beclomethasone dipropionate 0.00025 MG/MG Topical Ointment

1. INDICATIONS AND USAGE QNASL Nasal Aerosol is a corticosteroid indicated for the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in patients 4 years of age and older. ( 1.1 ) 1.1 Treatment of Nasal Symptoms of Allergic Rhinitis QNASL ® Nasal Aerosol is indicated for the treatment of the nasal symptoms associated with seasonal and perennial allergic rhinitis in patients 4 years of age and older.

2. DOSAGE AND ADMINISTRATION Administer QNASL Nasal Aerosol by the intranasal route only. The dose counter should read “120” for QNASL 80 mcg Nasal Aerosol 120-actuation product and “60” for QNASL 40 mcg Nasal Aerosol 60-actuation product. QNASL Nasal Aerosol does not require priming. See accompanying illustrated Patient Information and Instructions for Use leaflet for proper use of QNASL Nasal Aerosol. QNASL Nasal Aerosol is for intranasal use only. The recommended dose of QNASL 80 mcg Nasal Aerosol in patients 12 years and older is 320 mcg per day administered as 2 actuations in each nostril once daily (maximum total daily dose of 4 actuations per day). ( 2.1 ) The recommended dose of QNASL 40 mcg Nasal Aerosol in children aged 4 to 11 years of age is 80 mcg per day administered as 1 actuation in each nostril once daily (maximum total daily dose of 2 actuations per day). ( 2.1 ) 2.1 Allergic Rhinitis Adults and Adolescents (12 Years of Age and Older): The recommended dose of QNASL Nasal Aerosol is 320 mcg per day administered as 2 actuations in each nostril (QNASL 80 mcg Nasal Aerosol) once daily (maximum total daily dose of 4 actuations per day). Children (4 to 11 Years of Age) : The recommended dose of QNASL Nasal Aerosol is 80 mcg per day administered as 1 actuation in each nostril (QNASL 40 mcg Nasal Aerosol) once daily (maximum total daily dose of 2 actuations per day).

5. WARNINGS AND PRECAUTIONS Nasal discomfort, epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, impaired wound healing. Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma. ( 5.1 ) Eye Disorders. Monitor patients closely with a change in vision or with a history of increased intraocular pressure, blurred vision, glaucoma, and/or cataracts. ( 5.2 ) Hypersensitivity, rash, and urticaria may occur after administration of QNASL Nasal Aerosol. ( 5.3 ) Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections. ( 5.4 ) Hypercorticism and adrenal suppression with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue QNASL Nasal Aerosol slowly. ( 5.5 ) Potential reduction in growth velocity in pediatric patients. Monitor growth routinely in pediatric patients receiving QNASL Nasal Aerosol. ( 5.6 , 8.4 ) 5.1 Local Nasal Effects Nasal Discomfort, Epistaxis, and Nasal Ulceration : In clinical trials of 2 to 52 weeks duration, epistaxis and nasal ulcerations were observed more frequently and some epistaxis events were more severe in patients treated with QNASL Nasal Aerosol than those who received placebo. In the 52-week safety trial in patients with perennial allergic rhinitis, nasal erosions were identified in 4 of 415 patients and a nasal ulceration was identified in 1 of 415 patients treated with QNASL Nasal Aerosol. No nasal erosions or ulcerations were reported for patients who received placebo. In clinical trials conducted in pediatric patients ages 4 to 11 years, the local nasal effect was similar to those reported in patients 12 years of age and older. Patients using QNASL Nasal Aerosol over several months or longer should be examined periodically for possible changes in the nasal mucosa. If an adverse reaction (e.g., erosion, ulceration) is noted, discontinue QNASL Nasal Aerosol [see Adverse Reactions (6.1) ] . Candida Infection : In previous clinical trials with an aqueous formulation of beclomethasone dipropionate administered intranasally, localized infections of the nose and pharynx with Candida albicans had been reported. There were no instances of similar infections observed in clinical trials with QNASL Nasal Aerosol. If such an infection develops, it may require treatment with appropriate local therapy and discontinuation of QNASL Nasal Aerosol treatment. Thus, patients using QNASL Nasal Aerosol over several months or longer should be examined periodically for evidence of Candida infection. Nasal Septal Perforation : Instances of nasal septal perforation have been reported in patients following the intranasal application of beclomethasone dipropionate. There were no nasal septal perforations reported during clinical trials in the indicated dose of QNASL 80 mcg Nasal Aerosol administered as 320 mcg once daily in adults and adolescents. There was one report of nasal septal perforation observed in the dose-ranging pediatric clinical trial. Impaired Wound Healing : Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal ulcers, nasal surgery, or nasal trauma should not use QNASL Nasal Aerosol until healing has occurred. 5.2 Eye Disorders Use of intranasal and inhaled corticosteroids may result in the development of increased intraocular pressure, blurred vision, glaucoma and/or cataracts. 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. Glaucoma and cataract formation was evaluated with ocular assessments that included intraocular pressure measurements and slit lamp examinations in 245 adolescent and adult patients (12 years of age and older) with perennial allergic rhinitis who were treated with QNASL Nasal Aerosol 320 mcg daily (N=197) or placebo (N=48) for up to 52 weeks. In 94% of patients, intraocular pressure (IOP) remained within the normal range (<21 mmHg) during the treatment portion of the trial. There were 10 patients (5%) treated with QNASL Nasal Aerosol and 1 patient (2%) treated with placebo that had intraocular pressure that increased above normal levels (≥21 mmHg) and greater than baseline during the treatment portion of the trial. Two of these occurrences in patients treated with QNASL Nasal Aerosol were reported as adverse reactions, one serious. No instances of cataract formation or other clinically significant ocular incidents were reported in this 52-week safety trial [see Adverse Reactions (6.1) ] . 5.3 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions including anaphylaxis, angioedema, urticaria, and rash have been reported following administration of beclomethasone dipropionate nasally administered and inhalationally administered products. Angioedema, urticaria, and rash have been reported following administration of QNASL Nasal Aerosol. Discontinue QNASL Nasal Aerosol if any such reactions occur [see Contraindications (4) ] . 5.4 Immunosuppression Persons who are using drugs that suppress the immune system (e.g., corticosteroids) are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is 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 or measles develops, treatment with antiviral agents may be considered. Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract, untreated local or systemic fungal or bacterial infections, systemic viral or parasitic infections, or ocular herpes simplex because of the potential for worsening of these infections. 5.5 Hypothalamic-Pituitary-Adrenal Axis Effect When intranasal steroids are used at higher-than-recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of QNASL Nasal Aerosol should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy. The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, and depression). Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms. 5.6 Effect on Growth Corticosteroids may cause a reduction in growth

4. CONTRAINDICATIONS QNASL Nasal Aerosol is contraindicated in patients with a history of hypersensitivity to beclomethasone dipropionate and/or any other QNASL Nasal Aerosol ingredients [see Warnings and Precautions (5.3) ] . Patients with a history of hypersensitivity to beclomethasone dipropionate and/or any other QNASL Nasal Aerosol ingredients. ( 4 )

Mechanism of Action Beclomethasone dipropionate is a prodrug that is extensively converted to the active metabolite, beclomethasone-17-monopropionate. The precise mechanism through which beclomethasone dipropionate affects rhinitis symptoms is unknown. Corticosteroids have been shown to have multiple anti-inflammatory effects, inhibiting both inflammatory cells (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and the release of inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines). Beclomethasone-17-monopropionate has been shown in vitro 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.