BECOTIDE^™ JUNIOR
BECOTIDE^™ 100
BECLOFORTE^™

Beclomethasone dipropionate Inhaler

Qualitative and Quantitative Composition

BECOTIDE Junior Inhaler is a metered dose aerosol which delivers 50mcg of beclomethasone dipropionate per actuation.

BECOTIDE 100 Inhaler is a metered dose aerosol which delivers 100mcg of beclomethasone dipropionate per actuation.

BECLOFORTE Inhaler is a metered dose aerosol which delivers 250mcg of beclomethasone dipropionate per actuation.

Pharmaceutical Form

Pressurised inhalation, suspension.

Clinical Particulars

Therapeutic Indications

Beclomethasone dipropionate provides effective anti-inflammatory action in the lungs and offers preventive background treatment of asthma.

Severe asthma requires regular medical assessment as death may occur. Patients with severe asthma have constant symptoms and frequent exacerbations, with limited physical capacity, and PEF values below 60% predicted at baseline with greater than 30% variability, usually not returning entirely to normal after a bronchodilator. These patients will require high dose inhaled (see dosage instructions) or oral corticosteroid therapy. Sudden worsening of symptoms may require increased corticosteroid dosage which should be administered under urgent medical supervision.

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 beclomethasone 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.

Children:-

Any child who requires prophylactic asthma medication.

Posology and Method of Administration

BECOTIDE/BECLOFORTE Inhaler is administered by the inhaled route only.

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

The dosage of beclomethasone dipropionate should be adjusted according to the individual response.

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 patients who find co-ordination of a pressurised metered dose inhaler difficult a Volumatic spacer may be used with BECOTIDE/BECLOFORTE Inhaler.

Adults and children over 12 years of age:-

Patients should be given a starting dose of inhaled beclomethasone dipropionate (BECOTIDE Junior or BECOTIDE 100 Inhaler or BECLOFORTE Inhaler) which is appropriate for the severity of their disease based on the following guidance:

Mild asthma: 200 to 600mcg per day in divided doses.

Moderate asthma: 600 to 1000mcg per day in divided doses.

Severe asthma: 1000 to 2000mcg per day in divided doses.

The dose may then be adjusted until control is achieved or reduced to the minimum effective dose according to the individual response.

Children over 4 years of age:-

Up to 400mcg per day in divided doses.

Children should be given a starting dose of inhaled beclomethasone dipropionate which is appropriate for the severity of their disease.

The dose may then be adjusted until control is achieved or reduced to the minimum effective dose according to the individual response.

Special patient groups:-

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

Contra-indications

BECOTIDE/BECLOFORTE Inhaler is contra-indicated in patients with a history of hypersensitivity to any of its components.

Special Warnings and Special Precautions for Use

The management of asthma should follow a stepwise programme, and patient response should be monitored clinically and by lung function tests.

Sudden and progressive deterioration in asthma control is potentially life-threatening and consideration should be given to increasing corticosteroid dosage. In patients considered at risk, daily flow monitoring may be instituted.

BECOTIDE/BECLOFORTE Inhaler is not for use in acute attacks but for routine long-term management. Patients will require a fast- and short- acting inhaled bronchodilator to relieve acute asthmatic symptoms.

Patients' inhaler technique should be checked to make sure that aerosol actuation is synchronised with inspiration of breath for optimum delivery of the medicine to the lungs.

Lack of response or severe exacerbations of asthma should be treated 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.

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods; these effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. It is important, therefore, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control is maintained (see Undesirable Effects).

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

Certain individuals can show greater susceptibility to the effects of inhaled corticosteroid than do most patients.

Because of the possibility of impaired adrenal response, patients transferring from oral steroid therapy to inhaled beclomethasone dipropionate therapy should be treated with special care, and adrenocortical function regularly monitored.

Following introduction of inhaled beclomethasone dipropionate, withdrawal of systemic therapy should be gradual and patients encouraged to carry a steroid warning card indicating the possible need for additional therapy in times of stress.

