The active component of QVAR REDIHALER 40 mcg Inhalation Aerosol and QVAR REDIHALER 80 mcg Inhalation Aerosol is beclomethasone dipropionate, USP, a corticosteroid having the chemical name 9-chloro-11ß,17,21-trihydroxy-16ß-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate. Beclomethasone dipropionate 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: Chemical Structure QVAR REDIHALER is a pressurized, breath‑actuated, metered‑dose aerosol with a dose counter intended for oral inhalation only. Each unit consists of a sealed breath‑actuated inhaler device enclosing a canister containing a solution of beclomethasone dipropionate in propellant HFA‑134a (1,1,1,2 tetrafluoroethane) and ethanol (0.85 g). QVAR REDIHALER 40 mcg delivers 40 mcg of beclomethasone dipropionate from the actuator mouthpiece and 50 mcg from the canister valve. QVAR REDIHALER 80 mcg delivers 80 mcg of beclomethasone dipropionate from the actuator mouthpiece and 100 mcg from the canister valve. Both products deliver 50 microliters (59 milligrams) of solution formulation as an aerosol from the canister valve with each actuation. The 40‑mcg canisters and the 80‑mcg canisters provide 120 inhalations each. Since the QVAR REDIHALER canister is fitted with a primeless valve, no priming actuations are required before use. For both products, an actuation was always triggered by a 20 L/min inspiratory flow rate. structure

QVAR REDIHALER is indicated in the maintenance treatment of asthma as prophylactic therapy in adults and pediatric patients 4 years of age and older. Limitations of Use: QVAR REDIHALER is not indicated for the relief of acute bronchospasm. QVAR REDIHALER is a corticosteroid indicated for maintenance treatment of asthma as prophylactic therapy in adults and pediatric patients 4 years of age and older. Limitations of Use : Not indicated for the relief of acute bronchospasm.

Inhalation aerosol: a pressurized, breath‑actuated, metered-dose aerosol with a dose counter in 2 strengths 40 mcg in an aluminum canister contained within a beige plastic actuator and a hinged white cap 80 mcg in an aluminum canister contained within a maroon plastic actuator and a hinged white cap Inhalation aerosol: 40 mcg or 80 mcg per breath actuation.

For oral inhalation only. Starting dosage is based on prior asthma therapy and disease severity. Treatment of asthma in patients 4 to 11 years of age: 40 mcg or 80 mcg twice daily. Treatment of asthma in patients 12 years of age and older: 40 mcg, 80 mcg, 160 mcg, or 320 mcg twice daily Discard QVAR REDIHALER inhaler when the dose counter displays 0 or after the expiration date on the product, whichever comes first. Do not use a spacer or volume holding chamber 2.1 General Overview Administration Administer QVAR REDIHALER by oral inhalation. After inhalation, rinse mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. Consistent dose delivery is achieved, whether using the 40‑ or 80‑mcg strengths, due to proportionality of the 2 products (i.e., 2 actuations of 40‑mcg strength should provide a dose comparable to 1 actuation of the 80‑mcg strength). Inhaler Instructions Patients should be instructed on the proper use of their inhaler. Do not use QVAR REDIHALER with a spacer or volume holding chamber. Shaking the inhaler prior to use is not necessary. Do not shake the inhaler with the cap open to avoid possible actuation of the device. Priming QVAR REDIHALER does not require priming. Cleaning Keep the inhaler clean and dry at all times. Never wash or put any part of the inhaler in water. Routine maintenance is not required. If the mouthpiece needs cleaning, gently wipe the mouthpiece with a dry cloth or tissue as needed. Dose Counter QVAR REDIHALER has a dose counter attached to the actuator. When the patient receives the inhaler, the number 120 will be displayed. The dose counter will count down each time a spray is released. When the dose counter reaches 20, the color of the numbers will change to red to remind the patient to contact their pharmacist for a refill of medication or consult their physician for a prescription refill. When the dose counter reaches 0, the background will change to solid red. Discard QVAR REDIHALER inhaler when the dose counter displays 0 or after the expiration date on the product, whichever comes first

Recommended Dosage Adults and Adolescents 12 years of age and older The recommended starting dosage for patients 12 years of age and older who are not on an inhaled corticosteroid is 40 to 80 mcg twice daily by oral inhalation, approximately 12 hours apart. The starting dosage is based on previous asthma therapy and disease severity, including consideration of the patients’ current control of asthma symptoms and risk of future exacerbation. For patients switching to QVAR REDIHALER from another inhaled corticosteroid product, select the appropriate starting dosage strength of QVAR REDIHALER based on the strength of the previous inhaled corticosteroid product and disease severity: 40, 80, 160 or 320 mcg twice daily. For patients who do not respond adequately to the initial dosage after 2 weeks of therapy, increasing the dosage may provide additional asthma control. The maximum recommended dosage for patients 12 years of age and older is 320 mcg twice daily. Pediatric Patients 4 to 11 years The recommended starting dosage for patients aged 4 to 11 years of age is 40 mcg twice daily by oral inhalation, approximately 12 hours apart. The starting dosage is based on previous asthma therapy and disease severity, including consideration of the patients’ current control of asthma symptoms and risk of future exacerbation. For patients who do not respond adequately to QVAR REDIHALER 40 mcg after 2 weeks of therapy, increasing the dosage to QVAR REDIHALER 80 mcg twice daily may provide additional asthma control. The maximum recommended dosage for patients 4 to 11 years of age is 80 mcg twice daily. General Dosing Recommendations The onset and degree of symptom relief will vary in individual patients. Improvement in asthma symptoms can occur within 24 hours of the beginning of treatment and should be expected within the first or second week, but maximum benefit should not be expected until 3 to 4 weeks of therapy. Improvement in pulmonary function is usually apparent within 1 to 4 weeks after the start of therapy. If a dosage regimen of QVAR REDIHALER fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options (e.g., replacing the current strength of QVAR REDIHALER with a higher strength, or adding additional controller therapies) should be considered. As with any inhaled corticosteroid, physicians are advised to titrate the dose of QVAR REDIHALER 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 beclomethasone dipropionate has the potential to affect growth in children. The maximum number of inhalations should not exceed 8 per day.

