Active ingredients: Fluticasone (fluticasone propionate)
FLIXOTIDE 100 mcg Powder for inhalation
FLIXOTIDE 250 mcg Powder for inhalation
FLIXOTIDE 500 mcg Powder for inhalation
Flixotide package inserts are available for pack sizes: - FLIXOTIDE 100 mcg Powder for inhalation, FLIXOTIDE 250 mcg Powder for inhalation, FLIXOTIDE 500 mcg Powder for inhalation
- FLIXOTIDE 500 mcg / 2 ml Suspension to be nebulised
- FLIXOTIDE 50 mcg Pressurized inhalation suspension, FLIXOTIDE 125 mcg Pressurized inhalation suspension, FLIXOTIDE 250 mcg Pressurized inhalation suspension
Why is Flixotide used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Other drugs for obstructive respiratory tract syndromes by aerosols - Glycocorticoids.
THERAPEUTIC INDICATIONS
Control of the evolution of asthmatic disease and bronchostenosis conditions.
Contraindications When Flixotide should not be used
Hypersensitivity to the active substance or to any of the excipients (see "Composition").
Generally contraindicated in pregnancy and lactation (see "Special warnings").
Precautions for use What you need to know before taking Flixotide
The treatment of asthma must normally be performed within the framework of a therapeutic plan adapted to the severity of the disease; the patient's response to therapy should be verified both clinically and by pulmonary function tests, when available.
The need for rapid-acting inhaled beta2-agonists more frequently indicates worsening asthma control; in this circumstance the patient's treatment plan must be modified.
Sudden and progressive aggravation of asthma is potentially life-threatening and consideration should be given to increasing the dosage of corticosteroids. In patients considered at risk, daily peak flow monitoring is recommended.
Systemic effects may occur with inhaled corticosteroids, particularly when prescribed in high doses for prolonged periods. These effects are less likely to occur than with oral corticosteroid treatment. Possible systemic effects include Cushing's syndrome, Cushingoid aspect, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts and glaucoma and, rarely, a range of psychological and behavioral effects including psychomotor hyperactivity may occur. , irritability, sleep disturbances, anxiety, depression, aggression, behavioral disturbances (predominantly in children). It is important to take the dose as directed in the package leaflet or as prescribed by your doctor. You should not increase or decrease the dose without first consulting your doctor. There have been very rare cases of acute adrenal crisis in boys exposed to higher than recommended doses (approximately 1000 micrograms / day, when administered by inhalation with pressurized suspension, or equivalent doses of other inhaled corticosteroids or other forms of fluticasone propionate) for extended periods (several months or years).
It is recommended that the height of children receiving prolonged inhaled corticosteroid therapy is regularly monitored.
Due to the possibility of insufficient adrenal response, patients previously treated with oral steroids who are transferred to inhaled fluticasone propionate therapy should be treated with particular care and adrenal function monitored regularly, discontinuation of systemic steroid therapy should be gradual and patients should be advised to carry a marker indicating that they may require supplemental corticosteroid therapy during times of stress.
The possibility of an insufficient adrenal response in emergency situations (including surgery) and also in elective surgeries likely to cause stress should always be borne in mind, especially in patients taking high doses for prolonged periods. Additional corticosteroid treatment appropriate to the clinical situation should be considered (see "Overdose").
Replacing systemic corticosteroid therapy with inhalation therapy may reveal allergies such as allergic rhinitis or eczema that were previously masked by systemic drugs.
Treatment with fluticasone propionate should not be stopped abruptly.
There have been very rare reports of increases in blood glucose levels (see "Undesirable Effects") and this should be taken into consideration when prescribing the drug to patients with a history of diabetes mellitus.
As with all inhaled corticosteroids special care is needed in patients with active or dormant forms of pulmonary tuberculosis.
Cases of clinically significant drug interactions have been reported during post-marketing use in patients treated with fluticasone propionate and ritonavir resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risks of systemic corticosteroid side effects occurring (see "Interactions").
As with other drugs administered by inhalation, the possibility of paradoxical bronchospasm with increased wheezing immediately after taking the drug should be considered. In this case, immediately take a fast acting bronchodilator. discontinue fluticasone propionate therapy immediately, re-evaluate the patient and institute alternative therapy if necessary (see "Undesirable Effects").
There has been an increase in reports of pneumonia in studies of chronic obstructive pulmonary disease (COPD) patients receiving fluticasone propionate 500 micrograms (see Side Effects). Physicians should be vigilant about the possible development of pneumonia in COPD patients as the characteristics pneumonia and exacerbation clinics often overlap
Interactions What medications or foods may change the effect of Flixotide
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Under normal circumstances, low plasma concentrations of fluticasone propionate are obtained following inhaled administration due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the intestine and liver. Interactions are therefore unlikely. clinically significant drug mediated by fluticasone propionate.
An interaction study conducted in healthy volunteers has shown that ritonavir (a very potent inhibitor of cytochrome P450 3A4) can significantly increase plasma concentrations of fluticasone propionate, resulting in significantly reduced serum cortisol concentrations.
