Becloneb 400 micrograms/1 ml nebuliser suspension

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
BECLOMETASONE DIPROPIONATE
Available from:
Chiesi Farmaceutici S.p.A.
ATC code:
R03BA; R03BA01
INN (International Name):
BECLOMETASONE DIPROPIONATE
Dosage:
400 mcg/1 millilitre(s)
Pharmaceutical form:
Nebuliser suspension
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
Glucocorticoids; beclometasone
Authorization status:
Not marketed
Authorization number:
PA0584/003/001
Authorization date:
2005-03-18

Leaflet V(0.1) 12.2016

B. PACKAGE LEAFLET

Leaflet V(0.1) 12.2016

PACKAGE LEAFLET: INFORMATION FOR THE USER

BECLONEB

®

400 micrograms nebuliser suspension

BECLONEB

®

800 micrograms nebuliser suspension

Beclometasone dipropionate

Read all of this leaflet carefully before you start using 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 or pharmacist. This includes any possible side effects not

listed in this leaflet. See section 4.

In this leaflet:

What BECLONEB

is and what it is used for

What you need to know before you use BECLONEB

How to use BECLONEB

Possible side effects

How to store BECLONEB

Contents of the pack and other information

1. WHAT BECLONEB® IS AND WHAT IT IS USED FOR

BECLONEB

contains the active substance beclometasone dipropionate. It belongs to a group of medicines

called corticosteroids which have an anti-inflammatory action reducing the swelling and irritation in the

walls of the airways (e.g. nose, lungs), and so ease breathing problems.

BECLONEB

is indicated to treat asthma in adults and children up to 18 years of age when the use of

pressurised or dry powder inhalers is unsatisfactory or inappropriate.

BECLONEB

is also indicated to treat recurrent wheezing in children up to 5 years of age.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE BECLONEB

®

Do not use BECLONEB

®

:

If you are allergic to the active substance or any of the other ingredients of this medicine listed in section

Warnings and precautions

Talk to you doctor or pharmacist before using BECLONEB

if any of the following applies to you:

You are being, or have ever been, treated for tuberculosis (TB).

Your condition seems to be getting worse. Perhaps you are more wheezy and short of breath than usual,

or your nebuliser seems to be less effective.

Your doctor may need to increase the dose of BECLONEB

or give you a course of corticosteroid

tablets, or change your treatment altogether.

You have an infection in your chest. Your doctor may prescribe a course of antibiotics.

If you have an infection of nasal and paranasal cavities you have to be treated with suitable therapies,

although this does not represent specific contraindication to the use of BECLONEB

Leaflet V(0.1) 12.2016

If you develop an immediate increase in wheezing, shortness of breath and cough after using BECLONEB

you should discontinued immediately BECLONEB

and you should contact your doctor.

Immediately after inhalation the mouth should be rinsed with water to reduce the frequency of fungal

infections in the mouth.

Switching from corticosteroid tablets to BECLONEB

Switching from corticosteroid tablets to an inhaled corticosteroid treatment might make you feel generally

unwell or you might develop a rash, eczema or a runny nose and sneezing (rhinitis).

You should see your doctor as soon as possible if you experience these symptoms. Do not stop treatment

with BECLONEB

unless your doctor tells you to.

If you have been taking corticosteroid tablets at high doses or for a long time, your dose may be gradually

reduced, approximately one week after you started treatment with BECLONEB

. During this time your

doctor will monitor the level of corticosteroids in your body regularly.

If you have been treated for a long time with high doses of inhaled corticosteroid, you may require an extra

corticosteroid treatment in times of stress. For example:

during admission to hospital after a serious accident,

before an operation,

or if you have a chest infection or other serious illness.

Your doctor will decide if you need a course of corticosteroid tablets or possibly a corticosteroid injection

and will also advise you as to how long you need to take the course of corticosteroid tablets and how you

should reduce these as you get better.

Children and adolescents

If your child is below 5 years of age and is receiving prolonged treatment of recurrent wheezing with

BECLONEB

, your doctor will regularly monitor his/her height to evaluate if growth impairment occurs

and whether to stop the treatment.

Other medicines and BECLONEB

®

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines,

including medicines obtained without a prescription. .

Some medicines may increase the effects of BECLONEB

and your doctor may wish to monitor you

carefully if you are taking these medicines (including some medicines for HIV: ritonavir, cobicistat).

Tell your doctor if you are taking other corticosteroid medications as they may interact with BECLONEB

and could make any side effects worsening

Pregnancy, breast-feeding and fertility

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

your doctor or pharmacist for advice before using this medicine.

