Flixotide Diskus 50mcg

  • Name:

    Flixotide Diskus 50mcg

  • Company:
    info
  • Active Ingredients:

    Fluticasone Propionate

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 23/10/19

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Summary of Product Characteristics last updated on medicines.ie: 30/4/2018
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GlaxoSmithKline (Ireland) Ltd

GlaxoSmithKline (Ireland) Ltd

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Medicine Name Becotide Evohaler 50 Active Ingredients Beclometasone Dipropionate
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1 - 0 of 135 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 23 October 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 6 - date of revision

Updated on 30 April 2018

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 15 November 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 15 November 2017

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 15 November 2017 SPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update to section 4.4 – addition of Visual Disturbance section (blurred vision)

Update to section 4.8 – addition of Eye Disorders section (blurred vision)

Updated on 15 November 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 3 May 2017 SPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update section 4.5 of SmPC to align to PRAC recommendation on drug interactions.

Updated on 3 May 2017 PIL

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 6 - date of revision

Updated on 5 September 2016 SPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 Special Warnings and Precautions for Use

Information relevant to Pneumonia in patients with COPD

Updated on 5 September 2016 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision
  • Improved electronic presentation

Updated on 18 February 2016 SPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company



Section 4.6 - Updated information on pregnancy and lactation

Section 5.1 - Updated information on pregnancy and lactation

Updated on 22 July 2015 SPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Change to address of the Irish MA Holder

Updated on 21 July 2015 PIL

Reasons for updating

  • Change to date of revision
  • Change to MA holder contact details

Updated on 26 March 2015 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 26 March 2015 SPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.8 updated to include

Epistaxis in frequency table as not known

 

Updated on 3 September 2014 SPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 7 – Removal of A&H trading style

Updated on 14 July 2014 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to side-effects
  • Change to date of revision
  • Change to MA holder contact details
  • Addition of information on reporting a side effect.

Updated on 14 July 2014 SPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text
  • Improved electronic presentation

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.8 – Inclusion of adverse reaction


Updated on 17 February 2014 SPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.4 - Special precautions for storage

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes to:

Section 4.1 -Therapeutic indications,
Section 4.2 - Posology and method of administration,
Section 4.4 - Special warnings and precautions for use,
Section 4.8 - Undesirable effects,
Section 6.4 - Special precautions for storage

Updated on 11 February 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to side-effects
  • Change to dosage and administration

Updated on 22 November 2012 SPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.4 Special Warnings and Precautions for Use

The following paragraph was updated to specify the warning for asthma:

Flixotide Diskus is not for use in acute asthma attacks, but for routine long-term management. Patients will require a fast- and short-acting inhaled bronchodilator to relieve acute asthmatic symptoms.

 

Added Possible systemic effects Cushing’s syndrome, Cushingoid features

 

Added the following wording as required following the PhVWP decision:

Possible systemic effects include… a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

 

Replaced the previous warnings regarding adrenal suppression, adrenal crisis and impaired adrenal reserve with the following:

The possibility of impaired adrenal response should always be borne in mind in emergency situations, including surgery, and elective situations likely to produce stress and appropriate corticosteroid treatment must be considered (see section 4.9).

 

Adrenal function and adrenal reserve usually remain within the normal range on recommended doses of fluticasone propionate therapy.  The benefits of inhaled fluticasone propionate therapy should minimise the need for oral steroids.  However, the possibility of adverse effects in patients, resulting from prior or intermittent administration of oral steroids, may persist for some time.  The extent of the adrenal impairment may require specialist advice before elective procedures.

 

Deleted the following warning regarding use of topical corticosteroids:

Particular care should be taken to minimise use of topical corticosteroids in patients with immunosuppression.

 

Replaced the warning on co-administration with Ritonavir to read:

During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving 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 (see section 4.5).

 

Added the following warning regarding diabetes mellitus:

There have been very rare reports of increases in blood glucose levels (see section 4.8) and this should be considered when prescribing to patients with a history of diabetes mellitus.

 

4.5 Interaction with Other Medicinal Products and Other Forms of Interaction

Replaced the interaction warning regarding ritonavir with the following:

A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations.  During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving 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 risk of systemic corticosteroid side-effects.

 

Replaced the warning regarding co-administration with CYP3A inhibitors with a warning regarding other inhibitors of cytochrome P450 3A4, as follows

Studies have shown that other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations.  Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole) as there is potential for increased systemic exposure to fluticasone propionate.

