Betamethasone Dipropionate

1 INDICATIONS AND USAGE Betamethasone Dipropionate Cream USP (Augmented), 0.05% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age or older. Betamethasone Dipropionate Cream USP (Augmented), 0.05% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age and older.0

2 DOSAGE AND ADMINISTRATION Apply a thin film of Betamethasone Dipropionate Cream USP (Augmented), 0.05% to the affected skin areas once or twice daily. Therapy should be discontinued when control is achieved. Betamethasone Dipropionate Cream USP (Augmented), 0.05% is a high-potency corticosteroid. Treatment with Betamethasone Dipropionate Cream USP (Augmented), 0.05% should not exceed 50 g per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis [ see Warnings and Precautions (5.1) ]. Betamethasone Dipropionate Cream USP (Augmented), 0.05% should not be used with occlusive dressings unless directed by a physician. Avoid contact with eyes. Wash hands after each application. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Betamethasone Dipropionate Cream USP (Augmented), 0.05% is for topical use only. It is not for oral, ophthalmic, or intravaginal use. • Apply a thin film to the affected skin areas once or twice daily. (2) • Discontinue therapy when control is achieved. (2) • Use no more than 50 g per week. (2) • Do not use with occlusive dressings unless directed by a physician. (2) • Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. (2) • Not for oral, ophthalmic, or intravaginal use. (2)

3 DOSAGE FORMS AND STRENGTHS Cream, 0.05%. Each gram of Betamethasone Dipropionate Cream (augmented), 0.05% contains 0.643 mg betamethasone dipropionate, USP (equivalent to 0.5 mg betamethasone) in a white to off-white, uniform and smooth cream. • Cream, 0.05% ( 3 )

4 CONTRAINDICATIONS Betamethasone Dipropionate Cream USP (Augmented), 0.05% is contraindicated in patients who are hypersensitive to betamethasone dipropionate, to other corticosteroids, or to any ingredient in this preparation. • Hypersensitivity to any component of this medicine. (4)

