BECLATE Inhaler (Beclomethasone dipropionate)

Table of Content

Composition

BECLATE-100 Inhaler

Each actuation delivers:

Beclomethasone Dipropionate IP…………. 100 mcg

Suspended in propellant HFA 134a…..........q.s.

BECLATE-200 Inhaler

Each actuation delivers:

Beclomethasone Dipropionate IP………….. 200 mcg

Suspended in propellant HFA 134a…...........q.s.

Dosage Form

Inhalation Aerosol

Pharmacology

Pharmacodynamics

Beclomethasone dipropionate is a prodrug that is rapidly activated by hydrolysis to the active monoester, 17 monopropionate (17-BMP). Beclomethasone 17 monopropionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 13 times that of dexamethasone, 6 times that of triamcinolone acetonide, 1.5 times that of budesonide and 25 times that of beclomethasone dipropionate. The clinical significance of these findings is unknown.

Studies in patients with asthma have shown a favorable ratio between topical anti-inflammatory activity and systemic corticosteroid effects with beclomethasone.

Pharmacokinetics

Absorption    

Systemic absorption of unchanged beclomethasone dipropionate (BDP) occurs through the lungs. There is negligible oral absorption of the swallowed dose of unchanged BDP. Prior to absorption there is extensive conversion of BDP to its active metabolite B-17-MP. 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 60% of the nominal dose for unchanged B-17-MP, respectively. BDP is absorbed rapidly with peak plasma concentrations observed (tmax) at 0.3 hour. B-17-MP appears more slowly with a tmax 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 40% 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 (20 L) but more extensive for B-17-MP (424 L). Plasma protein binding is moderately high (87%).

Elimination

The elimination of BDP and B-17-MP are characterised by high plasma clearance (150 L/hour and 120 L/hour) with corresponding terminal elimination half-lives of 0.5 hour and 2.7 hour. 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.

Indications

Prophylactic management of mild, moderate or severe asthma

Dosage and Administration

Adults and Adolescents

Starting and Maintenance Dose

It is important to gain control of asthma symptoms and optimize pulmonary function as soon as possible. When patients' symptoms remain under satisfactory control, the dose should be titrated to the lowest dose at which effective control of asthma is maintained.

To be effective, inhaled BECLATE Inhaler must be used on a regular basis even when patients are asymptomatic.

Therapy in new patients should be initiated at the following dosages

Mild asthma             : 100 to 200 micrograms per day in two divided doses.

Moderate asthma     : 200 to 400 micrograms per day in two divided doses.

Severe asthma         : 400 to 800 micrograms per day in two divided doses.

The maximum recommended dose is 800 mcg per day in divided doses.

Children

There are no data to date on beclomethasone dipropionate  in children under 12 years of age, hence no definitive dosage recommendation can be made.

Special Patient Group

No special dosage recommendations are made for elderly patients or patients with hepatic or renal impairment.  

Contraindications

BECLATE Inhaler is contraindicated in patients with a history of hypersensitivity to any of its components.

Warnings and Precautions

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

Increasing use of short-acting inhaled beta2-agonists to control symptoms indicates deterioration of asthma control. Under these conditions, the patient's therapy plan should be reassessed and the need for increased anti-inflammatory therapy should be considered.

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.

BECLATE Inhaler is not indicated in the management of status asthmaticus.

BECLATE 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 synchronized with inspiration of breath for optimum delivery of the drug 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 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 behavourial 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 is maintained.

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.

Withdrawal of systemic steroid should be gradual starting approximately one week after initiating treatment with beclomethasone dipropionate Inhaler. The size of the reduction should correspond to the maintenance dose of systemic steroid. For patients receiving maintenance doses of 10mg daily or less of prednisolone (or equivalent) reductions in dose of not more than 1mg are suitable. For higher maintenance doses, larger reductions in dose may be appropriate. The dose reduction scheme should be chosen to correlate with the magnitude of the maintenance systemic steroid dose. These oral dosage reductions should be introduced at not less than weekly intervals.

Adrenocortical function should be monitored regularly as recovery from impaired adrenocortical function, caused by prolonged systemic steroid therapy is slow

Some patients feel unwell in a non-specific way during withdrawal of systemic steroids despite maintenance or even improvement of 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 HPA axis suppression.