During post-marketing use, cases of clinically significant drug interactions have been reported in patients treated with intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. .
Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risks of systemic corticosteroid side effects.
Studies have shown that other cytochrome P450 3A4 inhibitors produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate with no notable reductions in serum cortisol concentrations. Nevertheless, caution is advised when potent inhibitors of cytochrome P450 3A4 (eg ketoconazole) are administered concomitantly as there is a potential for increased systemic exposure to fluticasone propionate.
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
There are no adequate and controlled studies of fluticasone propionate in pregnant women. The effect of fluticasone propionate on pregnancy in women is not known. Information on the tolerability of fluticasone propionate in pregnancy is still limited.
Animal studies to evaluate any interference of fluticasone propionate on reproductive function have shown only those effects characteristic of glucocorticoids at systemic exposure levels far in excess of those observed at the recommended therapeutic inhaled dose.
Genotoxicity tests did not show mutagenic potential of the molecule
However, as with other drugs, administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother outweighs the possible risks to the fetus.
It is unknown whether fluticasone propionate is excreted in human breast milk. Following subcutaneous administration in rats, the presence of fluticasone propionate was found in breast milk at measurable plasma concentrations. However, plasma levels are likely to be low in patients receiving fluticasone propionate at recommended inhaled doses.
Effects on ability to drive and use machines
Fluticasone propionate is unlikely to affect the ability to drive and use machines.
Important information about some of the ingredients
FLIXOTIDE DISKUS contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Flixotide: Posology
Fluticasone propionate should only be administered by oral inhalation.
The content of each dose is inhaled directly from the special multidose inhaler (DISKUS) which allows the inhalation of the drug even to those patients who are unable to use a pressurized aerosol correctly.
Since inhalation therapy with fluticasone propionate is preventive, drug administration should be initiated even in the absence of evident symptoms and should be continued even after the symptoms have resolved.
Patients must be informed that the drug's effectiveness is not immediate and therefore it must be taken regularly; the onset of the therapeutic effect is between 4 and 7 days, although, in some cases, an improvement may occur as early as within the first 24 hours in patients not previously treated with inhaled steroids.
The dosage of fluticasone propionate should be adapted to the individual patient in relation to the severity of the asthma and the phase of therapy.
Once the patient's respiratory function is stabilized, the daily dose should be gradually reduced, according to individual response, until the minimum effective maintenance dose is reached.
If the patient notices a decrease in the efficacy of the fast-acting beta2-agonists or a higher frequency of their use, it is necessary to seek medical attention.
Treatment with fluticasone propionate should not be stopped abruptly.
There is no need to reduce the drug dose in elderly patients or patients with hepatic or renal insufficiency.
Adults
The standard dose is 200 micrograms per day, divided into two doses of 100 micrograms each.
The dosage can be increased up to 400 micrograms per day.
The starting dose can subsequently be adjusted until control is achieved, or reduced to the lowest effective dose, according to individual response.
The prescribing physician should be aware that fluticasone propionate is as effective as other inhaled steroids at a daily dose in approximately half micrograms. For example, 100 micrograms of fluticasone propionate is approximately equivalent to a 200 microgram dose of beclomethasone dipropionate or budesonide.
The efficacy and tolerability profile of fluticasone propionate allow to treat with this inhaled steroid even patients with severe forms who often have to resort to therapy with oral steroids.
In these patients, fluticasone propionate at a maximum dose of 2000 micrograms per day may allow adequate disease control by drastically reducing the use of oral steroids. During exacerbations, doses of 2000 micrograms per day of fluticasone propionate can replace in some cases, oral steroid cycles.
Children over 4 years old
The standard dose is 100 micrograms per day, divided into two doses of 50 micrograms each.
The dosage can be increased up to 200 micrograms per day.
For those patients whose asthma is not sufficiently controlled, an additional benefit can be obtained by increasing the dose up to 200 micrograms twice daily.
Therapy should be initiated at a dose appropriate to the severity of the disease.
The dose may subsequently be adjusted until control is achieved, or reduced to the lowest effective dose, according to individual response.
Children from 1 to 4 years
The inhalation powder pharmaceutical form is not suitable for children aged 1 to 4 years; as regards the dosage of the drug in this age group, refer to the information for FLIXOTIDE Pressurized suspension for inhalation.
The maximum authorized dose in children is 200 micrograms twice daily.
Instructions for use and handling
FLIXOTIDE must be inhaled by means of DISKUS inhalers in molded plastic material each containing a strip strip in which individual alveoli ("blister"), regularly spaced, are arranged, each of which contains a dose (100 - 250 - 500 micrograms) of powder inhalation of fluticasone propionate dispersed in lactose.
FLIXOTIDE - Inhalation powder in DISKUS inhaler
DISKUS INFORMATION
The DISKUS, once removed from the box, is in the "closed" position.
DISKUS contains 60 individually protected doses of the drug powder.