Because growth retardation and damage to the unborn child cannot be excluded upon prolonged treatment

with corticosteroids (such as beclometasone dipropionate contained in BECLONEB

) during pregnancy,

your doctor will decide whether your disease requires treatment with BECLONEB

Corticosteroids pass into breast milk at low amounts. Damage to the infant is not reported to date.

Nevertheless, as precautionary measure when high doses of beclometasone dipropionate are inhaled you

should avoid breast-feeding for 4 h after administration.

Driving and using machines

BECLONEB

is unlikely to affect your ability to drive and use machines. However if you experience side

effects such as dizziness and/or trembling, your ability to drive or operate machines may be affected.

Leaflet V(0.1) 12.2016

3. HOW TO TAKE BECLONEB

®

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you

are not sure.

The starting dose should be prescribed by your doctor according to the frequency and severity of your

disease. The dose may then be adjusted by your doctor until effective control of symptoms is reached.

The recommended initial doses are:

Adults and adolescents (from 12 years of age):

800-1600 micrograms twice daily which correspond to a total daily amount of 1600-3200

micrograms.

Children (up to 11 years of age):

400-800 micrograms twice daily which correspond to a total daily dose of 800-1600 micrograms.

BECLONEB

Normally, a daily dose of 3200 micrograms in adults and adolescents and 1600 micrograms in children up

to 11 years of age should not be exceeded.

In case of asthma disease, BECLONEB

must be used regularly on a daily basis. Your doctor will decide

the duration of your treatment.

If your child suffers from recurrent wheezing, the duration of treatment should not exceed 3 months, unless

otherwise prescribed by the paediatrician.

You can used BECLONEB

800 micrograms ampoule to get 400 micrograms (half the content) using the

graduation mark as described below.

Method of administration

BECLONEB

is for inhalation use only. Do not inject into a vein or use orally.

BECLONEB

must be administered by inhalation from a suitable device (jet nebuliser) according to your

doctor instructions.

Use of BECLONEB

with ultrasonic nebulisers is not recommended.

Instructions for use:

Use the ampoule according to the following instructions:

Bend the ampoule backwards and forwards to loosen it from the strip (Figure A).

Carefully separate a new ampoule from the strip. Starting from the top, then in the middle

(Figure B). Leave the rest in the pouch.

Vigorously shake and turn the ampoule upside-down in order to mix the suspension. Repeat

this operation, until the whole content is fully dispersed and mixed (Figure C).

Leaflet V(0.1) 12.2016

Open the ampoule by rotating the entrance flap as indicated by the arrow (Figure D).

Gently squeeze the ampoule content into the nebuliser chamber (Figure E).

The ampoule should be opened immediately before administration.

400 micrograms ampoule is for single use.

If only half dose of BECLONEB

800 micrograms is needed, hold the ampoule upside down, ensuring that

the graduation mark is clearly visible and apply moderate pressure. Carefully squeeze out the content until

the level of suspension in the ampoule reaches the graduation mark and no further. Once half the content is

used, reinsert the cap upside down by pushing it onto the container. The container closed in this way must

be stored at 2-8 C (in the refrigerator) and the remaining quantity has to be used within 12 hours after first

opening.

Dilution:

Your doctor may decide that your dose should be diluted.

In this case, empty the contents of the ampoule into the nebuliser bowl then add the quantity of sterile sodium

chloride 9 mg/ml (0.9%) solution that your doctor has told you to use. Then put the top on the nebuliser

bowl and shake gently to mix the contents.

The dose of nebuliser suspension may need to be diluted in order to obtain a final volume suitable for the

particular nebuliser being used, to aid administration of small volumes or if a prolonged delivery time is

desirable.

During nebulisation

Place the mask or mouth piece

Turn on the nebuliser.

Breathe normally. Nebulisation should not last more than 10 to 15 minutes.

After nebulisation

Do not forget to rinse the mouth, lips and the region of the face covered by the mask with water.

After inhalation, any unused suspension remaining in the nebuliser chamber must be discarded.

Cleaning:

Follow the manufacturer’s instructions for cleaning your nebuliser. It is important that your nebuliser is kept

clean.

If you use more BECLONEB

®

than you should:

It is important that you use your dose as advised by your doctor. You should not increase or decrease your

dose without seeking medical advice.

If you have used more BECLONEB

than you should, tell your doctor as soon as possible. Your doctor may

want to check the corticosteroid levels in your blood and therefore, may need to take a blood sample.

