Betamethasone dipropionate

RECENT MAJOR CHANGES Warnings and Precautions, Ophthalmic Adverse Reactions ( 5.2 ) 05/2019

1 INDICATIONS AND USAGE Betamethasone dipropionate ointment (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 ointment (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. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a thin film of betamethasone dipropionate ointment (augmented), 0.05% to the affected skin areas once or twice daily. Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Betamethasone dipropionate ointment (augmented), 0.05% is a super-high-potency topical corticosteroid. Treatment with betamethasone dipropionate ointment (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 ointment (augmented), 0.05% should not be used with occlusive dressings unless directed by a physician. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Avoid contact with eyes. Wash hands after each application. Betamethasone dipropionate ointment (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 ) • Limit therapy to no more than 2 consecutive weeks. ( 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 Ointment, 0.05%. Each gram of betamethasone dipropionate ointment USP (augmented), 0.05% contains 0.643 mg betamethasone dipropionate USP (equivalent to 0.5 mg betamethasone), in a white to off-white opaque ointment base. • Ointment, 0.05% ( 3 )

4 CONTRAINDICATIONS Betamethasone dipropionate ointment (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 Most common adverse reactions (<1%) are: erythema, folliculitis, pruritus, and vesiculation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fougera Pharmaceuticals Inc. at 1-800-645-9833 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, adverse reactions associated with the use of betamethasone dipropionate ointment (augmented), 0.05% reported at a frequency of less than 1% included erythema, folliculitis, pruritus, and vesiculation. 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: skin atrophy, telangiectasias, burning, irritation, dryness, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, hypertrichosis, 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 ointment (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 ointment (augmented), 0.05% may increase the risk of having a low birthweight infant and to use betamethasone dipropionate ointment (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 ointment (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 There are no data regarding the presence of betamethasone dipropionate in human milk, the effects on the breastfed infant, or the effects on milk production after topical application of betamethasone dipropionate ointment (augmented), 0.05% to women who are breastfeeding. It is possible that topical administration 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 ointment (augmented), 0.05% and any potential adverse effects on the breastfed infant from betamethasone dipropionate ointment (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 ointment (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 ointment (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 ointment (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% and 3 of the 4 (75%) had complete recove …

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 ointment (augmented), 0.05% in corticosteroid responsive dermatoses is unknown.

11 DESCRIPTION Betamethasone dipropionate ointment USP (augmented), 0.05% contains betamethasone dipropionate USP, a synthetic adrenocorticosteroid, for topical use. Betamethasone, an analog of prednisolone, has a high degree of corticosteroid activity and a slight degree of mineralocorticoid activity. Betamethasone dipropionate is the 17, 21-dipropionate ester of betamethasone. Chemically, betamethasone dipropionate is 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate, with the empirical formula C 28 H 37 FO 7 , a molecular weight of 504.6 and the following structural formula: It is a white to cream-white, odorless powder practically insoluble in water, freely soluble in acetone, in methylene chloride and in chloroform, sparingly soluble in ethanol (96%). Each gram of betamethasone dipropionate ointment USP (augmented), 0.05% contains 0.643 mg betamethasone dipropionate USP (equivalent to 0.5 mg betamethasone), in a white to off-white opaque ointment base of propylene glycol, propylene glycol monopalmitostearate, white petrolatum and white wax. structure

16 HOW SUPPLIED/STORAGE AND HANDLING Betamethasone dipropionate ointment USP (augmented), 0.05% is a white to off-white ointment supplied in: 15 g tube NDC 59651-699-14 45 g tube NDC 59651-699-46 50 g tube NDC 59651-699-50 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].