 

4.6 Pregnancy and Lactation

Replaced the entire text of this section with the following text under the new subheadings ‘Pregnancy’ and ‘Lactation’:

Pregnancy

There is inadequate evidence of safety of fluticasone propionate in human pregnancy.  Reproductive studies in animals have shown only those effects characteristic of glucocorticosteroids at systemic exposures in excess of those seen at the recommended inhaled therapeutic dose.  Tests for genotoxicity have shown no mutagenic potential.

 

However, as with other drugs the administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

 

Lactation

The excretion of fluticasone propionate into human breast milk has not been investigated.  When measurable plasma levels were obtained in lactating laboratory rats following subcutaneous administration there was evidence of fluticasone propionate in the breast milk.  However, plasma levels in patients following inhaled application of fluticasone propionate at recommended doses are likely to be low.

 

 

4.8 Undesirable Effects

 

Infections and Infestations

Updated the instructions on how to mitigate the effects of candidiasis of the mouth and throat (thrush) to read:

Such patients may find it helpful to rinse out their mouth with water after using their medication

 

Endocrine Disorders

Added very rare undesirable effects Cushing’s syndrome and Cushingoid features

 

Added the following undesirable effects:

Metabolism and nutrition disorders

Very rare: Hyperglycaemia.

 

Psychiatric disorders

Very rare: Anxiety, sleep disorders and behavioural changes, including hyperactivity and irritability (predominantly in children).

Frequency not known: Depression, aggression (predominantly in children)

 

Respiratory, Thoracic and Mediastinal Disorders

Updated the instructions on how to mitigate the effects of hoarseness to read:

In some patients inhaled fluticasone propionate may cause hoarseness.  It may be helpful to rinse out the mouth with water immediately after inhalation.

 

Updated the statement ‘As with other inhalation therapy, paradoxical bronchospasm may occur’ with the following additional statements:

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing.  This should be treated immediately with a fast-acting inhaled bronchodilator.  Fluticasone propionate should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

 

4.9 Overdose

Updated to include two subsections ‘Signs and symptoms’ and ‘Treatment’

Symptoms and Signs

Acute inhalation of fluticasone propionate doses in excess of those approved may lead to temporary suppression of the hypothalamic-pituitary-adrenal axis.  This does not usually require emergency action, as normal adrenal function typically recovers within a few days.

 

If higher than approved doses are continued over prolonged periods, significant adrenocortical suppression is possible.  There have been very rare reports of acute adrenal crisis occurring in children exposed to higher than approved doses (typically 1000 micrograms daily and above), over prolonged periods (several months or years); observed features included hypoglycaemia and sequelae of decreased consciousness and/or convulsions.  Situations which could potentially trigger acute adrenal crisis include exposure to trauma, surgery, infection or any rapid reduction in dosage.

 

Treatment

Patients receiving higher than approved doses should be managed closely and the dose reduced gradually.

 

Updated on 20 November 2012 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to drug interactions
  • Change due to harmonisation of PIL

Updated on 28 April 2011 SPC

Reasons for updating

  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

 

 

SUMMARY OF spc changes

(Changes in red)

 

1. NAME OF THE MEDICINAL PRODUCT

Flixotide Diskus 50 micrograms, Inhalation powder, pre-dispensed

Flixotide Diskus 100 micrograms, Inhalation powder, pre-dispensed

Flixotide Diskus 250 micrograms, Inhalation powder, pre-dispensed

Flixotide Diskus 500 micrograms, Inhalation powder, pre-dispensed

 

6.6 Instructions for Use and Handling

 

Patients should be carefully instructed in correct use of the Diskus.

 

The Diskus is sealed in a foil overwrap. The overwrap provides moisture protection and should only be opened when you are ready to use it for the first time. Once opened the foil overwrap should be discarded.

CLOSED:

When you take your Diskus out of its box and remove the foil overwrap, it will be in the closed position.

 

OPENED:

A new Diskus contains 28 or 60 doses of your medicine.  The dose indicator tells you how many doses are left.

 

This Diskus contains 28 or 60 individually protected doses of your medicine, in powder form.

 

Each dose is accurately measured and hygienically protected.  It requires no maintenance and no refilling.

The dose indicator on top of your Accuhaler/Diskus tells you how many doses are left.  Numbers 5 to 0 will appear in RED, to warn you when there are only a few doses left.

