BECLATE Rotacaps (Beclomethasone dipropionate)

Table of Content

Qualitative and Quantitative Composition

BECLATE-100 Rotacaps

Each capsule contains:

Beclomethasone Dipropionate IP....... 100 mcg

BECLATE-200 Rotacaps

Each capsule contains:

Beclomethasone Dipropionate IP....... 200 mcg

BECLATE-400 Rotacaps

Each capsule contains:

Beclomethasone Dipropionate IP....... 400 mcg

Dosage Form and Strength

Dry powder for inhalation

Clinical Particulars

Therapeutic Indications

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

Children

Any child who requires prophylactic asthma medication.

Posology and Method of Administration

Adults and Children over 12 Years of Age

Patients should be given a starting dose of inhaled beclomethasone dipropionate, which is appropriate for the severity of their disease based on the following guidance:

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

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

Severe asthma: 1000 to 2000 micrograms 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 400 micrograms 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 older people or in those with hepatic or renal impairment.

BECLATE Rotacaps are for inhalation use only through the Cipla Rotahaler/Revolizer. For optimum results, BECLATE Rotacaps should be used regularly.  BECLATE Rotacaps must not be swallowed.

Contraindications

BECLATE Rotacaps is contraindicated in patients with a history of hypersensitivity to any of the components of the drug product.

Special Warnings & Precautions for Use

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.

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 Rotacaps 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' inhalation 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.

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.

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 Rotacaps should not be stopped abruptly.

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

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

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.

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.

Use in Special Population

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. In animal reproduction studies with beclomethasone dipropionate, adverse effects typical of potent corticosteroids are only seen at high systemic exposure levels; direct inhaled application ensures minimal systemic exposure. Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.

Lactation

The excretion of beclomethasone dipropionate in milk has not been studied in animals.

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. Beclomethasone dipropionate should only be used in a nursing mother if the expected benefit justifies the risk to the newborn/infant.

Effects on Ability to Drive and Use Machines

Beclomethasone dipropionate has no or negligible influence on the ability to drive and use machines.

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) and very rare (<1/10,000) including isolated reports and not known. 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

Very 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 the inhalation. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the BECLATE Rotacaps.

Immune System Disorders

Hypersensitivity reactions with the following manifestations have been reported:

Uncommon: Rashes, urticaria, pruritus, erythema

Very rare: Angioedema 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

Psychiatric Disorders

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

Unknown: Depression and aggression (predominantly in children).

Respiratory, Thoracic and Mediastinal Disorders

Common: Hoarseness, throat irritationThe use of a large volume 'spacer' device may be considered.

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.

Very rare:

Paradoxical bronchospasm

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

Eye Disorder

Not known: Vision, blurred, cataract, glaucoma.

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 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product.

Overdose

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.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 clinically appropriate (within the approved range) dosage for symptom control.

Pharmacological Properties

Mechanism of Action

Pharmacodynamic Properties

Beclomethasone dipropionate is a prodrug with weak glucocorticoid receptor binding affinity. It is hydrolysed via esterase enzymes to the active metabolite17 monopropionate (17-BMP) which has high topical anti-inflammatory activity.

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 within the lungs. The systemic absorption of B-17-MP arises from both lung deposition and oral absorption of the swallowed dose. The absolute bioavailability following inhalation is approximately 60% of the nominal dose for B-17-MP. 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 approximately 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 systemic exposure.

Distribution

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

Excretion

The elimination of BDP and B-17-MP is characterized by high plasma clearance (150 and 120 L/h), 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.

Nonclinical Properties

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal Toxicology or Pharmacology

The carcinogenicity of beclomethasone dipropionate was evaluated in rats which were exposed for a total of 95 weeks, 13 weeks at inhalation doses up to 0.4 mg/kg/day and the remaining 82 weeks at combined oral and inhalation doses up to 2.4 mg/kg/day. There was no evidence of treatment-related increases in the incidence of tumors in this study at the highest dose, which is approximately 37 and 72 times the MRHDID in adults and children, respectively, on a mg/m2 basis. Beclomethasone dipropionate did not induce gene mutation in bacterial cells or mammalian Chinese Hamster ovary (CHO) cells in vitro. No significant clastogenic effect was seen in cultured CHO cells in vitro or in the mouse micronucleus test in vivo. In rats, beclomethasone dipropionate caused decreased conception rates at an oral dose of 16 mg/kg/day (approximately 250 times the MRHDID in adults on a mg/m2 basis). Impairment of fertility, as evidenced by inhibition of the estrous cycle in dogs, was observed following treatment by the oral route at a dose of 0.5 mg/kg/day (approximately 25 times the MRHDID in adults on a mg/m2 basis). No inhibition of the estrous cycle in dogs was seen following 12 months of exposure to beclomethasone dipropionate by the inhalation route at an estimated daily dose of 0.33 mg/kg (approximately 17 times the MRHDID in adults on a mg/m2 basis).

