Fluticasone Elpen 250 mikrogram/dos Inhalationspulver, avdelad dos

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

Bipacksedel Bipacksedel (PIL)

15-07-2019

Produktens egenskaper Produktens egenskaper (SPC)

15-07-2019

Aktiva substanser:
flutikasonpropionat
Tillgänglig från:
Elpen Pharmaceutical Co. Inc
ATC-kod:
R03BA05
INN (International namn):
fluticasone propionate
Dos:
250 mikrogram/dos
Läkemedelsform:
Inhalationspulver, avdelad dos
Sammansättning:
flutikasonpropionat 250 mikrog Aktiv substans; laktosmonohydrat Hjälpämne
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Inhalatorer, 120 (2 x 60) doser (2 st Elpenhaler); Inhalator, 30 doser (1 st Elpenhaler); Inhalator, 60 doser (1 st Elpenhaler)
Bemyndigande status:
Godkänd
Godkännandenummer:
57142
Tillstånd datum:
2019-03-28

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

15-07-2019

Produktens egenskaper Produktens egenskaper - engelska

15-07-2019

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

04-04-2019

Läs hela dokumentet

Package leaflet: Information for the patient

Fluticasone Elpen 250 microgram/dose Inhalation powder, pre-dispensed

Fluticasone Elpen 500 microgram/dose Inhalation powder, pre-dispensed

fluticasone propionate

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

What is and what it is used for

What you need to know before you use <Product name>

How to use <Product name>

Possible side effects

How to store <Product name>

Contents of the pack and other information

1.

What <Product name> is and what it is used for

<Product name> is a cortisone preparation that counteracts inflammation and allergy directly

in the lungs. Reducing inflammation can prevent asthma attacks.

<Product name> is used as a regular treatment for asthma and COPD (Chronic Obstructive

Pulmonary Disease) together with a long-acting bronchodilator. The full effect is first observed

after several days of regular treatment. <Product name> does not provide rapid relief in the event

of acute asthma attacks. If such event occur, a quick and short-acting bronchodilator medicine

should be used. If the treatment does not give the desired effect, consult a doctor.

2.

What you need to know before you use <Product name>

Do not use <Product name>

if you are allergic to fluticasone propionate or any of the other ingredients in this medicine

(specified in section 6). Lactose monohydrate may contain lactoprotein.

Warnings and precautions

Talk to your doctor, nurse or pharmacist before using <Product name>.

<Product name> is not intended for the treatment of acute asthma symptoms. You should use a fast

acting “reliever” inhaler, such as a short-acting bronchodilator, for acute asthma attacks.

Immediately after taking <Product name>, a paradoxical bronchospasm (respiratory cramp)

with increased wheezing may occur. If this does occur, you should immediately inhale a fast-

acting bronchodilator. Stop taking <Product name> and contact your doctor.

If you have previously been treated with cortisone tablets, you must carefully follow the doctor's

dosage instructions when switching to <Product name>. In the event of such a transition, your

previous allergy symptoms, such as sniffing and eczema, may return. You may also experience

fatigue, headache, muscular and joint aches, and sometimes nausea and vomiting. This is because

the total amount of cortisone in the body is reduced as the illness in the lungs is treated locally. The

systems will abate after a certain amount of time.

If the symptoms escalate, do not change the

dose without contacting a doctor.

In the event of acute deterioration, episodic stress events and surgical procedures, treatment may

need to be supplemented with cortisone in tablet form. Contact your doctor for written information

on how your cortisone treatment will proceed in the event of the aforementioned situations.

Treatment with <Product name> must not be discontinued abruptly, as this may risk

aggravating the symptoms. Your doctor will decide how quickly the dose can be reduced.

Tell your doctor if you suffer from pulmonary tuberculosis before you start <Product name> treatment.

In very rare cases, <Product name> may affect blood sugar levels. If you suffer from diabetes, consult

your doctor before using <Product name>.

Using high doses of <Product name> over a long period may cause the cortisone to affect the entire

body. You may experience symptoms such as weight gain with altered fat distribution (abdomen,

neck, face), thin and fragile skin, increased body hair, decreased bone density, high blood pressure

(Cushing's syndrome). Growth inhibition may be seen in children and adolescents. If any of these

symptoms are observed, consult your doctor.

The long-term growth of children treated with <Product name> should be checked regularly.

Contact a doctor if you experience blurred vision or other visual disorders.

Other medicines and <Product name>

Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take

any other medicines, including medicines obtained without prescription.