In rare cases inhaled therapy may unmask underlying eosinophilic conditions (e.g. Churg Strauss syndrome). These cases have usually been associated with reduction or withdrawal of oral corticosteroid therapy. A direct causal relationship has not been established.

Similarly replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies such as allergic rhinitis or eczema previously controlled by the systemic medicine. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids.

Treatment with BECOTIDE/BECLOFORTE Inhaler should not be stopped abruptly.

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

Use During Pregnancy and Lactation

There is inadequate evidence of safety of beclomethasone dipropionate in human pregnancy. In animal reproduction studies adverse effects typical of potent corticosteroids are only seen at high systemic exposure levels; direct inhaled application ensures minimal systemic exposure.

Administration of medicines during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

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 medicine be weighed against the potential hazards to the mother and baby.

Effects on Ability to Drive and Use Machines

Beclomethasone dipropionate is unlikely to produce an effect.

Interaction with Other Medicinal Products and Other Forms of Interaction

There are no proven drug interactions.

Undesirable Effects

Candidiasis of the mouth and throat (thrush) occurs in some patients, the incidence of which is increased with doses greater than 400mcg 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 out their mouth with water after using the inhaler. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the BECOTIDE/BECLOFORTE Inhaler.

In some patients inhaled beclomethasone dipropionate may cause hoarseness or throat irritation. It may be helpful to rinse out the mouth with water immediately after inhalation. The use of a large volume 'spacer' device may be considered.

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. BECOTIDE/BECLOFORTE Inhaler should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

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

Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma (see Special Warnings and Special Precautions for Use).

Overdose

Acute inhalation of beclomethasone dipropionate doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not need emergency action as adrenal function is recovered in a few days, as verified by plasma cortisol measurements. However if higher than recommended dosage is continued over prolonged periods, some degree of adrenal suppression may result. Monitoring of adrenal reserve may be necessary. In cases of beclomethasone dipropionate overdose, therapy may still be continued at a suitable dosage for symptom control.

Pharmacological Properties

Pharmacodynamic Properties

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

Pharmacokinetic Properties

Absorption

When administered via inhalation (via metered dose inhaler), systemic absorption of unchanged BDP occurs through the lungs with negligible oral absorption of the swallowed dose. There is extensive conversion of BDP to its active metabolite B-17-MP within the lung prior to absorption. The systemic absorption of B-17-MP arises from both lung deposition (36%) and oral absorption of the swallowed dose (26%). The absolute bioavailability following inhalation is approximately 2% and 62% of the nominal dose for unchanged BDP and B-17-MP respectively. BDP is absorbed rapidly with peak plasma concentrations first being observed (t_max) at 0.3 hours. B-17-MP appears more slowly with a t_max of 1 hour. There is an approximately linear increase in systemic exposure with increasing inhaled dose.

When administered orally the bioavailability of BDP is negligible but pre-systemic conversion to B-17-MP results in 41% of the dose being absorbed as B-17-MP.

Metabolism

BDP is cleared very rapidly from the systemic circulation, by metabolism mediated via esterase enzymes that are found in most tissues. The main product of metabolism is the active metabolite (B-17-MP). Minor inactive metabolites, beclomethasone-21-monopropionate (B-21-MP) and beclomethasone (BOH), are also formed but these contribute little to the 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/hour) with corresponding terminal elimination half-lives of 0.5 hours and 2.7 hours. Following oral administration of tritiated 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. The renal clearance of BDP and its metabolites is negligible.

Preclinical Safety Data

Preclinical safety studies indicate that beclomethasone dipropionate shows negligible systemic toxicity when administered by the inhaled route.

Pharmaceutical Particulars

List of Excipients

Oleic acid,
Trichlorofluoromethane,
Dichlorofluoromethane.

Incompatibilities

None reported.

Shelf Life

Special Precautions for Storage

Protect from frost and direct sunlight.

Do not store above 30°C.

As with most inhaled medications in aerosol canisters, the therapeutic effect of this medication may decrease when the canister is cold.

The canister should not be punctured, broken or burnt even when apparently empty.

Medicines Classification

Prescription Medicine