SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Becodisks 400 Micrograms

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Beclometasone Dipropionate Monohydrate (Micronised) 414pg equivalent to 400pg Beclometasone Dipropionate

3    PHARMACEUTICAL FORM

Dry Powder for Inhalation via Diskhaler Device

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Clinical Indications

Beclometasone dipropionate provides effective anti-inflammatory action in the lungs, with a lower incidence and severity of adverse effects than those observed when corticosteroids are administered systemically. It also offers preventive treatment of asthma.

Becodisks are indicated for the following:

Adults

Prophylactic management in:

Mild asthma (PEF values greater than 80% predicted at baseline with less than 20% variability):

Patients requiring intermittent symptomatic bronchodilator asthma medication on more than an occasional basis.

Moderate asthma (PEF values 60-80% predicted at baseline with 20-30% variability):

Patients requiring regular asthma medication and patients with unstable or worsening asthma on other prophylactic therapy or bronchodilator alone.

Severe asthma (PEF values less than 60% predicted at baseline with greater than 30% variability):

Patients with severe chronic asthma. On transfer to high dose inhaled beclometasone dipropionate, many patients who are dependent on systemic corticosteroids for adequate control of symptoms may be able to reduce significantly or eliminate their requirement for oral corticosteroids.

4.2 Posology and method of administration

Becodisks are for administration by the inhalation route only using a Diskhaler device.

Patients should be made aware of the prophylactic nature of therapy with inhaled beclometasone dipropionate and that it should be taken regularly everyday even when they are asymptomatic.

Patients should be given a starting dose of inhaled beclometasone dipropionate which is appropriate for the severity of their disease. The dose may then be adjusted until control is achieved and should be titrated to the lowest dose at which effective control of asthma is maintained.

Adults

The contents of one blister (400 micrograms) twice daily is the usual maintenance dose. This may be increased to two blisters (800 micrograms) twice daily in patients for whom there is a clinical need.

Children

Not recommended in children.

Special Patient Groups

There is no need to adjust the dose in elderly patients or in those with hepatic or renal impairment.

4.3 Contraindications

Hypersensitivity to Becodisks or any of its components is a contraindication. (See Pharmaceutical Particulars - List of Excipients).

Special care is necessary in patients with active or quiescent pulmonary tuberculosis.

4.4 Special warnings and precautions for use

Patients should be instructed in the proper use of the Diskhaler to ensure that the drug reaches the target areas within the lungs. They should be made aware that Becodisks have to be used regularly everyday for optimum benefit. Patients should be made aware of the prophylactic nature of therapy with Becodisks and that they should be used regularly, even when they are asymptomatic.

Becodisks are not designed to relieve acute asthmatic symptoms for which an inhaled short-acting bronchodilator is required. Patients should be advised to have such rescue medication available.

Severe asthma requires regular medical assessment including lung function testing as patients are at risk of severe attacks and even death.

Increasing use of bronchodilators, in particular short-acting inhaled beta2

agonists to relieve symptoms indicates deterioration of asthma control. If 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.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and 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 dose of inhaled corticosteroid is titrated 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 corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.

Prolonged treatment with high doses of inhaled corticosteroids, particularly higher than recommended doses, may result in clinically significant adrenal suppression. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled beclometasone dipropionate and, if necessary, by giving a systemic steroid and/or antibiotic if there is an infection, and by use of beta-agonist therapy.

For the transfer of patients being treated with oral corticosteroids:

The transfer of oral steroid-dependent patients to Becodisks and their subsequent management needs special care as recovery from impaired adrenocortical function, caused by prolonged systemic steroid therapy, may take a considerable time.

Patients who have been treated with systemic steroids for long periods of time or at a high dose may have adrenocortical suppression. With these patients adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously.

After approximately a week, gradual withdrawal of the systemic steroid is commenced. Decrements in dosages should be appropriate to the level of maintenance systemic steroid, and introduced at not less than weekly intervals. For maintenance doses of prednisolone (or equivalent) of 10mg daily or less, the decrements in dose should not be greater than 1mg per day, at not less than weekly intervals. For maintenance doses of prednisolone in excess of 10mg daily, it may be appropriate to employ cautiously, larger decrements in dose at weekly intervals.

Some patients feel unwell in a non-specific way during the withdrawal phase despite maintenance or even improvement of the respiratory function. They should be encouraged to persevere with the Diskhaler and withdrawal of systemic steroid continued, unless there are objective signs of adrenal insufficiency.

Patients weaned off oral steroids whose adrenocortical function is impaired should carry a steroid warning card indicating that they may need supplementary systemic steroid during periods of stress, e.g. Worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.

Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks 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 Becodisks should not be stopped abruptly.

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

4.5 Interaction with other medicinal products and other forms of interaction

No interactions have been reported

4.6 Pregnancy and lactation

There is inadequate evidence of safety in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human foetus. It should be noted, however, that the foetal changes in animals occur after relatively high systemic exposure. Because beclometasone dipropionate is delivered directly to the lungs by the inhaled route it avoids the high level of exposure that occurs when corticosteroids are given by systemic routes.

The use of beclometasone dipropionate in pregnancy requires that the possible benefits of the drug be weighed against the possible hazards. It should be noted that the drug has been in widespread use for many years without apparent ill consequence.

No specific studies examining the transference of beclometasone dipropionate into the milk of lactating animals have been performed. It is reasonable to assume that beclometasone dipropionate is secreted in milk but at the dosages used for direct inhalation, there is low potential for significant levels in breast milk. The use of beclometasone dipropionate in mothers breast feeding their babies requires that the therapeutic benefits of the drug be weighed against the potential hazards to the mother and baby.

