Easyhaler^® Beclometasone 200 micrograms/dose inhalation powder

For excipients, see section 6.1

Inhalation powder administered from multidose powder inhaler.

Beclomethasone dipropionate given by inhalation offers preventative treatment for asthma. It provides effective anti-inflammatory action in the lungs without the problems of systemic corticosteroid treatment.

Easyhaler^® Beclometasone 200 micrograms/dose is indicated in the prophylactic management of mild, moderate, or severe asthma in adults.

Mild asthma: Patients requiring symptomatic bronchodilator asthma medication on a regular basis.

Moderate asthma: Patients with unstable or worsening asthma despite prophylactic therapy or bronchodilator alone.

Severe asthma: Patients with severe chronic asthma and those who are dependent on systemic corticosteroids for adequate control of symptoms. 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 when they are transferred to high dose inhaled beclomethasone dipropionate.

Easyhaler^® Beclometasone 200 micrograms/dose is for oral inhalation use only. Patients should be given a starting dose of inhaled beclomethasone dipropionate appropriate to the severity of their disease. The dose may then be adjusted until control is achieved, or reduced to the minimum effective dose according to individual response.

Adults (including the elderly): The usual starting dose is 200 micrograms twice a day. In more severe cases the starting dose may need to increase to 600 to 800 micrograms per day which may then be reduced when the patient's asthma has stabilised. The total daily dose may be administered as two, three, or four divided doses.

Easyhaler^® Beclometasone 200 micrograms/dose is not recommended for children.

Hypersensitivity to any of the components.

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

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 Easyhaler^® Beclometasone 200 micrograms/dose has to be used regularly, every day, even when they are asymptomatic, for optimum benefit.

Easyhaler^® Beclometasone 200 micrograms/dose 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.

Severe asthma requires regular medical assessment, including lung-function testing, as patients are at risk of severe attacks and even death. Patients must be instructed to seek medical attention if short-acting relief bronchodilator treatment becomes less effective, or more inhalations than usual are required as this may indicate deterioration of asthma control. In this situation, patients should be assessed and the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroid or a course of oral corticosteroid) considered.

Severe exacerbations of asthma must be treated in the normal way, e.g. by increasing the dose of inhaled beclomethasone dipropionate and, if necessary by giving a systemic steroid, and/or an antibiotic if there is an infection, and by use of β-agonist therapy.

Treatment with Easyhaler^®Beclometasone 200 micrograms/dose should not be stopped abruptly.

Significant adrenal suppression rarely occurs before doses of 1,500 micrograms per day of inhaled beclomethasone dipropionate are exceeded. Reduction of plasma cortisol levels has been reported in some patients taking 2,000 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. Prolonged suppression of the hypothalamic-pituitary-adrenal (HPA) axis may eventually lead to systemic effects, including growth retardation in children and adolescents.

The transfer to Easyhaler^® Beclometasone 200 micrograms/dose 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 Easyhaler^® Beclometasone 200 micrograms/dose, reduction of the dose of systemic steroid can be commenced. The size of the reduction should correspond to the maintenance dose of systemic steroid. Reductions in dose of not more than 1mg are suitable for patients receiving maintenance doses of 10mg daily or less of prednisolone or its equivalent. Larger reductions in dose may be appropriate for higher maintenance doses. The reductions in dose should be introduced at not less than weekly intervals. 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 beclomethasone 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 antihistamine and/or topical preparations, including topical steroids.

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

None reported.

There is inadequate evidence of safety in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human fetus. It should be noted, however, that the fetal changes in animals occur after relatively high systemic exposure. Easyhaler^® Beclometasone 200 micrograms/dose delivers the drug directly to the lungs by the inhaled route and so avoids the high level of exposure that occurs when corticosteroids are given by systemic routes.

The use of beclomethasone dipropionate in pregnancy requires that the possible benefits of the drug be weighed against the possible hazards.