Certain other medicines may increase the effect of <Product name>, and your doctor may want to

monitor you carefully if you are taking these medicines (e.g. certain medicines for HIV: ritonavir,

cobicistat, or antifungal medicines: ketoconazole, itraconazole).

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby,

ask your doctor or pharmacist for advice before taking this medicine.

There is limited experience of use during pregnancy. You should, therefore, consult a doctor

before

using <Product name> during pregnancy.

It is unknown whether fluticasone propionate passes through human milk. For this reason, consult a

doctor

before

using while breastfeeding.

Driving and using machines

<Product name> is not likely to affect you being able to drive or use any tools or machines, unless side

effect such as blurred vision occurs.

<Product name> contains lactose

Each dose of <Product name> 250 microgram & 500 microgram contains approximately 14 mg of

lactose.

The amount of lactose in this medicine does not normally cause problems in people who are lactose

intolerant. The excipient lactose contains small amounts of milk proteins, which may cause allergic

reactions.

3.

How to use <Product name>

Always use this medicine exactly as your doctor or pharmacist has told you. The dose is determined

by the doctor, who will adapt it specifically for you. Do not exceed the dosage. Check with your

doctor, nurse or pharmacist if you are not sure.

<Product name> is generally inhaled in the morning and evening. In order to achieve full effect,

<Product name> should be used regularly.

The mouth should be rinsed with water after each

inhalation.

See the user instructions for more information.

Instructions for use

Your doctor, nurse or pharmacist should show you how to use your inhaler. They should check

how you use it from time to time. Not using the <Product name> properly or as prescribed may

mean that it will not help your asthma as it should.

The Elpenhaler device holds a blister on each strip containing <Product name> as a powder.

Do not use your inhaler more often than the doctor told you to. Tell your doctor if your medicine does

not seem to be working as well as usual, as your chest problem may be getting worse and you may need

a different medicine.

INSTRUCTIONS FOR USE OF THE ELPENHALER

Elpenhaler is a device for the intake of powder for inhalation in doses. Each dose is stored in the

blister of a specially designed single dose blister strip.

Elpenhaler device is comprised of 3 parts:

The mouthpiece and its cap

(1)

The surface

(2)

on which the blister strip is placed (drug supporting

surface).

The storage case

(3)

which houses the blister strips.

The three parts are connected to each other and can be opened separately.

The drug supporting surface contains:

An attachment point

(2A)

where the blister strip is attached.

A cavity

(2B)

which accommodates the blister of the strip.

Two strip guides

(2C)

which firmly secure the blister strip in the correct

position on the drug supporting surface.

The blister strip consists of:

Two aluminium sheets

(4)

A blister

(5)

, containing the medicine.

A hole

(6)

USE OF THE ELPENHALER

Α. Preparing the device

Open the storage case by pressing as in the figure, take a strip and close

the storage case again.

Uncover the mouthpiece completely by applying light pressure on the

striped area.

Unlock and push the mouthpiece backwards so as to reveal the drug

supporting surface.

Hold the blister strip with its shiny surface upwards, so as to see the blue

line, as shown by the arrow in the figure. The labeled surface of the strip

should face downwards.

Place the hole of the strip on the attachment point of the drug supporting

surface. By applying light pressure make sure that the strip is securely

attached on the attachment point.

The blister of the strip will fit in the cavity of the drug supporting surface

and the guides will secure the strip in the correct position.

Close

mouthpiece

pull

away

horizontally

embossed

protruding end of the strip to be detached.

The dose is now ready to be inhaled.

B. Inhalation of the dose

Hold the device away from your mouth. Exhale completely. Be careful not to exhale on the

mouthpiece of the device. Bring Elpenhaler to your mouth and place your lips tightly around the

mouthpiece.

Breathe in slowly and deeply through your mouth (and not through your

nose) until your lungs are full.

Hold

your

breath

approximately

seconds

long

comfortably can and at the same time remove the device from your

mouth.

Exhale and continue to breathe normally.

Open the mouthpiece.

You will notice that you have inhaled all the powder and that the blister

of the strip is empty.

Remove the empty strip and proceed to step C.

C. Cleaning the device

Following each use, wipe the mouthpiece and the drug supporting surface with a dry cloth or dry

paper tissue. Do not use water to clean the device.

Close the mouthpiece and its cap.

If you take more <Product name> than you should

It is important that you take the dose as indicated on the packaging label, or as your doctor has

directed. Do not increase or decrease the dose without consulting a doctor.

