SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Pulvinal® Beclometasone Dipropionate 100 micrograms/metered dose inhalation powder.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Pulvinal® Dipropionate 100: Each actuation provides beclometasone 100 micrograms (metered dose) or 95 micrograms as emitted dose.

3 PHARMACEUTICAL FORM

Inhalation powder administered from a multidose powder inhaler.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Pulvinal® Beclometasone Dipropionate is indicated in the treatment of persistent bronchial asthma.

4.2. Posology and Method of Administration

Pulvinal® Beclometasone Dipropionate 100 micrograms/metered dose inhalation powder is for respiratory use only. Each inhalation provides 100 micrograms of beclometasone dipropionate.

STARTING DOSE

Adults

In mild asthma the starting dose is 200 - 400 micrograms per day. In moderate and severe asthma, the starting dose can be 800 to 1600 micrograms per day.

Children aged above 6 years

The starting dose is 100 micrograms 2 to 4 times daily according to the clinical response.

MAXIMUM DOSE

The maximum daily dose for adults is 2000 micrograms and 400 micrograms in children aged above 6 years.

No dose adjustment is required in elderly patients or in those with renal or hepatic impairment.

Instructions for use-

Do not remove the cap protecting the inhaler until the moment of use.

Unscrew the protective cap and before twisting the inhaler, hold it upright and tap it gently against a hard surface to level the powder in the chamber.

Press the dark brown button and rotate the inhaler body anti-clockwise until the red mark on the body shows through the hole in the mouthpiece (doseloading position).

While still holding the inhaler upright, rotate the inhaler body clockwise until the green mark on the body shows through the hole in the mouthpiece (dose-delivery position).

Breathe out deeply. While still holding the inhaler upright, put the mouthpiece between your lips and breathe in through your mouth. Hold your breath for a few seconds.

To obtain full therapeutic benefit, it is essential that the patient follows the instructions for use (see patient information leaflet) carefully.

4.3. Contra-indications

Known hypersensitivity to corticosteroids (or to the excipients).

4.4 Special warnings and precautions for use

Patients should be instructed in the proper use of the inhaler, and their technique checked, to ensure that the drug reaches the target areas within the lungs. They should also be made aware that Pulvinal Beclometasone Dipropionate has to be used regularly, every day, even when they are asymptomatic, if so advised.

Pulvinal Beclometasone Dipropionate is not designed to relieve acute asthma symptoms for which an inhaled short-acting bronchodilator is required. Patients should be advised to have such relief medication available.

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 or 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.

Treatment with Pulvinal Beclometasone Dipropionate should not be stopped abruptly.

Significant adrenal suppression rarely occurs before doses of 1500 micrograms per day of inhaled beclometasone dipropionate are exceeded. Reduction of plasma cortisol levels has been reported in some patients taking 2000 micrograms per day. In such patients, the risks of developing adrenal suppression should be balanced against the therapeutic advantages, and precautions taken to provide systemic steroid cover in situations of prolonged stress (e.g. elective surgery). Prolonged suppression of the hypothalamic-pituitary-adrenal (HPA) axis may eventually lead to systemic effects, including growth retardation in children and adolescents, decrease in bone mineral density, Cushing syndrome, Cushingoid features, 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 dose of inhaled steroid is titrated to the lowest dose at which effective control of symptoms is achieved.

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.

The transfer to Pulvinal Beclometasone Dipropionate 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 a considerable time. Approximately one week after initiating treatment with Pulvinal Beclometasone Dipropionate, reduction of the dose of systemic steroid can be commenced. The size of the reduction should correspond to the maintenance dose of systemic steroid. Adrenocortical function should be monitored regularly as the dose of systemic steroid is gradually reduced.

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 inhaled beclometasone dipropionate and to continue withdrawal of systemic steroid, 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 antihistamines and/or topical preparations, including topical steroids.

As with all inhaled corticosteroids, special care is necessary in patients with active or quiescent pulmonary tuberculosis, in patients with viral, bacterial & fungal infection of the eye, mouth or respiratory tract. In the case of bacterial infection of the respiratory tract adequate antibiotics co-medication will be required.

This product contains approximately 25mg of lactose monohydrate per dose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5.    Interactions with other medicinal products and other forms of Interaction

Due to the very low plasma concentration achieved after inhaled dosing, clinically significant drug interactions are in general unlikely. Care should be taken when co-administering known strong CYP 3A4 inhibitors (e.g. ketoconazole, itraconazole, nelfinavir, ritonavir) as there is a potential for increased systemic exposure to beclometasone.

4.6.    Pregnancy and Lactation

The safety of beclometasone dipropionate for use in human pregnancy has not been established. Reproduction toxicity studies in animals have revealed an increased incidence of foetal damage, the significance of which is considered uncertain in man. Since the possibility of suppression of the adrenal cortex in the newborn baby after long-term treatment must be considered the needs of the mother must be carefully weighed against the risk to the foetus. It is reasonable to assume that the drug is distributed into the breast milk, but at the dosages used for direct inhalation, there is low potential for significant levels in breast milk.