If you forget to use BECLONEB

®

:

If you forget to use a dose, use it as soon as you remember. If it is almost time for your next dose, do not

use the missed dose, just use the next dose when it is due. Do not use a double dose to make up for a

forgotten dose.

BECLONEB

®

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

4. POSSIBLE SIDE EFFECTS

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

The following side effects have been reported. Tell your doctor as soon as possible if you suffer from any

of these side effects but do not stop treatment unless told to do so. Your doctor will try to prevent these

effects by prescribing BECLONEB

in the lowest effective dose.

Leaflet V(0.1) 12.2016

Very common side effects (may affect more than 1 in 10 people):

sore throat (pharyngitis, laryngitis). Gargling with water immediately after inhalation may help to

prevent this effect.

Common side effects (may affect up to 1 in 10 people):

cough

nausea (feeling sick) and stomach pains.

thrush in the mouth, tongue and throat. Rinsing your mouth or gargling with water immediately

after inhalation may help to prevent these effects.

Uncommon side effects (may affect up to 1 in 100 people):

headache

throat irritation, hoarse voice

worsening shortness of breath, cough and wheezing (which is known as paradoxical bronchospasm).

If this occurs do not take another dose of BECLONEB

. Then contact your doctor straightaway.

Your doctor is likely to assess your asthma or wheezing and if necessary may start you on another

course of treatment. You may be told that you should not use BECLONEB

again.

Rare side effects (may affect up to 1 in 1000people):

cold sores (herpes simplex) painful blisterlike vesicles on your lips and in your mouth

tremor (involuntary trembling)

feeling tired.

an allergic reaction (swelling of the eyes, face, lips and throat leading to severe difficulty in

breathing, skin rashes, hives, itching or redness)

The following effects may also occur more likely in children

Sleeping problems, depression or feeling worried, restless, nervous, over-excited or irritable

At high doses over a long period of time, BECLONEB

may affect the normal production of corticosteroids

in the body. Affected children and adolescents may grow more slowly than others, so it is important that

they will have their height checked regularly by their doctor. Bone thinning and eye problems, which include

clouding of the lens of the eye (cataract), increase in pressure in the eye (glaucoma) have been reported.

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. 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 BECLONEB

®

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

Do not use BECLONEB

after the expiry date which is stated on the carton, pouch and ampoule.

Store the ampoules in the upright position in the original package (carton box) in order to protect from light.

After first opening the pouch, write the date in the box provided on the pouch. Do not use the ampoule after

3 months from the date of first opening the pouch.

For 800 micrograms ampoule: after the first opening of the ampoule, store it in a refrigerator (2–8

C). The

remaining quantity has to be used within 12 hours after first opening.

Do not use BECLONEB

if the packaging is damaged.

Leaflet V(0.1) 12.2016

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.

6.

Contents of the pack and other information

What BECLONEB

®

contains

The active substance is beclometasone dipropionate.

Each ampoule contains 400 micrograms beclometasone dipropionate suspension in 1 ml.

Each ampoule contains 800 micrograms beclometasone dipropionate suspension in 2 ml.

The 800 micrograms ampoule has a graduation mark to indicate half the content (corresponding to 400

micrograms).

The other ingredients are polysorbate 20, sorbitan laurate, sodium chloride, water for injections.

What BECLONEB

®

looks like and contents of the pack

BECLONEB

is a white or almost white nebuliser suspension.

BECLONEB

nebuliser suspension comes in polyethylene ampoules containing 1 ml (BECLONEB

micrograms) or 2 ml (BECLONEB

800 micrograms). There are strips 5 ampoules in each sealed pouch, in

pack sizes of 10 ampoules (2 pouches), 20 ampoules (4 pouches) or 40 ampoules (8 pouches).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: Chiesi Farmaceutici S.p.A., 26/A Via Palermo, 43122 Parma-Italy

Manufacturer: Chiesi Farmaceutici S.p.A., 26/A Via Palermo, 43122 Parma-Italy

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

Ireland

Beclospin/Becloneb

Germany

Sanasthmax

Greece

Beclospin/Becloneb

France

Beclospin

Italy

Clenil

This leaflet was last revised in 12/2016

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Becloneb 400 micrograms/1 ml nebuliser suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1 ml single dose container contains 400 micrograms beclometasone dipropionate anhydrous.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Nebuliser suspension.

A white or almost white suspension.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

BECLONEB

is indicated for the:

maintenance treatment

asthma,

when the

use of

pressurised metered dose or

dry powder

inhalers

unsatisfactory or inappropriate, in adults and children up to 18 years of age;

treatment of recurrent wheezing in children up to 5 years of age (see sections 4.2 and 4.4 paediatric population).