Each dose is carefully measured and hygienically protected. The DISKUS requires no maintenance and is not rechargeable.
The dose indicator on the top of the DISKUS shows the number of doses still available.
Numbers from 5 to 0 are in RED to indicate that only a few doses remain.
The DISKUS is easy to use.
To take a dose of the drug, follow the four simple steps below:
1. Opening
2. Preparing the dose
3. Inhalation
4. Closing
HOW THE DISKUS WORKS
By sliding the lever of the DISKUS, a small hole is opened in the mouthpiece and a dose is prepared ready to be inhaled. When the DISKUS is closed, the lever automatically returns to its original position, ready to prepare the next dose of drug.
The outer cover protects the DISKUS when not in use.
1. Opening
To open the DISKUS, hold the outer part with one hand and place the thumb of the other hand on the recess. Push with your thumb while rotating the inside of the device until you hear a click.
2. Preparing the dose
Hold the DISKUS with the mouthpiece facing the user. Slide the lever forward until it clicks. The DISKUS is now ready for use.
Each time the lever is slid, a dose is made available for inhalation as shown by the dose indicator.
Use the lever only when you have to inhale the drug so as not to waste doses.
3. Inhalation
Read this section carefully before inhaling.
Keep the DISKUS away from your mouth. Breathe out as deeply as possible. Never blow into the DISKUS.
Put the mouthpiece between your lips.
Inhale deeply and regularly through the DISKUS and not through the nose.
Remove the DISKUS from your mouth.
Hold your breath for about 10 seconds or as long as possible.
Breathe out slowly.
4. Closing
To close the DISKUS, place your thumb in the recess and slide it back as far as it will go.
When the DISKUS is closed, it produces a sharp closing sound. This will automatically return the lever to its original position.
The DISKUS is now ready to be used again.
If two inhalations have been prescribed, it is necessary to close the DISKUS after the first inhalation and then repeat steps 1 to 4.
ATTENTION: keep the DISKUS dry
Keep the DISKUS closed when not in use
Never blow into the DISKUS
Only slide the lever when you are ready to take the drug
Inhale from the DISKUS with your mouth only
Do not exceed the recommended dose
Overdose What to do if you have taken too much Flixotide
In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of FLIXOTIDE, ask your doctor or pharmacist.
Acute inhalation of the drug in higher than recommended doses may lead to temporary suppression of the hypothalamus-pituitary-adrenal axis. This does not normally require the institution of emergency interventions since adrenal function typically returns to normal within a few days.
If doses higher than those approved are used for prolonged periods, significant adrenal suppression may occur. Monitoring of the adrenal reserve may be necessary. There have been very rare cases of acute adrenal crisis in children exposed to higher than recommended doses (typically 1000 micrograms / day and above) for prolonged periods (several months or years); manifestations observed included hypoglycemia and sequelae of decreased consciousness and / or convulsions.
Situations that can potentially trigger an acute adrenal crisis include exposure to trauma, surgery, infection, or any rapid reduction in dosage.
Patients treated with doses higher than those approved should be closely monitored and the dose reduced gradually
Side Effects What are the side effects of Flixotide
Like all medicines, FLIXOTIDE can cause side effects, although not everybody gets them.
The undesirable effects are listed below by organ, system / system and by frequency. Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100 to
Infections and infestations
Very common: candidiasis of the mouth and throat.
Oropharyngeal candidiasis (thrush) may occur in some patients. Such patients may benefit from rinsing their mouth with water after taking the drug. Symptomatic candidiasis can be treated with topical antifungal therapy without stopping the use of fluticasone propionate.
Common: pneumonia (in COPD patients)
Very rare: oesophageal candidiasis.
Disorders of the immune system
Hypersensitivity reactions manifesting as follows have been reported:
Uncommon: skin hypersensitivity reactions.
Very rare: angioedema (mainly edema of the face and oropharynx), respiratory symptoms (dyspnoea and / or bronchospasm) and anaphylactic reactions.
Endocrine pathologies
Possible systemic effects include (see "Precautions for" use "):
Very rare: Cushing's syndrome, Cushingoid appearance, adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma.
Metabolism and nutrition disorders
Very rare: hyperglycaemia.
Psychiatric disorders
Very rare: anxiety, sleep disturbances, and behavioral disturbances, including psychomotor hyperactivity and irritability (predominantly in children).
Not known: depression and aggression (predominantly in children).
Respiratory, thoracic and mediastinal disorders
Common: hoarseness. Hoarseness may occur in some patients; even in these cases it may be advantageous to rinse the mouth with water immediately after inhalation.
Very rare: paradoxical bronchospasm (see "Precautions for use").
Skin and subcutaneous tissue disorders
Common: bruises Compliance with the instructions contained in the package leaflet reduces the risk of side effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Conservation rules
Store in a dry place
Store in the original package to protect the medicine from moisture.
