QVAR EASI-BREATHE 50 MICROGRAMS PER ACTUATION INHALER - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Qvar Easi-Breathe 50 micrograms per actuation pressurised inhalation solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Beclometasone Dipropionate 50 micrograms per metered (ex-valve) dose.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Pressurised inhalation, solution.

A colourless solution in a pressurised aluminium canister fitted with a metering valve and an actuator.

Qvar Easi-Breathe contains a propellant, which does not contain any chlorofluorocarbons (CFCs).

4 CLINICAL PARTICULARS

4.1. Therapeutic indications

Prophylactic management of mild, moderate or severe asthma.

4.2 Posology and method of administration

Posology

Qvar Easi-Breathe is for inhalation use only.

Patients should be instructed in the proper use of their inhaler, including rinsing out their mouth with water after use.

NOTE: The recommended total daily dose of Qvar Easi-Breathe is lower than that for current beclometasone dipropionate containing products and should be adjusted to the needs of the individual patient.

ADULT STARTING AND MAINTENANCE DOSE:

It is important to gain control of asthma symptoms and optimise 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 Qvar Easi-Breathe must be used on a regular basis even when patients are asymptomatic.

THERAPY IN NEW PATIENTS SHOULD BE INITIATED AT THE FOLLOWING 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.

Patients on budesonide inhalers may be transferred to Qvar as described below.

The general approach to switching patients to Qvar involves two steps as detailed below. Specific guidance on switching well-controlled and poorly-controlled (symptomatic) patients is given below the table.

Step 1: Consider the dose of budesonide-containing inhalers appropriate to the patient’s current condition.

Step 2: Convert the budesonide inhaler dose to the Qvar dose according to the table below.

Patients with well-controlled asthma using budesonide inhaler products should be switched to Qvar at a dose in accordance with the table above.

For example:

Patients on 2 puffs twice daily of budesonide 100 micrograms would change to 2 puffs twice daily of Qvar 50 micrograms.

Patients with poorly-controlled asthma may be switched from budesonide inhaler products to Qvar at the same microgram for microgram dose up to 800 microgram­s daily.

Alternatively the patient’s current budesonide inhaler dose can be doubled and this dose can be converted to the Qvar dose according to the table above.

Patients on fluticasone inhalers may be transferred to the same total daily dose of Qvar up to 800 microgram­s daily.

Once transferred to Qvar Easi-Breathe the dose should be adjusted to meet the needs of the individual patient.

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

The same total daily dose in micrograms from either Qvar Easi-Breathe 50 (a lower strength) or Qvar Easi-Breathe 100 Inhaler provides the same clinical effect.

Patients should be instructed in the proper use of their inhaler, including rinsing out their mouth with water after use. Patients should be advised that Qvar Easi-Breathe may have a different taste and feel than a CFC inhaler.

Paediatric population

There are no data to date on Qvar Easi-Breathe in children under 12 years of age, hence no definitive dosage recommendation can be made.

Special patient groups

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

Method of administration

The aerosol spray is inhaled through the mouth into the lungs. The inhaler should be primed by firing two shots into the air before first use or if the inhaler has not been used for a period of two weeks or longer.

After removal of the cap the inhaler mouthpiece should be placed in the mouth with the lips closed around it. The patient should breathe in slowly and deeply through the mouthpiece. They should be advised not to stop breathing when the inhaler delivers the dose into their mouth but carry on until they have taken a deep breath to ensure optimal delivery of the product.

For normal hygiene, the mouthpiece of the inhaler should be cleaned weekly with a clean dry tissue or cloth. The inhaler should not be washed or immersed in water at any time.

Full instructions for use are given in the Patient Information Leaflet, which should be read carefully by the patient before use.

Qvar Easi-Breathe delivers a consistent dose

– whether or not the canister is shaken by the patient

– without the need for the patient to wait between individual actuations – regardless of storage orientation or periods without use of up to 14 days – at temperatures as low as –10°C.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Patients should be properly instructed on the use of the inhaler to ensure that the drug reaches the target areas within the lungs. To be effective, Qvar Easi-Breathe must be used by patients on a regular basis, even when patients do not have asthma symptoms. When symptoms are controlled, maintenance Qvar Easi-Breathe therapy should be reduced in a stepwise manner to the minimum effective dose. Inhaled steroid treatment should not be stopped abruptly.

