QVAR™ 50 Inhaler
QVAR™ 100 Inhaler
QVAR™ 50 Autohaler™
QVAR™ 100 Autohaler™
Each actuation of QVAR Inhaler or Autohaler delivers extrafine beclomethasone dipropionate 50 mcg or 100 mcg ex-valve for inhalation.
Presentation
QVAR is available in a metered dose inhaler (MDI) and a breath actuated Autohaler device. QVAR contains beclomethasone dipropionate in solution in norflurane (HFA-134a) and delivers an extrafine aerosol. The aerosol droplets are on average much smaller than the beclomethasone dipropionate particles delivered by CFC-suspension formulations or dry powder formulations of beclomethasone dipropionate.
Uses
Actions
Inhaled beclomethasone dipropionate is well characterised for the management of asthma. It is a synthetic glucocorticoid and at usual doses exerts a topical, anti-inflammatory effect on the lungs, without significant systemic activity.
Pharmacokinetics
The pharmacokinetic profile of QVAR shows that the peak serum concentration for total BOH (total of any beclomethasone dipropionate or monopropionate) after single and multiple doses is achieved after 30 minutes. The value at the peak is approximately 2 ng/ml after the highest recommended dose of 800 mcg and the serum levels after 100, 200 and 400 mcg are proportionally lower. In both single dose and multiple dose pharmacokinetic studies, a daily dose of 200 mcg of QVAR achieved comparable total-BOH levels as a dose of 400 mcg of CFC beclomethasone aerosol.
Radio-labelled deposition studies have demonstrated that the majority of drug (>55% ex-actuator) is deposited in the lung and a small amount (<35%) is deposited in the oropharynx. These delivery characteristics result in equivalent therapeutic effects at lower total daily doses of QVAR compared to CFC beclomethasone inhalers.
Pharmacodynamic studies in patients with mild asthma given QVAR for 14 days have shown that there is a linear correlation between urinary free cortisol suppression, dose administered and serum total-BOH levels obtained. At a daily dose of 800 mcg QVAR, suppression of urinary free cortisol was comparable to that observed with the same daily dose of CFC beclomethasone, indicating that there is a wider safety margin if QVAR is administered at lower doses than CFC inhalers.
The principal route of elimination of beclomethasone 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. Pharmacokinetic studies with QVAR have not been carried out in any special populations.
Indications
Prophylactic anti-inflammatory treatment of reversible obstructive airways disease including asthma.
Dosage and Administration
Note
The recommended total daily dose of beclomethasone dipropionate extrafine aerosol (QVAR) is lower than that for current CFC beclomethasone inhalers and should be adjusted to suit the individual patient.
QVAR is for use by inhalation only. To be effective inhaled QVAR must be used on a regular basis even when patients are asymptomatic.
Adults
Starting and maintenance dose for mild to moderate asthma is 50 to 200 mcg twice daily. In more severe cases, doses up to 400 mcg twice daily may be used. The maximum recommended daily dose is 800 mcg. The same total daily dose from either QVAR 50 or QVAR 100 aerosol provides the same clinical effect.
Comparative clinical studies have demonstrated that asthma patients achieve equivalent pulmonary function and control of symptoms with QVAR at lower total daily doses than CFC beclomethasone inhalers.
Transferring patients to QVAR from a CFC beclomethasone inhaler
The general approach to switching patients to QVAR involves two steps as detailed below.
Step 1
Consider the dose of CFC beclomethasone product appropriate to treat the patients current condition. Symptomatic patients may require an increased dose of CFC beclomethasone and this increased dose should be considered in transferring patients to QVAR.
Step 2
Convert the CFC beclomethasone dose to the QVAR dose according to the table below.
| | Daily dose of beclomethasone (micrograms) |
CFC
QVAR | 200 - 250
↓
100 | 400 - 500
↓
200 | 600 - 750
↓
300 | 800 - 1000
↓
400 | 1200 - 1500
↓
600 |
1600 - 2000
↓
800 |
Patients should be instructed on the proper use of their inhaler, including rinsing out their mouth after use. Patients should be advised that QVAR inhaler has a softer spray and may have a different taste and feel to a CFC beclomethasone inhaler.
Patients on budesonide inhalers may be transferred to QVAR as described for CFC beclomethasone products. Patients on fluticasone inhalers may be transferred to the same total daily dose of QVAR up to 800 micrograms daily.
Inhaler cleaning
For normal hygiene, the mouthpiece of the inhaler or Autohaler should be cleaned weekly with a clean, dry tissue or cloth. DO NOT WASH OR PUT ANY PART OF THE INHALER OR AUTOHALER IN WATER.
Use of a spacer
QVAR extrafine beclomethasone has been developed to be used without a spacer device being necessary. Unlike with traditional CFC MDIs the aerosol characteristics of QVAR MDI provide for greater lung deposition. Where a spacer is considered necessary the Aerochamber™ is a suitable device for use with QVAR MDI as the extrafine particle fraction is maintained.
Children
Children aged over 5 years: the recommended starting dose for mild to moderate asthma is 50 mcg twice daily. In more severe cases this may be increased up to 100 mcg twice daily, which is the maximum recommended dose. To minimise the systemic effects of orally inhaled corticosteroids, the dose should be titrated down to the lowest that provides effective asthma control.
Special patient groups
No special dosage recommendations are made for elderly or patients with hepatic or renal impairment.
Contraindications
Hypersensitivity to beclomethasone dipropionate or any other ingredient in QVAR.
Warnings and Precautions
QVAR is not indicated for immediate relief of asthma attacks or status asthmaticus. Patients should be made aware of the prophylactic nature of treatment with inhaled beclomethasone and that it should be taken regularly, even when they are asymptomatic.