No specific studies examining the transference of beclomethasone dipropionate into the milk of lactating animals have been performed. It is reasonable to assume that beclomethasone 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 beclomethasone 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.

None reported.

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. Easyhaler^® Beclometasone 200 micrograms/dose should be discontinued immediately, the patient assessed and, if necessary, alternative therapy instituted.

Hypersensitivity reactions including anaphylactic shock, urticaria, rashes, angioedema, pruritus and erythema, and oedema of the eyes, face, lips and throat, have been reported.

Candidiasis of the mouth and throat (thrush) occurs in some patients, the incidence increasing with doses greater that 400 micrograms of beclomethasone dipropionate per day. Patients with high blood levels of Candida precipitins, indicating a previous infection, are most likely to develop this complication. Patients may find it helpful to rinse their mouth thoroughly with water after using the inhaler. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with Easyhaler^® Beclometasone 200 micrograms/dose.

In some patients inhaled beclomethasone dipropionate may cause hoarseness, cough, throat irritation and sore throat. It may be helpful to rinse the mouth out with water immediately after inhalation.

Miscellaneous undesirable effects - eosinophilic pneumonia, disturbance of growth in children, behavioural changes in children, subcapsular cataracts, easy bruising, skin thinning, decrease of bone metabolism.

With higher than the recommended doses or during long-term therapy in rare cases systemic undesirable effects like increase of intraocular pressure, glaucoma, and osteoporosis can occur.

Acute: Inhalation of the drug in doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not require emergency action. In these patients treatment 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 beclomethasone dipropionate in daily doses in excess of 1,500 micrograms over prolonged periods may lead to some degree of adrenal suppression. Monitoring of adrenal reserve may be indicated. Treatment should be continued at a dose sufficient to control asthma.

In case of an overdose, the contra-indications, side effects and warnings with regard to systemically applied corticosteroids should be taken into account.

Beclomethasone dipropionate is a synthetic steroid derivative. It has a potent local anti-inflammatory effect on the respiratory mucosa when administered topically. Long-term studies have shown that after the initiation of inhaled Beclomethasone in patients with bronchial asthma, the dose of systemic corticosteroids may be gradually reduced. There is no evidence that the drug damages tracheobronchial mucosa or increases the incidence of respiratory infections.

The exact mechanisms responsible for the anti-inflammatory effect of Beclomethasone dipropionate are unknown.

Approximately 10-25 % of the inhaled drug dose reaches the lungs and the biggest fraction of the dose is retained in the upper airways and mouth and is swallowed. The drug absorbed from the lungs is ultimately metabolized in the liver. Beclomethasone dipropionate is metabolized to active 17-Beclomethasone mono-propionate, and free Beclomethasone and metabolites are mainly excreted to faeces. Less than 10 % of the drug and its metabolites is excreted in urine.

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 animal studies. Reproduction toxicity studies in animals have, as with other glucocorticoids, revealed teratological and embryocidal effects and evidence of impaired fertility. No data concerning mutagenicity are available. No evidence of carcinogenicity was observed in a 95-week study in rats. Beclomethasone dipropionate is non-genotoxic.

Lactose monohydrate

None

2 years in aluminium foil and 6 months after opening of the foil.

Do not store above 25°C.

The Easyhaler inhaler, which consists of seven plastic parts and a stainless steel spring, is wrapped in aluminium foil. The inhaler with aluminium foil and the protective cover are packed in a cardboard box.

Packages:

Easyhaler^® Beclometasone 200 micrograms/dose inhalation powder:

200 doses protective cover

200 doses

2 x 200 doses

Patients have to be instructed to perform a rapid and forced inhalation through the Easyhaler device. Patients have to be instructed not to exhale into the device. Illustrated user's instructions for use accompany each package.

Orion Corporation

PO Box 65

02101 Espoo

Finland

PL 27925/0001

21 December 1999/August 2004

27 February 2007