Fluocinolone Acetonide Oil

1 INDICATIONS AND USAGE Fluocinolone acetonide oil is indicated for the topical treatment of chronic eczematous external otitis in adults and pediatric patients 2 years of age and older. Fluocinolone acetonide oil is a corticosteroid indicated for the topical treatment of chronic eczematous external otitis in adults and pediatric patients 2 years of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Fluocinolone acetonide oil is for otic administration only. Not for oral, ophthalmic, or intravaginal use. Apply fluocinolone acetonide oil into the affected ear using the supplied ear dropper. To apply, tilt head to one side so that the ear is facing up. Then gently pull the ear lobe backward and upward and apply 5 drops of fluocinolone acetonide oil into the ear. Keep head tilted for about a minute to allow fluocinolone acetonide oil to penetrate lower into the ear canal. Gently pat excess material dripping out of the ear using a clean cotton ball. Follow these instructions twice each day for 7 to 14 days. Discontinue fluocinolone acetonide oil when control of disease is achieved within 2 weeks, or contact the healthcare provider if no improvement is seen within 2 weeks. Do not use on the face, axillae, or groin unless directed by the healthcare provider. Do not apply to intertriginous areas due to the increased risk of local adverse reactions [ see Adverse Reactions (6) and Use in Specific Populations (8.4) ]. • Fluocinolone acetonide oil is not for oral, ophthalmic, or intravaginal use. ( 2 ) • Apply 5 drops of fluocinolone acetonide oil into the affected ear twice daily for 7 to 14 days. ( 2 ) • Do not use on face or intertriginous areas. ( 2 )

4 CONTRAINDICATIONS None. None. ( 4 )

5 WARNINGS AND PRECAUTIONS Endocrine System Adverse Reactions: o Topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome, hyperglycemia, and glucosuria. (5.1) o Pediatric patients may be more susceptible to systemic toxicity from equivalent doses. (5.1,8.4) o Systemic absorption may require evaluation for HPA axis suppression. Potent corticosteroids use on large areas, prolonged use or occlusive use, altered skin barrier, liver failure, and young age may increase systemic absorption. Modify use should HPA axis suppression develop. ( 5.1 ). Local Adverse Reactions: Local adverse reactions may include atrophy, striae irritation, acneiform eruptions, hypopigmentation, and allergic contact dermatitis, and may be more likely with occlusive use or more potent corticosteroids. (5.2, 6.1) Ophthalmic Adverse Reactions: May increase the risks of glaucoma and posterior subcapsular cataract. Avoid contact of fluocinolone acetonide oil with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. (5.3) 5.1 Endocrine System Adverse Reactions Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. Cushing’s syndrome, hyperglycemia, and glucosuria can result from systemic absorption of topical corticosteroids. HPA axis suppression and Cushing’s syndrome have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and subnormal response to ACTH stimulation. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios [see Use in Specific Populations ( 8.4 )] . Conditions which increase systemic absorption include the use of more potent corticosteroids, use over large surface areas, use over prolonged periods, use of occlusive dressings, altered skin barrier, liver failure, and young age. Use of more than one corticosteroid-containing product at the same time may increase total systemic corticosteroid exposure. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. The 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 withdraw the drug to reduce the frequency of application, or to substitute a less potent corticosteroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. 5.2 Local Adverse Reactions Local adverse reactions may occur with use of topical corticosteroids, including fluocinolone acetonide oil, and may be more likely to occur with occlusive use, prolonged use, or use of higher potency corticosteroids. Some local adverse reactions may be irreversible. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria [see Adverse Reactions ( 6.1 )] . 5.3 Ophthalmic Adverse Reactions Use of topical corticosteroids 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. Avoid contact of fluocinolone acetonide oil with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.4 Allergic Contact Dermatitis Use of topical corticosteroids can cause 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 Use of topical corticosteroids may delay healing or worsen concomitant skin infections. Treat concomitant skin infections with an appropriate antimicrobial agent. If the infection persists unchanged, discontinue fluocinolone acetonide oil until the infection has been adequately treated. 5.6 Use in Peanut Sensitive Individuals Use caution in prescribing fluocinolone acetonide oil for peanut sensitive individuals [see Description (11)] . Should signs of hypersensitivity present (wheal and flare reactions, pruritus, or other manifestations), or should disease exacerbations occur, discontinue fluocinolone acetonide oil immediately and institute appropriate therapy.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in more detail in other sections of the labeling: • Endocrine System Adverse Reactions [see Warnings and Precautions (5.1 ), Use in Specific Populations (8.4)] • Local Adverse Reactions [see Warnings and Precautions (5.2 )] • Ophthalmic Adverse Reactions [ see Warnings and Precautions (5.3) ] The most commonly reported adverse reactions (≥ 1%) were headache (3%), URI (2%), cough (2%), eczematous otitis (1%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies 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 trials that enrolled 154 subjects (adults and pediatric subjects 2 years and older) with chronic eczematous external otitis who were treated with five drops per ear of fluocinolone acetonide oil twice daily for a maximum 14 days of treatment, the following adverse reactions were reported: Table 1: Adverse Reactions in ≥1% of Fluocinolone Acetonide Oil - Treated Adult and Pediatric Subjects 2 Years of Age and Older with Chronic Eczematous External Otitis, N=154 Adverse Reaction n (%) Headache 4 (3) URI 3 (2) Cough 3 (2) Eczematous otitis 2 (1) 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of products containing topical corticosteroids. Because postmarketing 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. Endocrine Disorders: HPA axis suppression and Cushing’s syndrome [see Use in Specific Populations (8.4) ] Eye Disorders : glaucoma and cataracts [see Warnings and Precautions (5.3) ] Nervous System Disorders: intracranial hypertension including bulging fontanelles, headaches, and bilateral papilledema [see Use in Specific Populations (8.4) ]

8.1 Pregnancy Risk Summary Available data from case reports, case series, and observational studies on fluocinolone acetonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Observational studies suggest maternal use of high to super-high potency topical steroids may be associated with an increased risk of low birthweight infants. Advise pregnant women to use fluocinolone acetonide oil on the smallest area of skin and for the shortest duration possible. Corticosteroids can cause fetal malformations in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids cause fetal malformations after dermal application in laboratory animals. 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 background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.