4.7. Effects on Ability to Drive and Use Machines

No effects of beclometasone dipropionate on the ability to drive and use machines have ever been reported.

4.8. Undesirable effects

Adverse events are listed below by system class and frequency. Frequencies are defined as: very common (^ 1/10), common (^ 1/100 and <1/10),

uncommon (s 1/1,000 and <1/100), rare 1/10,000 < 1/1,000), very rare (<1/10,000) and not known (cannot be estimated from available 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 and bruising	Uncommon
	Oedema of the eyes, face, lips and throat	Very Rare
	Respiratory symptoms (dyspnoea and/or bronchospasm)	Very Rare
	Anaphylactoid/anaphylactic reactions	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	Psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural changes (predominantly in children)	Unknown
Respiratory, Thoracic & Mediastinal Disorders	Hoarseness/throat irritation	Common
	Paradoxical bronchospasm	Very Rare

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. Pulvinal Beclometasone Dipropionate should be discontinued immediately, the patient assessed and, if necessary, alternative therapy instituted.

Candidiasis of the mouth and throat (thrush) occurs in some patients especially at higher dose. It may be recommended to rinse the mouth with water immediately after inhalation. Symptomatic candidiasis can be treated with topical anti-fungal therapy.

Inhaled corticosteroids may have some systemic effects, particularly at high doses prescribed for prolonged periods. These effects are adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density leading to osteoporosis, cataract and glaucoma and easy bruising of the skin, lower respiratory tract infections, including pneumonia, in older patient with chronic obstructive pulmonary disease (COPD).

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9. Overdose

No special emergency action needs to be taken. Adrenal function recovers in a few days and can be verified by measuring plasma cortisol. Treatment with Pulvinal® Beclometasone Dipropionate should be continued at the recommended dose to control the asthma.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

The active ingredient of Pulvinal® Beclometasone Dipropionate is beclometasone dipropionate (BDP) (ATC-Code R03 AB01) a topical corticosteroid endowed with potent anti-inflammatory and anti-allergic activity on the airways mucosa.

Beclometasone dipropionate, administered by inhalation and in recommended doses, has a glucocorticoid anti-inflammatory action within the lungs but no systemic effect.

5.2. Pharmacokinetic Properties

After inhalation, the beclometasone dipropionate absorbed directly from the lungs is rapidly metabolised by hepatic route to beclometasone-17-monopropionate and subsequently to the inactive alcohol derivative.

When BDP is administered by inhalation, only a reduced percentage of the dose is inhaled and reaches the respiratory tract, the majority of the dose being deposited in the mouth and subsequently swallowed. The pharmacological activity and metabolic fate of inhaled BDP may differ depending upon whether the steroid is absorbed from the lung or the gastrointestinal tract. The portion of the dose of inhaled BDP which is directly absorbed from the lung into the blood stream is rapidly metabolised by hepatic route to beclometasone-17-monopropionate and subsequently to the inactive alcohol derivative. The extent of biotransformation of BDP in the lung is limited.

Preclinical Safety Data

Preclinical data were confined to those associated with over-stimulation of the recognised pharmacological action, which is the only safety concern for human use derived from animals studies of beclometasone dipropionate. Reproduction toxicity studies in animals have, as with other glucocorticoids, revealed teratological and embryocidal effects and evidence of impaired fertility. In mice no adverse effects were seen at a dose of 11 micrograms/kg (LOAEL).

No data concerning mutagenicity is available. No evidence of carcinogenicity was observed in a 95-week study in rats.

Subacute toxicity inhalation studies conducted with magnesium stearate in rats and dogs did not evidence signs of toxicity up to doses about 260 and 12000 times higher than the maximum exposure achievable during the daily treatment with the new formulation. Subchronic inhalation studies in rats with the new formulation did not evidence signs of local irritancy to respiratory tract or systemic toxicity attributable to the magnesium stearate up to the highest dose (24-times the maximum possible exposure) tested. In addition, magnesium stearate has been shown to be non-toxic in acute (dermal, oral) through teratogenicity and carcinogenicity (oral) studies.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose monohydrate, magnesium stearate.

6.2.    Incompatibilities

Not applicable

6.3.    Shelf Life

3 years.

6.4.    Special Precautions for Storage

Do not store above 30°C. Keep the container tightly closed.

Nature and Contents of Container

Multidose dry powder inhaler (Pulvinal ®) consisting of a light brown mouthpiece, a transparent body-reservoir, a dark brown base containing a desiccant and a light brown protective cap. Each Pulvinal® Beclometasone Dipropionate 100 micrograms/metered dose inhalation powder provides 100 metered doses.

6.6. Instruction for Use/Handling

Do not remove the cap protecting the inhaler until the moment of use.

To obtain full therapeutic success, it is essential that the patient carefully follows the instructions for use.

7. MARKETING AUTHORISATION HOLDER

Chiesi Limited 333 Styal Road Manchester M22 5LG United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 08829/0124

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

16/12/2008

10 DATE OF REVISION OF THE TEXT

27/08/2015