1. Name Of The Medicinal Product
Qvar Easi-Breathe 100 micrograms per actuation pressurised inhalation solution
2. Qualitative And Quantitative Composition
Beclometasone Dipropionate 100 micrograms per metered (ex-valve) dose.
(The dose delivered from the mouthpiece is an average 75 micrograms).
For a 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
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. Patients should be advised that Qvar may have a different taste and feel than a CFC inhaler.
NOTE: The recommended total daily dose of Qvar Easi-Breathe is lower than that for current beclometasone dipropionate CFC 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 DOSAGES
Mild asthma:
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100 to 200 micrograms per day in two divided doses.
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Moderate asthma:
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200 to 400 micrograms per day in two divided doses.
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Severe asthma:
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400 to 800 micrograms per day in two divided doses.
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TRANSFERRING PATIENTS TO QVAR EASI-BREATHE FROM A CFC-CONTAINING INHALER
The general approach to switching patients to Qvar Easi-Breathe 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 CFC containing beclometasone dipropionate product appropriate to the patient's current condition.
Step 2: Convert the CFC containing beclometasone dipropionate dose to the Qvar Easi-Breathe dose according to the table below.
Total Daily Dose (mcg/day)
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CFC BDP*
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200-250
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300
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400-500
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600-750
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800-1000
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1100
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1200-1500
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1600-2000
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QVAR EASI-BREATHE
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100
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150
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200
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300
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400
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500
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600
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800
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*CFC-BDP = CFC beclometasone dipropionate
1. Dosing in well-controlled patients with asthma
Patients with well-controlled asthma using beclometasone dipropionate CFC containing product should be switched to Qvar Easi-Breathe at a dose in accordance with the table above.
For example:
Patients on 2 puffs twice daily of CFC beclometasone dipropionate 200 micrograms would change to 2 puffs twice daily of Qvar Easi-Breathe 100 micrograms.
2. Dosing in poorly-controlled (symptomatic) patients with asthma
Patients with poorly-controlled asthma may be switched from CFC containing beclometasone dipropionate products to Qvar Easi-Breathe at the same microgram for microgram dose up to 800 micrograms daily. Comparative clinical studies have demonstrated that asthma patients achieve equivalent pulmonary function and control of symptoms with Qvar aerosol (an equivalent inhaler) at lower total daily doses than with CFC containing beclometasone dipropionate products.
Alternatively the patient's current CFC containing beclometasone dipropionate dose can be doubled and this dose can be converted to the Qvar Easi-Breathe dose according to the table above.
Patients on budesonide inhalers may be transferred to Qvar Easi-Breathe as described for CFC containing beclometasone dipropionate products.
Patients on fluticasone inhalers may be transferred to the same total daily dose of Qvar Easi-Breathe 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.
CHILDREN
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.
INSTRUCTIONS FOR USE
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 beclometasone dipropionate or to any of the excipients.
4.4 Special Warnings And Precautions For Use
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.
Qvar Easi-Breathe is not indicated in the management of status asthmaticus.
Severe asthma exacerbations should be managed in the usual way. Subsequently, it may be necessary to increase the dose of Qvar Easi-Breathe up to the maximum daily dose. Systemic steroid treatment may be needed and/or an antibiotic, if there is an infection.
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.
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.
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. 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.
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.
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 aerosol (an equivalent inhaler) have demonstrated mean values for adrenal function and responsiveness within the normal range. 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, 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.
Like other corticosteroids, caution is necessary in patients with active or latent pulmonary tuberculosis.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
No interaction studies have been performed.
4.6 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
There is inadequate evidence of safety in human pregnancy.
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.
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.