4.7 Effects on ability to drive and use machines

No adverse effect has been reported.

4.8 Undesirable effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1000 and <1/100), rare (>1/10,000 and <1/1000), very rare (<1/10,000) including isolated reports and not known (cannot be estimated from the available data). Very common, common and uncommon events were generally determined from clinical trial data. The incidence in placebo and comparator group has not been taken into account in estimation of these frequencies. Rare and very rare events were generally determined from spontaneous data.

System Organ Class	Adverse Event	Frequency
Infections & Infestations	Candidiasis of the mouth and throat.	Very Common
Immune System Disorders	Hypersensitivity reactions with the following manifestations:
	Rashes, urticaria, pruritis, erythema.	Uncommon
	Oedema of the eyes, face, lips and throat	Very Rare
	Respiratory symptoms (dyspnoea and/or bronchospasm)	Very Rare
	Anaphyl actoi d/anaphyl acti c reacti ons	Very Rare
Endocrine Disorders	Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract, glaucoma	Very Rare
Psychiatric Disorders	Anxiety, sleep disorders, behavioural changes, including hyperactivity and irritability (predominantly in children)	Very Rare
	Depression, aggression (predominantly in children)	Not known
Respiratory,	Hoarseness/throat irritation	Common
Thoracic & Mediastinal Disorders	Paradoxical bronchospasm	Very Rare

Candidiasis of the mouth and throat (thrush) occurs in some patients, the incidence of which is increased with doses greater than 400 micrograms beclometasone dipropionate per day. Patients with high blood levels of Candidaprecipitins, indicating a previous infection, are most likely to develop this complication. Patients may find it helpful to rinse out their mouth with water after using the Diskhaler. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with beclometasone dipropionate treatment.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract, glaucoma (see 4.4 Special Warnings and Precautions for Use).

In some patients inhaled beclometasone dipropionate may cause hoarseness or throat irritation. It may be helpful to rinse out the mouth with water immediately after inhalation.

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. The beclometasone dipropionate preparation should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

4.9 Overdose

Acute - inhalation of the drug in doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not necessitate emergency action being taken. In these patients treatment with beclometasone dipropionate by inhalation should be continued at a dose sufficient to control asthma; adrenal function recovers in a few days and can be verified by measuring plasma cortisol.

Chronic - use of inhaled beclometasone dipropionate in daily doses in excess of 1500 micrograms over prolonged periods may lead to adrenal suppression. Monitoring of adrenal reserve may be indicated. Treatment with inhaled beclometasone dipropionate should be continued at a dose sufficient to control asthma.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

BDP is a pro-drug with weak glucocorticoid receptor binding activity. It is hydrolysed via esterase enzymes to the active metabolite beclometasone -17-monopropionate (B-i 7-MP), which has high topical anti-inflammatory activity.

5.2 Pharmacokinetic properties Absorption

When administered via inhalation (via metered dose inhaler) there is extensive conversion of BDP to the active metabolite B-17-MP within the lungs prior to systemic absorption. The systemic absorption of B-17-MP arises from both lung deposition and oral absorption of the swallowed dose. When administered orally, in healthy male volunteers, the bioavailability of BDP is negligible but pre-systemic conversion to B-17-MP results in 41% (95% CI 27- 62 %) of the dose being available as B-17-MP.

Metabolism

BDP is cleared very rapidly from the systemic circulation, owing to extensive first pass metabolism. The main product of metabolism is the active metabolite (B-1 7-MP). Minor inactive metabolites, beclometasone-2 1-monopropionate (B-21-MP) and beclometasone (BOH), are also formed but these contribute little to systemic exposure.

Distribution

The tissue distribution at steady state for BDP is moderate (20L) but more extensive for B-17-MP (424L). Plasma protein binding is moderately high (87%).

Elimination

The elimination of BDP and B-17-MP are characterised by high plasma clearance (150 and 120L/h) with corresponding terminal elimination half lives of 0.5h and 2.7h. Following oral administration of titrated BDP, approximately 60% of the dose was excreted in the faeces within 96 hours mainly as free and conjugated polar metabolites. Approximately 12% of the dose was excreted as free and conjugated polar metabolites in the urine.

5.3    Preclinical safety data

No clinically relevant findings were observed in preclinical studies.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose(which contains milk protein)

6.2    Incompatibilities

No incompatibilities have been reported.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Do not store above 30°C

Nature and contents of container

Circular double foil blister pack consisting of:

A) Lidding material (i) polyester over-lacquer/hard tempered aluminium foil/heat seal lacquer of total thickness = 39.4 - 48.6p or (ii) nitrocellulose over-lacquer/hard tempered aluminium foil/heat seal lacquer of total thickness

= 37.0 42.0p.

B) Blister material - PVC film/aluminium foil/orientated polyamide. Becodisks are supplied as 8 blisters per Becodisk as follows:

-Carton containing 7 disks plus a Diskhaler -Carton Containing 15 disks plus a Diskhaler -Carton containing 2 disks plus a Diskhaler -Refill pack of 7 disks -Refill pack of 15 disks

-A starter pack consisting of a Diskhaler pre-load with one disk Not all pack sizes may be marketed

6.6 Special precautions for disposal

See Patient Information Leaflet

7 MARKETING AUTHORISATION HOLDER

Glaxo Wellcome UK Ltd.

Trading as Allen & Hanburys

Stockley Park West

Uxbridge

Middlesex

UB11 1BT

MARKETING AUTHORISATION NUMBER(S)

PL 10949/0057

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/01/1994 / 30/03/2005

DATE OF REVISION OF THE TEXT

23/08/2011