Description

The active component of beclomethasone dipropionate, is an anti-inflammatory corticosteroid having the chemical name 9-chloro-11ß,17,21-trihydroxy-16ßmethylpregna-1,4-diene-3,20-dione 17,21-dipropionate. Beclomethasone dipropionate (BDP) is a diester of beclomethasone, a synthetic corticosteroid chemically related to dexamethasone. Beclomethasone differs from dexamethasone in having a chlorine at the 9-alpha carbon in place of a fluorine, and in having a 16 beta-methyl group instead of a 16 alpha-methyl group. Beclomethasone dipropionate is a white to creamy white, odorless powder with a molecular formula of C28H37ClO7 and a molecular weight of 521.1. Its chemical structure is:

Pharmaceutical Particulars

Incompatibilities

Not Applicable

Shelf-Life

Refer to the carton

Packaging Information

BECLATE-100 Rotacaps .......30 Rotacaps

BECLATE-200 Rotacaps ....... 30 Rotacaps

BECLATE-400 Rotacaps ....... 30 Rotacaps

Storage and Handling Instructions

Store below 30⁰C

Do not freeze.

Patient Counselling Information

Beclomethasone dipropionate belongs to a group of medicines called corticosteroids (often just called steroids). A very small dose of steroid is needed when it is inhaled. This is because it is inhaled straight to your lungs. BECLATE Rotacaps works by reducing swelling and irritation in the lungs. They have what is called an ‘anti-inflammatory action’. BECLATE Rotacaps helps to prevent asthma in people who need regular treatment. This is why they are sometimes called ‘preventers’. They need to be used regularly, every day. BECLATE Rotacaps will not help treat sudden asthma attacks where you feel breathless.  A different medicine is used for treating sudden attacks (called a ‘reliever’). If you have more than one medicine, be careful not to confuse them.

What You Need to Know Before You Use BECLATE Rotacaps?

Do not use BECLATE Rotacaps if you are allergic (hypersensitive) to beclometasone dipropionate or lactose (which contains small amount of milk proteins) or any of the other ingredients of BECLATE Rotacaps. Do not use BECLATE Rotacaps if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before using BECLATE Rotacaps.

Warnings and precautions:

Talk to your doctor, nurse or pharmacist before using BECLATE Rotacaps: · if you have ever been treated for tuberculosis (TB) ·

If you are using BECLATE Rotacaps at the same time as taking steroid tablets. Also if you have just finished taking steroid tablets. In both cases, you should carry a steroid warning card until your doctor tells you not to carry one. If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before using BECLATE Rotacaps.

Children: BECLATE Rotacaps is not recommended for use in children under 12yrs.

Other medicines and BECLATE Rotacaps: Tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines, including herbal medicines and medicines obtained without a prescription. Remember to take this medicine with you if you have to go into hospital.

Some medicines may increase the effects of BECLATE Rotacaps and your doctor may wish to monitor you carefully if you are taking these medicines (including some medicines for HIV: ritonavir, cobicistat).

BECLATE Rotacaps with food and drink: You can use BECLATE Rotacaps at any time of day, with or without food.

Pregnancy and breast-feeding: If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby ask your doctor for advice before taking this medicine.

Driving and using machines : BECLATE Rotacaps is not likely to affect you being able to drive or use any tools or machines.

BECLATE Rotacaps contains lactose Lactose contains small amounts of milk proteins, which may cause allergic reaction. If you have been told by your doctor that you do not tolerate certain kinds of sugars, talk to your doctor before using this medicine.

How to Use BECLATE Rotacaps?

