PRODUCT INFORMATION�QVAR 40mcg(beclomethasone dipropionate HFA, 40 mcg)INHALATION AEROSOLFor Oral Inhalation Only �QVAR 80mcg(beclomethasone dipropionate HFA, 80 mcg)INHALATION AEROSOLFor Oral Inhalation Only
QVAR Information
Company Name Teva Respiratory, LLC
Qvar (Beclomethasone dipropionate) Description
The active component of Qvar (Beclomethasone dipropionate) 40 mcg Inhalation Aerosol and Qvar (Beclomethasone dipropionate) 80 mcg Inhalation Aerosol is beclomethasone dipropionate, USP, an anti-inflammatory corticosteroid having the chemical name 9-chloro-11β,17,21-trihydroxy-16β-methylpregna-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 CHClO and a molecular weight of 521.1. Its chemical structure is:
Qvar (Beclomethasone dipropionate) is a pressurized, metered-dose aerosol intended for oral inhalation only. Each unit contains a solution of beclomethasone dipropionate in propellant HFA-134a (1,1,1,2 tetrafluoroethane) and ethanol. Qvar (Beclomethasone dipropionate) 40 mcg delivers 40 mcg of beclomethasone dipropionate from the actuator and 50 mcg from the valve. Qvar (Beclomethasone dipropionate) 80 mcg delivers 80 mcg of beclomethasone dipropionate from the actuator and 100 mcg from the valve. Both products deliver 50 microliters (59 milligrams) of solution formulation from the valve with each actuation. The 40 mcg and the 80 mcg canisters provide either 100 inhalations or 120 inhalations. Qvar (Beclomethasone dipropionate) should be "primed" or actuated twice prior to taking the first dose from a new canister, or when the inhaler has not been used for more than ten days. Avoid spraying in the eyes or face while priming Qvar (Beclomethasone dipropionate) . This product does not contain chlorofluorocarbons (CFCs).
Qvar (Beclomethasone dipropionate) Clinical Pharmacology
Airway inflammation is known to be an important component in the pathogenesis of asthma. Inflammation occurs in both large and small airways. Corticosteroids have multiple anti-inflammatory effects, inhibiting both inflammatory cells (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and release of inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines). These anti-inflammatory actions of corticosteroids such as beclomethasone dipropionate contribute to their efficacy in asthma.
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 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 recommended doses of Qvar (Beclomethasone dipropionate) .
Qvar (Beclomethasone dipropionate) Clinical Trials
Blinded, randomized, parallel, placebo-controlled and active-controlled clinical studies were conducted in 940 adult asthma patients to assess the efficacy and safety of Qvar (Beclomethasone dipropionate) in the treatment of asthma. Fixed doses ranging from 40 mcg to 160 mcg twice daily were compared to placebo, and doses ranging from 40 mcg to 320 mcg twice daily were compared with doses of 42 mcg to 336 mcg twice daily of an active CFC-BDP comparator. These studies provided information about appropriate dosing through a range of asthma severity. A blinded, randomized, parallel, placebo-controlled study was conducted in 353 pediatric patients (age 5-12 years) to assess the efficacy and safety of HFA beclomethasone dipropionate in the treatment of asthma. Fixed doses of 40 mcg and 80 mcg twice daily were compared with placebo in this study. In these adult and pediatric efficacy trials, at the doses studied, measures of pulmonary function [forced expiratory volume in 1 second (FEV) and morning peak expiratory flow (AM PEF)] and asthma symptoms were significantly improved with Qvar (Beclomethasone dipropionate) treatment when compared to placebo.
In controlled clinical trials with adult patients not adequately controlled with beta-agonist alone, Qvar (Beclomethasone dipropionate) was effective at improving asthma control at doses as low as 40 mcg twice daily (80 mcg/day). Comparable asthma control was achieved at lower daily doses of Qvar (Beclomethasone dipropionate) than with CFC-BDP. Treatment with increasing doses of both Qvar (Beclomethasone dipropionate) and CFC-BDP generally resulted in increased improvement in FEV. In this trial the improvement in FEV across doses was greater for Qvar (Beclomethasone dipropionate) than for CFC-BDP, indicating a shift in the dose response curve for Qvar (Beclomethasone dipropionate) .