The DISKUS is sealed with a protective laminate cover which only needs to be opened when the medicinal product is used for the first time. Once opened, the protective laminate envelope must be discarded
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children
COMPOSITION
FLIXOTIDE 100 mcg
Powder for inhalation
One serving contains:
Active ingredient: fluticasone propionate 100 mcg
Excipients: lactose (which contains milk proteins)
FLIXOTIDE 250 mcg Powder for inhalation
One serving contains:
Active ingredient: fluticasone propionate 250 mcg
Excipients: lactose (which contains milk proteins)
FLIXOTIDE 500 mcg Powder for inhalation
One serving contains:
Active ingredient: fluticasone propionate 500 mcg
Excipients: lactose (which contains milk proteins)
PHARMACEUTICAL FORM AND CONTENT
Inhalation powder in 60-dose DISKUS inhaler.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
FLIXOTIDE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
FLIXOTIDE 125 mcg - Pressurized suspension for inhalation
A pressurized container of 120 puffs contains:
Active ingredient: fluticasone propionate (125 mcg per actuation) 15.00 mg
FLIXOTIDE 250 mcg - Pressurized suspension for inhalation
A pressurized container of 120 puffs contains:
Active ingredient: fluticasone propionate (250 mcg per supply) 30.00 mg
FLIXOTIDE 50 mcg - Pressurized suspension for inhalation
A pressurized container of 120 puffs contains:
Active ingredient: fluticasone propionate (50 mcg per actuation) 6.00 mg
FLIXOTIDE 250 mcg - Powder for inhalation in DISKUS inhaler with 60 dose strips
One serving contains:
Active ingredient: fluticasone propionate 250 mcg
Excipients: lactose
FLIXOTIDE 500 mcg - Powder for inhalation in DISKUS inhaler with 60 dose strips
One serving contains:
Active ingredient: fluticasone propionate 500 mcg
Excipients: lactose
FLIXOTIDE 100 mcg - Powder for inhalation in DISKUS inhaler with 60 dose strips
One serving contains:
Active ingredient: fluticasone propionate 100 mcg
Excipients: lactose
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Pressurized suspension for inhalation. Powder for inhalation.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Control of the evolution of asthmatic disease and bronchostenosis conditions.
04.2 Posology and method of administration
Fluticasone propionate should only be administered by oral inhalation.
Patients should be advised of the prophylactic nature of inhaled fluticasone propionate therapy and that it should be used regularly even after symptoms resolve.
Patients must be informed that the drug's effectiveness is not immediate and therefore it must be taken regularly; the onset of the therapeutic effect is between 4 and 7 days, although, in some cases, an improvement may occur as early as within the first 24 hours in patients not previously treated with inhaled steroids.
If the patient notices a decrease in the efficacy of the fast-acting beta2-agonists or a higher frequency of their use, it is necessary to seek medical attention.
The dosage of fluticasone propionate should be adapted to the individual patient in relation to the severity of asthma and the stage of therapy.
Once the patient's respiratory function is stabilized, the daily dose should be gradually reduced, according to individual response, until the minimum effective maintenance dose is reached.
Treatment with fluticasone propionate should not be stopped abruptly.
There is no need to reduce the drug dose in elderly patients or patients with hepatic or renal insufficiency.
FLIXOTIDE - Pressurized suspension for inhalation
As with all drugs, administered by inhalation, by means of a dosed aerosol, it is advisable to take the dose in two inhalations.
In patients with poor coordination of movements, appropriate spacer devices can be used.
FLIXOTIDE - Powder for inhalation
The content of each dose is inhaled directly from the special multidose inhaler (DISKUS) which allows the inhalation of the drug even to those patients who are unable to use a pressurized aerosol correctly.
Adults
The standard dose is 200 mcg per day, divided into two doses of 100 mcg each.
The dosage can be increased up to 400 mcg per day.
The starting dose can subsequently be adjusted until control is achieved, or reduced to the lowest effective dose, according to individual response.
The prescribing physician should be aware that fluticasone propionate is as effective as other inhaled steroids at approximately one-half mcg daily dose. For example, 100 mcg of fluticasone propionate is approximately equivalent to a dose of 200 mcg of beclomethasone dipropionate (in CFC-containing formulations) or budesonide.
The efficacy and tolerability profile of fluticasone propionate allow to treat with this inhaled steroid even patients with severe forms who often have to resort to therapy with oral steroids. In these patients fluticasone propionate at a maximum dosage of 2000 mcg per day can allow adequate disease control by drastically reducing the use of oral steroids.
During exacerbations, doses of 2000 mcg per day of fluticasone propionate can replace oral steroid cycles in some cases.
Children over 4 years old
The standard dose is 100 mcg per day, divided into two doses of 50 mcg each.
The dosage can be increased up to 200 mcg per day.
For those patients whose asthma is not sufficiently controlled, an additional benefit can be obtained by increasing the dose up to 200 micrograms twice daily.
Therapy should be initiated at a dose appropriate to the severity of the disease.
The dose may subsequently be adjusted until control is achieved, or reduced to the lowest effective dose, according to individual response.
It should be noted that only the 50 mcg pressurized inhalation suspension is suitable for administration of this dose.
