Flixotide, 125 mcg/dose aerosol 60 doses

Pharmaceutical group:

Glucocorticosteroid for topical use.

Pharmic action:

Flixotide is a GKS for inhaled use. In recommended doses it has a strong anti-inflammatory and anti-allergic effect, which leads to reduction of symptoms and decreases the frequency of exacerbations of diseases accompanied by airway obstruction (bronchial asthma, chronic bronchitis, emphysema).

Fluticasone propionate inhibits proliferation of mast cells, eosinophils, lymphocytes, macrophages, neutrophils, reduces production and release of inflammatory mediators and other biologically active substances (histamine, prostaglandins, leukotriens, cytokines).

In chronic obstructive pulmonary disease (COPD) the efficacy of inhaled fluticasone propionate on pulmonary function has been confirmed with a decrease in the severity and frequency of symptoms and exacerbations, a reduced need for additional courses of GCS in tablet form and increased quality of life.

The systemic action of fluticasone is minimal: at therapeutic doses it has practically no effect on the hypothalamic-pituitary-adrenal system.

The drug Flixotide restores the patient’s response to bronchodilators, allowing to reduce the frequency of their use.
Therapeutic effect after inhaled use of fluticasone begins within 24 h, reaches its maximum within 1-2 weeks or more after the start of treatment and lasts for several days after withdrawal.

Pharmacokinetics:

Absorption

After inhaled administration, the absolute bioavailability of fluticasone propionate is 10-30%, depending on the type of inhaler.

Systemic absorption occurs primarily in the lungs. Part of the inhaled dose may be swallowed, but its systemic effect is minimal due to the weak solubility of the drug in water and intense metabolism during “first passage” through the liver (the bioavailability of fluticasone propionate when taken orally is less than 1%).

There is a direct correlation between the amount of inhaled dose and the systemic effects of fluticasone propionate.

Distribution

The binding to plasma proteins is 91%.

Fluticasone propionate has a large Vd of about 300L.

Metabolism

Fluticasone propionate is metabolized in the liver with the participation of CYP3A4, with the formation of an inactive metabolite.

Fluticasone propionate has a high plasma clearance of 1150 ml/min. T1/2 is about 8 hours. Renal clearance is less than 0.2%. Less than 5% is excreted in the urine as a metabolite.

Indications

Bronchial asthma (basic anti-inflammatory therapy) in adults and children 1 year and older (including those with severe disease, with dependence on systemic GCS), chronic obstructive pulmonary disease in adults.

Active ingredient

Composition

1 dose contains:

fluticasone 125 mcg,

excipients:

Propellant tetrafluoroethane GR106642X (the drug contains no Freon).

How to take, the dosage

Flixotide is used by inhalation; after inhalation, the mouth should be rinsed with water.

Bronchial asthma. Adults and adolescents over 16 years old: 100-1000 mcg 2 times a day, depending on disease severity: mild form of asthma – 100-250 mcg, moderate form – 250-500 mcg, severe form – 500-1000 mcg. Depending on the individual response of the patient, the initial dose of Flixotide is either increased until clinical effect appears or reduced to the minimum effective dose.

Children over 4 years of age (in inhalation aerosol form only, dosed with 50 mcg of fluticasone in a single dose): recommended dose is 50-100 mcg 2 times daily.

Children from 1 to 4 years of age: (only in the form of 50 mcg fluticasone single-dose aerosol for inhalation): 100 mcg 2 times a day. Younger children require higher doses compared to older children due to reduced drug intake during inhalation administration (use of spacer, smaller bronchial lumen, intense nasal breathing).

Flixotide is administered using an inhaler through a spacer with a face mask (“Babyhaler”). Chronic obstructive pulmonary disease. Adults, 500 mcg twice daily.

Interaction

As plasma concentrations of fluticasone propionate are very low when administered by inhalation, interactions with other medicinal products are unlikely.

In concomitant use of fluticasone propionate and CYP3A4 enzyme inhibitors (e.g., ketoconazole, ritonavir) the systemic effects of Flixotide may be enhanced (use of this combination requires caution).

Special Instructions

Flixotide is intended for long-term treatment of bronchial asthma, not for seizure management. Patients should be prescribed short-acting inhaled bronchodilators to control attacks.

If the effectiveness of short-acting bronchodilators diminishes or if more frequent use is necessary, patients should see their physician.

An increased need for the use of short-acting inhaled beta2-adrenoceptor agonists indicates a worsening of the disease. In these cases, a review of the patient’s treatment plan is recommended.

The sudden and progressive worsening of bronchial asthma may be life-threatening; therefore, in these situations, an increase in the dose of GCS must be urgently addressed.

The abrupt discontinuation of Flixotide treatment is not recommended.

Particular caution should be exercised when treating patients with inhaled GCS with active or inactive pulmonary tuberculosis.
In case of severe exacerbation of bronchial asthma or insufficient effectiveness of current therapy the dose of inhaled fluticasone propionate should be increased and if necessary a drug from the group of systemic GCS and/or an antibiotic should be prescribed if infection develops.
It is recommended to check whether the patient knows how to use the inhaler correctly.