Qvar (Beclomethasone dipropionate) Indications And Usage
Qvar (Beclomethasone dipropionate) is indicated in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. Qvar (Beclomethasone dipropionate) is also indicated for asthma patients who require systemic corticosteroid administration, where adding Qvar (Beclomethasone dipropionate) may reduce or eliminate the need for the systemic corticosteroids.
Beclomethasone dipropionate is NOT indicated for the relief of acute bronchospasm.
Qvar (Beclomethasone dipropionate) Contraindications
Qvar (Beclomethasone dipropionate) is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Hypersensitivity to any of the ingredients of this preparation contraindicates its use.
Qvar (Beclomethasone dipropionate) Warnings
Particular care is needed in patients who are transferred from systemically active corticosteroids to Qvar (Beclomethasone dipropionate) because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.
Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infections (particularly gastroenteritis) or other conditions with severe electrolyte loss. Although Qvar (Beclomethasone dipropionate) may provide control of asthmatic symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid that is necessary for coping with these emergencies.
During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthma attack.
Transfer of patients from systemic steroid therapy to Qvar (Beclomethasone dipropionate) may unmask allergic conditions previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, and eczema.
Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. It is not known how the dose, route and duration of corticosteroid administration affects the risk of developing a disseminated infection. Nor is the contribution of the underlying disease and/or prior corticosteroid treatment known. If exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.
Qvar (Beclomethasone dipropionate) is not a bronchodilator and is not indicated for rapid relief of bronchospasm.
As with other inhaled asthma medications, bronchospasm, with an immediate increase in wheezing, may occur after dosing. If bronchospasm occurs following dosing with Qvar (Beclomethasone dipropionate) , it should be treated immediately with a short acting inhaled bronchodilator. Treatment with Qvar (Beclomethasone dipropionate) should be discontinued and alternate therapy instituted. Patients should be instructed to contact their physician immediately when episodes of asthma, which are not responsive to bronchodilators, occur during the course of treatment with Qvar (Beclomethasone dipropionate) . During such episodes, patients may require therapy with oral corticosteroids.
Qvar (Beclomethasone dipropionate) Precautions
During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude and depression, despite maintenance or even improvement of respiratory function. Although suppression of HPA function below the clinical normal range did not occur with doses of Qvar (Beclomethasone dipropionate) up to and including 640 mcg/day, a dose dependent reduction of adrenal cortisol production was observed. Since inhaled beclomethasone dipropionate is absorbed into the circulation and can be systemically active, HPA axis suppression by Qvar (Beclomethasone dipropionate) could occur when recommended doses are exceeded or in particularly sensitive individuals. Since individual sensitivity to effects on cortisol production exist, physicians should consider this information when prescribing Qvar (Beclomethasone dipropionate) . Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with these drugs should be observed carefully for any evidence of systemic corticosteroid effect. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects, such as hypercorticism and adrenal suppression, may appear in a small number of patients, particularly at higher doses. If such changes occur, Qvar (Beclomethasone dipropionate) should be reduced slowly, consistent with accepted procedures for management of asthma symptoms and for tapering of systemic steroids.
A 12 month randomized controlled clinical trial evaluated the effects of HFA beclomethasone dipropionate without spacer versus CFC beclomethasone dipropionate with large volume spacer on growth in children age 5-11. A total of 520 patients were enrolled, of whom 394 received HFA-BDP (100 – 400 mcg/day ex-valve) and 126 received CFC-BDP (200 – 800 mcg/day ex-valve). Similar control of asthma was noted in each treatment arm. When comparing results at month 12 to baseline, the mean growth velocity in children treated with HFA-BDP was approximately 0.5 cm/year less than that noted with children treated with CFC-BDP via large volume spacer.