If you forget to take <Product name>

Continue treatment as usual if you have forgotten to take a dose. Do not

take a double dose to make up for a forgotten dose.

If you stop using <Product name>

Treatment with <Product name> must not be discontinued abruptly, as this may risk

aggravating the symptoms. Your doctor will decide how quickly the dose can be reduced.

If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact a doctor immediately if you experience any of the following symptoms

(signs of an allergic/anaphylactic reaction):

swelling of the face, mouth and throat, spasms in the trachea

(windpipe), shortness of breath. This is a very rare adverse

reaction.

Inform your doctor if you experience any of the following symptoms while taking <Product name>,

as they may be symptoms of pneumonia:

fever or chills

increased mucus production, altered colour of the mucus

increased coughing or increased breathing difficulties.

COPD patients have reported pneumonia as a common adverse reaction (may affect up to 1 in 10

people).

Other possible side effects

Very common

(may affect more than 1 in 10 people):

fungal infection ("thrush", Candida) in the oral cavity, larynx and pharynx. The risk of

infection can be decreased by rinsing the mouth with water after each inhalation.

Common

(may affect up to 1 in 10 people):

bruising

throat irritation and hoarseness

Less common side effects

(may affect up to 1 in 100 people):

hypersensitivity reactions in the form of skin rashes.

Rare side effects

(may affect up to 1 in 1000 people):

fungal infection in the oesophagus.

Very rare side effects

(may affect up to 1 in 10,000 people):

inhalation treatment may cause cramps in the trachea due to uncertain mechanisms

sleeping issues, apprehension, restlessness, anxiety (these adverse reactions are more likely

to occur in children)

Cushing-like symptoms (moon face, abdominal obesity)

reduced cortisone formation in adrenal glands

reduced bone density

glaucoma (green star), cataracts (grey star)

delayed long-term growth in children has been observed in very rare cases when cortisone

has been administered in high doses over a long period

Elevated blood sugar levels have been reported in very rare cases.

Have been reported

(occurs for an unknown number of people):

depression, feeling irritable and/or very upset. These adverse reactions are more likely to

occur in children.

nosebleeds

blurred vision.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. You can also report side effects directly via the national

reporting system listed in Appendix V*.

By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store <Product name>

Keep this medicine out of the sight and reach of children.

Do not store above 25°C.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The

expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how

to throw away medicines you no longer use. These measures will help protect the environment.

As medicine residues may remain in the empty packages, do not throw them into the trash. The

empty packages should also be returned to the pharmacy.

6.

Contents of the pack and other information

What <Product name> contains

The active substance is fluticasone propionate

Each dose of <Product Name> 250 microgram contains 250 microgram of fluticasone propionate

Each dose of <Product Name> 500 microgram contains 500 microgram of fluticasone propionate

The other ingredient is lactose.

What <Product name> looks like and contents of the pack

<Product name> contains fluticasone propionate packed in blisters, which are stored in the inhaler

Elpenhaler.

The foil protects the powder for inhalation from the effects of the atmosphere.

A white plastic device containing alu-alu blisters, is packed in a carton box together with the instruction

leaflet.

Each carton box contains:

30 doses: one inhaler Elpenhaler with 30 alu-alu blisters.

60 doses: one inhaler Elpenhaler with 60 alu-alu blisters.

120 doses: two inhalers Elpenhaler with 60 alu-alu blisters.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

<To be completed nationally>

Manufacturer

<To be completed nationally>

This medicinal product is authorised in the Member States of the EEA under the following names:

<To be completed nationally>

This leaflet was last revised in 2019-07-15.

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1.

ΝΑΜΕ OF THE MEDICINAL PRODUCT

Fluticasone Elpen 250 microgram per dose inhalation powder, pre-dispensed

Fluticasone Elpen 500 microgram per dose inhalation powder, pre-dispensed

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each dose of <Product name> 250 microgram contains 250 microgram of fluticasone propionate.

Each dose of <Product name> 500 microgram contains 500 microgram of fluticasone propionate

Excipient with known effect:

Each dose of <Product name> 250 microgram & 500 microgram contains approximately 14 mg of

lactose.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Inhalation powder, pre-dispensed.

White powder.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Bronchial asthma

in adults

For the treatment of severe chronic obstructive pulmonary disease, COPD (FEV1 <50% the predicted

normal value) in combination with long-acting bronchodilators in patients with a history of recurrent

exacerbations

4.2

Posology and method of administration

<Product name> is intended for oral inhalation only.

Patients should be made aware that treatment with <Product name> is prophylactic and that it must be

used daily for optimum therapeutic effect, even in the absence of symptoms.

