Clonat 0,0005

1 INDICATIONS AND USAGE Clobetasol propionate topical spray, 0.05% is a corticosteroid indicated for the topical treatment of moderate to severe plaque psoriasis affecting up to 20% body surface area (BSA) in patients 18 years of age or older ( 1.1 ) Limitations of Use: Do not use on the face, axillae or groin.( 1.2 ) Do not use if atrophy is present at the treatment site.( 1.2 ) Do not use for rosacea or perioral dermatitis.( 1.2 ) 1.1 Indication Clobetasol propionate topical spray, 0.05% is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe plaque psoriasis affecting up to 20% body surface area (BSA) in patients 18 years of age or older. Patients should be instructed to use clobetasol propionate topical spray, 0.05% for the minimum amount of time necessary to achieve the desired results [ see Dosage and Administration (2) ] . Use in patients under 18 years of age is not recommended because safety has not been established and because numerically high rates of HPA axis suppression were seen with other clobetasol propionate topical formulations. [ see Use in Specific Populations (8.4) ]. 1.2 Limitations of Use Clobetasol propionate topical spray, 0.05% should not be used on the face, axillae, or groin. Clobetasol propionate topical spray, 0.05% should not be used if there is atrophy at the treatment site. Clobetasol propionate topical spray, 0.05% should not be used in the treatment of rosacea or perioral dermatitis.

2 DOSAGE AND ADMINISTRATION Clobetasol propionate topical spray, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use. Clobetasol propionate topical spray, 0.05% should be sprayed directly onto the affected skin areas twice daily and rubbed in gently and completely. The total dosage should not exceed 50 g (59 mL or 2 fluid ounces) per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Do not use more than 26 sprays per application or 52 sprays per day. Clobetasol propionate topical spray, 0.05% contains a topical corticosteroid; therefore treatment should be limited to 4 weeks. Therapy should be discontinued when control has been achieved. Treatment beyond 2 weeks should be limited to localized lesions of moderate to severe plaque psoriasis that have not sufficiently improved after the initial 2 weeks of treatment with clobetasol propionate topical spray, 0.05%. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Before prescribing for more than 2 weeks, any additional benefits of extending treatment to 4 weeks should be weighed against the risk of HPA axis suppression. Unless directed by physician, clobetasol propionate topical spray, 0.05% should not be used with occlusive dressings. Not for oral, ophthalmic, or intravaginal use. ( 1.2 ) Sprayed directly onto the affected skin areas twice daily and rub in gently. ( 2 ) The total dosage should not exceed 50 g (59 mL or 2 fluid ounces) per week. Do not use more than 26 sprays per application or 52 sprays per day. ( 2 ) Treatment beyond 2 weeks should be limited to localized lesions of moderate to severe plaque psoriasis that have not sufficiently improved after the initial 2 weeks of treatment with clobetasol propionate topical spray, 0.05%. ( 2 ) Do not use for more than 4 weeks. ( 2 )

5 WARNINGS AND PRECAUTIONS Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested. ( 5.1 ) Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. ( 5.1 ) Systemic absorption may require periodic evaluation for HPA axis suppression. Modify use if HPA axis suppression develops. ( 5.1 ) Children may be more susceptible to systemic toxicity from use of topical corticosteroids. ( 5.1 , 8.4 ) Clobetasol propionate topical spray may increase the risk of cataract and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. ( 5.2) Local adverse reactions with topical corticosteroids may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. ( 5.3 ) Clobetasol propionate spray topical, 0.05% is flammable; keep away from heat or flame. ( 5.6 ) 5.1 Effects on the Endocrine System Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested. Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, using the Cosyntropin Stimulation Test, clobetasol propionate topical spray, 0.05% demonstrated rates of suppression that were comparable after 2 and 4 weeks of twice-daily use (19% and 15 to 20%, respectively), in adult patients with moderate to severe plaque psoriasis (≥ 20% BSA). In these studies, HPA axis suppression was defined as serum cortisol level ≤ 18 mcg/dL 30-min post cosyntropin stimulation [ see Clinical Pharmacology (12) ]. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure. An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure. Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. [ see Use in Specific Populations (8.4) ] 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids, including clobetasol propionate topical spray may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including topical clobetasol products [ see Adverse Reactions (6.2) ]. Avoid contact of clobetasol propionate topical spray with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Local Adverse Reactions with Topical Corticosteroids The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria. 5.4 Allergic Contact Dermatitis Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing. 5.5 Concomitant Skin Infections In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of clobetasol propionate topical spray, 0.05% should be discontinued until the infection has been adequately controlled. 5.6 Flammable Contents Clobetasol propionate topical spray, 0.05% is flammable; keep away from heat or flame.

6 ADVERSE REACTIONS In controlled, clinical trials with clobetasol propionate topical spray, 0.05%, the most common adverse reactions (incidence > 2%) were burning, pruritus, nasopharyngitis, upper respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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. In controlled, clinical trials with clobetasol propionate topical spray, 0.05%, the most common adverse reaction was burning at the site of application [40% of subjects treated with clobetasol propionate topical spray, 0.05% and 47% of subjects treated with Spray Vehicle]. Other commonly reported adverse reactions for clobetasol propionate topical spray, 0.05% and Spray Vehicle, respectively, are noted in Table 1. Table 1 - Commonly Occurring Adverse Reactions (≥1% Incidence) Adverse Reaction Clobetasol Propionate 0.05% Spray (N=120) Vehicle Spray (N=120) System Organ Class General disorders and administration site conditions 50 (42%) 56 (47%) Application site burning 48 (40%) 56 (47%) Application site dryness 2 (2%) 0 (0%) Application site irritation 1 (1%) 0 (0%) Application site pain 1 (1%) 2 (2%) Application site pigmentation changes 1 (1%) 0 (0%) Application site pruritus 4 (3%) 3 (3%) Infections and infestations 17 (14%) 12 (10%) Nasopharyngitis 6 (5%) 3 (3%) Pharyngitis streptococcal 1 (1%) 0 (0%) Upper respiratory tract infection 10 (8%) 2 (2%) Skin and subcutaneous tissue disorders 4 (3%) 2 (2%) Eczema asteatotic 2 (2%) 0 (0%) Most local adverse reactions were rated as mild to moderate and they are not affected by age, race or gender. Systemic absorption of topical corticosteroids has produced hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glycosuria in some patients. 6.2 Postmarketing Experience 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. The following adverse reactions have been identified during post-approval use clobetasol propionate topical spray, 0.05%. Skin: Burning, pruritus, erythema, pain, irritation, rash, peeling, urticaria, and contact dermatitis. Ophthalmic adverse reactions of blurred vision, cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported with the use of topical corticosteroids.