 

The Diskus is easy to use.  When you need a dose, just follow the five simple steps illustrated:

1.             Open.

2.             Slide.

3.             Inhale.

4.             Close.

5.             Rinse.

 

How your Diskus works:

 

Sliding the lever of your Diskus opens a small hole in the mouthpiece and unwraps a dose, ready for you to inhale it.  When you close the Diskus, the lever automatically moves back to its original position, ready for your next dose when you need it.  The outer case protects your Diskus when it is not in use.

 

1. Open

To open your Diskus, hold the outer case in one hand and put the thumb of your other hand on the thumbgrip.  Push your thumb away from you as far as it will go.

 

2. Slide

Hold your Diskus with the mouthpiece towards you.  Slide the lever away from you, as far as it will go - until it clicks.  Your Diskus is now ready to use.  Every time the lever is pushed back, a dose is made available for inhaling.  This is shown by the dose counter.  Do not play with the lever as this releases doses which will be wasted.

 

3. Inhale

Before you start to inhale the dose, read through this section carefully.

Hold the Diskus away from your mouth.  Breathe out as far as is comfortable.  Remember - never breathe into your Diskus.

Put the mouthpiece to your lips.  Breathe in steadily and deeply - through the Diskus, not through your nose.

Remove the Diskus from your mouth.

Hold your breath for about 10 seconds, or for as long as is comfortable.

Breathe out slowly.

 

4. Close

To close your Diskus, put your thumb in the thumbgrip, and slide the thumbgrip back towards you, as far as it will go.

When you close the Diskus, it clicks shut.  The lever automatically returns to its original position and is reset.  Your Diskus is now ready for you to use again.

5. Rinse

Afterwards, rinse your mouth with water and spit it out.

 

If you have been instructed to take two inhalations you must close the Diskus and repeat stages 1 to 4.

 

REMEMBER:

  • Keep your Diskus dry.
  • Keep it closed when not in use.
  • Never breathe into your Diskus.
  • Only slide the lever when you are ready to take a dose.
  • Do not exceed the stated dose.
  • Keep out of reach of children.

 

 

 

 

Updated on 7 January 2010 SPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

SUMMARY OF spc changes (marked in red)

1. NAME OF THE MEDICINAL PRODUCT

Flixotide Diskus 50 micrograms, Inhalation powder, pre-dispensed

Flixotide Diskus 100 micrograms, Inhalation powder, pre-dispensed

Flixotide Diskus 250 micrograms, Inhalation powder, pre-dispensed

Flixotide Diskus 500 micrograms, Inhalation powder, pre-dispensed

 

6.4 Special Precautions for Storage

Do not store above 30ºC.

 

The Diskus is sealed in a foil overwrap which should only be opened when it is to be used for the first time. Once opened the foil overwrap should be discarded.

 

6.5 Nature and Contents of Container

The inhalation powder is contained in blisters held on a formed PVC coated base, with a peelable foil laminate lid.  The strip is contained in a moulded plastic device. The plastic device is packaged within a foil overwrap. The plastic devices are available in cardboard containers, which hold a 1 x 28 dose or 1 x 60 dose Diskus.

 

 

Updated on 24 November 2009 PIL

Reasons for updating

  • Change to packaging
  • Change to storage instructions

Updated on 20 August 2008 PIL

Reasons for updating

  • Change to side-effects

Updated on 18 August 2008 SPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.6 Pregnancy and Lactation

There are insufficient data on the use of fluticasone propionate during pregnancy and lactation in man to assess the possible harmful effects.  In animal studies foetal abnormalities occur after administration of glucocorticosteroids Reproductive studies in animals have shown only those effects characteristic of glucocorticosteroids at systemic exposures in excess of those seen at the recommended inhaled therapeutic dose. (see 5.3 Preclinical Safety Data).

Administration of fluticasone propionate to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

The lowest effective dose of fluticasone propionate needed to maintain adequate asthma control should be used in the treatment of pregnant women.

There are no data available for human breast milk.  Fluticasone propionate is excreted into breast milk in rats.  Administration of fluticasone propionate to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

 

 

4.8 Undesirable Effects

Adverse events are listed below by system organ class and frequency.  Frequencies are defined as: very common ( ©ø1/10), common ( ©ø1/100 and <1/10), uncommon ( ©ø1/1000 and <1/100), rare ( ©ø1/10,000 and <1/1000) and very rare ( <1/10,000) including isolated reports.  Very common, common and uncommon events were generally determined from clinical trial data.  Rare and very rare events were generally determined from spontaneous data.