Long-term use of any inhaled GCS, especially in high doses, may result in systemic effects, but these are much less likely than with oral GCS. Possible systemic effects include decreased adrenal cortical function, osteoporosis, growth retardation in children, cataracts, glaucoma. Therefore, it is especially important that when a therapeutic effect is achieved, the dose of inhaled GCS be reduced to the lowest effective dose to control the course of the disease.

The conversion of patients with hormone-dependent bronchial asthma from systemic GCS to fluticasone inhalation requires special attention because it takes a long time to restore adrenal function. Adrenal function should be monitored regularly and care should be taken when reducing the dose of systemic GCS.

Gradual reduction of systemic GCS dosage may be initiated approximately one week after administration of fluticasone. If the maintenance dose of prednisolone (or other GCS equivalent dose) is less than 10 mg/day, dose reduction should not exceed 1 mg/day and should be performed at intervals of at least 1 week. If the maintenance dose of prednisolone is more than 10 mg/day. (in recalculation per day) – in high doses also at intervals of at least 1 week.

Some patients during dose reduction of systemic GCS complain of general malaise against the background of stabilization or even improvement of respiratory function. If there are no objective signs of adrenal insufficiency, patients should be encouraged to continue switching to inhaled GCS and gradually withdrawing systemic GCS.

In individual cases, individual hypersensitivity to inhaled GCS may be noted. Adrenal function in fluticasone propionate at recommended doses is usually within normal limits. The benefits of inhaled fluticasone propionate minimize the need for systemic GCS. However, there may still be the possibility of side effects in patients who have previously or intermittently received oral GCSs. When resuscitation or surgical interventions are performed, a specialist consultation may be required to determine the degree of adrenal insufficiency. Possible adrenal insufficiency should always be considered in these stressful situations and additional GCS should be prescribed if necessary.

In view of possible adrenal insufficiency, special care should be taken and adrenal function parameters should be monitored regularly if patients who were on oral GCS are switched to inhaled fluticasone propionate. Withdrawal of systemic GCS against inhaled fluticasone propionate should be done gradually, and patients should carry a card indicating that they may need additional GCS during a period of stress.

In rare cases, conditions accompanied by hypereosinophilia (e.g., Cerj-Strauss syndrome) may occur when patients are transferred from systemic GCS administration to inhaled therapy. This usually occurs during dose reduction or discontinuation of systemic GCSs, but a direct cause-and-effect relationship has not been established.

Accompanying allergic diseases (e.g., allergic rhinitis, eczema) that were previously inhibited by systemic medications may also worsen when patients are switched from systemic GCS to inhaled therapy. In such situations, symptomatic treatment with antihistamines and/or topical agents, including GKS for topical use, is recommended.

In order to prevent the development of candidiasis, mouthwash after using Flixotide; if necessary, topical antifungal therapy may be administered throughout the treatment period.

To prevent hoarseness of voice, it is recommended that immediately after inhalation, the mouth and throat be rinsed with water.

If paradoxical bronchospasm develops, Flixotide administration should be stopped immediately, the patient’s condition should be evaluated, the necessary examination should be performed, and other medications should be prescribed if necessary. Paradoxical bronchospasm should be treated immediately with a rapid-acting inhaled bronchodilator.

There are very rare reports of elevated blood glucose levels, and this should be kept in mind when prescribing fluticasone propionate for patients with diabetes mellitus.

Like most other aerosol-packed inhalers, this medication may be less effective when the can is refrigerated.

Pediatric use

The growth rate of children receiving inhaled GCSs over a long period of time should be monitored regularly.

Impact on driving and operating machinery

The effect of fluticasone propionate on driving and operating machinery is unlikely.

Contraindications

Hypersensitivity, acute bronchospasm, asthmatic status (as the primary means), bronchitis of non-asthmatic nature, childhood (under 1 year).

With caution – in liver cirrhosis, glaucoma, hypothyroidism, systemic infections (bacterial, fungal, parasitic, viral), osteoporosis, pulmonary tuberculosis, pregnancy and during lactation.

Side effects

Mouth and pharyngeal candidiasis, hoarseness (mouth and throat should be rinsed with water after inhalation), paradoxical bronchospasm (requires discontinuation of the drug, and continuation of therapy with other agents);

rarely – development of allergic reactions (skin rash, angioedema, dyspnea or bronchospasm, anaphylactic reactions); decreased adrenal function, osteoporosis, growth retardation in children, cataracts, increased intraocular pressure.

Overdose

An acute overdose of the drug may lead to a temporary decrease in adrenal cortical function, which usually does not require emergency therapy because adrenal function recovers within a few days.

If Flixotide is taken in high doses for a long time, significant suppression of adrenal cortical function is possible. There have been very rare reports of adrenal crisis in children receiving fluticasone propionate at a dose of 1 mg/day or higher for several months or years. Hypoglycemia, depression of consciousness and seizures have been reported in such patients.

Acute adrenal crisis may develop against the background of the following conditions: severe trauma, surgery, infection, and a sharp decrease in the dose of fluticasone propionate.

In cases where the patient receives a dose higher than the recommended dose, it should be gradually reduced.

Similarities