6 ADVERSE REACTIONS • The most common adverse reaction reported in 0.4% of adult patients is stinging. ( 6.1 ) • The most common adverse reactions reported in 10% of pediatric patients are signs of skin atrophy, telangiectasia, bruising, shininess. ( 6.1 , 8.4 ) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 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 clinical practice. In controlled clinical trials, involving 242 adult subjects, the adverse reaction associated with the use of betamethasone dipropionate cream (augmented) reported at a frequency of 0.4% was stinging. It occurred in 1 subject. In a controlled clinical trial involving 67 pediatric subjects from 3 months to 12 years of age, the adverse reactions associated with the use of betamethasone dipropionate cream (augmented) occurred in 7 of 67 (10%) subjects. Reported reactions included signs of skin atrophy (telangiectasia, bruising, shininess). 6.2 Postmarketing Experience Because adverse 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. Postmarketing reports for local adverse reactions to topical corticosteroids may also include: burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, skin atrophy, striae, and miliaria. Hypersensitivity reactions, consisting of predominantly skin signs and symptoms, e.g., contact dermatitis, pruritus, bullous dermatitis, and erythematous rash have been reported. Ophthalmic adverse reactions of cataracts, glaucoma, increased intraocular pressure, and central serous chorioretinopathy have been reported with the use of topical corticosteroids, including topical betamethasone products.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on Betamethasone Dipropionate Cream USP (Augmented), 0.05% use in pregnant women to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Observational studies suggest an increased risk of low birthweight infants with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. Advise pregnant women that Betamethasone Dipropionate Cream USP (Augmented), 0.05% may increase the risk of having a low birthweight infant and to use Betamethasone Dipropionate Cream USP (Augmented), 0.05% on the smallest area of skin and for the shortest duration possible. In animal reproduction studies, increased malformations, including umbilical hernias, cephalocele, and cleft palate, were observed after intramuscular administration of betamethasone dipropionate to pregnant rabbits. The available data do not allow the calculation of relevant comparisons between the systemic exposure of betamethasone dipropionate in animal studies to the systemic exposure that would be expected in humans after topical use of Betamethasone Dipropionate Cream USP (Augmented), 0.05% (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Betamethasone dipropionate has been shown to cause malformations in rabbits when given by the intramuscular route at doses of 0.05 mg/kg. The abnormalities observed included umbilical hernias, cephalocele, and cleft palate. 8.2 Lactation Risk Summary There are no data regarding the excretion of betamethasone dipropionate in breast milk, the effects on the breastfed infant, or the effects on milk production after topical application of Betamethasone Dipropionate Cream USP (Augmented), 0.05% to women who are breastfeeding. It is possible that topical administration of large amounts of betamethasone dipropionate could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Betamethasone Dipropionate Cream USP (Augmented), 0.05% and any potential adverse effects on the breastfed infant from Betamethasone Dipropionate Cream USP (Augmented), 0.05% or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use Betamethasone Dipropionate Cream USP (Augmented), 0.05% on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply Betamethasone Dipropionate Cream USP (Augmented), 0.05% directly to the nipple and areola to avoid direct infant exposure [ see Use in Specific Populations (8.4) ]. 8.4 Pediatric Use Use of Betamethasone Dipropionate Cream USP (Augmented), 0.05% in pediatric patients younger than 13 years of age is not recommended due to the potential for HPA axis suppression [ see Warnings and Precautions (5.1) ]. In an open-label HPA axis safety trial in subjects 3 months to 12 years of age with atopic dermatitis, betamethasone dipropionate cream (augmented), 0.05% was applied twice daily for 2 to 3 weeks over a mean body surface area of 58% (range 35% to 95%). In 19 of 60 (32%) evaluable subjects, adrenal suppression was indicated by either a ≤5 mcg/dL pre-stimulation cortisol, or a cosyntropin post-stimulation cortisol ≤18 mcg/dL and/or an increase of <7 mcg/dL from the baseline cortisol. Out of the 19 subjects with HPA axis suppression, 4 subjects were tested 2 weeks after discontinuation of betamethasone dipropionate cream (augmented), 0.05 …

12.1 Mechanism of Action Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of Betamethasone Dipropionate Cream USP (Augmented), 0.05% in corticosteroid responsive dermatoses is unknown.

DESCRIPTION: Betamethasone Dipropionate Cream, Ointment and Lotion contain betamethasone dipropionate USP, a synthetic adrenocorticosteroid, for dermatologic use. Betamethasone, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity. Betamethasone dipropionate is a white to cream white odorless crystalline powder insoluble in water. Chemically, it is 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate. The structural formula is: Each gram of the 0.05% Cream contains 0.64 mg betamethasone dipropionate (equivalent to 0.5 mg betamethasone) in a soft, white, hydrophilic cream of purified water, mineral oil, white petrolatum, polyoxyl 20 cetostearyl ether, cetostearyl alcohol, monobasic sodium phosphate (monohydrate); chlorocresol is present as a preservative. Sodium hydroxide or phosphoric acid solution to adjust pH, if required. Each gram of the 0.05% Ointment contains 0.64 mg betamethasone dipropionate (equivalent to 0.5 mg betamethasone) in an ointment base of mineral oil and white petrolatum. Each gram of the 0.05% Lotion contains 0.64 mg betamethasone dipropionate (equivalent to 0.5 mg betamethasone) in a vehicle of isopropyl alcohol and purified water slightly thickened with carbomer 934P. Sodium hydroxide solution to adjust pH, if required. Structural Formula

OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects (See PRECAUTIONS ).

HOW SUPPLIED Each gram contains betamethasone dipropionate 0.64 mg equivalent to betamethasone, USP 0.5 mg. Betamethasone Dipropionate Cream USP, 0.05% is white to off white cream, free from lumps and foreign matter with no phase separation is supplied as: NDC 70710-1233-1 in tube of 15 g NDC 70710-1233-4 in tube of 45 g Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light and freezing. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please address medical inquiries to, MedicalAffairs@zydususa.com or Tel.: 1-877-993-8779.