4.2 Posology and method of administration

The starting dose of nebulised beclometasone dipropionate should take into account

the frequency and severity of

symptoms.

The recommended initial doses are:

Adults and adolescents (from 12 years of age) :

800-1,600 micrograms twice daily

(total daily dose: 1600 – 3200 micrograms)

Children (up 11 years of age):

400-800 micrograms twice daily

(total daily dose: 800 – 1600 micrograms)

Normally, a daily dose of 3200 micrograms in adults and adolescents and 1600 micrograms in children up to 11 years

of age should not be exceeded.

After improvement of control of asthma or wheezing, the total daily dose should be reduced to the lowest effective dose

and a once daily dosing can be applied.

In patients with asthma,

BECLONEB

must be used regularly on a daily basis; the duration of treatment

should be

defined on the basis of symptoms.

In children with recurrent wheezing, if no treatment benefit of is observed within 2-3 months, BECLONEB

should be

discontinued. In addition, the duration of treatment of recurrent wheezing should not exceed 3 months, unless diagnosis

of asthma is likely to avoid an unnecessary long-term exposure (see section 4.4).

Method of administration

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For inhalation use only. BECLONEB

should not be injected or administered orally.

BECLONEB

should be administered preferably via jet nebuliser and the compressor equipped with the mouthpiece or

suitable face mask.

Patients should be advised to carefully follow the manufacturer’s instructions for the nebulizer device and should only

use the settings recommended.

Incorrect

use of the nebuliser device could lead to incorrect

dosing of the medicinal

product.

Use of BECLONEB

with ultrasonic nebulisers is not recommended because it doesn’t allow a correct administration

of the medicinal product.

For instruction on preparation and dilution of the medicinal product, see section 6.6.

After inhaling the prescribed dose patients should rinse their mouth with water to minimise the risk of oropharyngeal

thrush (see section 4.4).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

The management of asthma should normally follow a stepwise programme and patient response should be monitored clinically

and by lung function tests.

Becloneb is not indicated to relieve acute asthma symptoms for which an inhaled short-acting beta 2-agonists is required. Patients

should be advised to have such relief medicinal product readily available.

Increasing use of bronchodilators, in particular short-acting inhaled beta 2-agonists to relieve symptoms indicates deterioration of

asthma control.

patients find that

short-acting relief

bronchodilator

treatment

becomes less effective or

they need more

inhalations than usual, medical attention must be sought. In this situation patients should be reassessed and consideration given to

the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroids or a course of oral corticosteroids).

Severe exacerbations of

asthma must

be treated in the normal

way,

e.g.

by increasing the dose of

inhaled beclometasone

dipropionate and,

if necessary,

by giving a systemic steroid,

and/or an antibiotic if appropriate,

and by use of beta 2-agonist

therapy.

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses administered for long periods of time. These

effects are much less likely to occur than with oral

corticosteroids.

Possible systemic effects include hypothalamic-pituitary-

adrenal

(HPA)-axis suppression,

growth retardation in children and adolescents,

decrease in bone mineral density,

cataract

glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders,

anxiety, depression or aggression (particularly in children). 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 disease is maintained.

Some patients feel

unwell

for approximately 2 weeks during the withdrawal

of treatment

with systemic corticosteroids,

even

though their respiratory function remains the same or even improves.

Such patients should be encouraged to continue treatment

with beclometasone dipropionate by inhalation and withdrawal of the systemic corticosteroid,

unless objective clinical signs of

adrenal impairment are present.

The switch to Becloneb of patients who have been treated with systemic steroids for long periods of time, or at a high dose, needs

special

care,

since

recovery from any adrenocortical

suppression sustained may take

considerable

time.

In any case,

beclometasone dipropionate should be administered without discontinuing the systemic treatment; after approximately one week,

the latter should be gradually reduced (the size of the reduction should correspond to the maintenance dose of the systemic

steroid), patient should be checked at regular intervals (in particular, adrenocortical function tests should be carried out) and dose

of inhaled beclometsone dipropionate should be adjusted according to the results obtained.

Special care is necessary in patients with active or quiescent pulmonary tuberculosis and other infections. Patients suffering from

tuberculosis should receive tuberculostatic therapy while being treated with beclometasone propionate.

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Special care is needed in patients with viral, bacterial and fungal infections of the eye or of the mouth or respiratory tract. In case

of bacterial infection of the respiratory tract an adequate antibiotic co-medication may be required.

The incidence of

candidiasis seems to be related to the administered dose and treatment

duration.