Infections and Infestations
Very common:          Candidiasis of mouth and throat.

Candidiasis (thrush) of the mouth and throat occurs in some patients. The incidence of candidiasis may be relieved by gargling with water using the Diskus.  Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the Flixotide Diskus.

Common: Pneumonia (in COPD patients).

 

Immune System Disorders


Hypersensitivity reactions with the following manifestations have been reported:

Uncommon:      Cutaneous hypersensitivity reactions.

Very rare:         Angioedema (mainly facial and oropharyngeal oedema), respiratory symptoms (dyspnoea and/or bronchospasm) and anaphylactic reactions.

Endocrine Disorders


Possible systemic effects (see 4.4 Special Warnings and Special Precautions for Use) include:
Very rare:         Adrenal suppression, growth retardation in children and adolescents, decreased bone
mineral density, cataract, glaucoma.

Respiratory, Thoracic and Mediastinal Disorders


Common:          Hoarseness.
Hoarseness can occur in some patients.  Hoarseness may be relieved by gargling with water after using the product.

Very rare:         Paradoxical bronchospasm.

As with other inhalation therapy, paradoxical bronchospasm may occur.

 

Skin and subcutaneous tissue disorders

 

Common: Contusions

 

 

5.1 Pharmacodynamic Properties

Fluticasone propionate given by inhalation at recommended doses has a glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma, without the adverse effects observed when corticosteroids are administered systemically.

 

COPD clinical trials

 

TORCH was a 3-year study to assess the effect of treatment with Seretide Diskus 50/500mcg bd, salmeterol Diskus 50mcg bd, fluticasone propionate (FP) Diskus 500mcg bd or placebo on all-cause mortality in patients with COPD.  COPD patients with a baseline (pre‑bronchodilator) FEV1 <60% of predicted normal were randomised to double-blind medication.  During the study, patients were permitted usual COPD therapy with the exception of other inhaled corticosteroids, long‑acting bronchodilators and long-term systemic corticosteroids.  Survival status at 3 years was determined for all patients regardless of withdrawal from study medication.  The primary endpoint was reduction in all cause mortality at 3 years for Seretide vs Placebo. 

 

 

Placebo

N = 1524

Salmeterol 50

N = 1521

FP 500

N = 1534

Seretide 50/500

N = 1533

All cause mortality at 3 years

Number of deaths (%)

231

(15.2%)

205

(13.5%)

246

(16.0%)

193

(12.6%)

Hazard Ratio vs Placebo (CIs)
p value

N/A

0.879
(0.73, 1.06)
0.180

1.060
(0.89, 1.27)
0.525

0.825
(0.68, 1.00 )
0.0521

Hazard Ratio Seretide 50/500 vs components (CIs)
p value

N/A

0.932
(0.77, 1.13)
0.481

0.774
(0.64, 0.93)
0.007

N/A

1. Non significant P value after adjustment for 2 interim analyses on the primary efficacy comparison from a log-rank analysis stratified by smoking status

 

There was a trend towards improved survival in subjects treated with Seretide compared with placebo over 3 years however this did not achieve the statistical significance level p¡Â0.05.

 

The percentage of patients who died within 3 years due to COPD-related causes was 6.0% for placebo, 6.1% for salmeterol, 6.9% for FP and 4.7% for Seretide.

 

The mean number of moderate to severe exacerbations per year was significantly reduced with Seretide as compared with treatment with salmeterol, FP and placebo (mean rate in the Seretide group 0.85 compared with 0.97 in the salmeterol group, 0.93 in the FP group and 1.13 in the placebo).  This translates to a reduction in the rate of moderate to severe exacerbations of 25% (95% CI: 19% to 31%; p<0.001) compared with placebo, 12% compared with salmeterol (95% CI: 5% to 19%, p=0.002) and 9% compared with FP (95% CI: 1% to 16%, p=0.024).  Salmeterol and FP significantly reduced exacerbation rates compared with placebo by 15% (95% CI: 7% to 22%; p<0.001) and 18% (95% CI: 11% to 24%; p<0.001) respectively.

 

Health Related Quality of Life, as measured by the St George¡¯s Respiratory Questionnaire (SGRQ) was improved by all active treatments in comparison with placebo. The average improvement over three years for Seretide compared with placebo was -3.1 units (95% CI: -4.1 to -2.1; p<0.001), compared with salmeterol was -2.2 units (p<0.001) and compared with FP was ‑1.2 units (p=0.017).  A 4-unit decrease is considered clinically relevant.

