2.1 Important Administration Instructions

Fluocinolone acetonide topical oil is for topical use only. Not for oral, ophthalmic, or intravaginal use.

Apply the least amount of fluocinolone acetonide topical oil needed to cover the affected areas. Discontinue use 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)].

Do not apply to the diaper area; diapers or plastic pants may constitute occlusive use [see Warnings and Precautions (5.1)].

2.2 Recommended Dosage in Adults

Apply fluocinolone acetonide topical oil as a thin film to the affected areas three times daily.

2.3 Recommended Dosage in Pediatric Patients

Moisten skin and apply fluocinolone acetonide topical oil as a thin film to the affected areas twice daily for up to four weeks.

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, reduce the frequency of application or discontinue fluocinolone acetonide topical oil, or substitute with a less potent corticosteroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. 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 topical 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 topical 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 topical oil until the infection has been adequately treated.

5.6 Use in Peanut-Sensitive Individuals

Use caution in prescribing fluocinolone acetonide topical 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 topical oil immediately and institute appropriate therapy.

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.

An open-label trial was conducted in 58 pediatric subjects 2 years to 12 years of age with moderate to severe atopic dermatitis to evaluate the safety of fluocinolone acetonide topical oil when applied to the face twice daily for 4 weeks. Adverse reactions reported by ≥2% of pediatric subjects treated with fluocinolone acetonide topical oil are shown in Table 1.

Table 1: Adverse Reactions in ≥2% of Pediatric Subjects 2 Years to 12 Years of Age with Moderate to Severe Atopic Dermatitis, Treated with Fluocinolone Acetonide Topical Oil (Body Oil), N=58

*The number of individual adverse reactions reported does not necessarily reflect the number of individual subjects, since one subject could have multiple reports of an adverse reaction.

**End of Treatment

***Four Weeks Post Treatment

An open-label safety trial was conducted in 29 pediatric subjects 3 months to 2 years of age to assess the HPA axis by ACTH stimulation testing following use of fluocinolone acetonide topical oil twice daily for 4 weeks. The trial included 7 subjects ages 3 to 6 months, 7 subjects ages > 6 to 12 months, and 15 subjects ages > 12 months to 2 years. All subjects had moderate to severe atopic dermatitis with disease involvement on at least 20% body surface area (BSA). Eleven (11) subjects had baseline BSA involvement of 50% to 75% and 7 subjects had BSA involvement of greater than 75% [see Use in Specific Populations (8.4)]. The most common adverse reactions reported in the study (≥2%) are shown in Table 2.

Table 2: Adverse Reactions in ≥ 2% of Pediatric Subjects 3 Months to 2 Years of Age with Moderate to Severe Atopic Dermatitis, Treated with Fluocinolone Acetonide Topical Oil (Body Oil), N=30*

*Includes one subject who withdrew at Week 2

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 topical 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.

8.2 Lactation

Risk Summary

There is no information regarding the presence of fluocinolone acetonide in breast milk or its effects on the breastfed infant or on milk production. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. To minimize potential exposure to the breastfed infant via breast milk, use fluocinolone acetonide topical oil on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply fluocinolone acetonide topical oil directly to the nipple and areola to avoid direct infant exposure [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fluocinolone acetonide topical oil and any potential adverse effects on the breastfed infant from fluocinolone acetonide topical oil or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of fluocinolone acetonide topical oil for the topical treatment of moderate to severe atopic dermatitis have been established in pediatric patients aged 3 months and older for up to 4 weeks.

Safety and effectiveness of fluocinolone acetonide topical oil in pediatric patients with atopic dermatitis below the age of 3 months have not been established.

Systemic Adverse Reactions in Pediatric Patients

HPA axis suppression, Cushing’s syndrome, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and subnormal response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk for systemic adverse reactions than are adults when treated with topical corticosteroids [see Warnings and Precautions (5.1)].

Evaluation in Peanut-Sensitive Pediatric Patients

A clinical trial was conducted to assess the safety of fluocinolone acetonide topical oil, which contains refined peanut oil, on pediatric subjects with known peanut allergies. The study enrolled 13 pediatric subjects with atopic dermatitis, 6 to 17 years of age. Of the 13 subjects, 9 were Radioallergosorbent Test (RAST) positive to peanuts and 4 had no peanut sensitivity (controls). The trial evaluated the subjects' responses to both prick test and patch test utilizing refined peanut oil, fluocinolone acetonide topical oil and histamine/saline controls. Subjects were also treated with fluocinolone acetonide topical oil twice daily for 7 days. Prick test and patch test results for all 13 patients were negative to fluocinolone acetonide topical oil and the refined peanut oil. One of the 9 peanut-sensitive patients experienced an exacerbation of atopic dermatitis after 5 days of fluocinolone acetonide topical oil.