This affection generally

responds to a suitable topical antimycotic therapy, without discontinuing the treatment with beclometasone dipropionate.

It must be recommended that patients rinse their mouth with water immediately after inhalation to reduce the frequency of oral

candidiasis.

Hoarseness is reversible and disappears after discontinuation of treatment and / or rest of the voice.

Paradoxical bronchospasm may occur with an immediate increase in wheezing, shortness of breath and cough after dosing. This

should be treated immediately with a fast-acting inhaled bronchodilator. Becloneb should be discontinued immediately, the patient

assessed and, if necessary, alternative therapy instituted.

Reduction or

withdrawal

oral

corticosteroid therapy may unmask clinical

features of

Churg-Strauss syndrome and hyper

eosinophilic state.

Replacement

of systemic steroid treatment

with inhaled therapy sometimes also unmasks allergies such as allergic rhinitis or

eczema previously controlled by the systemic medicinal

product.

These allergies

should be symptomatically treated with

antihistamines and/or topical medicinal product, including steroids for local use.

Visual disturbance

Visual

disturbance may be reported with systemic and topical

corticosteroid use.

If a patient

presents with symptoms such as

blurred vision or other visual disturbances,

the patient should be considered for referral to an ophthalmologist for evaluation of

possible causes which may include cataract,

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

have been reported after use of systemic and topical corticosteroids.

Paediatric population

The decision to start nebulised beclometasone dipropionate for treatment of recurrent wheezing in children up to 5 years of age

should be determined by the severity and frequency of wheezing episodes. Regular follow-up is essential to review the treatment

response.

If no treatment

benefit

is observed within 2-3 months or if a diagnosis of asthma is not

likely,

Becloneb should be

discontinued to avoid unnecessary long-term exposure to inhaled corticosteroids and associated risks in children including growth

retardation (see section 4.8).

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

growth impairment

occurs,

the treatment

should be assessed with the aim of reducing the dose of inhaled corticosteroid.

benefits of the corticosteroid treatment and the possible risks on the growth suppression must be carefully weighed against one

another. Consideration can be given to referring the patient to paediatric pulmonologist.

There is insufficient data available regarding the possible growth-inhibiting effect of inhaled corticosteroids in infants and toddlers

less than 2 years.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacokinetic interactions

No formal pharmacokinetic drug-drug interaction studies have been conducted.

Beclometasone

dipropionate

undergoes

very

rapid

pre-systemic

metabolism via

esterase

enzymes

without

involvement of cytochrome P450 system.

Beclomethasone is less dependent on CYP3A metabolism than some other corticosteroids, and in general interactions

are unlikely;

however

the possibility of

systemic effects with concomitant

use of

strong CYP3A inhibitors (e.g.

ritonavir,

cobicistat) cannot be excluded,

and therefore caution and appropriate monitoring is advised with the use of

such agents.

Pharmacodynamic interactions

If used concomitantly with systemic or intranasal steroids the suppressive effect on adrenal function will be additive.

4.6 Fertility, pregnancy and lactation

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Pregnancy

No evidence of

teratogenic effects

in pregnant

women using inhaled beclometasone was

observed according to

published data.

However,

possible effects on foetal development after high dose inhaled beclometasone dipropionate

therapy could not be excluded.

Animal studies have shown reproductive toxicity (see section 5.3).

The possible benefits of inhaled beclometasone dipropionate for the mother must be weighed against the possible risk

the fetus or

neonate.

treatment

during pregnancy is necessary,

the lowest

effective dose of

beclometasone

dipropionate should be used.

Infants and neonates born to mothers receiving substantial

doses of beclometasone dipropionate during pregnancy

should be observed for adrenal suppression.

Breast-feeding

Since glucocorticoids are excreted in breast-milk,

it is reasonable to assume that beclometasone dipropionate and its

metabolites are also excreted into breast milk. However, at therapeutic doses of beclometasone dipropionate no effect

on the breastfed newborns/infants are anticipated.

No harmful effects on the suckling infants have been reported for glucocorticoids.

The benefits of breast-feeding are

likely to outweigh any theoretical risk.

Beclometasone

dipropionate

can be

used during breast-feeding.

However,

high dose

inhaled beclometasone

dipropionate is used it is recommended to avoid breast-feeding for 4 h after administration.

Fertility

No specific studies have been performed with beclometasone dipropionate with regard to the safety in human fertility.

Although results of animal studies have shown some impaired fertility, this occurs at high doses levels.

4.7 Effects on ability to drive and use machines

BECLONEB

has no or negligible influence on the ability to drive or use machines.