The pressurized inhalation suspension may not allow the administration of the required pediatric dose; if so, consider administering powdered fluticasone propionate by inhalation via the DISKUS inhaler.
Children from 1 to 4 years
FLIXOTIDE - Pressurized suspension for inhalation
100 mcg twice / day administered by means of a spacer device equipped with a face mask (spacer device for pediatric use).
Administration of fluticasone propionate to younger children is beneficial in the control of frequent and persistent asthma symptoms and is indicated only if symptoms are not adequately controlled by once daily beta agonist therapy.
The maximum authorized dose in children is 200 mcg twice daily.
Clinical studies conducted in children aged 1 to 4 years have shown that optimal control of asthma symptoms is achieved by administering 100 mcg twice a day. Younger children need higher doses than older children. the reduced efficiency of drug distribution resulting from the smaller caliber of the airways, the need to use a spacer device and the increase in the amount of nasal inhalation.
Diagnosis and treatment of asthma must be monitored constantly.
FLIXOTIDE - Powder for inhalation
The inhalation powder pharmaceutical form is not suitable for children aged 1 to 4 years; as regards the dosage of the drug in this age group, refer to the information for FLIXOTIDE Pressurized suspension for inhalation.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Generally contraindicated in pregnancy and lactation (see section 4.6).
04.4 Special warnings and appropriate precautions for use
The treatment of asthma must normally be performed within the framework of a therapeutic plan adapted to the severity of the disease; the patient's response to therapy should be verified both clinically and by pulmonary function tests, when available.
The need for rapid-acting inhaled beta2-agonists more frequently indicates worsening asthma control; in this circumstance the patient's treatment plan must be modified.
Sudden and progressive aggravation of asthma is potentially life-threatening and consideration should be given to increasing the dosage of corticosteroids. In patients considered at risk, daily peak flow monitoring is recommended.
Systemic effects may occur with inhaled corticosteroids, particularly when prescribed in high doses for prolonged periods.These effects are less likely to occur than with oral corticosteroid treatment. Possible systemic effects include Cushing's syndrome, Cushingoid aspect, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataracts, glaucoma and, more rarely, a range of psychological or behavioral effects including psychomotor hyperactivity, irritability , sleep disturbances, anxiety, depression, aggression or behavior disturbances (particularly in children). It is therefore important that the dose of inhaled corticosteroid is the lowest possible dose with which effective control of asthma is maintained. There have been very rare cases of acute adrenal crisis in boys exposed to higher than recommended doses (approximately 1000 mcg / day, when administered by inhalation with pressurized suspension, or equivalent doses of other inhaled corticosteroids or other forms of fluticasone propionate) for prolonged periods (several months or years) (see section 4.8).
It is recommended that the height of children receiving prolonged inhaled corticosteroid therapy is regularly monitored.
Compared to the majority of patients, some people may be more sensitive to the effects of inhaled corticosteroids.
Due to the possibility of insufficient adrenal response, patients previously treated with oral steroids who are transferred to inhaled fluticasone propionate therapy should be treated with particular care, adrenal function should be monitored regularly, discontinuation of systemic steroid therapy should be gradual and patients should be advised to carry a marker indicating that they may require supplemental corticosteroid therapy during times of stress.
The possibility of an insufficient adrenal response in emergency situations (including surgery) and also in elective surgeries likely to cause stress should always be borne in mind, especially in patients taking high doses for prolonged periods. Additional corticosteroid treatment appropriate to the clinical situation should be considered (see section 4.9).
Replacing systemic corticosteroid therapy with inhalation therapy may reveal allergies such as allergic rhinitis or eczema that were previously masked by systemic drugs.
Treatment with fluticasone propionate should not be stopped abruptly.
There have been very rare reports of increases in blood glucose levels (see section 4.8) and this should be considered when prescribing the drug to patients with a history of diabetes mellitus.
As with all inhaled corticosteroids special care is needed in patients with active or dormant forms of pulmonary tuberculosis.
Cases of clinically significant drug interactions have been reported during post-marketing use in patients treated with fluticasone propionate and ritonavir resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects occurring (see section 4.5).
As with other inhaled drugs, paradoxical bronchospasm with increased dyspnoea may occur immediately after taking the drug. In this case, immediately take a fast acting bronchodilator, discontinue fluticasone propionate therapy immediately, re-evaluate the patient and institute alternative therapy if necessary (see section 4.8)
There was an increase in reports of pneumonia in studies of COPD patients receiving fluticasone propionate 500 mcg (see section 4.8). Physicians should be vigilant for the possible development of pneumonia in COPD patients as the clinical features of pneumonia and exacerbation they often overlap.
FLIXOTIDE - Pressurized suspension for inhalation
If the pressurized suspension is used, the patient's inhalation technique should be verified to ensure that the activation of the inhaler is synchronized with the inspiration to ensure optimal delivery of the drug to the lungs.
Since systemic absorption of the drug occurs through the lung, the use of the spacer may increase the concentration of the drug in the lung and consequently the risk of systemic adverse reactions.