A reduction in growth velocity in growing children may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment. Physicians should closely follow the growth of all pediatric patients taking corticosteroids by any route and weigh the benefits of corticosteroid therapy and asthma control against the possibility of growth suppression.
The long-term and systemic effects of Qvar (Beclomethasone dipropionate) in humans are still not fully known. In particular, the effects resulting from chronic use of the agent on developmental or immunologic processes in the mouth, pharynx, trachea, and lung are unknown.
Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, parasitic or viral infections; or ocular herpes simplex.
Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids.
Patients being treated with Qvar (Beclomethasone dipropionate) should receive the following information and instructions. This information is intended to aid them in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed to these diseases, medical advice should be sought without delay.
Patients should use Qvar (Beclomethasone dipropionate) at regular intervals as directed. Results of clinical trials indicated significant improvements may occur within the first 24 hours of treatment in some patients; however, the full benefit may not be achieved until treatment has been administered for 1 to 2 weeks, or longer. The patient should not increase the prescribed dosage but should contact their physician if symptoms do not improve or if the condition worsens.
Patients should be advised that Qvar (Beclomethasone dipropionate) is not intended for use in the treatment of acute asthma. The patient should be instructed to contact their physician immediately if there is any deterioration of their asthma.
Patients should be instructed on the proper use of their inhaler. Patients may wish to rinse their mouth after Qvar (Beclomethasone dipropionate) use. The patient should also be advised that Qvar (Beclomethasone dipropionate) may have a different taste and inhalation sensation than that of an inhaler containing CFC propellant.
Qvar (Beclomethasone dipropionate) use should not be stopped abruptly. The patient should contact their physician immediately if use of Qvar (Beclomethasone dipropionate) is discontinued.
For the proper use of Qvar (Beclomethasone dipropionate) , the patient should read and carefully follow the accompanying Patient's Instructions.
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 carcinogenicity in this study at the highest dose, which is approximately 30 and 55 times the maximum recommended daily inhalation dose in adults and children, respectively, on a mg/m basis.
Beclomethasone dipropionate did not induce gene mutation in the bacterial cells or mammalian Chinese Hamster ovary (CHO) cells . No significant clastogenic effect was seen in cultured CHO cells or in the mouse micronucleus test .
In rats, beclomethasone dipropionate caused decreased conception rates at an oral dose of 16 mg/kg/day (approximately 200 times the maximum recommended daily inhalation dose in adults on a mg/m basis). Impairment of fertility, as evidence 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 20 times the maximum recommended daily inhalation dose in adults on a mg/m 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 15 times the maximum recommended daily inhalation dose in adults on a mg/m basis).
Eight-hundred and thirty-four children between the ages of 5 and 12 were treated with HFA beclomethasone dipropionate (HFA BDP) in clinical trials. The safety and effectiveness of Qvar (Beclomethasone dipropionate) in children below 5 years of age have not been established.
Use of Qvar (Beclomethasone dipropionate) with a spacer device in children less than 5 years of age is not recommended. dose characterization studies were performed with Qvar (Beclomethasone dipropionate) 40 mcg/actuation with the Optichamber and AeroChamber Plus® spacer utilizing inspiratory flows representative of children under 5 years old. These studies indicated that the amount of medication delivered through the spacing device decreased rapidly with increasing wait times of 5 to 10 seconds as shown in Table 1. If Qvar (Beclomethasone dipropionate) is used with a spacer device, it is important to inhale immediately.
Based on the average inspiratory flow rates generated by children 6 months to 5 years old, the projected daily dose derived from Qvar (Beclomethasone dipropionate) 40 mcg at one puff per day at various wait times is depicted in the table below:
Oral inhaled corticosteroids have been shown to cause a reduction in growth velocity in children and teenagers with extended use. If a child or teenager on any corticosteroid appears to have growth suppression, the possibility that they are particularly sensitive to this effect of corticosteroids should be considered (see ).