4.8 Undesirable effects

Summary of the safety profile

The most common adverse reactions observed during clinical trials using inhaled beclometasone in the treatment of asthma and

wheezing were laryngitis, pharyngitis and oral candidiasis.

A serious hypersensitivity reaction including oedema of the eye, face, lips and throat (angioedema) has been reported rarely.

Paradoxical bronchospasm may occur after dosing.

Tabulated list of adverse reactions

Adverse reactions observed in clinical trials with inhaled beclometasone in the treatment of asthma and wheezing are listed in the

table below according the MedDRA system organ class and frequencies:

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), not known (cannot be estimated from the

available data).

System Organ Class

Adverse Reaction

Frequency

Infections and infestations

Laryngitis, pharyngitis

Very common

Oral candidiasis

Common

Herpes simplex

*Rare

Endocrine disorders

Adrenal suppression**

Very Rare

Immune system disorders

Hypersensitivity reactions with the

following manifestations: angioedema,

rash, urticaria, pruritus,

*Rare

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* from spontaneous reporting

**systemic effects of inhaled corticosteroids

Description of selected adverse reactions

Systemic effect

of inhaled corticosteroids (including beclometasone dipropionate) may occur particularly when administered at

high doses for

prolonged periods of

time:

these may include adrenal

suppression,

decrease in bone mineral

density,

growth

retardation in children and adolescents, cataract and glaucoma (see section 4.4).

Measures to minimize the occurrence of candidiasis, hoarseness and paradoxical bronchospasm are described in section 4.4.

Paediatric population

Growth retardation and behavioural

disorders may be more prevalent

in children than in adults,

particularly at

high doses

administered for prolonged periods of time.

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

HPRA Pharmacovigilance,

Earlsfort

Terrace,

IRL -

Dublin 2;

Tel:

+353 1 6764971;

Fax:

+353 1 6762517.

Website:

http://www.hpra.ie/; E-mail: medsafety@hpra.ie.

4.9 Overdose

The use of beclometasone dipropionate nebuliser suspension in doses exceeding those recommended over a long period

of time could lead to the suppression of hypothalamic-pituitary-adrenal (HPA)-axis function. In this case monitoring of

adrenal

function is recommended.

Patients with adrenal

suppression are steroid dependent

and have to be treated

accordingly with supplementary systemic glucocorticosteroids.

Treatment

with BECLONEB

may continue at

lowest dose at which effective control of disease (asthma or wheezing) is maintained (see section 4.4).

With high doses for

a very short

period of

time,

suppression of

HPA-axis may occur.

In these cases no special

emergency action needs to be taken. The HPA-axis function will recover within 1-2 days.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Psychiatric disorders

Psychomotor hyperactivity, sleep

disorders anxiety, depression,

aggressiveness, behavioural changes

(predominantly in children)

Not known

Nervous system disorders

Headache

Uncommon

Tremor

*Rare

Eye disorders

Cataract**, glaucoma**

Very Rare

Vision, blurred (see also section 4.4)

Uncommon

Respiratory, thoracic and

mediastinal disorders

Cough

Common

Throat irritation, hoarseness,

dysphonia, paradoxical bronchospasm,

wheezing

Uncommon

Dyspnoea

*Rare

Gastrointestinal disorders

Nausea, dyspepsia

Common

Musculoskeletal and connective

tissue disorders

Growth retardation* (in children and

adolescents), bone density decreased*

Very rare

General disorders and

administration site conditions

Asthenia

*Rare

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Pharmacotherapeutic group: Other drugs for obstructive airway diseases, inhalants; Glucocorticoids

ATC code: R03 BA01.

Mechanism of action

The affinity of beclometasone dipropionate and its main active metabolite, beclometasone monopropionate (B17MP),

for the human glucocorticoid receptor has been determined.

The potency of B17MP is approximately 30-fold higher

than the parent compound. Therefore the majority of the effect is related to B17MP systemic exposure.

Pharmacodynamic effects

Beclometasone dipropionate is a glucocorticoid with potent anti-inflammatory activity with limited mineralocorticoid

activity; following administration to the respiratory system by inhalation a local effect in the lower respiratory tract is

obtained.

The systemic pharmacodynamic effects of beclometasone dipropionate and its active metabolite B17MP is

assessed by measuring the effects on hypothalamo-pituitary adrenal (HPA)-axis function.

In healthy males a single dose of 1600 µg beclometasone dipropionate by nebulisation had no effect on 24-h urinary

cortisol excretion, while a single dose of 3200 µg produced a urinary cortisol excretion reduction of about 10% without

any significant differences between the two dosage treatments.