FLIXOTIDE - Powder for inhalation
Flixotide inhalation powder contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product (see also section 4.5).
The lactose excipient contains milk proteins so it is not suitable for people with intolerance to milk proteins.
04.5 Interactions with other medicinal products and other forms of interaction
Under normal circumstances, low plasma concentrations of fluticasone propionate are obtained following inhaled administration due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the intestine and liver. Interactions are therefore unlikely. clinically significant drug mediated by fluticasone propionate.
An interaction study conducted in healthy volunteers has shown that ritonavir (a very potent inhibitor of cytochrome P450 3A4) can significantly increase the plasma concentrations of fluticasone propionate, resulting in significantly lower serum cortisol concentrations. During post-marketing use, cases of clinically significant drug interactions have been reported in patients treated with intranasal or inhaled fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. .
Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided unless the potential benefit to the patient outweighs the risks of systemic corticosteroid side effects.
Studies have shown that other cytochrome P450 3A4 inhibitors produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate with no notable reductions in serum cortisol concentrations. Nevertheless, caution is advised when potent inhibitors of cytochrome P450 3A4 (eg ketoconazole) are administered concomitantly as there is a potential for increased systemic exposure to fluticasone propionate.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate and controlled studies of fluticasone propionate in pregnant women. The effect of fluticasone propionate on pregnancy in women is not known. Animal studies to evaluate possible reproductive interference of fluticasone propionate have shown only those effects characteristic of glucocorticoids at systemic exposure levels far in excess of those. observed at the recommended therapeutic dose by inhalation The genotoxicity tests did not reveal any mutagenic potential of the molecule.
However, as with other drugs, administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother outweighs the possible risks to the fetus.
Feeding time
It is unknown whether fluticasone propionate is excreted in human breast milk.
Following subcutaneous administration in rats, the presence of fluticasone propionate was found in breast milk at measurable plasma concentrations. However, plasma levels are likely to be low in patients receiving fluticasone propionate at recommended inhaled doses.
04.7 Effects on ability to drive and use machines
Fluticasone propionate is unlikely to affect the ability to drive and use machines.
04.8 Undesirable effects
Adverse events are listed below by organ, organ / system and by frequency. Frequencies are defined as: very common (≥1 / 10), common (≥1 / 100 to
Infections and infestations
Very common: candidiasis of the mouth and throat.
Oropharyngeal candidiasis (thrush) may occur in some patients. Such patients may benefit from rinsing their mouth with water after taking the drug. Symptomatic candidiasis can be treated with topical antifungal therapy without stopping the use of fluticasone propionate.
Common: pneumonia (in COPD patients)
Very rare: oesophageal candidiasis.
Disorders of the immune system
Hypersensitivity reactions manifesting as follows have been reported:
Uncommon: skin hypersensitivity reactions.
Very rare: angioedema (mainly edema of the face and oropharynx), respiratory symptoms (dyspnoea and / or bronchospasm) and anaphylactic reactions.
Endocrine pathologies
Possible systemic effects include (see section 4.4):
Very rare: Cushing's syndrome, Cushingoid appearance, adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma.
Disorders metabolism and nutrition
Very rare: hyperglycaemia.
Psychiatric disorders
Very rare: anxiety, sleep disturbances and behavioral disturbances, including psychomotor hyperactivity and irritability (predominantly in children).
Not known: depression and aggression (predominantly in children).
Respiratory pathologies , thoracic and mediastinal
Common: hoarseness.
Hoarseness may occur in some patients; even in these cases it may be advantageous to rinse the mouth with water immediately after inhalation.
Very rare: paradoxical bronchospasm (see section 4.4).
Skin and subcutaneous tissue disorders
Common: bruises.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Symptoms and signs
Acute inhalation of the drug in higher than recommended doses may lead to temporary suppression of the hypothalamic-pituitary-adrenal axis. This does not normally require the institution of emergency interventions, since adrenal function typically returns to normal within a few days.
If doses higher than those approved are used for prolonged periods, significant adrenal suppression may occur. Monitoring of the adrenal reserve may be necessary.
There have been very rare cases of acute adrenal crisis in children exposed to higher than recommended doses (typically 1000 mcg / day and above) for prolonged periods (several months or years); manifestations observed included hypoglycemia and sequelae of decreased consciousness and / or convulsions).
Situations that can potentially trigger an acute adrenal crisis include exposure to trauma, surgery, infection, or any rapid reduction in dosage.
Treatment
Patients treated with doses higher than those approved should be closely monitored and the dose reduced gradually.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other drugs for obstructive respiratory tract syndromes by aerosol - glucocorticoids.
ATC code: R03BA05.
Mechanism of action
Fluticasone propionate, administered by inhalation at recommended doses, exerts a powerful anti-inflammatory activity in the lungs, reducing symptoms and episodes of asthma exacerbation.