Patients should be instructed to seek medical advice if the prescribed dose of QVAR is no longer effective or if symptoms get worse.
Inhaled corticosteroids are designed to direct glucocorticoid activity to the lungs in order to reduce the overall systemic glucocorticoid exposure and side effects. In sufficient doses, however, all inhaled corticosteroids can have adverse effects, notably depression of the hypothalamic-pituitary-adrenal (HPA) axis, reduction of bone density and retardation of growth in children. In steroid dependent patients prior systemic corticosteroid usage may be a contributing factor, but such effects can occur amongst patients who regularly use only inhaled corticosteroids.
Individual patients may vary in their sensitivity to the systemic effects of inhaled corticosteroids. Beclomethasone, like other inhaled corticosteroids, is absorbed into the systemic circulation from the lungs. Beclomethasone and its metabolites may exert detectable suppression of adrenal function. However, within the dose range 100 to 800 mcg daily clinical studies with QVAR have demonstrated that parameters of adrenal function usually remain within the normal range. The lowest dose of QVAR that causes suppression of the HPA axis (as indicated by 24 hour urinary cortisol concentrations), effects on bone mineral density or growth retardation in children has not yet been established.
Patients who have received systemic corticosteroids for long periods of time or at high doses, or both, need special care and subsequent management when being transferred to inhaled corticosteroid therapy. Recovery from impaired adrenocortical function caused by prolonged treatment with systemic corticosteroids is slow. Patients asthma should be in a stable state before being given inhaled corticosteroids in addition to the usual maintenance dose of systemic corticosteroid.
Most patients can be successfully transferred to inhaled corticosteroids with maintenance of good respiratory function, but special care is necessary for the first months after the transfer, until the hypothalamic-pituitary-adrenal (HPA) system has sufficiently recovered to enable the patient to cope with emergencies such as trauma, surgery or serious infections.
Withdrawal of systemic corticosteroids should be gradual, starting after about seven days by reducing the daily oral dose by 1 to 2.5 mg prednisone, or equivalent, at intervals not less than one week. Adrenocortical function should be monitored regularly.
In patients who have been transferred from oral corticosteroids to inhalation therapy, systemic therapy may need to be reinstated during periods of stress or where airways obstruction or mucus prevents absorption by inhalation.
It may be advisable to provide such patients with a supply of oral corticosteroid to use in emergencies. The dose of inhaled corticosteroids should be increased at this time and then gradually reduced to the maintenance level after the systemic corticosteroid has been discontinued.
Discontinuation of systemic corticosteroids may cause exacerbation of allergic diseases such as atopic eczema and rhinitis. These should be treated as required with appropriate therapy.
Like other corticosteroids, caution is advised for patients with active or latent pulmonary tuberculosis.
Pregnancy and lactation
There is no experience of this product in pregnancy and lactation in humans, therefore the product should only be used if the benefits outweigh any potential risk to the patient. An inhalation reproductive study with this product in rats did not exhibit any teratogenic effects.
Norflurane propellant
Studies of norflurane administered to pregnant and lactating rats and rabbits have not revealed any special hazard.
Beclomethasone dipropionate
There is inadequate evidence of safety in human pregnancy. 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 small risk of such effects in the human foetus. However, inhalation of beclomethasone into the lungs avoids the high level of corticosteroid exposure that occurs with administration by systemic routes. The use of beclomethasone in pregnancy requires that the possible benefits of the drug be weighed against the possible hazards. It should be noted that the drug has been in widespread use for many years without apparent hazard.
It is probable that beclomethasone is excreted in milk. However, given the relatively reduced doses used by the inhalation route, the levels are likely to be low. In mothers who are breast feeding their baby, the therapeutic effects of the medicine should be weighed against the potential hazards to mother and baby.
Adverse Effects
When taking any inhaled medicine containing beclomethasone there may be infrequent occurrences of hoarseness and rare occurrences of either post inhalation bronchospasm or candidiasis of throat and mouth. Patients may find it helpful to rinse out their mouth after using their inhaler to reduce the risk of candidiasis. Across a number of studies it was found the incidence of adverse effects related to the respiratory system or to inhalation effects was lower with QVAR. Nausea has been rarely reported with treatment with beclomethasone extrafine aerosol.
Interactions
None known.
Overdosage
Acute overdose 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 Inhaler or Autohaler should be continued at the recommended dose to control the asthma and HPA function can be expected to recover in a day or two.
If very large and excessive doses of beclomethasone 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 corticosteroid dependent and transferred to a suitable maintenance dose of a systemic corticosteroid such as prednisone. Once the condition is stabilised, the patient should be transferred to QVAR at the doses recommended above according to the instructions in the PRECAUTIONS section.
Pharmaceutical Precautions
QVAR should be stored below 30°C. Storage in direct sunlight or heat should be avoided. Protect from frost. As the canister is pressurised, no attempt should be made to puncture or dispose of it by burning.
Package Quantities
Inhaler or Autohaler device, containing 200 doses.
Further Information
The patient should read the instruction leaflet before use.
QVAR Inhaler and Autohaler deliver 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 for periods without use of up to 14 days
- at temperatures as low as -10°C.
Propellant
QVAR Autohaler and MDI contain norflurane propellant. In animal studies, norflurane has been shown to have no significant pharmacological effects other than at very high exposure concentrations, where narcosis and a relatively weak cardiac sensitising effect were found. The potency of cardiac sensitisation is less than that of CFC-11 (trichlorofluoromethane). There are no reasons to consider norflurane as a potential mutagen, clastogen or carcinogen judged from in vitro and in vivo studies including long-term administration by inhalation in rodents.
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