No significant

effect

on morning serum cortisol

levels was reported in asthmatic patients after a 3-week treatment

period of 1600 and 3200 µg per day b.i.d. via a nebulizer.

Clinical efficacy and safety

Besides evidence coming from long lasting use of inhaled beclometasone in the treatment of asthma and wheezing, the

following data are a collection of the main supportive published data.

Asthma

A study in which the objective was to compare the efficacy and safety of nebulised beclometasone dipropionate versus

fluticasone propionate suspension for nebulization was conducted in 205 adults patients aged 18-65 years with asthma

randomized to a 12-week treatment period.

Comparable efficacy in controlling asthma was demonstrated by the two

treatments at study end in terms of pulmonary function tests,

asthma exacerbations,

symptoms and the use of rescue

salbutamol (Terzano et al., 2003).

Paediatric population

Asthma

A double-blind,

double-dummy,

multicentre,

randomized,

parallel-group study compared the efficacy and safety of

nebulised beclometasone dipropionate and beclometasone dipropionate administered with metered-dose inhalation in

151 patients,

aged 6-16 years, with moderate to severe asthma for 4 weeks. Comparable improvements over baseline

were reported at study end for the two treatment groups in morning pulmonary expiratory flow rate (primary endpoint),

clinical symptoms scores and the use of rescue salbutamol.

The two treatments were equally well tolerated (Bisca et

al., 2003).

Efficacy and safety of

nebulised beclometasone dipropionate in the treatment of severe persistent asthma in infants and

young children aged 6 months to 6 years,

in comparison to budesonide suspension for nebulization was assessed in a

multicentre, randomized, controlled open-labelled study for 14 weeks. In the study 40.4% and 51.7% patients in the of

nebulised beclometasone dipropionate and budesonide groups respectively did not experience any major exacerbation

(primary endpoint).

Both treatments were associated with a marked reduction in night-time wheezing and in the

number of days of steroid use.

Urinary cortisol

and the time course of height

and weight

were unaffected by both

treatments and of

nebulised beclometasone dipropionate confirmed to have a neutral

effect

on bone metabolism

(Delacourt et al., 2003).

Wheezing

Nebulised beclometasone dipropionate was evaluated in 276 children aged 1-4 years with frequent

wheezing in a

randomized,

double-blind,

12-week controlled trial.

Regular

nebulised beclometasone

dipropionate

plus

rescue

salbutamol

significantly increased the percentage of

symptom-free days (primary endpoint,

defined as a lack of

wheezing,

coughing,

shortness of breath and patients/parents nocturnal awakenings in 24 h) (69.6 ± 20.89 [SD]; P =

0.034)

placebo/rescue

salbutamol

(61.0

± 24.83

[SD])

combination

nebulised

beclometasone

dipropionate /rescue salbutamol (64.9 ± 24.74 [SD]) regardless of the presence of risk factors for developing asthma. In

addition,

the time to first

exacerbation was longer in children treated with nebulised beclometasone dipropionate.

terms of safety, no change in the values of morning salivary cortisol was detected (Papi et al., 2009).

5.2 Pharmacokinetic properties

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Beclometasone dipropionate (BDP)

is a pro-drug that

is hydrolysed via esterase enzymes to an active metabolite

beclometasone monopropionate (B17MP) the most abundant metabolite in plasma.

Absorption

Following inhalation,

systemic absorption of unchanged BDP occurs mainly through the lungs with negligible oral

absorption of the swallowed dose. The systemic absorption of the main active metabolite B17MP arises from both lung

deposition and oral absorption of the swallowed dose. The bioavailability of orally administered BDP is negligible but

pre-systemic conversion to B17MP results in absorption of approximately 40% of the swallowed portion as B17MP.

The absolute bioavailability following inhalation is approximately 2% and 62% of the nominal

dose for BDP and

B17MP respectively.

Distribution

Plasma protein binding is moderately high.

Following intravenous dosing,

the disposition of

BDP and its active

metabolite, B17MP, are characterised by high plasma clearance (150 and 120 L/h respectively), with a small volume of

distribution at steady state for BDP (20 L) and larger tissue distribution for its active metabolite (424 L).

Biotransformation

The main product

of metabolism is the active metabolite (B17MP).

Minor inactive metabolites,

beclometasone-21-

monopropionate (B21MP)

and beclometasone (BOH),

are also formed but

these contribute little to the systemic

exposure.

Elimination

BDP is cleared very rapidly from the systemic circulation, by metabolism mediated via esterase enzymes that are found

in most tissues. The renal excretion of BDP and its metabolites is negligible, faecal excretion is the major route of BDP

elimination mainly as polar metabolites.