Patients with asthma are at risk of acute attacks and should have regular assessments of their asthma control including pulmonary function tests.

Qvar Easi-Breathe is not indicated for the immediate relief of asthma attacks. Patients therefore need to have relief medication (inhaled short-acting bronchodilator) available for such circumstances.

Severe asthma requires regular medical assessment, including lung-function testing, as there is a risk of severe attacks and even death. Patients should 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. If this occurs, patients should be assessed and the need for increased anti-inflammatory therapy considered (eg. higher doses of inhaled corticosteroid or a course of oral corticosteroid).

Severe asthma exacerbations should be managed in the usual way i.e. by increasing the dose of inhaled beclometasone dipropionate, giving a systemic steroid if necessary, and/or an appropriate antibiotic if there is an infection, together with P-agonist therapy.

Treatment with Qvar should not be stopped abruptly.

However, systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged 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, glaucoma, blurred vision, 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 corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

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.

Prolonged treatment with high doses of inhaled corticosteroids, particularly higher than the recommended doses, may result in clinically significant adrenal suppression.

Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Patients who have received systemic steroids for long periods of time or at high doses, or both, need special care and subsequent management when being transferred to inhaled steroid therapy. Patients should have stable asthma before being given inhaled steroids in addition to the usual maintenance dose of systemic steroid. Withdrawal of systemic steroids should be gradual, starting about seven days after the introduction of Qvar Easi-Breathe therapy. For daily oral doses of prednisolone of 10mg or less, dose reduction in 1mg steps, at intervals of not less than one week is recommended. For patients on daily maintenance doses of oral prednisolone greater than 10mg, larger weekly reductions in the dose might be acceptable. The dose reduction scheme should be chosen to correlate with the magnitude of the maintenance systemic steroid dose.

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

Patients should be advised that they may feel unwell in a non-specific way during systemic steroid withdrawal despite maintenance of, or even improved respiratory function. Patients should be advised to persevere with their inhaled product and to continue withdrawal of systemic steroids, even if feeling unwell, unless there is evidence of HPA axis suppression.

Patients weaned off oral steroids whose adrenocortical function is impaired should carry a steroid warning card indicating that they may need supplementary systemic steroids during periods of stress, eg. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.

Discontinuation of systemic steroids may also cause exacerbation of allergic diseases such as atopic eczema and rhinitis. These should be treated as required with topical therapy, including corticosteroids and/or antihistamines.

Like other corticosteroids, caution is necessary in patients with active or latent pulmonary tuberculosis.

Patients should be advised to seek medical attention for review of maintenance Qvar Easi-Breathe therapy if peak flow falls, symptoms worsen or if the short-acting bronchodilator becomes less effective and increased inhalations are required. This may indicate worsening asthma.

Most patients can be successfully transferred to inhaled steroids with maintenance of good respiratory function, but special care is necessary for the first few months after the transfer, until the hypothalamic-pituitary-adrenal (HPA) system has sufficiently recovered to enable the patient to cope with stressful emergencies such as trauma, surgery or serious infections. Patients should, therefore, carry a steroid warning card to indicate the possible need to re-instate systemic steroid therapy rapidly during periods of stress or where airways obstruction or mucus significantly compromises the inhaled route of administration. In addition, it may be advisable to provide such patients with a supply of corticosteroid tablets to use in these circumstances. The dose of inhaled steroids should be increased at this time and then gradually reduced to the maintenance level after the systemic steroid has been discontinued.

Beclometasone dipropionate, like other inhaled steroids, is absorbed into the systemic circulation from the lungs. Beclometasone dipropionate and its metabolites may exert detectable suppression of adrenal function. Within the dose range 100–800 micrograms daily, clinical studies with Qvar Easi-Breathe have demonstrated mean values for adrenal function and responsiveness within the normal range.

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

Patients should be advised that this product contains small amounts of ethanol. At the normal doses, the amounts of ethanol are negligible and do not pose a risk to patients (see section 4.5).

Excipient(s)

Ethanol

This medicine contains 4.74 mg of alcohol (ethanol) in each puff (metered dose) which is equivalent to 4.74 mg/59.30 mg (7.99% w/w). The amount in each puff (metered dose) of this medicine is equivalent to 1 ml beer or 1 ml wine.

The small amount of alcohol in this medicine will not have any noticeable effects.