If the patient experiences that the treatment with a short-acting bronchodilator becomes less effective

or that more inhalations than usual are needed, he should seek medical attention.

The dose should be titrated until effective control of symptoms is achieved, or reduced to the lowest

effective dose according to individual response.

Asthma

Dosage is individual.

Adults 250 or 500 microgram twice daily.

Prescribers should be awareasthma that fluticasone propionate is as effective as other inhaled steroids

at approximately half the daily dose expressed in micrograms, e.g. 100 micrograms fluticasone

propionate corresponds to approximately 200 micrograms beclomethasone dipropionate (inhalation

spray with freons) or budesonide.

A temporary dose increase may become necessary (in adults, up to 2,000 micrograms/day), as an

alternative to oral steroids, in patients with severe asthma or in connection with exacerbations.

The response to treatment should be monitored and every attempt should be made to determine the

lowest effective dose for maintenance treatment.

COPD

Adult:

500 micrograms twice daily.

Treatment with <Product name> may in some cases replace oral steroid treatment or in many cases,

allow the dose of oral steroids to be reduced.

Recovery of suppressed pituitary-adrenocortical function is possible after a period of treatment with

<Product name> following withdrawal of oral steroids.

For patients who are dependent on oral steroids, it is recommended that <Product name> is given for

10 days together with the previously used dose of oral steroids. The oral dose is then reduced

successively by e.g. 2.5 mg prednisolone or the equivalent per month to the lowest possible level.

In case of acute deterioration, particularly in connection with increased viscosity and mucus plugs, the

treatment should be supplemented with a short course of oral steroids.

Children and adolescents

<Product Name> is not recommended for children and adolescents below the age of 18 years.

Special patient groups:

No dose adjustment is needed in elderly patients or patients with impaired renal function. There is no

experience with treatment of patients with impaired hepatic function.

Handling:

A dose is loaded by opening the inhaler. Place the inhaler in your mouth and close your lips around the

mouthpiece. The dose can now be inhaled. Close the inhaler after use.

4.3

Contraindications

Hypersensitivity to fluticasone propionate or to any of the excipients listed in section 6.1.

4.4

Special warnings and precautions for use

Deterioration of disease

Any bronchoconstriction should be treated prior to start of medication, as the effect might otherwise

be weaker than expected.

<Product name> is not intended for treatment of acute asthmatic symptoms, when a fast and short-

acting bronchodilator should be used, but for routine long-term treatment. The patient should be

instructed to always have reliever medication available to treat acute asthmatic symptoms.

Increased use of short-acting bronchodilators to relieve symptoms indicates deterioration of asthma

control. In such cases, the patient's treatment programme should be reassessed and the patient should

therefore be advised to seek medical attention.

Sudden and progressive deterioration of asthma control is potentially life-threatening and the patient

should be advised to seek medical attention immediately for assessment. Treatment with an increased

dose of corticosteroids should be considered. In patients considered at risk, daily lung function

measurements should be instituted.

In some patients, inhalation of fluticasone propionate may cause hoarseness and soaring of the throat.

Therefore, immediately after inhalation, the mouth should be rinsed with water. If possible, inhalation

should be done before meals. For symptomatic cases of sourness, a local antifungal treatment is

recommended with continued inhalation treatment with <Product Name>.For respiratory infections,

treatment with antibiotics may be required.

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses during long

periods of treatment. These effects are much less likely to occur with inhalation therapy than with oral

corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal

suppression, growth retardation in children and adolescents, reduction in bone density and more rarely,

a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders,

anxiety, depression or aggression (particularly in children). It is therefore important that the dose of an

inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained

(see section 4.8).

Visual disturbance

Visual disturbances may be reported with systemic and topical use of corticosteroids. If a patient

presents with symptoms such as blurred vision or other visual disturbances, he should be considered

for referral to an ophthalmologist for evaluation of possible causes. These may include cataracts,

glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported

after use of systemic and topical corticosteroids.

Patients who receive higher than recommended doses should be carefully monitored and the dose

gradually reduced.

It is recommended that the height of children receiving prolonged treatment with inhaled

corticosteroids is regularly monitored.

Due to the risk of impaired adrenocortical function, patients transferring from oral steroid therapy to

inhaled fluticasone propionate therapy should be treated with special care, and their adrenocortical

function monitored regularly.

Following introduction of treatment with <Product name>, withdrawal of systemic therapy should be

gradual. Patients are encouraged to carry a steroid warning card indicating the possible need for

supplemental therapy in times of stress.