05.2 Pharmacokinetic properties
Absorption
The absolute bioavailability of fluticasone propionate for each inhalation regulator type was evaluated in comparator studies and comparator studies of pharmacokinetic data following inhaled or intravenous administration. In healthy adult subjects, it was evaluated. the absolute bioavailability of Fluticasone propionate powder for inhalation in the Diskus inhaler (7.8%) and fluticasone propionate inhalation pressurized suspension (10.9%) was assessed, respectively. In subjects with asthma or Chronic Obstructive Pulmonary Disease (COPD) was observed a lower level of systemic exposure to inhaled fluticasone propionate. Systemic absorption occurs primarily via the lungs and is initially rapid and then prolonged. The remaining portion of the inhaled dose can be ingested but contributes negligibly to systemic exposure due to low aqueous solubility and pre-systemic metabolism, with oral availability of less than 1%. There is a linear increase in systemic exposure in relation to the increase in the inhaled dose.
Distribution
Fluticasone propionate has a large steady-state volume of distribution (approximately 300 l). Plasma protein binding is moderately high (91%).
Biotransformation
Fluticasone propionate is cleared very rapidly from the systemic circulation, mainly by metabolism to an inactive carboxylic acid compound, by the cytochrome P450 of the CYP3A4 enzyme system. Care should be taken when administering drugs known to inhibit the CYP3A4 enzyme system as there is a potential for increased systemic exposure to fluticasone propionate.
Elimination
The elimination of fluticasone propionate is characterized by a "high plasma clearance (1150 ml / min) and a" terminal elimination half-life of approximately 8 hours. The renal clearance of fluticasone propionate is negligible (less than 0.2%) and less than 5% is eliminated as metabolite.
05.3 Preclinical safety data
The toxicological tests have shown, at doses higher than those proposed for therapeutic use, the only class of effects typical of a high potency corticosteroid.
Chronic toxicity studies did not highlight effects of a different nature, as did reproductive toxicology and teratogenesis studies.
Fluticasone propionate was found to be non-mutagenic in vitro and in vivo and non-oncogenic in rodents. In animal models, fluticasone propionate was found to be non-irritating and non-sensitizing.
The propellant HFA 134a, non-CFC, has been shown, in numerous animal species, exposed daily to the propellant for periods of two years, not to cause toxic effects at very high vapor concentrations, much higher than those to which patients will be exposed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Pressurized suspension for inhalation Propellant HFA 134a
Powder for inhalation
Lactose (which contains milk proteins).
06.2 Incompatibility
Not relevant
06.3 Period of validity
FLIXOTIDE - Pressurized suspension for inhalation: 2 years.
FLIXOTIDE 100 mcg
Inhalation powder: 2 years; FLIXOTIDE 250 mcg
Inhalation powder, FLIXOTIDE 500 mcg
Inhalation powder: 3 years.
06.4 Special precautions for storage
Pressurized suspension for inhalation
Firmly replace the inhaler lid until you hear a click.
Packages must be kept out of sunlight and protected from freezing.
As with most pressurized metered aerosol drugs, the therapeutic effect may be less if the pressurized container is cold.
Pressurized containers must not be broken, punctured or burned, even if apparently empty.
Powder for inhalation
Store in a dry place.
Store in the original package to protect the medicine from moisture.
The DISKUS is sealed with a protective laminate cover which only needs to be opened when the medicinal product is used for the first time. Once opened, the protective laminate envelope must be discarded
06.5 Nature of the immediate packaging and contents of the package
Cartons containing an aluminum pressurized container with metering valve and relative inhaler.
FLIXOTIDE 125 mcg - Pressurized suspension for inhalation
- pressurized container with 120 sprays of 125 mcg each
FLIXOTIDE 250 mcg - Pressurized suspension for inhalation
- pressurized container with 120 puffs of 250 mcg each
FLIXOTIDE 50 mcg - Pressurized suspension for inhalation
- pressurized container with 120 sprays of 50 mcg each
Multidose inhalers in molded plastic material (DISKUS) each containing a strip strip in which individual alveoli ("blister"), regularly spaced, are arranged, each of which contains a dose (100 - 250 - 500 mcg) of inhalation powder of fluticasone dispersed in lactose.
FLIXOTIDE 250 mcg - Powder for inhalation in DISKUS inhaler with strips of 60 doses of 250 mcg
FLIXOTIDE 500 mcg - Powder for inhalation in DISKUS inhaler with strips of 60 doses of 500 mcg
FLIXOTIDE 100 mcg - Powder for inhalation in DISKUS inhaler with strips of 60 doses of 100 mcg
06.6 Instructions for use and handling
FLIXOTIDE - Pressurized suspension for inhalation
Check the functioning of the inhaler
Before using the inhaler for the first time, or when it has not been used for a week, remove the protective cap from the mouthpiece by squeezing it lightly at the sides, shake the inhaler vigorously, then spray a dose into the air to make sure it works.
Use of the inhaler
1. Remove the protective cap from the mouthpiece by squeezing it lightly at the sides.
2. Check the inside and outside of the inhaler including the mouthpiece for the presence of foreign bodies.
3. Shake the inhaler vigorously to ensure that any foreign matter is removed and that the contents of the inhaler are mixed evenly.