4.5 Interaction with other medicinal products and other forms of interaction

Qvar Easi-Breathe contains a small amount of ethanol. There is a theoretical potential for interaction in particularly sensitive patients taking disulfiram or metronidazole.

Beclometasone 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.

4.6 Fertility, pregnancy and lactation

The potential risk of this product for humans is unknown.

Qvar Easi-Breathe

There is no experience of this product in pregnancy and lactation in humans, therefore the product should only be used if the expected benefits to the mother are thought to outweigh any potential risk to the foetus or neonate.

Beclometasone dipropionate

Pregnancy

There is inadequate evidence of safety in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intra-uterine growth retardation. There may therefore, be a risk of such effects in the human foetus. It should be noted, however, that the foetal changes in animals occur after relatively high systemic exposure. Beclometasone 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 beclometasone 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.

Breast-feeding

No specific studies examining the transfer of beclometasone dipropionate into the milk of lactating animals have been performed. It is probable that beclometasone dipropionate is excreted in milk. However, given the relatively low doses used by the inhalation route, the levels are likely to be low. 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 no experience with or evidence of safety of propellant HFA 134a in human pregnancy or lactation. However, studies on the effect of HFA 134a on reproductive function and embryofoetal development in animals have revealed no clinically relevant adverse effects.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 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, Qvar 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 Qvar, 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.

Based on the MedDra system organ class and frequencies, adverse events are listed in the table below according to the following frequency estimate: very common (> 1/10); common (>1/100 to <1/10); Uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

*Systemic reactions are a possible response to inhaled corticosteroids, especially when a high dose is prescribed for a prolonged time (see section 4.4 Special warnings and precautions for use).

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9

Acute overdosage is unlikely to cause problems. The only harmful effect that follows inhalation of large amounts of the drug over a short time period is suppression of HPA function. Specific emergency action need not be taken. Treatment with Qvar Easi-Breathe should be continued at the recommended dose to control the asthma; HPA function recovers in a day or two.

If excessive doses of beclometasone dipropionate were taken over a prolonged period a degree of atrophy of the adrenal cortex could occur in addition to HPA suppression. In this event the patient should be treated as steroid dependent and transferred to a suitable maintenance dose of a systemic steroid such as prednisolone. Once the condition is stabilised, the patient should be returned to Qvar Easi-Breathe by the method described above in Section 4.4.

5 PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: Glucocorticoids, ATC code: R03BA01

Qvar Easi-Breathe contains beclometasone dipropionate in solution in propellant HFA-134a resulting in an extra fine aerosol. The aerosol droplets are on average much smaller than the beclometasone dipropionate particles delivered by CFC-suspension formulations or dry powder formulations of beclometasone dipropionate.

In studies to detect toxicity, repeated high dose levels of propellant HFA-134a indicated that safety margins based on systemic exposure would be of the order 2200, 1314 and 381 for mouse, rat and dog with respect to humans.

There are no reasons to consider propellant HFA-134a as a potential mutagen, clastogen or carcinogen judged from in vitro and in vivo studies including long-term administration by inhalation in rodents.

Studies of propellant HFA-134a administered to pregnant and lactating rats and rabbits have not revealed any special hazard.

In animals, systemic administration of relatively high doses can cause abnormalities of foetal development including growth retardation and cleft palate. There may therefore be a very small risk of such effects in the human foetus. However, inhalation of beclometasone dipropionate into the lungs avoids the high level of exposure that occurs with administration by systemic routes.

Safety studies with Qvar aerosol (an equivalent inhaler) in rat and dog showed few, if any, adverse effects other than those normally associated with general steroid exposure including lymphoid tissue alterations such as reduction in thymus, adrenal and spleen weights. An inhalation reproductive study Qvar aerosol (an equivalent inhaler) in rats did not exhibit any teratogenic effects.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Propellant HFA-134a (Norflurane) Ethanol.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 Years.

6.4 Special precautions for storage

Do not store above 25°C. Protect from frost and direct sunlight.

The canister contains a pressurised liquid. Do not expose to temperatures higher that 50°C. Do not pierce the canister.

6.5 Nature and contents of container

Pressurised aluminium canister closed with a metering valve containing either 100 or 200 actuations.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Teva UK Limited

Brampton Road

Hampden Park

Eastbourne

East Sussex

BN22 9AG

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 00289/1375

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

1st July 2010