The possibility of suppressed adrenal function should always be borne in mind in various situations of

stress, including surgery and elective stressful situations, particularly in patients who have used high

doses for a prolonged period, in order to introduce appropriate corticosteroid treatment (see section

4.9).

Similarly, replacing systemic steroid treatment with inhalation therapy may unmask allergies such as

allergic rhinitis or eczema that were previously controlled by the systemic drug.

These patients may initially get symptoms of tiredness, headache, muscle and joint pain, and

occasionally nausea and vomiting. These are signs of a reduced general steroid effect.

Treatment with <Product name> should not be stopped abruptly in asthma patients due to the risk of

exacerbations. Tapering of the dose should be done under medical supervision. Worsening of

symptoms can also be seen in patients with COPD when the treatment is discontinued, and this should

therefore be done under medical supervision.

<Product name> should be given with caution to patients with active or quiescent pulmonary

tuberculosis.

Hyperglycaemia

There have been very rare reports of increases in blood glucose levels (see section 4.8). This should be

considered when prescribing to patients with a history of diabetes mellitus.

Interactions with potent CYP3A4 inhibitors

There have been reports of clinically significant drug interactions in patients being treated with

fluticasone propionate and the potent CYP3A4 inhibitor, ritonavir, resulting in systemic corticosteroid

effects including Cushing's syndrome and adrenocortical suppression. Ritonavir may considerably

increase the levels of fluticasone propionate in plasma. Therefore, concomitant use of fluticasone

propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the

risk of systemic corticosteroid adverse reactions. The risk of systemic adverse reactions is also

increased when fluticasone propionate is combined with other potent CYP3A4 inhibitors (see section

4.5).

Paradoxical bronchospasm

Paradoxical bronchospasm may occur with an increase in wheezing immediately after dosing. This

should be treated immediately with a fast-acting inhaled bronchodilator. Fluticasone propionate

therapy should be discontinued immediately, the patient assessed, and, if necessary, alternative therapy

instituted.

Systemic corticoid effects

Precautions should be taken when transferring patients to <Product name>, particularly when it is

suspected that adrenal function is impaired from previous systemic steroid therapy.

Prolonged treatment with high doses of inhaled corticosteroids may result in adrenal suppression and

acute adrenal crisis. Children and adolescents under 16 years of age who receive high doses of

fluticasone propionate (usually ≥ 1,000 micrograms per day) are a special group at risk.

In very rare cases, adrenal suppression and acute adrenal crisis have occurred at doses between 500

and 1,000 micrograms of fluticasone propionate. Acute adrenal crisis can be induced by e.g. trauma,

surgery, infection or a rapid reduction of the dose. Initial symptoms are usually uncharacteristic and

may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting,

hypotension, decreased level of consciousness, hypoglycaemia and seizures.

Additional oral corticosteroid cover should be considered during periods of stress or elective surgery.

Patients who have previously needed high doses of corticosteroids in emergency situations may also

be at risk. A specialist assessment of the degree of impairment of the adrenal function may be needed

prior to elective surgery.

Pneumonia in patients with COPD

An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been

observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an

increased risk of pneumonia when the steroid dose is increased, but this has not been demonstrated

conclusively across all studies.

There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia

risk among inhaled corticosteroid products.

Physicians should remain vigilant for the possible development of pneumonia in patients with COPD

as the clinical signs of such infections overlap with the symptoms of COPD exacerbations.

Risk factors for pneumonia in patients with COPD include current smoking, old age, low body mass

index (BMI) and severe COPD.

Excipients

Each dose of <Product name> 250 microgram & 500 microgram contains approximately 14 mg of

lactose. The amount of lactose in this medicine does not normally cause problems in people who are

lactose intolerant. The excipient lactose contains small amounts of milk proteins, which may cause

allergic reactions.

4.5

Interaction with other medicinal products and other forms of interaction

Under normal circumstances, only low plasma concentrations of inhaled fluticasone propionate are

achieved due to extensive first pass metabolism and high systemic clearance mediated by CYP3A4

metabolism in the gut and liver. Hence, clinically significant drug interactions are unlikely.

A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome

CYP3A4 inhibitor) greatly increased fluticasone propionate plasma concentrations, resulting in

markedly reduced serum cortisol concentrations. There have been reports of clinically significant drug

interactions in patients receiving intranasal or inhaled fluticasone propionate together with ritonavir,

resulting in systemic corticosteroid effects including Cushing's syndrome and adrenocortical

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 adverse

reactions.

