steroids to inhaled fluticasone propionate, the risk of adrenal dysfunction may persist for a long time. The degree of dysfunction in individual situations may require specialist assessment.
The possibility of adrenal insufficiency should be considered in emergency situations, including surgery and other stressful situations, and appropriate corticosteroid treatment should be considered.
Insufficient treatment efficacy or severe asthma exacerbation requires an increase in the dose of Flixotide and, if necessary, the administration of systemic steroids and/or antibiotics in the presence of infection.
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 other inhaled corticosteroids, Flixotide Evohaler should be administered with extreme caution to patients with active or latent pulmonary tuberculosis.
Treatment with Flixotide Evohaler should not be stopped suddenly.
Switching patients treated with oral corticosteroids to inhaled use.
Due to the possibility of adrenal suppression, the transfer of patients from oral corticosteroids to Flixotide Evohaler requires special attention, since the restoration of adrenal function weakened by prolonged systemic steroid therapy may require a long time.
Adrenal suppression may occur in patients treated with systemic steroids for prolonged periods or in high doses. Adrenal function should be monitored regularly in such patients and the dose of systemic steroids should be reduced with caution.
Gradual withdrawal of systemic steroids begins after about a week. Dose reductions correspond to the maintenance level of systemic steroids and occur at intervals of at least one week. In general, for a maintenance dose of prednisolone (or analogues) 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.
Some patients experience nonspecific worsening during the transition period, despite maintenance or even improvement in respiratory function. The transition from systemic steroids to inhaled fluticasone propionate should be continued unless objective symptoms of adrenal insufficiency appear.
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, or 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
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 through the mouth only.
Patients who have difficulty synchronizing breathing with pressing the valve are recommended to use a spacer (a device to facilitate the administration of inhaled medications).
Patients should be informed that inhaled Flixotide should be used regularly for prophylaxis, even in the absence of asthma attacks. The onset of therapeutic effect is observed after 4-7 days.
If the effectiveness of short-acting bronchodilators decreases or if they need to be used more frequently, the patient should consult a doctor.
The physician should bear in mind that 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.
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 children aged 16 years and over: 100-1000 mcg 2 times a day, usually 2 inhalations 2 times a day.
Due to the risk of systemic effects, doses above 500 mcg twice daily should only be prescribed to adult patients with severe bronchial asthma when improvement in lung function and/or symptom control is expected, or a reduction in the use of oral corticosteroids is expected (see sections "Special warnings and precautions for use" and "Adverse reactions").
Typical starting dose for adults
For patients with mild asthma, the typical starting dose is 100 mcg twice daily. For moderate to severe persistent asthma, the starting dose may be 250 to 500 mcg twice daily. Doses up to 1000 mcg twice daily may be given if necessary. Such doses should only be prescribed by a specialist in the treatment of asthma.
The dosage should be reduced to the minimum effective dose that allows effective control of the disease.
Typical starting dose for children ages 4 and up: 50-100 mcg 2 times a day.
In many children, asthma is well controlled with doses of 50-100 mcg twice daily.
For those patients for whom these doses are not sufficient to control the disease, the dose may be increased to 200 mcg twice daily. The maximum dose for children is 200 mcg twice daily.
The dosage should be reduced to the minimum effective dose that allows effective control of the disease.
Doses greater than 1000 mcg (500 mcg twice daily) should be administered through a spacer to reduce adverse reactions in the mouth and throat (see section "Special precautions for use").
Special patient groups
No dose adjustment is required for the treatment of elderly patients or patients with hepatic or renal insufficiency.
Instructions for using the inhaler
As with other inhaled medications, the therapeutic effect may be reduced if the canister cools. Canisters should not be broken, punctured or burned, even when empty.
Checking the inhaler
Before using the inhaler for the first time or after a break in use of more than one week, remove the mouthpiece cap by lightly pressing on it from the sides, shake the inhaler well and spray it into the air twice to make sure that it is working properly.
Using an inhaler
1. Remove the mouthpiece cap by pressing lightly on the sides.
2. Make sure that there are no foreign objects inside and outside the inhaler, including the mouthpiece.
3. Shake the inhaler thoroughly to remove any foreign object from the inhaler and to mix the contents of the inhaler evenly.
