Beclomethasone

1 INDICATIONS AND USAGE 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. ( 1 ) Limitations of Use : Not indicated for the relief of acute bronchospasm. ( 1 )

2 DOSAGE AND ADMINISTRATION For oral inhalation only. ( 2.1 ) Starting dosage is based on prior asthma therapy and disease severity. ( 2.2 ) Treatment of asthma in patients 4 to 11 years of age: 40 mcg or 80 mcg twice daily. ( 2.2 ) Treatment of asthma in patients 12 years of age and older: 40 mcg, 80 mcg, 160 mcg, or 320 mcg twice daily ( 2.2 ) Discard QVAR REDIHALER inhaler when the dose counter displays 0 or after the expiration date on the product, whichever comes first. ( 2.1 ) Do not use a spacer or volume holding chamber ( 2.1 ) 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 [see Patient Counseling Information ( 17 )] . 2.2 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.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Oropharyngeal candidiasis [see Warnings and Precautions ( 5.1 )] Immunosuppression and risk of infections [see Warnings and Precautions ( 5.4 )] Hypercorticism and adrenal suppression [see Warnings and Precautions ( 5.7 )] Reduction in bone mineral density [see Warnings and Precautions ( 5.9 )] Growth effects [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.4 )] Glaucoma and cataracts [see Warnings and Precautions ( 5.10 )] Most common adverse reactions (incidence > 3% and > placebo) include oral candidiasis, upper respiratory tract infection, nasopharyngitis, allergic rhinitis, oropharyngeal pain and sinusitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience A total of 1858 subjects participated in the QVAR REDIHALER clinical development program. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults and Adolescent Patients 12 years of Age and Older: The adverse reaction information presented in Table 1 is derived from 3 double-blind, placebo-controlled clinical trials in which 1230 patients (751 female and 479 male adults previously treated with as‑needed bronchodilators and/or inhaled corticosteroids) were treated with QVAR REDIHALER (doses of 40, 80, 160, or 320 mcg twice daily) or QVAR (beclomethasone dipropionate HFA) Inhalation Aerosol (QVAR MDI; doses of 160 or 320 mcg twice daily) or placebo. In considering these data, difference in average duration of exposure and clinical trial design should be taken into account. Table 1: Adverse Reactions Experienced by at Least 3% of Adult and Adolescent Patients in the QVAR REDIHALER or QVAR MDI Groups and Greater Than Placebo by Treatment and Daily Dose Preferred Term Number (%) of patients QVAR REDIHALER QVAR MDI Placebo 80 mcg N=90 160 mcg N=92 320 mcg N=214 640 mcg N=211 320 mcg N=212 640 mcg N=107 N=304 Oral Candidiasis 0 2 (2) 7 (3) 15 (7) 6 (3) 9 (8) 1 (<1) Upper Respiratory Tract Infection 3 (3) 3 (3) 9 (4) 6 (3) 17 (8) 4 (4) 6 (2) Nasopharyngitis 4 (4) 2 (2) 3 (1) 3 (1) 6 (3) 4 (4) 4 (1) Oropharyngeal Pain 2 (2) 2 (2) 1 (<1) 3 (1) 6 (3) 4 (4) 2 (<1) Viral Upper Respiratory Tract Infection 3 (3) 0 1 (<1) 3 (1) 4 (2) 2 (<1) 4 (1) Sinusitis 3 (3) 0 1 (<1) 2 (<1) 1 (<1) 1 (<1) 2 (<1) Rhinitis Allergic 0 3 (3) 0 2 (<1) 0 1 (<1) 0 *QVAR MDI=QVAR Inhalation Aerosol Other adverse reactions that occurred in clinical trials using QVAR REDIHALER with an incidence of 1% to 3% and which occurred at a greater incidence than placebo were back pain, headache, pain, nausea and cough. Pediatric Patients 4 to 11 Years of Age: The adverse reaction information presented in Table 2 concerning QVAR REDIHALER and QVAR MDI is derived from one 12‑week placebo-controlled study in pediatric patients 4 to 11 years of age with persistent asthma. Table 2: Adverse Reactions Experienced by at Least 3% of Patients 4 to 11 Years of Age in the QVAR REDIHALER or QVAR MDI Groups and Greater Than Placebo by Treatment and Daily Dose Preferred Term Number (%) of patients QVAR REDIHALER QVAR MDI Placebo 80 mcg N=126 160 mcg N=125 80 mcg N=125 160 mcg N=125 N=127 Upper Respiratory Tract Infection 3 (2.4) 1 (0.8) 6 (4.8) 5 (4.0) 5 (3.9) Nasopharyngitis 5 (4.0) 11 (8.8) 6 (4.8) 6 (4.8) 4 (3.1) Viral Upper Respiratory Tract Infection 5 (4.0) 5 (4.0) 3 (2.4) 1 (0.8) 4 (3.1) Pharyngitis 4 (3.2) 4 (3.2) 4 (3.2) 4 (3.2) 2 (1.6) Cough 1 (0.8) 3 (2.4) 9 (7.2) 6 (4.8) 4 (3.1) Vomiting 2 (1.6) 2 (1.6) 4 (3.2) 0 2 (1.6) Headache 2 (1.6) 5 (4.0) 0 4 (3.2) 5 (3.9) Pyrexia 1 (0.8) 4 (3.2) 4 (3.2) 3 (2.4) 3 (2.4) *QVAR MDI=QVAR Inhalation Aerosol Other adverse reactions that occurred in clinical trials using QVAR REDIHALER with an incidence of 1% to 3% and which occurred at a greater incidence than placebo were influenza, gastroenteritis viral, ear infection, oral candidiasis, diarrhea, and myalgia. 6.2 Postmarketing Experience In addition to the adverse reactions reported from clinical trials with QVAR REDIHALER, the following adverse reactions have been identified during post-approval use of QVAR MDI and other inhaled corticosteroids. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Local Effects: Localized infections with Candida albicans have occurred in patients treated with beclomethasone dipropionate or other orally inhaled corticosteroids [see Warnings and Precautions ( 5.1 )] . Psychiatric and Behavioral Changes: Aggression, depression, sleep disorders, psychomotor hyperacti