 

The estimated 3-year probability of having pneumonia reported as an adverse event was 12.3% for placebo, 13.3% for salmeterol, 18.3% for FP and 19.6% for Seretide (Hazard ratio for Seretide vs placebo: 1.64, 95% CI: 1.33 to 2.01, p<0.001).  There was no increase in pneumonia related deaths; deaths while on treatment that were adjudicated as primarily due to pneumonia were 7 for placebo, 9 for salmeterol, 13 for FP and 8 for Seretide.  There was no significant difference in probability of bone fracture (5.1% placebo, 5.1% salmeterol, 5.4% FP and 6.3% Seretide; Hazard ratio for Seretide vs placebo: 1.22, 95% CI: 0.87 to 1.72, p=0.248.

 

 

5.2 Pharmacokinetic Properties

The absolute bioavailability of inhaled fluticasone propionate for each of the available inhaler devices has been estimated from within and between study comparisons of inhaled and intravenous pharmacokinetic data.  In healthy adult subjects the absolute bioavailability has been estimated for fluticasone propionate Accuhaler/Diskus (7.8%), fluticasone propionate Diskhaler (9.0%) and fluticasone propionate Evohaler (10.9%) respectively. in healthy subjects varies between approximately 10-30% of the nominal dose depending on the inhalation device used.  In patients with asthma or COPD a lesser degree of systemic exposure to inhaled fluticasone propionate has been observed.

 

Systemic absorption occurs mainly through the lungs and is initially rapid then prolonged.  The remainder of the inhaled dose may be swallowed but contributes minimally to systemic exposure due to the low aqueous solubility and pre-systemic metabolism, resulting in oral availability of less than 1%.  There is a linear increase in systemic exposure with increasing inhaled dose. 

The disposition of fluticasone propionate is characterised by high plasma clearance (1150ml/min), a large volume of distribution at steady-state (approximately 300l) and a terminal half-life of approximately 8 hours. 

Plasma protein binding is (91%). 

Fluticasone propionate is cleared very rapidly from the systemic circulation.  The main pathway is metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450 enzyme CYP3A4. Other unidentified metabolites are also found in the faeces.

 

The renal clearance of fluticasone propionate is negligible.  Less than 5% of the dose is excreted in urine, mainly as metabolites.  The main part of the dose is excreted in faeces as metabolites and unchanged drug.

 

5.3 Preclinical Safety Data

Toxicology has shown only those class effects typical of potent corticosteroids, and these only at doses greatly in excess of that those proposed for therapeutic use.  No novel effects were identified in repeat dose toxicity tests, reproductive studies or teratology studies.  Fluticasone propionate is devoid of mutagenic activity in vitro and in vivo and showed no tumorigenic potential in rodents.  It is both non-irritant and non-sensitising in animal models.

 

Updated on 18 June 2007 PIL

Reasons for updating

  • Change to side-effects

Updated on 31 May 2007 SPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

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4.4 Special Warnings and Precautions for Use

The management of asthma should follow a stepwise programme and patient response should be monitored clinically and by lung function tests.

 

Increasing use of short-acting inhaled â2-agonists to control asthma symptoms indicates deterioration of asthma control.  Under these conditions, the patient's therapy plan should be reassessed.

 

Sudden and progressive deterioration in asthma control is potentially life-threatening and consideration should be given to increasing corticosteroid dosage.  In patients considered at risk, daily peak flow monitoring may be instituted.

Flixotide Diskus is not for use in acute attacks, but for routine long-term management. Patients will require a fast- and short-acting inhaled bronchodilator to relieve acute asthmatic symptoms.

Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled fluticasone propionate and, if necessary, by giving a systemic steroid and/or an antibiotic if there is an infection.

There was an increased reporting of pneumonia in studies of patients with COPD receiving FP 500 micrograms (see Section 4.8).  Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbation frequently overlap.

Because of the possibility of impaired adrenal response, patients transferring from oral steroid therapy to inhaled fluticasone propionate therapy should be treated with special care, and adrenocortical function regularly monitored.

Following introduction of inhaled fluticasone propionate, withdrawal of systemic therapy should be gradual and patients are encouraged to carry a steroid warning cards indicating the possible need for additional therapy in times of stress.