4. Hold the inhaler vertically between your thumb and all other fingers, with your thumb on the base of the inhaler below the mouthpiece.
5. Exhale as deeply as possible, then place the mouthpiece between your teeth and cover it with your lips without biting.
6. Starting to inhale through your mouth, press the top of the inhaler to spray Flixotide, while continuing to inhale slowly and deeply.
8. If further sprays are required, wait approximately 30 seconds, holding the inhaler vertically. Then follow steps 3-7.
9. Rinse your mouth with water and spit it out.
10. Replace the mouthpiece cap by pressing in the required direction until it clicks.
IMPORTANTLY:
Perform the steps described in points 5, 6 and 7 without rushing. It is important to start inhaling as slowly as possible before spraying. The first few times you should practice in front of a mirror. If a cloud of aerosol appears near the top of the inhaler or on the sides of your mouth, you must start the steps described in point 2 again. Immediately after use, close the mouthpiece with the cap, pressing it gently until it clicks. As with other inhalation drugs, the therapeutic effectiveness may be reduced when the canister cools. Do not disassemble, pierce or burn the canister, even after it has been completely used.
Cleaning
The inhaler should be cleaned at least once a week.
1. Remove the mouthpiece cap.
2. Do not remove the metal cylinder from the plastic case.
3. Wipe the inside and outside of the mouthpiece cap with a dry cloth.
4. Put the mouthpiece cap back in place.
DO NOT PUT THE METAL BALLOON IN WATER.
Children
Use for children aged 4 and over.
Overdose
When Flixotide Evohaler is used in doses exceeding the recommended ones, 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 a long time, significant suppression of adrenal function may occur. There have been isolated reports of acute adrenal crises occurring in children treated with higher than recommended doses (usually 1000 mcg and above) for a long time (several months or years). Symptoms observed in this case included hypoglycemia and the consequences of loss of consciousness and/or convulsions. Situations that can potentially provoke acute adrenal crisis include trauma, surgery, infections or abrupt dose reduction.
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").
Adverse reactions
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
Very common: candidiasis of the mouth and throat.
Some patients may develop oral and pharyngeal candidiasis (thrush). To prevent this, rinse your mouth after using Flixotide Evohaler. If necessary, a topical antifungal medication may be prescribed throughout the treatment period, while continuing to use Flixotide Evohaler.
Common: Pneumonia may develop in patients with COPD.
In clinical trials of patients with COPD treated with fluticasone propionate 500 micrograms (see section 4.8), 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.
Immune system
Hypersensitivity reactions have been reported with the following manifestations:
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.
Endocrine system
Very rare: possible systemic effects including (see section "Special warnings and precautions for use") Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineralization, cataracts and glaucoma.
Metabolism and digestive disorders
Very rare: hyperglycemia (see section "Special warnings and precautions for use").
Digestive system
Very rare: dyspepsia.
Musculoskeletal system
Very rare: arthralgia.
Psychiatric disorders
Very rare: restlessness, sleep disorders, behavioral changes including hyperactivity and agitation (mainly in children).
Frequency unknown: depression, aggression (mainly in children).
Respiratory system and chest
Common: hoarseness/dysphonia.
Very rare: paradoxical bronchospasm (see section "Special warnings and precautions for use").
Frequency unknown: nosebleeds.
Skin and subcutaneous tissue
Common: bruising.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 30 °C. Do not freeze. Protect from direct sunlight. Keep out of the reach of children.
Immediately after use, close the mouthpiece with the cap, gently pressing it until it clicks.
The cylinder is under pressure. Do not heat above 50°C.
Packaging
120 doses in an aerosol can with a metering valve; 1 can in a box.
Vacation category
According to the recipe.
Producer
Glaxo Wellcome Production, France.
Location of the manufacturer and its business address.
Industrial Zone No. 2, 23, rue Lavoisier, 27000 Evreux, France/ Zone Industrielle No. 2, 23, rue Lavoisier, 27000 Evreux, France.