Qvar (Beclomethasone dipropionate) Adverse Reactions
The following reporting rates of common adverse experiences are based upon four clinical trials in which 1196 Patients (671 female and 525 male adults previously treated with as-needed bronchodilators and/or inhaled corticosteroids) were treated with Qvar (Beclomethasone dipropionate) (doses of 40, 80, 160, or 320 mcg twice daily) or CFC-BDP (doses of 42, 168, or 336 mcg twice daily) or placebo. The table below includes all events reported by patients taking Qvar (Beclomethasone dipropionate) (whether considered drug related or not) that occurred at a rate over 3% for either Qvar (Beclomethasone dipropionate) or CFC-BDP. In considering these data, difference in average duration of exposure and clinical trial design should be taken into account.
Other adverse events that occurred in these clinical trials using Qvar (Beclomethasone dipropionate) with an incidence of 1% to 3% and which occurred at a greater incidence than placebo were: dysphonia, dysmenorrhea and coughing.
No patients treated with Qvar (Beclomethasone dipropionate) in the clinical development program developed symptomatic oropharyngeal candidiasis.
If such an infection develops, treatment with appropriate antifungal therapy or discontinuance of treatment with Qvar (Beclomethasone dipropionate) may be required.
Qvar (Beclomethasone dipropionate) Overdosage
There were no deaths over 15 days following the oral administration of a single dose of 3000 mg/kg in mice, 2000 mg/kg in rats, and 1000 mg/kg in rabbits. The doses in mice, rats, and rabbits were 19,000, 25,000, and 25,000 times, respectively, the maximum recommended daily inhalation in adults or 36,000, 48,000, and 48,000 times, respectively the maximum recommended daily inhalation dose in children on a mg/m basis.
Qvar (Beclomethasone dipropionate) Dosage And Administration
Patients should prime Qvar (Beclomethasone dipropionate) by actuating into the air twice before using for the first time or if Qvar (Beclomethasone dipropionate) has not been used for over ten days. Avoid spraying in the eyes or face when priming Qvar (Beclomethasone dipropionate) . Qvar (Beclomethasone dipropionate) is a solution aerosol, which does not require shaking. Consistent dose delivery is achieved, whether using the 40 or 80 mcg strengths, due to proportionality of the two products (i.e., two actuations of 40 mcg strength should provide a dose comparable to one actuation of the 80 mcg strength).
Qvar (Beclomethasone dipropionate) should be administered by the oral inhaled route in patients 5 years of age and older. Use of Qvar (Beclomethasone dipropionate) with a spacer device in children less than 5 years of age is not recommended (see ). The onset and degree of symptom relief will vary in individual patients. Improvement in asthma symptoms should be expected within the first or second week of starting treatment, but maximum benefit should not be expected until 3-4 weeks of therapy. For patients who do not respond adequately to the starting dose after 3-4 weeks of therapy, higher doses may provide additional asthma control. The safety and efficacy of Qvar (Beclomethasone dipropionate) when administered in excess of recommended doses has not been established.
As with any inhaled corticosteroid, physicians are advised to titrate the dose of Qvar (Beclomethasone dipropionate) downward over time to the lowest level that maintains proper asthma control. This is particularly important in children since a controlled study has shown that Qvar (Beclomethasone dipropionate) has the potential to affect growth in children. Patients should be instructed on the proper use of their inhaler.
Qvar (Beclomethasone dipropionate) How Supplied
Qvar (Beclomethasone dipropionate) is supplied in two strengths:
The correct amount of medication in each inhalation cannot be assured after 100 actuations from the 7.3 g canister or 120 actuations from the 8.7 g canister even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used.
Qvar (Beclomethasone dipropionate)
Qvar (Beclomethasone dipropionate) Patient's Instructions
It is important that you read these instructions before using Qvar (Beclomethasone dipropionate) .
Correct and regular use of the inhaler will prevent or lessen the severity of asthma attacks.
