beclomethasone dipropionate 40 MCG/ACTUAT Metered Dose Inhaler, 100 ACTUAT
WARNINGS
Particular care is needed in patients who are transferred from systemically active corticosteroids to QVAR 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its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn.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 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During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further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 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 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, it should be treated immediately with a short acting inhaled bronchodilator.
Treatment with QVAR 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.
During such episodes, patients may require therapy with oral corticosteroids.
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 2 basis.
DESCRIPTION
The active component of QVAR 40 mcg Inhalation Aerosol and QVAR 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 C 28 H 37 ClO 7 and a molecular weight of 521.1.
Its chemical structure is: QVAR 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 40 mcg delivers 40 mcg of beclomethasone dipropionate from the actuator and 50 mcg from the valve.
QVAR 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.
Each canister provides 100 inhalations.
QVAR 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.
This product does not contain chlorofluorocarbons (CFCs).
image of QVAR chemical structure
CLINICAL STUDIES
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 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 1 ) and morning peak expiratory flow (AM PEF)] and asthma symptoms were significantly improved with QVAR treatment when compared to placebo.
In controlled clinical trials with adult patients not adequately controlled with beta-agonist alone, QVAR 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 than with CFC-BDP.
Treatment with increasing doses of both QVAR and CFC-BDP generally resulted in increased improvement in FEV 1 .
In this trial the improvement in FEV 1 across doses was greater for QVAR than for CFC-BDP, indicating a shift in the dose response curve for QVAR.
Patients Not Previously Receiving Corticosteroid Therapy In a 6 week clinical trial, 270 steroid naive patients with symptomatic asthma being treated with as-needed beta-agonist bronchodilators, were randomized to receive either 40 mcg twice daily of QVAR, 80 mcg twice daily of QVAR, or placebo.
Both doses of QVAR were effective in improving asthma control with significantly greater improvements in FEV 1 , AM PEF, and asthma symptoms than with placebo.
Shown below is the change from baseline in AM PEF during this trial.
A 6-Week Clinical Trial in Patients with Mild to Moderate Asthma Not on Corticosteroid Therapy Prior to Study Entry: Mean Change in AM PEF In a 6-week clinical trial, 256 patients with symptomatic asthma being treated with as-needed beta-agonist bronchodilators, were randomized to receive either 160 mcg twice daily of QVAR (delivered as either 40 mcg/actuation or 80 mcg/actuation) or placebo.
Treatment with QVAR significantly improved asthma control, as assessed by FEV 1 , AM PEF, and asthma symptoms, when compared to treatment with placebo.
Comparable improvement in AM PEF was seen for patients receiving 160 mcg twice daily QVAR from the 40 mcg and 80 mcg strength products.
Patients Responsive to a Short Course of Oral Corticosteroids In another clinical trial, 347 patients with symptomatic asthma, being treated with as-needed inhaled beta-agonist bronchodilators and, in some cases, inhaled corticosteroids, were given a 7-12 day course of oral corticosteroids and then randomized to receive either 320 mcg daily of QVAR, 672 mcg of CFC-BDP, or placebo.
Patients treated with either QVAR or CFC-BDP had significantly better asthma control, as assessed by AM PEF, FEV 1 and asthma symptoms, and fewer study withdrawals due to asthma symptoms, than those treated with placebo over 12 weeks of treatment.
A daily dose of 320 mcg QVAR administered in divided doses provided comparable control of AM PEF and FEV 1 as 672 mcg of CFC-BDP.
Shown below are the mean AM PEF results from this trial.
A 12-Week Clinical Trial in Moderate Symptomatic Patients with Asthma Responding to Oral Corticosteroid Therapy: Mean AM PEF by Study Week Patients Previously on Inhaled Corticosteroids In a 6-week clinical trial, 323 patients, who exhibited a deterioration in asthma control during an inhaled corticosteroid washout period, were randomized to daily treatment with either 40, 160, or 320 mcg twice daily QVAR or 42, 168, or 336 mcg twice daily CFC-BDP.
Treatment with increasing doses of both QVAR and CFC-BDP resulted in increased improvement in FEV 1 , FEF 25-75% (forced expiratory flow over 25-75% of the vital capacity), and asthma symptoms.
Shown below is the change from baseline in FEV 1 as percent predicted after 6 weeks of treatment.
A 6-Week Dose Response Clinical Trial in Patients with Inhaled Corticosteroid Dependent Asthma: Mean Change in FEV 1 as Percent of Predicted Patients Previously Maintained on Oral Corticosteroids Clinical experience has shown that some patients with asthma who require oral corticosteroid therapy for control of symptoms can be partially or completely withdrawn from oral corticosteroids if therapy with beclomethasone dipropionate aerosol is substituted.
Inhaled corticosteroids may not be effective for all patients with asthma or at all stages of the disease in a given patient.
Pediatric Experience In one 12-week clinical trial, pediatric patients (age 5-12 years) with symptomatic asthma (N=353) being treated with as-needed beta-agonist bronchodilators were randomized to receive either 40 mcg or 80 mcg twice daily of HFA beclomethasone dipropionate or placebo.
Both doses were effective in improving asthma control with significantly greater improvements in FEV 1 (9% and 10% predicted change from baseline at week 12 in FEV 1 percent predicted, respectively) than with placebo (4% predicted change).