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 (
MedDra – system organ class
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Frequency and Symptom
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Infections and infestations
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Common: Candidiasis in mouth and throat
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Immune system disorders
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Rare: Allergic reactions, angioedema in eyes, throat, lips and face
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Endocrine disorders
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Very rare: Adrenal suppression, growth retardation in children
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Nervous system disorders
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Uncommon: Headache, vertigo, tremor
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Eye disorders
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Very rare: Cataract, glaucoma
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Respiratory, thoracic and mediastinal disorders
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Common: Hoarseness, pharyngitis
Uncommon: Cough, increased asthma symptoms
Rare: Paradoxical bronchospasm
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Gastrointestinal disorders
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Common: Taste disturbances
Uncommon: Nausea
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Skin and subcutaneous tissue disorders
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Uncommon: Urticaria, rash, pruritus, erythema, purpura
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Musculoskeletal and connective tissue disorders
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Very rare: Decrease bone mineral density
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Psychiatric Disorders
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Unknown: Psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioural changes (predominantly in children)
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4.9 Overdose
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. The extra fine particle fraction will be 60% ± 20% of the drug particles
Radiolabelled deposition studies in adults with mild asthma have demonstrated that the majority of drug (> 55% ex-actuator) is deposited in the lung and a small amount (< 35% ex-actuator) is deposited in the oropharynx. These studies were performed with Qvar Aerosol. Qvar Aerosol is a 'press and breathe' inhaler, whereas Qvar Easi-Breathe is a breath-activated inhaler.
Inhaled beclometasone dipropionate is now well established in the management of asthma. It is a synthetic glucocorticoid and exerts a topical, anti-inflammatory effect on the lungs, with fewer systemic effects than oral corticosteroids.
Comparative clinical studies of Qvar aerosol have demonstrated that asthma patients achieve equivalent pulmonary function and control of symptoms with Qvar aerosol at lower total daily doses than CFC containing beclometasone dipropionate aerosol inhalers.
Pharmacodynamic studies in patients with mild asthma given Qvar aerosol for 14 days, have shown that there is a linear correlation among urinary free cortisol suppression, dose administered, and serum total-beclometasone levels obtained. At a daily dose of 800 micrograms Qvar aerosol, suppression of urinary free cortisol was comparable with that observed with the same daily dose of CFC containing beclometasone dipropionate, indicating a wider safety margin, as Qvar Easi-Breathe is administered at lower doses than the CFC product.
5.2 Pharmacokinetic Properties
The pharmacokinetic profile of Qvar aerosol (an equivalent inhaler) shows that the peak serum concentration for total- beclometasone (BOH) (total of any beclometasone OH and beclometasone dipropionate or monopropionate hydrolysed to beclometasone OH) or after single and multiple doses is achieved after 30 minutes.
The value at the peak is approximately 2 nanograms/ml after a total daily dose of 800 micrograms and the serum levels after 100, 200 and 400 micrograms are proportional. The principal route of elimination of beclometasone dipropionate and its several metabolites is in the faeces. Between 10% and 15% of an orally administered dose is excreted in the urine, as both conjugated and free metabolites of the drug.
In both single dose and multiple dose pharmacokinetic studies of Qvar aerosol, a dose of 200 micrograms of Qvar aerosol achieved comparable total-BOH levels, as a dose of 400 micrograms of CFC containing beclometasone dipropionate Aerosol. This provided the scientific rationale for investigating lower total daily doses of Qvar aerosol to achieve the same clinical effect.
Pharmacokinetic studies with Qvar Easi-Breathe have not been carried out in any special populations.
5.3 Preclinical Safety Data
In animal studies, propellant HFA-134a has been shown to have no significant pharmacological effects other than at very high exposure concentrations, then narcosis and a relatively weak cardiac sensitising effect were found. The potency of the cardiac sensitisation was less than that of CFC-11 (trichlorofluoromethane).
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 And Other Handling
Not applicable.
7. Marketing Authorisation Holder
Teva UK Limited
Brampton Road
Hampden Park
Eastbourne
East Sussex
BN22 9AG
United Kingdom
8. Marketing Authorisation Number(S)
PL 00289/1376
9. Date Of First Authorisation/Renewal Of The Authorisation
1st July 2010
10. Date Of Revision Of The Text
11/05/2011