A small study in healthy volunteers showed that the somewhat less potent cytochrome CYP3A4

inhibitor, ketoconazole, increased the exposure by 150% after a single dose of inhaled fluticasone

propionate. This resulted in a marked reduction of plasma cortisol compared with fluticasone

propionate alone.

Co-treatment with other potent CYP3A inhibitors, such as medicinal products containing itraconazole

and cobicistat, is also expected to increase the systemic exposure to fluticasone propionate and the risk

of systemic side-effects. The combination should be avoided unless the benefit outweighs the

potential increased risk of systemic corticosteroid side-effects, in which case patients should be

monitored for systemic corticosteroid side-effects.

Therefore, caution should be exercised and prolonged treatment with this kind of medicinal product

should be avoided, if possible. Studies have also shown that erythromycin produces a negligible

increase in systemic exposure to fluticasone propionate without any notable reduction in the level of

serum cortisol.

4.6

Fertility, pregnancy and lactation

Fertility

There are no data on human fertility. Animal studies indicate no effects of fluticasone propionate on

male or female fertility.

Pregnancy

There are limited data in pregnant women. 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. The lowest effective dose of fluticasone propionate needed should be used, while taking into

consideration the risk of a worsened asthma condition.

Results from a retrospective epidemiological study did not show any increased risk of major

congenital malformations following exposure to fluticasone propionate when compared to other

inhaled corticosteroids during the first trimester of pregnancy.

Reproductive studies in animals have shown only effects characteristic of glucocorticosteroids at

systemic exposures in excess of those seen

at the

recommended inhaled therapeutic doses.

Breast-feeding

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 also evidence of fluticasone propionate in the milk. However, plasma levels

in patients following inhalation of fluticasone propionate at recommended doses are expected to be

low.

The mother’s need for treatment with <Product name> and the benefits of breast-feeding must be

weighed against the potential risks to the child.

4.7

Effects on ability to drive and use machines

Specific studies of whether <Product name> has an effect on the ability to drive and use machines

have not been conducted. However, it is unlikely that fluticasone propionate has any such effects

unless side effect such as blurred vision occurs.

4.8

Undesirable effects

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as:

very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000

to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Very common, common and uncommon adverse reactions are taken from clinical trials. The incidence

of placebo was not taken into account. Very rare adverse reactions are taken from spontaneously

reported cases (post-marketing).

The adverse reactions are presented within each frequency range in descending order of severity.

System organ class

Adverse reactions

Frequency

Infections and infestations

Candidiasis (oropharyngeal)

Pneumonia (in COPD patients)

Candidiasis (oesophageal)

Very common

Common

Rare

Immune system disorders

Hypersensitivity reactions in the form of:

Cutaneous hypersensitivity reactions

Angioedema (mainly facial and oropharyngeal),

respiratory symptoms (dyspnoea and/or

bronchospasm). Anaphylactic reactions

Uncommon

Very rare

Endocrine disorders

Cushing's syndrome, Cushingoid features,

adrenocortical suppression, growth retardation in

children and adolescents, reduced bone density

Very rare

Metabolism and nutrition

disorders

Increased blood glucose levels

Very rare

Psychiatric disorders

Anxiety, sleep disorders and behavioural

changes, including hyperactivity and irritability

(predominantly in children)

Depression, aggression (predominantly in

children)

Very rare

Not known

Respiratory, thoracic and

mediastinal disorders

Throat irritation

Hoarseness/dysphonia

Paradoxical bronchospasm

Epistaxis

Common

Common

Very rare

Not known

Skin and subcutaneous

tissue disorders

Bruising

*Common

Eye disorders

Cataracts and glaucoma

Blurred vision (see also section 4.4)

Very rare

Not known

*Bruising has been reported during 3 years in a COPD study.

Both hoarseness and candidiasis may be alleviated if the patient gargles with water after each use of

<Product name>. Symptom-inducing candidiasis can be treated with topical anti-fungal agents during

continued treatment with <Product name>.

Any systemic adverse reactions include Cushing's syndrome, Cushingoid features, adrenocortical

suppression, growth retardation in children and adolescents, reduced bone density, cataracts and

glaukoma (see section 4.4).

Increased blood glucose levels have been reported in very rare cases (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued 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

listed in Appendix V*.

4.9

Overdose

Acute overdose: doses of fluticasone propionate well in excess of those recommended and inhaled

during a short period of time may lead to temporary suppression of the adrenal function. This does not

usually require emergency action since normal adrenal function is recovered within a few days which

may be verified by measurements of cortisol in plasma.