The terminal elimination half-lives are 0.5 h and 2.7 h for BDP and B17MP

respectively.

Linearity/non-linearity

There is an approximately linear increase in systemic exposure of the active metabolite B17MP with increasing inhaled

dose.

Special populations

The pharmacokinetics of BDP in patients with renal

or hepatic impairment

has not

been studied;

however,

as BDP

undergoes a very rapid metabolism via esterase enzymes present in intestinal fluids, serum, lungs and liver to originate

more polar products B21MP,

B17MP and BOH,

hepatic impairment is not expected to modify the pharmacokinetics

and safety profile of BDP. As BDP or its metabolites were not traced in urine, an increase in systemic exposure is not

envisaged in patients with renal impairment.

5.3 Preclinical safety data

Preclinical toxic effects of beclometasone dipropionate were confined to those associated with over-stimulation of the

recognised pharmacological action.

In repeat-dose toxicity studies, administration of beclometasone dipropionate by nebulisation to rats (for 180 days) and

dogs (for 90 days) had no effect on body weight and blood cells or on trophism of the airways mucosa.

Hepatic and

renal functions remained within normal values.

Beclometasone was teratogenic and embryolethal

in animals after,

subcutaneous and oral

administration.

Animal

studies indicate that administration of glucocorticoids during pregnancy may increase the risk for intrauterine growth

retardation, adult cardiovascular and/or metabolic disease and/or neurobehavioral development.

Beclometasone dipropionate demonstrated to be non-genotoxic.

No evidence of carcinogenicity was observed in a 95-week study in rats treated by inhalation.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Polysorbate 20

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Sorbitan laurate

Sodium chloride

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

2 years.

Use the ampoules within 3 months from the first opening of the pouch.

For 800 micrograms ampoule only: after the first opening of the ampoule,

store it in a refrigerator (2

C – 8

remaining quantity has to be used within 12 hours after first opening.

6.4 Special precautions for storage

Store the ampoules in the upright position in the original package (carton box) in order to protect from light.

6.5 Nature and contents of container

Each polyethylene ampoule contains 400 micrograms beclometasone dipropionate suspension in 1 ml.

The 800 micrograms ampoule has a graduation mark to indicate half the content (corresponding to 400 micrograms).

Strips

ampoules

packed

heat

sealed

pouch

PET/Al/PE

(Polyethylene

Terephthalate/Aluminium/Polyethylene).

2, 4 or 8 pouches are packed into a carton, i.e. each carton contains 10, 20 or 40 ampoules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The ampoule should be used according to the following instructions:

Bend the ampoule backwards and forwards (Figure A).

Carefully separate a new ampoule from the strip, firstly from the top, then in the middle (Figure B), leaving the

rest in the pouch.

Vigorously shake and turn the ampoule upside-down in order to make the suspension homogeneous. Repeat this

operation, until the whole content is fully re-dispersed and mixed (Figure C).

Open the ampoule by rotating the flap as indicated by the arrow (Figure D).

Gently squeeze the ampoule content into the nebuliser chamber (Figure E).

The ampoule should be opened immediately before administration.

400 micrograms ampoule is for single use.

only half

dose of

BECLONEB

800 micrograms is needed hold the ampoule upside down,

ensuring that

graduation mark is clearly visible and apply moderate pressure.

Carefully squeeze out

the content

until

the level

suspension in the ampoule reaches the graduation mark and no further. Once half the content is used, reinsert the cap

upside down by pushing it

onto the container.

The ampoule closed in this way must

be stored at

2-8 C (in the

refrigerator) and the remaining quantity has to be used within 12 hours after first opening.

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BECLONEB

can be diluted. In this case, the content of the ampoule should be emptied into the nebuliser bowl. The

quantity of sterile sodium chloride 9 mg/ml (0.9%) solution required should be added. Once the nebuliser bowl cap is

inserted, the nebuliser should be shaken gently to mix the content.

ONLY sterile sodium chloride 9 mg/ml (0.9%) solution should be used.

The manufacturer’s instructions for use, maintenance and cleaning of the nebuliser must be followed.

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

7 MARKETING AUTHORISATION HOLDER

Chiesi Farmaceutici S.p.A.

26/A Via Palermo, 43122 Parma

Italy

8 MARKETING AUTHORISATION NUMBER

PA0584/003/001

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:

March 2005

Date of last renewal: 18

March 2010

10 DATE OF REVISION OF THE TEXT

April 2018

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