QVAR REDIHALER

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. Wipe the mouthpiece weekly with a clean, dry cloth or tissue. 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.

4 CONTRAINDICATIONS QVAR REDIHALER is contraindicated in: the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required [see Warnings and Precautions ( 5.2 )] . in patients with known hypersensitivity to beclomethasone dipropionate or any of the ingredients in QVAR REDIHALER [see Warnings and Precautions ( 5.6 )] . Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. ( 4 ) Hypersensitivity to any of the ingredients of QVAR REDIHALER. ( 4 )

5 WARNINGS AND PRECAUTIONS 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. ( 5.1 ) 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. ( 5.2 ) 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. ( 5.3 ) 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. ( 5.4 ) 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. ( 5.5 ) Hypersensitivity reactions: Hypersensitivity reactions, such as urticaria, angioedema, rash, and bronchospasm may occur. Discontinue QVAR REDIHALER if such reactions occur. ( 5.6 ) 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. ( 5.7 ) Effects on growth: Monitor growth of pediatric patients. ( 5.8 ) Decreases in bone mineral density: Monitor patients with major risk factors for decreased bone mineral content. ( 5.9 ) Glaucoma and cataracts: Monitor patients with change in vision or with a history of increased intraocular pressure, blurred vision, glaucoma, and/or cataracts closely. ( 5.10 ) 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. 5.2 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. 5.3 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. 5.4 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 (See the respective package inserts for complete VZIG and IG prescribing information.) 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. 5.5 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. 5.6 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 [see Contraindications ( 4 )] . 5.7 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. 5.8 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 [see Use in Specific Populations ( 8.4) ] . 5.9 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. 5.10 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.

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 hyperactivity, and suicidal ideation have been reported (primarily in children). Eye Disorders: Blurred vision, central serous chorioretinopathy (CSC).

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well‑controlled studies with QVAR REDIHALER or beclomethasone dipropionate in pregnant women. There are clinical considerations with the use of inhaled corticosteroids (ICS), including beclomethasone dipropionate, in pregnant women [see Clinical Considerations] . Also, no published studies, including studies of large birth registries, have to date related the use of ICS to any increases in congenital malformations or other adverse perinatal outcomes. Thus, available human data do not establish the presence or absence of drug‑associated risk to the fetus. In animal reproduction studies, beclomethasone dipropionate resulted in adverse developmental effects in mice and rabbits at subcutaneous doses equal to or greater than approximately 0.75 times the maximum recommended human daily inhalation dose (MRHDID) in adults (0.64 mg/day) [see Data] . In rats exposed to beclomethasone dipropionate by inhalation, dose‑related gross injury to the fetal adrenal glands was observed at doses greater than 180 times the MRHDID, but there was no evidence of external or skeletal malformations or embryolethality at inhalation doses of up to 440 times the MRHDID. The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the US general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2‑4% and 15‑20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk The risk of complications to the mother and developing fetus from inadequate control of asthma must be balanced against the risks from exposure to beclomethasone dipropionate. In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age for the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted to maintain optimal control. Labor or Delivery There are no specific human data regarding any adverse effects of inhaled beclomethasone dipropionate on labor and delivery. Data Animal Data In an embryofetal development study in pregnant rats, beclomethasone dipropionate administration during organogenesis from gestation days 6 to 15 at inhaled doses 180 times the MRHDID in adults and higher (on a mg/m 2 basis at maternal doses of 11.5 and 28.3 mg/kg/day) produced dose‑dependent gross injury (characterized by red foci) of the adrenal glands in fetuses. There were no findings in the adrenal glands of rat fetuses at an inhaled dose that was 40 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 2.4 mg/kg/day). There was no evidence of external or skeletal malformations or embryolethality in rat at inhaled doses up to 440 times the MRHDID (on a mg/m 2 basis at maternal doses up to 28.3 mg/kg/day). In an embryofetal development study in pregnant mice, beclomethasone dipropionate administration from gestation days 1 to 18 at subcutaneous doses equal to and greater than 0.75 times the MRHDID in adults (on a mg/m 2 basis at maternal doses of 0.1 mg/kg/day and higher) produced adverse developmental effects (increased incidence of cleft palate). A no-effect dose in mice was not identified. In a second embryofetal development study in pregnant mice, beclomethasone dipropionate administration from gestation days 1 to 13 at subcutaneous doses equal to and greater than 2.3 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 0.3 mg/kg/day) produced embryolethal effects (increased fetal resorptions) and decreased pup survival. In an embryofetal development study in pregnant rabbits, beclomethasone dipropionate administration during organogenesis from gestation days 7 to 16 at subcutaneous doses equal to and greater than 0.75 times the MRHDID in adults (on a mg/m 2 basis at maternal doses of 0.025 mg/kg/day and higher) produced external and skeletal malformations and embryolethal effects (increased fetal resorptions). There were no effects in fetuses of pregnant rabbits administered a subcutaneous dose 0.2 times the MRHDID in adults (on a mg/m 2 basis at a maternal dose of 0.006 mg/kg/day). 8.2 Lactation Risk Summary There are no data available on the presence of beclomethasone dipropionate in human milk, the effects on the breastfed child, or the effects on milk production. However, other inhaled corticosteroids have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for QVAR REDIHALER and any potential adverse effects on the breastfed child from beclomethasone dipropionate or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Impairment of fertility was observed in rats and dogs at oral doses of beclomethasone dipropionate corresponding to 250 and 25 times the MRHDID for adults on a mg/m 2 basis, respectively. [see Nonclinical Toxicology ( 13.1 )] . 8.4 Pediatric Use The safety and effectiveness of QVAR REDIHALER for the maintenance treatment of asthma as prophylactic therapy have been established in pediatric patients aged 4 years and older. Use of QVAR REDIHALER for this indication is supported by evidence from adequate and well-controlled studies. Five-hundred and one children between the ages of 4 and 11 were treated with at least one dose of QVAR REDIHALER or QVAR MDI in one 12‑week clinical trial. The safety and effectiveness of QVAR REDIHALER in children below 4 years of age have not been established. Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. A 12‑month, randomized, controlled clinical trial evaluated the effects of QVAR MDI versus beclomethasone dipropionate in a CFC propellant‑based formulation (CFC‑BDP) on growth in children age 5 to 11. A total of 520 patients were enrolled, of whom 394 received QVAR MDI (100 to 400 mcg/day ex‑valve) and 126 received CFC‑BDP (200 to 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 QVAR MDI was approximately 0.5 cm/year less than that noted with children treated with CFC‑BDP via large‑volume spacer. The long‑term effects of the reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for "catch‑up" growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The growth of children and adolescents receiving orally inhaled corticosteroids, including QVAR REDIHALER, should be monitored routinely (e.g., via stadiometry). If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including QVAR REDIHALER, each patient should be titrated to his/her lowest effective dose [see Dosage and Administration ( 2.2 )] . 8.5 Geriatric Use Clinical studies of QVAR REDIHALER did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.