fluocinolone acetonide

Indication and Usage, Pediatric Patients with Atopic Dermatitis ( 1.2 ) 11/2007

1 INDICATIONS AND USAGE Fluocinolone Acetonide Topical Oil, 0.01% is a corticosteroid indicated for the • topical treatment of atopic dermatitis in adult patients ( 1.1 ) • topical treatment of moderate to severe atopic dermatitis in pediatric patients 3 months and older for up to 4 weeks ( 1.2 ) Limitations of Use: • Apply the least amount to cover affected areas. Discontinue when disease is controlled. ( 1.3 ) • Do not use in the diaper area. ( 1.3 ) • Do not use on the face, axillae, or groin. ( 1.3 , 6.2 , 8.4 ) 1.1 Adult Patients with Atopic Dermatitis Fluocinolone Acetonide Topical Oil, 0.01% is indicated for the topical treatment of atopic dermatitis in adult patients. 1.2 Pediatric Patients with Atopic Dermatitis Fluocinolone Acetonide Topical Oil, 0.01% is indicated for the topical treatment of moderate to severe atopic dermatitis in pediatric patients, 3 months and older for up to 4 weeks. Safety and effectiveness in pediatric patients younger than 3 months of age have not been established. 1.3 Limitations of Use Apply the least amount of Fluocinolone Acetonide Topical Oil, 0.01% needed to cover the affected areas. As with other corticosteroids, Fluocinolone Acetonide Topical Oil, 0.01% should be discontinued when control of disease is achieved. Contact the physician if no improvement is seen within 2 weeks. Fluocinolone Acetonide Topical Oil, 0.01% should not be applied to the diaper area; diapers or plastic pants may constitute occlusive use. Fluocinolone Acetonide Topical Oil, 0.01% should not be used on the face, axillae, or groin unless directed by the physician. Application to intertriginous areas should be avoided due to the increased risk of local adverse reactions. [see Adverse Reactions ( 6 ) and Use in Specific Populations ( 8.4 )] .

2 DOSAGE AND ADMINISTRATION • Fluocinolone acetonide topical oil is not for oral, ophthalmic, or intravaginal use. ( 2.1 ) • Do not use on face or intertriginous areas. ( 2.1 ) • Adult patients: Apply to affected areas 3 times daily. ( 2.2 ) • Pediatric patients: Moisten skin and apply to affected areas twice daily for up to 4 weeks. ( 2.3 ) 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 .

3 DOSAGE FORMS AND STRENGTHS Fluocinolone Acetonide Topical Oil, 0.01% (Scalp Oil) is a topical oil containing 0.01% fluocinolone acetonide, supplied in bottles containing 4 fluid ounces and with 2 shower caps. Fluocinolone Acetonide Topical Oil, 0.01% (Scalp Oil) is a topical oil containing 0.01% fluocinolone acetonide, supplied in bottles containing 4 fluid ounces and with 2 shower caps. ( 3 )

CONTRAINDICATIONS Fluocinolone acetonide topical oil, 0.01% is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation. This product contains refined peanut oil NF (see PRECAUTIONS section).

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 common adverse reactions (≥ 5%) were cough (20%), rhinorrhea (13%), pyrexia (10%), telangiectasia (7%), nasopharyngitis (7%), and hypopigmentation (7%). ( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 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. 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 Adverse Reaction (AR)* n (%) Day 14 Day 28** Day 56*** Any AE 15 (26) 6 (10) 7 (12) 7 (12) Telangiectasia 5 (9) 3 (5) 4 (7) 2 (4) Erythema 3 (5) 3 (5) Itching 3 (5) 3 (5) Irritation 3 (5) 3 (5) Burning 3 (5) 3 (5) Hypopigmentation 2 (4) 2 (4) Shiny skin 1 (2) 1 (2) Secondary atopic dermatitis 1 (2) 1 (2) Papules and pustules 1 (2) 1 (2) Keratosis pilaris 1 (2) 1 (2) Folliculitis 1 (2) 1 (2) Facial herpes simplex 1 (2) 1 (2) Acneiform eruption 1 (2) 1 (2) Ear infection 1 (2) 1 (2) *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* Adverse Reaction n (%) Cough 6 (20) Rhinorrhea 4 (13) Pyrexia 3 (10) Nasopharyngitis 2 (7) Hypopigmentation 2 (7) Abscess 1 (3) Atopic Dermatitis 1 (3) Eczema 1 (3) Hyperpigmentation 1 (3) Molluscum 1 (3) Rash 1 (3) Diarrhea 1 (3) Otitis Media 1 (3) URI 1 (3) Vomiting 1 (3) *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 [se …

8 USE IN SPECIFIC POPULATIONS 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 fluo …

12.1 Mechanism of Action Like other topical corticosteroids, fluocinolone acetonide has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2 .

11 DESCRIPTION Fluocinolone Acetonide Topical Oil, 0.01% (Body Oil) contains fluocinolone acetonide [(6α, 11β, 16α)-6,9-difluoro-11,21-dihydroxy-16,17[(1-methylethylidene) bis(oxy)]-pregna-1,4-diene-3,20-dione, cyclic 16,17 acetal with acetone], a synthetic corticosteroid for topical dermatologic use. This formulation is also marketed as Fluocinolone Acetonide Topical Oil, 0.01% (Scalp Oil) for use with shower caps for treatment of scalp psoriasis in adults and as Fluocinolone Acetonide Oil, 0.01% (Ear Drops) for treatment of chronic eczematous external otitis. Chemically, fluocinolone acetonide is C 24 H 30 F 2 O 6 . It has the following structural formula: Fluocinolone acetonide in Fluocinolone Acetonide Topical Oil, 0.01% has a molecular weight of 452.50. It is a white crystalline powder that is odorless, stable in light, and melts at 270°C with decomposition; soluble in alcohol, acetone and methanol; slightly soluble in chloroform; insoluble in water. Each gram of Fluocinolone Acetonide Topical Oil, 0.01% contains approximately 0.11 mg of fluocinolone acetonide in a blend of oils, which contains isopropyl alcohol, isopropyl myristate, light mineral oil, oleth-2 and refined peanut oil NF. Fluocinolone Acetonide Topical Oil, 0.01% is formulated with 48% refined peanut oil NF. Physicians should use caution in prescribing Fluocinolone Acetonide Topical Oil, 0.01% for peanut-sensitive individuals. Structural Formula

10 OVERDOSAGE Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects, including under conditions of normal use. [See Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.4 )] .

HOW SUPPLIED Fluocinolone Acetonide Topical Oil, 0.01% is supplied in bottles containing 4 fluid ounces. It is labeled as Scalp Oil (NDC # 68462-590-89). Scalp Oil is supplied with 2 shower caps. Keep tightly closed. Store at 20oC to 25oC (68° to 77°F); excursions permitted to 15oC to 30oC (59° to 86°F) [see USP Controlled Room Temperature]. CAUTION: Rx only Manufactured by: Glenmark Pharmaceuticals Ltd. Village Kishanpura, Baddi Nalagarh Road, District: Solan, Himachal Pradesh – 173205, India Manufactured for: Glenmark Pharmaceuticals Inc., USA Mahwah, NJ 07430 Questions? 1(888)721-7115 www.glenmarkpharma.com/usa November 2018 glenmark-logo