Chronic overdose of inhaled fluticasone propionate leads to risk of significant adrenocortical

suppression (see section 4.4). It may then be necessary to check the adrenal function. There have been

very rare reports of acute adrenal crisis occurring in children exposed to higher than approved doses

(typically 1,000 micrograms daily and above) over prolonged periods (several months or years).

Observed reactions include hypoglycaemia and sequelae of decreased consciousness and/or

convulsions. Situations which could potentially trigger acute adrenal crisis include trauma, surgery,

infection or any rapid reduction of the dose.

If overdose of fluticasone propionate has occurred, treatment with <Product name> can continue at a

suitable dose for symptom control.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Other drugs for obstructive airway diseases, inhalants (glucocorticoids)

ATC code: R03BA05

<Product name> contains fluticasone propionate, a glucocorticoid with anti-inflammatory action.

Treatment with inhaled <Product name> powder is a prophylactic therapy. Full effect of Flutide is

achieved only after 4–7 days of treatment.

Fluticasone propionate is micronised and mixed with lactose in the inhalation powder. Most particles

are less than 5 micrometers in diameter.

The inhalation method works even at low inspiratory flow.

Clinical COPD studies

TORCH study

TORCH was a 3-year study to assess the effect of treatment with salmeterol/fluticasone propionate 50

micrograms/500 micrograms twice daily, salmeterol Diskus 50 micrograms twice daily, fluticasone

propionate (FP) Diskus 500 micrograms twice daily or placebo on all-cause mortality in patients with

COPD. COPD patients with a baseline (pre-bronchodilator) value of FEV

<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 a reduction in all cause mortality at 3

years for salmeterol/fluticasone propionate vs. placebo.

Placebo

N = 1,524

Salmeterol 50

N = 1,521

FP 500

N = 1,534

salmeterol/fluticasone

propionate 50/500

N = 1,533

All cause mortality after 3 years

Number of deaths

(15.2%)

(13.5%)

(16.0%)

(12.6%)

Hazard ratio vs.

placebo (CI)

p value

0.879

(0.73, 1.06)

0.180

1.060

(0.89, 1.27)

0.525

0.825

(0.68, 1.00 )

0.052

Hazard Ratio

salmeterol/fluticasone

propionate 50/500 vs.

active substances (CI)

p value

0.932

(0.77, 1.13)

0.481

0.774

(0.64, 0.93)

0.007

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

CI = confidence interval

There was a trend towards improved survival in subjects treated with salmeterol/fluticasone propionate

compared with placebo over the 3–year period. However, this did not achieve the statistical significance

level p≤0.05.

The number 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 salmeterol/fluticasone propionate.

number

moderate

severe

exacerbations

year

significantly

reduced

with

salmeterol/fluticasone propionate as compared with treatment with salmeterol, FP and placebo (mean

rate in the salmeterol/fluticasone propionate group 0.85 compared with 0.97 in the salmeterol group,

0.93 in the FP group and 1.13 in the placebo). This corresponds 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 salmeterol/fluticasone propionate 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 as clinically relevant.

The estimated 3-year probability of having pneumonia reported as an adverse reaction was 12.3% for

placebo, 13.3% for salmeterol, 18.3% for FP and 19.6% for salmeterol/fluticasone propionate (Hazard

ratio for salmeterol/fluticasone propionate vs. placebo: 1.64, 95% CI: 1.33 to 2.01, p<0.001). No

increase of pneumonia-related deaths was seen. The number of deaths during the treatment period where

pneumonia was considered to be the primary cause was 7 for placebo, 9 for salmeterol, 13 for FP and 8

for salmeterol/fluticasone propionate. There was no significant difference in probability of bone fracture

(5.1% placebo, 5.1% salmeterol, 5.4% FP and 6.3% salmeterol/fluticasone propionate; hazard ratio for

salmeterol/fluticasone propionate vs. placebo: 1.22, 95% CI: 0.87 to 1.72, p=0.248).

5.2

Pharmacokinetic properties

The absolute bioavailability after inhalation of fluticasone propionate varies in healthy subjects and is

approximately 5–11% of the nominal dose depending on what inhaler device is used. In patients with

asthma or COPD a lesser degree of systemic exposure to inhaled fluticasone propionate has been

observed.

The systemic absorption occurs mainly through the lungs and is initially rapid then prolonged. The

part of the dose which is swallowed after inhalation contributes minimally to systemic exposure. The

oral bioavailability is less than 1% due to low aqueous solubility and extensive first pass metabolism.