Evaluation in Pediatric Patients 2 to 6 years old

Use of fluocinolone acetonide topical oil in pediatric patients 2 to 6 years old is supported by open-label safety trials conducted in 33 pediatric subjects (20 subjects ages 2 to 6 years, 13 subjects ages 7 to 12 years) with moderate to severe stable atopic dermatitis. Baseline body surface area involvement was 50% to 75% in 15 subjects and greater than 75% in 18 subjects. Subjects were treated with fluocinolone acetonide topical oil twice daily for 4 weeks. Morning pre-stimulation cortisol and post-ACTH stimulation cortisol levels were obtained in each subject at the beginning of the trial and at the end of 4 weeks of treatment. At the end of treatment, 4 out of 18 subjects aged 2 to 5 years showed low pre-stimulation cortisol levels (3.2 to 6.6 µg/dL; normal: cortisol > 7µg/dL) but all had normal responses to 0.25 mg of ACTH stimulation (cortisol > 18 µg/dL) [see Clinical Pharmacology (12.2)].

Evaluation in Pediatric Patients 3 months to 2 years old

Use of fluocinolone acetonide topical oil in pediatric patients 3 months to 2 years old is supported by an open-label safety trial conducted in 29 pediatric subjects (7 subjects ages 3 to 6 months, 7 subjects ages > 6 to 12 months, and 15 subjects ages > 12 months to 2 years) to assess the HPA axis by ACTH stimulation testing following use of fluocinolone acetonide topical oil twice daily for 4 weeks [see Adverse Reactions (6.1)]. Morning pre-stimulation and post-ACTH stimulation cortisol levels were obtained in each subject at the beginning of the trial and at the end of 4 weeks of treatment. All subjects had normal responses to 0.125 mg of ACTH stimulation (cortisol > 18 µg/dL) [see Clinical Pharmacology (12.2)].

12.1 Mechanism of Action

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action in atopic dermatitis is unknown.

12.2 Pharmacodynamics

Vasoconstrictor Assay

Fluocinolone acetonide topical oil is in the low to medium range of potency as compared with other topical corticosteroids in vasoconstrictor studies. However, similar blanching scores do not necessarily imply therapeutic equivalence.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

HPA axis suppression was evaluated in 29 pediatric subjects 3 months to 2 years old (7 subjects ages 3 to 6 months, 7

subjects ages > 6 to 12 months, and 15 subjects ages > 12 months to 2 years) and 33 pediatric subjects 2 years to 12 years old (20 subjects ages 2 to 6 years, 13 subjects ages 7 to 12 years) with moderate to severe atopic dermatitis. Subjects were treated with fluocinolone acetonide topical oil twice daily for 4 weeks. Morning pre-stimulation and post-ACTH stimulation cortisol levels were obtained in each subject at the beginning of the trial and at the end of 4 weeks of treatment. In subjects 3 months to 2 years old, all subjects had normal responses to 0.125 mg of ACTH stimulation (cortisol > 18 µg/dL). In subjects 2 to 12 years old, 4 out of 18 subjects 2 to 5 years old showed low pre-stimulation cortisol levels (3.2 to 6.6 µg/dL; normal: cortisol > 7µg/dL) but all had normal responses to 0.25 mg of ACTH stimulation (cortisol > 18 µg/dL) at the end of treatment [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].

12.3 Pharmacokinetics

Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the product formulation and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may increase percutaneous absorption.

The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids may be necessary due to the fact that circulating levels are often below the level of detection. Once absorbed through the skin, topical corticosteroids are metabolized primarily in the liver, and are then excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.

13.1 Carcinogenesis, mutagenesis, impairment of fertility

No carcinogenicity, genotoxicity, or fertility studies were conducted with fluocinolone acetonide topical oil. However, some corticosteroids are genotoxic in various genotoxicity tests (i.e., the in vitro human peripheral blood lymphocyte chromosome aberration assay with metabolic activation, the in vivo mouse bone marrow micronucleus assay, the Chinese hamster micronucleus test, and the in vitro mouse lymphoma gene mutation assay).