Oropharyngeal candidiasis: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk. Deterioration of asthma and acute episodes: Do not use QVAR REDIHALER for relief of acute symptoms. Patients require immediate re-evaluation during rapidly deteriorating asthma. Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids. Taper patients slowly from systemic corticosteroids if transferring to QVAR REDIHALER. Immunosuppression: Potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Use with caution in patients with these infections because of the potential for worsening of these infections. Paradoxical bronchospasm: Bronchospasm, with an immediate increase in wheezing, may occur after dosing. Treat bronchospasm immediately with inhaled, short-acting bronchodilator and discontinue QVAR REDIHALER. Hypersensitivity reactions: Hypersensitivity reactions, such as urticaria, angioedema, rash, and bronchospasm may occur. Discontinue QVAR REDIHALER if such reactions occur. Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue QVAR REDIHALER slowly. Effects on growth: Monitor growth of pediatric patients. Decreases in bone mineral density: Monitor patients with major risk factors for decreased bone mineral content. Glaucoma and cataracts: Monitor patients with change in vision or with a history of increased intraocular pressure, blurred vision, glaucoma, and/or cataracts closely. 5.1 Oropharyngeal Candidiasis Localized infections with Candida albicans have occurred in the mouth and pharynx in some patients receiving QVAR REDIHALER. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing with QVAR REDIHALER therapy, but at times therapy with QVAR REDIHALER may need to be temporarily interrupted under close medical supervision. After inhalation, the patient should rinse his/her mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis

Deterioration of Asthma and Acute Episodes QVAR REDIHALER is not indicated for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short‑acting beta 2 ‑agonist, not QVAR REDIHALER, should be used to relieve acute symptoms such as shortness of breath. Instruct patients to contact their physician immediately if episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with QVAR REDIHALER. During such episodes, patients may require therapy with oral corticosteroids

Transferring Patients from Systemic Corticosteroid Therapy HPA Suppression/Adrenal Insufficiency Particular care is needed in patients who are transferred from systemically active corticosteroids to QVAR REDIHALER 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 REDIHALER 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. Patients requiring oral or other systemic corticosteroids should be weaned slowly from oral or other systemic corticosteroid use after transferring to QVAR REDIHALER. Lung function (FEV 1 or PEF), beta‑agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral or other systemic corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids Transfer of patients from systemic corticosteroid therapy to QVAR REDIHALER may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. Corticosteroid Withdrawal Symptoms 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

Immunosuppression and Risk of Infections 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 patients on corticosteroids. In such patients 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 affect the risk of developing a disseminated infection, and 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 If chickenpox develops, treatment with antiviral agents may be considered. 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

Paradoxical Bronchospasm Inhaled corticosteroids may produce inhalation‑induced bronchospasm with an immediate increase in wheezing after dosing that may be life-threatening. If inhalation induced bronchospasm occurs following dosing with QVAR REDIHALER, it should be treated immediately with an inhaled, short‑acting bronchodilator. Treatment with QVAR REDIHALER should be discontinued and alternate therapy instituted

Immediate Hypersensitivity Reactions Hypersensitivity reactions, such as urticaria, angioedema, rash, and bronchospasm, may occur after administration of QVAR REDIHALER. Discontinue QVAR REDIHALER if such reactions occur

Hypercorticism and Adrenal Suppression QVAR REDIHALER will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since beclomethasone dipropionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of QVAR REDIHALER in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with QVAR REDIHALER should be observed carefully for any evidence of systemic corticosteroid effects. 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 (including adrenal crisis) may appear in a small number of patients, particularly when beclomethasone dipropionate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of QVAR REDIHALER should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms

Effects on Growth Orally inhaled corticosteroids, including QVAR REDIHALER, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving QVAR REDIHALER routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including QVAR REDIHALER, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms

Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long‑term administration of products containing inhaled corticosteroids. The clinical significance of small changes in BMD with regard to long‑term outcomes, such as fracture, is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care

Glaucoma and Cataracts Glaucoma, increased intraocular pressure, blurred vision and cataracts have been reported following the use of long-term administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, blurred vision, glaucoma, and/or cataracts while using QVAR REDIHALER.