There is a linear increase in systemic exposure with increasing inhaled dose.

The disposition of fluticasone propionate is characterised by high plasma clearance (1,150 ml/min), a

large volume of distribution at steady-state (approximately 300 l) and a terminal half-life of

approximately 8 hours.

Plasma protein binding is 91%.

Fluticasone propionate is eliminated rapidly from the systemic circulation. This occurs mainly by the

drug being metabolised by CYP3A4 enzymes to produce an inactive carboxylic acid metabolite. Other

metabolites of unknown structure have also been found in the faeces.

The renal clearance of fluticasone propionate is negligible. Less than 5% of the dose is excreted in the

urine, mainly as metabolites. The main part of the dose is excreted in faeces as metabolites and

unchanged drug.

5.3

Preclinical safety data

In animal studies, corticosteroids have been shown to induce malformations (cleft palate, skeletal

malformations). However, these animal experimental results do not seem to be of any relevance to

humans at the recommended doses.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Lactose monohydrate (may contain milk proteins)

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

2 years

6.4

Special precautions for storage

Do not store above 25°C.

6.5

Nature and contents of container

A white plastic device containing alu-alu blisters, is packed in a carton box together with the instruction

leaflet.

Each carton box contains:

30 doses: one inhaler Elpenhaler with 30 alu-alu blisters.

60 doses: one inhaler Elpenhaler with 60 alu-alu blisters.

120 doses: two inhalers Elpenhaler with 60 alu-alu blisters each.

6.6

Special precautions for disposal and other handling

To ensure proper administration of the drug, the patient should be shown how to use the inhaler by a

physician or other health professional.

Any unused medicinal product or waste material should be disposed of in accordance with local

requirements.

INSTRUCTIONS FOR USE OF THE ELPENHALER

Elpenhaler is a device for the intake of powder for inhalation in doses. Each dose is stored in the

blister of a specially designed single dose blister strip.

Elpenhaler device is comprised of 3 parts:

The mouthpiece and its cap

(1)

The surface

(2)

on which the blister strip is placed (drug supporting

surface).

The storage case

(3)

which houses the blister strips.

The three parts are connected to each other and can be opened separately.

The drug supporting surface contains:

An attachment point

(2A)

where the blister strip is attached.

A cavity

(2B)

which accommodates the blister of the strip.

Two strip guides

(2C)

which firmly secure the blister strip in the correct

position on the drug supporting surface.

The blister strip consists of:

Two aluminium sheets

(4)

A blister

(5)

, containing the medicine.

A hole

(6)

USE OF THE ELPENHALER

Α. Preparing the device

Open the storage case by pressing as in the figure, take a strip and close

the storage case again.

Uncover the mouthpiece completely by applying light pressure on the

striped area.

Unlock and push the mouthpiece backwards so as to reveal the drug

supporting surface.

Hold the blister strip with its shiny surface upwards, so as to see the blue

line, as shown by the arrow in the figure. The labeled surface of the strip

should face downwards.

Place the hole of the strip on the attachment point of the drug supporting

surface. By applying light pressure make sure that the strip is securely

attached on the attachment point.

The blister of the strip will fit in the cavity of the drug supporting surface

and the guides will secure the strip in the correct position.

Close

mouthpiece

pull

away

horizontally

embossed

protruding end of the strip to be detached.

The dose is now ready to be inhaled.

B. Inhalation of the dose

Hold the device away from your mouth. Exhale completely. Be careful not to exhale on the

mouthpiece of the device. Bring Elpenhaler to your mouth and place your lips tightly around the

mouthpiece.

Breathe in slowly and deeply through your mouth (and not through your

nose) until your lungs are full.

Hold

your

breath

approximately

seconds

long

comfortably can and at the same time remove the device from your

mouth.

Exhale and continue to breathe normally.

Open the mouthpiece.

You will notice that you have inhaled all the powder and that the blister

of the strip is empty.

Remove the empty strip and proceed to step C.

C. Cleaning the device

Following each use, wipe the mouthpiece and the drug supporting surface with a dry cloth or dry

paper tissue. Do not use water to clean the device.

Close the mouthpiece and its cap.

7.

MARKETING AUTHORISATION HOLDER

<To be completed nationally>

8.

MARKETING AUTHORISATION NUMBER(S)

<To be completed nationally>

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

<To be completed nationally>

10.

DATE OF REVISION OF THE TEXT

<To be completed nationally> 2019-07-15

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