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods.  These effects are much less likely to occur than with oral corticosteroids.  Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.  It is important, therefore, that the patient is reviewed regularly and the dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of asthma is maintained.

 

It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroid is regularly monitored.

Certain individuals can show greater susceptibility to the effects of inhaled corticosteroid than do most patients.

Prolonged treatment of patients with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Children and adolescents < 16 years taking high doses of fluticasone propionate (typically ³ 1000mcg/day) may be at particular risk.  Very rare cases of adrenal suppression and acute adrenal crisis have been described with doses of fluticasone between 500mcg and less than 1000mcg.  Situations, which could potentially trigger acute adrenal crisis include trauma, surgery, infection or any rapid reduction in dosage.  Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, decreased level of consciousness, hypoglycemia and seizures.  Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

 

The benefits of inhaled fluticasone propionate therapy should minimise the need for oral steroids, but patients transferring from oral steroids may remain at risk of impairedadrenal reserve for a considerable time. Patients who have required high dose emergency corticosteroid therapy in the past may also be at risk.  This possibility of residual impairment should always be borne in mind in emergency and elective situations likely to produce stress, and appropriate corticosteroid treatment must be considered. The extent of the adrenal impairment may require specialist advice before elective procedures.

Similarly replacement of systemic steroid treatment with inhaled therapy may unmask allergies such as allergic rhinitis or eczema previously controlled by the systemic drug. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids.

 

Treatment with Flixotide Diskus should not be stopped abruptly.

 

As with all inhaled corticosteroids, special care is necessary in patients with active or quiescent pulmonary tuberculosis.

 

Particular care should be taken to minimise use of topical corticosteroids in patients with immunosuppression.

 

Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects. There is also an increased risk of systemic side effects when combining fluticasone propionate with other potent CYP3A inhibitors (see 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction).

4.8 Undesirable Effects

Adverse events are listed below by system organ class and frequency.  Frequencies are defined as: very common ( ³1/10), common ( ³1/100 and <1/10), uncommon ( ³1/1000 and <1/100), rare ( ³1/10,000 and <1/1000) and very rare ( <1/10,000) including isolated reports.  Very common, common and uncommon events were generally determined from clinical trial data.  Rare and very rare events were generally determined from spontaneous data.

Infections and Infestations
Very common:  Candidiasis of mouth and throat.

Candidiasis (thrush) of the mouth and throat occurs in some patients. The incidence of candidiasis may be relieved by gargling with water after using the Diskus.  Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the Flixotide Diskus.

Common: Pneumonia (in COPD patients).

 

Immune System Disorders


Hypersensitivity reactions with the following manifestations have been reported:

Uncommon:      Cutaneous hypersensitivity reactions.

Very rare:         Angioedema (mainly facial and oropharyngeal oedema), respiratory symptoms (dyspnoea and/or bronchospasm) and anaphylactic reactions.

Endocrine Disorders


Possible systemic effects (see 4.4 Special Warnings and Special Precautions for Use) include:
Very rare:         Adrenal suppression, growth retardation in children and adolescents, decreased bone
mineral density, cataract, glaucoma.

Respiratory, Thoracic and Mediastinal Disorders


Common:          Hoarseness.
Hoarseness can occur in some patients.  Hoarseness may be relieved by gargling with water after using the product.

Very rare:         Paradoxical bronchospasm.

As with other inhalation therapy, paradoxical bronchospasm may occur.

 

Updated on 26 March 2007 SPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Flixotide Diskus 50 micrograms

Each blister each contains 50 micrograms fluticasone propionate.

Excipients: Each blister contains 11.82mg lactose (as monohydrate)

Flixotide Diskus 100 micrograms

Each blister each contains 100 micrograms fluticasone propionate.

Excipients: Each blister contains 11.9mg lactose (as monohydrate)

Flixotide Diskus 250 micrograms

Each blister each contains 250 micrograms fluticasone propionate.

Excipients: Each blister contains 11.6mg lactose (as monohydrate)

Flixotide Diskus 500 micrograms

Each blister each contains 500 micrograms fluticasone propionate.

Excipients: Each blister contains 11.4mg lactose (as monohydrate)

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Inhalation powder, pre-dispensed

Fine, white to off-white powder.

Updated on 26 March 2007 PIL

Reasons for updating

  • Change of active ingredient

Updated on 12 March 2007 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 25 May 2005 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 22 February 2005 SPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 12 December 2003 SPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - MA number

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 3 June 2003 SPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)