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 corticosteroids), chronic obstructive pulmonary disease in adults.

Pharmacological effect

Pharmaceutical group:

glucocorticosteroid for local use.

Pharmaceutical action:

Flixotide – GCS for inhalation use. In recommended doses, it has a pronounced anti-inflammatory and antiallergic effect, which leads to a decrease in the severity of symptoms and a decrease in the frequency of exacerbations of diseases accompanied by airway obstruction (bronchial asthma, chronic bronchitis, emphysema).

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

In chronic obstructive pulmonary disease (COPD), the effectiveness of inhaled fluticasone propionate on lung function has been confirmed, which is characterized by a decrease in the severity of symptoms of the disease, the frequency and severity of exacerbations, a decrease in the need to prescribe additional courses of GCS in the form of tablets and an increase in the quality of life of patients.

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

The drug Flixotide restores the patient’s response to bronchodilators, making it possible to reduce the frequency of their use.
The therapeutic effect after inhaled use of fluticasone begins within 24 hours, reaches a maximum within 1-2 weeks or more after the start of treatment and persists for several days after discontinuation.

Pharmacokinetics:

Suction

After inhalation 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 can be swallowed, but its systemic effect is minimal due to the drug’s poor solubility in water and intensive “first pass” metabolism through the liver (the bioavailability of fluticasone propionate when taken orally is less than 1%).

There is a direct relationship between the inhaled dose and the systemic effect of fluticasone propionate.

Distribution

Plasma protein binding is 91%.

Fluticasone propionate has a large Vd – about 300 l.

Metabolism

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

Removal

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.

Special instructions

Flixotide is intended for the long-term treatment of bronchial asthma, and not for the relief of attacks. To relieve attacks, patients should be prescribed short-acting inhaled bronchodilators.

If the effectiveness of short-acting bronchodilators decreases or if more frequent use is necessary, the patient should consult a doctor.

An increased need for the use of short-acting inhaled beta2-adrenergic agonists indicates a worsening of the disease. In such cases, it is recommended to reconsider the patient’s treatment plan.

A sudden and progressive deterioration of bronchial asthma can pose a threat to the patient’s life, so in such situations it is necessary to urgently address the issue of increasing the dose of GCS.

Abruptly stopping treatment with Flixotide is not recommended.

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

With long-term use of any inhaled corticosteroids, especially in high doses, systemic effects may be observed, but the likelihood of their development is much lower than when taking corticosteroids orally. Possible systemic effects include decreased adrenal function, osteoporosis, growth retardation in children, cataracts, and glaucoma. Therefore, it is especially important that when a therapeutic effect is achieved, the dose of inhaled corticosteroids is reduced to the minimum effective dose that controls the course of the disease.

The transfer of patients suffering from hormone-dependent bronchial asthma from systemic corticosteroids to inhaled fluticasone requires special attention, since restoration of adrenal function takes a long time. Adrenal cortex function should be regularly monitored and caution should be exercised when reducing the dose of systemic corticosteroids.

A gradual reduction in the dose of systemic corticosteroids can begin approximately one week after the appointment of fluticasone. With a maintenance dose of prednisolone (or other corticosteroids in an equivalent dose) less than 10 mg/day. the dose reduction should not exceed 1 mg/day. and should be carried out at intervals of at least 1 week. With a maintenance dose of prednisolone more than 10 mg/day. (calculated per day) – in high doses, also at intervals of at least 1 week.

Some patients, during the period of reducing the dose of systemic corticosteroids, complain of general malaise against the background of stabilization or even improvement of respiratory function indicators. If there are no objective signs of adrenal insufficiency, patients should be persuaded to continue switching to inhaled GCS and gradual withdrawal of systemic GCS.

In some cases, individual high sensitivity to inhaled corticosteroids may be observed. The function of the adrenal cortex when prescribing fluticasone propionate in recommended doses, as a rule, remains within normal limits. The advantages of inhaled fluticasone propionate minimize the need for systemic corticosteroids. However, there may remain a possibility of developing side effects in patients who have previously received or periodically take GCS orally. During resuscitation or surgery, consultation with a specialist may be required to determine the degree of adrenal insufficiency. In such stressful situations, one should always take into account possible adrenal insufficiency and, if necessary, additionally prescribe corticosteroids.

Due to possible adrenal insufficiency, special caution should be exercised and regular monitoring of adrenal function indicators when transferring patients who have taken oral corticosteroids to treatment with inhaled fluticasone propionate. Discontinuation of systemic corticosteroids during inhaled fluticasone propionate should be gradual, and patients should carry a card indicating that they may require additional corticosteroids during periods of stress.

In rare cases, when transferring patients from taking systemic corticosteroids to inhaled therapy, conditions accompanied by hypereosinophilia (for example, Churg-Strauss syndrome) may occur. As a rule, this occurs during dose reduction or withdrawal of systemic corticosteroids, but a direct cause-and-effect relationship has not been established.

When transferring patients from taking systemic corticosteroids to inhalation therapy, concomitant allergic diseases (for example, allergic rhinitis, eczema), which were previously suppressed by systemic drugs, may also worsen. In such situations, it is recommended to carry out symptomatic treatment with antihistamines and/or topical drugs, incl. GCS for local use.

To prevent the development of candidiasis, you should rinse your mouth after using Flixotide; If necessary, local antifungal therapy can be prescribed throughout the entire treatment period.

To prevent hoarseness, it is recommended to rinse your mouth and throat with water immediately after inhalation.

If paradoxical bronchospasm develops, you should immediately stop administering Flixotide, assess the patient’s condition, conduct the necessary examination and, if necessary, prescribe other medications. Paradoxical bronchospasm should be treated immediately with a fast-acting inhaled bronchodilator.

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

Like most other inhalation aerosol products, this product may be less effective if the canister is refrigerated.

Use in pediatrics

The growth dynamics of children receiving inhaled corticosteroids for a long time should be regularly monitored.

Impact on the ability to drive vehicles and operate machinery

The effect of fluticasone propionate on the ability to drive a car and operate machinery is unlikely.

Active ingredient

Fluticasone

Composition

1 dose contains:

fluticasone 125 mcg,

excipients:

propellant tetrafluoroethane GR106642X (the product does not contain freon).

Contraindications

Hypersensitivity, acute bronchospasm, status asthmaticus (as a first-line remedy), bronchitis of non-asthmatic nature, children’s age (up to 1 year).

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

Side Effects

Candidiasis of the oral cavity and pharynx, hoarseness (after inhalation it is necessary to rinse the mouth and throat with water), paradoxical bronchospasm (requires discontinuation of the drug and continuation of therapy with other means);

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

Interaction

Since fluticasone propionate plasma concentrations are very low when administered via inhalation, interaction with other drugs is unlikely.

With the simultaneous use of fluticasone propionate and CYP3A4 enzyme inhibitors (for example, ketoconazole, ritonavir), the systemic effect of Flixotide may be enhanced (the use of such a combination requires caution).

Overdose

An acute overdose of the drug can lead to a temporary decrease in the function of the adrenal cortex, which usually does not require emergency treatment, because the function of the adrenal cortex is restored within a few days.

If Flixotide is taken in high doses for a long time, significant suppression of adrenal function is possible. Very rare reports have been received of the development of adrenal crisis in children receiving fluticasone propionate at a dose of 1 mg/day. and higher for several months or years. Such patients experienced hypoglycemia, depression of consciousness and convulsive states.

Acute adrenal crisis can develop against the background of the following conditions: severe trauma, surgery, infection, sharp reduction in the dose of fluticasone propionate.

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

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

2 years

Manufacturer

Glaxo Wellcome S.A., Spain