4. Hold the inhaler with your thumb and forefinger without pressing (forefinger should rest on the bottom of the pressurized container).
5. Breathe out fully, then place the mouthpiece firmly between your lips, avoiding biting.
6. Then take a deep inhalation and press once with the index finger on the bottom of the container under pressure while continuing to inhale deeply. It is important that the inhalation is started slowly just before operating the inhaler.
7. Hold your breath for as long as possible, remove the mouthpiece and slowly exhale.
8. Wait at least half a minute if a subsequent inhalation is needed, then repeating steps 3 to 7.
9. Put the protective cap back on the mouthpiece, pressing it until it clicks.
Important: do not hurriedly carry out the operations indicated in points 5, 6 and 7. The spillage of nebulized material above the inhaler or from the sides of the mouth indicates that the inhalation was not carried out correctly; then repeat the operations from point 2.
If your doctor gives you different information on how to use the inhaler, you should follow them carefully. It is also advisable to inform the doctor of any difficulties.
Cleaning the inhaler
The inhaler should be cleaned at least once a week.
1. Remove the pressurized canister from the inhaler and remove the protective cap from the mouthpiece.
2. Clean the inhaler and mouthpiece protective cap with a damp cloth.
3. Place them to dry in a warm place. Avoid excessive heat.
4. Put the pressurized canister back into the inhaler and the protective cap back into the mouthpiece.
DO NOT IMMERSE THE CONTAINER UNDER PRESSURE IN WATER
FLIXOTIDE - Inhalation powder in DISKUS inhaler
DISKUS INFORMATION
The DISKUS, once removed from the box, is in the "closed" position.
DISKUS contains 60 individually protected doses of the drug powder.
Each dose is carefully measured and hygienically protected. The DISKUS requires no maintenance and is not rechargeable.
The dose indicator on the top of the DISKUS shows the number of doses still available.
Numbers from 5 to 0 are in RED to indicate that only a few doses remain. The DISKUS is easy to use.
To take a dose of the drug, follow the four simple steps below:
1. Opening
2. Preparing the dose
3. Inhalation
4. Closing
HOW THE DISKUS WORKS
By sliding the lever of the DISKUS, a small hole is opened in the mouthpiece and a dose is prepared ready to be inhaled. When the DISKUS is closed, the lever automatically returns to its original position, ready to prepare the next dose of drug.
The outer cover protects the DISKUS when not in use.
1. Opening
To open the DISKUS, hold the outer part with one hand and place the thumb of the other hand on the recess. Push with your thumb while rotating the inside of the device until you hear a click.
2. Preparing the dose
Hold the DISKUS with the mouthpiece facing the user. Slide the lever forward until it clicks. The DISKUS is now ready for use.
Each time the lever is slid, a dose is made available for inhalation as shown by the dose indicator.
Use the lever only when you have to inhale the drug so as not to waste doses.
3. Inhalation
Read this section carefully before inhaling.
Keep the DISKUS away from your mouth. Breathe out as deeply as possible. Never blow into the DISKUS.
Put the mouthpiece between your lips.
Inhale deeply and regularly through the DISKUS and not through the nose. Remove the DISKUS from your mouth.
Hold your breath for about 10 seconds or as long as possible.
Breathe out slowly.
4. Closing
To close the DISKUS, place your thumb in the recess and slide it back as far as it will go.
When the DISKUS is closed, it produces a sharp closing sound. This will automatically return the lever to its original position.
The DISKUS is now ready to be used again.
If two inhalations have been prescribed, it is necessary to close the DISKUS after the first inhalation and then repeat steps 1 to 4.
ATTENTION
Keep the DISKUS dry.
Keep the DISKUS closed when not in use. Never blow into the DISKUS.
Only slide the lever when you are ready to take the drug. Inhale from the DISKUS with your mouth only.
Do not exceed the recommended dose.
07.0 MARKETING AUTHORIZATION HOLDER
GlaxoSmithKline S.p.A. - Via A. Fleming, 2 - Verona
08.0 MARKETING AUTHORIZATION NUMBER
Pressurized suspension for inhalation
FLIXOTIDE 125 mcg 120 puffs of 125 mcg A.I.C .: 028667095
FLIXOTIDE 250 mcg 120 puffs of 250 mcg A.I.C .: 028667107
FLIXOTIDE 50 mcg 120 puffs of 50 mcg A.I.C .: 028667020
FLIXOTIDE 250 mcg - Powder for inhalation in DISKUS inhaler with strips of 60 doses of 250 mcg A.I.C .: 028667184
FLIXOTIDE 500 mcg - Powder for inhalation in DISKUS inhaler with strips of 60 doses of 500 mcg A.I.C .: 028667208
FLIXOTIDE 100 mcg - Powder for inhalation in DISKUS inhaler with strips of 60 doses of 100 mcg A.I.C .: 028667160
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
April 27, 1993 / February 2008