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 supplementary systemic steroids in times of stress, e.g. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.

Similarly 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 BECLATE Inhaler should not be stopped abruptly.

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

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

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 which have been reported after use of systemic and topical corticosteroids.

Patients should be advised that this product contains small amounts of ethanol and glycerol. At the normal doses the amounts of ethanol and glycerol are negligible and do not pose a risk to patients.

Drug Interactions

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.

BECLATE Inhaler contains a small amount of ethanol. There is a theoretical potential for interaction in particularly sensitive patients taking disulfiram or metronidazole.

Hepatic Impairment

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

Renal Impairment

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

Pregnancy

There is inadequate evidence of safety of beclomethasone dipropionate 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 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. Beclomethasone dipropionate is delivered 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. The drug has been in widespread use for many years without apparent ill consequence.

Lactation

No specific studies examining the transfer of beclomethasone dipropionate into the milk of lactating animals have been performed.

It is reasonable to assume that beclomethasone dipropionate is excreted in milk but at the dosages used for direct inhalation, there is low potential for significant levels in breast milk. In mothers breast feeding their baby the therapeutic benefits of the drug should be weighed against the potential hazards to mother and baby.

There is inadequate evidence of the safety of beclomethasone dipropionate or HFA-134a or propellant in human pregnancy or lactation.

Studies of the effect of HFA-134a on reproductive function and embryo-foetal development in animals have revealed no clinically relevant adverse events.

Undesirable Effects

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

As with other inhaled therapy, paradoxical bronchospasm may occur after dosing. Immediate treatment with a short-acting bronchodilator should be initiated, beclomethasone dipropionate  should be discontinued immediately and an alternate prophylactic treatment introduced.

Systemic effects of inhaled corticosteroids may occur, particularly with high doses prescribed for prolonged periods. These include adrenal suppression, growth retardation in children, decrease in bone mineral density and the occurrence of cataract and glaucoma.

Commonly, when taking beclomethasone dipropionate, hoarseness and candidiasis of the throat and mouth may occur.

To reduce the risk of hoarseness and candida infection, patients are advised to rinse their mouth after using their Inhaler.

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), and not known (cannot be estimated from the available data) including isolated reports. 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.

Infections and Infestations

Common: Candidiasis of the mouth and throat.

Candidiasis of the mouth and throat (thrush) occurs in some patients, the incidence of which is increased with doses greater than 400 micrograms 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 BECLATE Inhaler.

Immune System Disorders

Uncommon: Rash, urticaria, pruritus, erythema,  

Rare: Allergic reactions, angioedema of the eyes, face, lips and throat

Very rare: Respiratory symptoms (dyspnoea and/or bronchospasm) and anaphylactoid/anaphylactic reactions

Endocrine Disorders

Possible systemic effects include:

Very rare: Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.

Nervous System Disorders

Uncommon: Headache, vertigo, tremor

Psychiatric Disorders

Very rare: Anxiety, sleep disorders and behavioural changes, including hyperactivity, irritability (predominantly in children,

Unknown: Depression and aggression.

Gastrointestinal Disorders

Common: Taste disturbances

Uncommon: Nausea

Respiratory, Thoracic and Mediastinal Disorders

Common: Hoarseness, throat irritation, pharyngitis

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.

Uncommon: Cough, increased asthma symptoms

Rare: Paradoxical bronchospasm

Skin and Subcutaneous Tissue Disorders

Uncommon: Urticaria, rash, pruritus, erythema, purpura

Musculoskeletal and connective tissue disorders: Very rare: Decrease

Eye Disorders

Uncommon: Vision blurred

Very rare: Cataract*, glaucoma*

Not known: Central serous retinopathy

*Systemic reactions are a possible response to inhaled corticosteroids, especially when a high dose is prescribed for a prolonged time

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

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024.

By reporting side-effects, you can help provide more information on the safety of this product.

Overdosage

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.

There is no specific treatment for an overdose of beclomethasone dipropionate. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.

Packaging Information

BECLATE 100 Inhaler.......... Canister containing 200 metered doses

BECLATE 200 Inhaler.......... Canister containing 200 metered doses

Last Updated: Jan 2019

Last Reviewed: Jan 2019