6 Week graph 12 Week graph 6 Week graph
HOW SUPPLIED
QVAR is supplied in two strengths: QVAR 40 mcg is supplied in a 7.3 g canister containing 100 actuations with a beige plastic actuator and gray dust cap, and Patient’s Instructions; box of one; 100 Actuations – NDC 54868-5857-0 or in an 8.7 g canister containing 120 actuations with a beige plastic actuator and gray dust cap, and Patient’s Instructions; box of one; 120 Actuations – NDC 54868-5857-1 QVAR 80 mcg is supplied in a 7.3 g canister containing 100 actuations with a dark mauve plastic actuator and gray dust cap, and Patient’s Instructions; box of one; 100 Actuations – NDC 54868-5858-0 or in an 8.7 g canister containing 120 actuations with a dark mauve plastic actuator and gray dust cap, and Patient’s Instructions; box of one; 120 Actuations – NDC 54868-5858-1 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.
Store QVAR Inhalation Aerosol when not being used, so that the product rests on the concave end of the canister with the plastic actuator on top.
Store at 25°C (77°F).
Excursions between 15° and 30°C (59° and 86°F) are permitted (see USP).
For optimal results, the canister should be at room temperature when used.
QVAR Inhalation Aerosol canister should only be used with the QVAR Inhalation Aerosol actuator and the actuator should not be used with any other inhalation drug product.
CONTENTS UNDER PRESSURE 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.
Keep out of reach of children.
Rx only U.S.
Patent Nos.
5605674, 5683677, 5695743, 5776432 Mktd by: Teva Respiratory, LLC– Horsham, PA 19044 Developed and Manufactured by: 3M Drug Delivery System Northridge, CA 91324 OR 3M Health Care, Ltd.
Loughborough, UK September, 2010 © 2010 Teva Respiratory, LLC 639300 QVAR® is a registered trademark of IVAX LLC, a member of the TEVA Group.
Rev.
09/10 OptiChamber is a registered trademark of Respironics Healthscan, Inc.
and AeroChamber Plus is a registered trademark of Trudell Medical International Trudell Partnership Holdings Limited and Packard Medical Supply Centre Ltd.
Relabeling of “Additional” barcode label by: Physicians Total Care, Inc.
Tulsa, OK 74146
INDICATIONS AND USAGE
QVAR is indicated in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older.
QVAR is also indicated for asthma patients who require systemic corticosteroid administration, where adding QVAR may reduce or eliminate the need for the systemic corticosteroids.
Beclomethasone dipropionate is NOT indicated for the relief of acute bronchospasm.
DOSAGE AND ADMINISTRATION
Patients should prime QVAR by actuating into the air twice before using for the first time or if QVAR has not been used for over ten days.
Avoid spraying in the eyes or face when priming QVAR.
QVAR 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 should be administered by the oral inhaled route in patients 5 years of age and older.
Use of QVAR with a spacer device in children less than 5 years of age is not recommended (see PRECAUTIONS, Pediatric Use ).
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 when administered in excess of recommended doses has not been established.
Recommended Dosage for QVAR: Previous Therapy Recommended Starting Dose Highest Recommended Dose Adults and Adolescents: Bronchodilators Alone 40 to 80 mcg twice daily 320 mcg twice daily Inhaled Corticosteroids 40 to 160 mcg twice daily 320 mcg twice daily Children 5 to 11 years: Bronchodilators Alone 40 mcg twice daily 80 mcg twice daily Inhaled Corticosteroids 40 mcg twice daily 80 mcg twice daily As with any inhaled corticosteroid, physicians are advised to titrate the dose of QVAR 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 has the potential to affect growth in children.
Patients should be instructed on the proper use of their inhaler.
Patients Not Receiving Systemic Corticosteroids Patients who require maintenance therapy of their asthma may benefit from treatment with QVAR at the doses recommended above.
In patients who respond to QVAR, improvement in pulmonary function is usually apparent within 1 to 4 weeks after the start of therapy.
Once the desired effect is achieved, consideration should be given to tapering to the lowest effective dose.
Patients Maintained on Systemic Corticosteroids QVAR may be effective in the management of asthmatics maintained on systemic corticosteroids and may permit replacement or significant reduction in the dosage of systemic corticosteroids.
The patient’s asthma should be reasonably stable before treatment with QVAR is started.
Initially, QVAR should be used concurrently with the patient’s usual maintenance dose of systemic corticosteroids.
After approximately one week, gradual withdrawal of the systemic corticosteroids is started by reducing the daily or alternate daily dose.
Reductions may be made after an interval of one or two weeks, depending on the response of the patient.
A slow rate of withdrawal is strongly recommended.
Generally these decrements should not exceed 2.5 mg of prednisone or its equivalent.
During withdrawal, some patients may experience symptoms of systemic corticosteroid withdrawal, e.g.
joint and/or muscular pain, lassitude and depression, despite maintenance or even improvement in pulmonary function.
Such patients should be encouraged to continue with the inhaler but should be monitored for objective signs of adrenal insufficiency.
If evidence of adrenal insufficiency occurs, the systemic corticosteroid doses should be increased temporarily and thereafter withdrawal should continue more slowly.
During periods of stress or a severe asthma attack, transfer patients may require supplementary treatment with systemic corticosteroids.
DIRECTIONS FOR USE Illustrated Patient’s Instructions for proper use accompany each package of QVAR.