Always use this medicine exactly as your doctor has told you. Check with your doctor, nurse or pharmacist if you are not sure. It takes a few days for this medicine to work and it is very important that you use it regularly. The usual dose for BECLATE Rotacaps Beclometasone is: Adults (over 18 years) including the Older people: Your doctor will start you on a dose appropriate to your condition. For prevention and long-term use the usual starting dose is one puff (actuation) (200 micrograms) twice a day. This may be increased to three to four puffs (actuations) (600-800 micrograms) per day, and then reduced when your condition has improved. The total daily dose may be given in two, three or four divided doses. Children: BECLATE Rotacaps is not recommended for use in children below 12yrs. If you are using high doses of an inhaled steroid for a long time you may sometimes need extra steroids for example during stressful circumstances such as a road traffic accident or before an operation. Your doctor may decide to give you extra steroid medicines during this time. If you use more BECLATE Rotacaps than you, talk to your doctor as soon as possible. It is important that you take your dose as stated on the pharmacist’s label or as advised by your doctor. You should not increase or decrease your dose without seeking medical advice. If you forget to use BECLATE Rotacaps. Take the next dose when it is due.Do not take a double dose to make up for a forgotten dose. If you stop using BECLATE Rotacaps. Do not stop treatment even if you feel better unless told to do so by your doctor. If you have any further questions on the use of this medicine, ask your doctor, nurse or pharmacist.

 Possible side effects:

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you notice any of the following serious side effects, stop using this medicine and talk to your doctor straight away. You may need urgent medical treatment. ·

Allergic reactions (affects less than 1 in 100 people) – the signs include skin rashes, redness, itching or weals like nettle rash or hives · severe allergic reactions (affects less than 1 in 10,000 people) - the signs include swelling of your face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing, itchy rash, feeling faint and light headed and collapse · your breathing or wheezing gets worse straight after using your inhaler.

Talk to your doctor as soon as possible if after 7 days of using BECLATE Rotacaps your shortness of breath or wheezing does not get better, or gets worse.

Other side effects include: Very Common (may affect more than 1 in 10 people) · thrush in the mouth and throat Common (may affect up to 1 in 10 people) · sore tongue or throat · hoarseness of voice · cough Problems with your mouth and throat can be reduced by doing certain things straight after inhaling your dose. These are brushing your teeth, rinsing your mouth or gargling with water and spitting it out. Tell your doctor if you have these problems with your mouth or throat, but do not stop treatment unless you are told to. Very rare (may affect up to 1 in 10,000 people) · a round, puffy face (called ‘moon face’) · weight gain, especially on the neck and shoulders · shortness of breath Using high-dose inhaled corticosteroids over a long time can cause, in very rare cases, systemic effects. These include: · decrease in bone mineral density (thinning bones) · growth retardation (slowing of growth) in children and adolescents. Your doctor may wish to check the height of your children regularly · increase pressure in your eyes (glaucoma) · cataract · lower respiratory tract infection · problems with how your adrenal glands work (adrenosuppression) - causing loss of appetite, abdominal pain, weight loss, tiredness, feeling sick, being sick, feeling faint, sweating and possible fits, you should consult your doctor. This is particularly important if you have been exposed to stress such as surgery, infection, an acute attack of asthma, or other serious illness. Your doctor may carry out blood test from time to time to monitor the level of steroids in your body. Your doctor will help stop this happening by making sure you use the lowest dose of steroid which controls your symptoms. Not known (frequency cannot be estimated from the available data). Although the frequency is not known, the following side effects may also occur: · Sleeping problems, depression or feeling worried, restless, nervous over-excited or irritable. These effects are more likely to occur in children.

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 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product

How to Store BECLATE Rotacaps ?

Keep this medicine out of the sight and reach of children. ·

Before the first use: store in unopened laminate pouch. After opening the laminate pouch: store below 30°C protected from moisture.

It is recommended to keep BECLATE Rotacaps in its protective cover. If your BECLATE Rotacaps gets damp, you need to replace it with a new one.

Replace BECLATE Rotacaps with a new one at the latest 6 months after you opened the laminate pouch, write down the date you opened the pouch to help you remember.

Do not use BECLATE Rotacaps after the expiry date which is stated on the BECLATE Rotacaps label and carton (EXP). The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Details of Manufacturer

Cipla Ltd.

Peninsula Business Park, Ganapatrao Kadam Marg,

Lower Parel West, Mumbai,

Maharashtra 400013

Details of Permission or Licence Number with Date

28/2/2010

Date of Revision

August 2019