1. Remove the plastic cap (see ) and be sure there are no foreign objects in the mouthpiece.
2. As with all aerosol medications, it is recommended to prime the Qvar (Beclomethasone dipropionate) inhaler before using for the very first time after purchase, and in cases where the inhaler has not been used for more than ten days. Prime by releasing two actuations into the air, away from your eyes and face. Be sure the canister is firmly seated in the plastic mouthpiece adapter before each use.
3. BREATHE OUT AS FULLY AS YOU COMFORTABLY CAN. Hold the inhaler as shown in Figure 2. Close your lips around the mouthpiece, keeping your tongue below it.
4. WHILE BREATHING IN DEEPLY AND SLOWLY, PRESS DOWN ON THE CAN WITH YOUR FINGER. When you have finished breathing in, hold your breath as long as you comfortably can (i.e., 5 - 10 seconds).
5. TAKE YOUR FINGER OFF THE CAN and remove the inhaler from your mouth. Breathe out gently.
6. If your physician has told you to take more than one inhalation per treatment repeat steps 3 through 5.
7. You should rinse your mouth with water after treatment.
8. For normal hygiene, the mouthpiece of your inhaler should be cleaned weekly with a clean, dry tissue or cloth.
DO NOT WASH OR PUT ANY PART OF YOUR INHALER IN WATER.
9. DISCARD THE CANISTER AFTER the date calculated by your physician or pharmacist. The correct amount of medication in each inhalation cannot be assured after 100 actuations from the 7.3 g canister or 120 actuations from the 8.7 g canister even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used. Before the discard date you should consult your physician to determine whether a refill is needed. It is advisable to keep track of the number of doses taken from the canister to better predict when a refill is necessary. Just as you should not take extra doses without consulting your physician, you also should not stop taking Qvar (Beclomethasone dipropionate) without consulting your physician.
DO NOT CONFUSE Qvar (Beclomethasone dipropionate) WITH OTHER ASTHMA MEDICATION. Qvar (Beclomethasone dipropionate) WILL NOT PROVIDE IMMEDIATE RELIEF IF YOU ARE HAVING AN ASTHMA ATTACK.
Your physician will decide whether other medication is needed should you require immediate relief. If you also use another medicine by inhalation, you should consult your physician for instructions on when to use it in relation to using Qvar (Beclomethasone dipropionate) . If this is the first time you will be using Qvar (Beclomethasone dipropionate) , it may take from 1 to 4 weeks before you feel the full benefits.
Qvar (Beclomethasone dipropionate) Inhalation Aerosol canister should only be used with the Qvar (Beclomethasone dipropionate) Inhalation Aerosol mouthpiece and the mouthpiece should not be used with any other inhalation drug product.
Use only as directed by your physician.
Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 49°C (120°F) may cause bursting. Never throw container into fire or incinerator.
Avoid spraying in eyes.
Mktd by:Teva Respiratory, LLCHorsham, PA 19044
© 2010 Teva Respiratory, LLCQvar (Beclomethasone dipropionate) ® is a registered trademark of IVAX LLC, a member of the TEVA Group.
639300Rev. 09/10
Qvar (Beclomethasone dipropionate) Principal Display Panel - Mcg Carton
NDC 59310-175-40
For oral inhalation with Qvar (Beclomethasone dipropionate) Actuator only
CFC FREE
Qvar (Beclomethasone dipropionate) Principal Display Panel - Mcg Carton
(beclomethasonedipropionate HFA, 40 mcg)
For Oral Inhalation withQvar (Beclomethasone dipropionate) Actuator Only
CFC FREE
Qvar (Beclomethasone dipropionate) Principal Display Panel - Mcg Carton
NDC 59310-177-80
For oral inhalation with Qvar (Beclomethasone dipropionate) Actuator only
CFC FREE
Qvar (Beclomethasone dipropionate) Principal Display Panel - Mcg Carton
(beclomethasonedipropionate HFA, 80 mcg)
For Oral Inhalation withQvar (Beclomethasone dipropionate) Actuator Only
CFC FREE
