Hydrocortisone Butyrate

1 INDICATIONS AND USAGE Hydrocortisone Butyrate Cream (lipid), 0.1% is indicated for: Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adults. The topical treatment of mild to moderate atopic dermatitis in pediatric patients 3 months of age and older. Hydrocortisone Butyrate Cream (lipid), 0.1% is a corticosteroid indicated for: Relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adults. ( 1 ) The topical treatment of mild to moderate atopic dermatitis in pediatric patients 3 months of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Recommended Dosage for Corticosteroid-Responsive Dermatoses For corticosteroid-responsive dermatoses in adults, apply a thin layer to the affected skin areas 2 or 3 times daily, depending on the severity of the condition, and rub in gently. Recommended Dosage for Atopic Dermatitis For atopic dermatitis in patients 3 months of age and older, apply a thin layer to the affected skin areas 2 times daily and rub in gently. Administration Instructions Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. Before prescribing for more than 2 weeks, weigh any additional benefits of extending treatment to 4 weeks against the risk of HPA-axis suppression and local adverse events [see Warnings and Precautions ( 5.1 )] . Hydrocortisone Butyrate Cream (lipid), 0.1% is not for oral, ophthalmic, or intravaginal use. Do not use Hydrocortisone Butyrate Cream (lipid), 0.1%: With occlusive dressings unless directed by a healthcare provider. Avoid use in the diaper area, as diapers or plastic pants may constitute occlusive dressings. On the face, underarms, or groin areas unless directed by a healthcare provider. Corticosteroid-Responsive Dermatoses: Apply a thin layer to the affected skin areas 2 or 3 times daily for corticosteroid-responsive dermatoses in adults. Rub in gently. ( 2 ) Atopic Dermatitis: Apply a thin layer to the affected skin areas 2 times daily for atopic dermatitis in pediatric patients 3 months of age and older. Rub in gently. ( 2 ) Discontinue Hydrocortisone Butyrate Cream (lipid), 0.1% when control is achieved. ( 2 ) Reassess diagnosis if no improvement is seen within 2 weeks. Before prescribing for more than 2 weeks, weigh any additional benefits of extending treatment up to 4 weeks against the risk of hypothalamic-pituitary-adrenal (HPA) axis suppression and local adverse reactions. ( 2 ) Avoid use under occlusion or in the diaper area. ( 2 ) Hydrocortisone Butyrate Cream (lipid), 0.1% is not for oral, ophthalmic, or intravaginal use. ( 2 )

5 WARNINGS AND PRECAUTIONS Endocrine System Adverse Reactions: Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression may occur, with the potential for glucocorticosteroid insufficiency. Consider periodic evaluations for HPA-axis suppression if Hydrocortisone Butyrate Cream (lipid), 0.1% is applied to large surface areas or used under occlusion. If HPA-axis suppression is noted, reduce the application frequency, discontinue use, or switch to a lower potency corticosteroid. ( 5.1 , 8.4 ) Systemic effects of topical corticosteroids may also include manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria. ( 5.1 , 8.4 ) Pediatric patients may be more susceptible to systemic toxicity due to their larger skin-surface-to-body-mass ratios. ( 5.1 , 8.4 ) Ophthalmic Adverse Reactions: Topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may increase the risk of cataracts and glaucoma. If visual symptoms occur, consider referral to an ophthalmologist. ( 5.2 ) Skin Infections: Initiate appropriate therapy if concomitant skin infections develop. ( 5.3 ) 5.1 Endocrine System Adverse Reactions Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, can cause systemic adverse reactions including HPA-axis suppression with the potential for clinical glucocorticosteroid insufficiency. Factors that predispose a patient to HPA axis suppression include the use of high-potency steroids, large treatment surface areas, prolonged use, use of occlusive dressings, altered skin barrier, liver failure, and young age. Consider patients for periodic evaluation of the HPA axis. This may be done by using cosyntropin (ACTH1-24) stimulation testing (CST). If HPA-axis suppression is noted, reduce the frequency of application or withdraw Hydrocortisone Butyrate Cream (lipid), 0.1%, or substitute a less potent corticosteroid. Signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids. Studies conducted in pediatric subjects demonstrated reversible HPA-axis suppression after use of Hydrocortisone Butyrate Cream (lipid), 0.1%. Pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of Hydrocortisone Butyrate Cream (lipid), 0.1% due to their larger skin-surface-to-body-mass ratios [ see Use in Specific Populations ( 8.4 ) , Clinical Pharmacology ( 12.2 ) ]. Cushing’s Syndrome, Hyperglycemia, and Glucosuria Systemic adverse reactions of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may also include manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria. Additional Considerations for Endocrine Adverse Reactions Use of more than one corticosteroid-containing product at the same time may increase total systemic corticosteroid exposure. Minimize systemic corticosteroid effects by mitigating the risk factors for increased systemic absorption and using Hydrocortisone Butyrate Cream (lipid), 0.1% as recommended [ see Dosage and Administration ( 2 ) ]. 5.2 Ophthalmic Adverse Reactions Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may increase the risk of posterior subcapsular cataracts and glaucoma. Cataracts and glaucoma have been reported in postmarketing experience with the use of topical corticosteroid products [ see Adverse Reactions ( 6.2 ) ]. Avoid contact of Hydrocortisone Butyrate Cream (lipid), 0.1% with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation. 5.3 Skin Infections Use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%, may delay healing or worsen concomitant skin infections. If skin infections are present or develop, use an appropriate antifungal, antibacterial or antiviral agent. If a favorable response does not occur promptly, discontinue use of Hydro…

4 CONTRAINDICATIONS None. None. ( 4 )

8.1 Pregnancy Risk Summary There are no controlled or large-scale epidemiologic studies with Hydrocortisone Butyrate Cream (lipid), 0.1% use in pregnant women, and available data on hydrocortisone butyrate use in pregnant women have not identified a drug-associated risk for major birth defects, miscarriages or adverse maternal or fetal outcomes. In animal reproduction studies, when administered subcutaneously or topically to pregnant rats, rabbits, and mice, hydrocortisone butyrate induced adverse reproductive and developmental outcomes, including abortion, fetal death, malformation, delayed ossification, decrease in fetal weight, and delay in sexual maturation (see Data) . The available data do not allow the calculation of relevant comparisons between the systemic exposure of hydrocortisone butyrate observed in animal studies and the systemic exposure that would be expected in humans after topical use of Hydrocortisone Butyrate Cream (lipid), 0.1%. 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. Data Animal Data Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 0.6, 1.8, and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 6 - 17. In the presence of maternal toxicity, fetal effects noted at 5.4 mg/kg/day included increased ossification variations and unossified sternebra. No treatment-related embryofetal toxicity or malformation were noted at doses of 5.4 and 1.8 mg/kg/day, respectively. Subcutaneous doses of 0.1, 0.2, and 0.3 mg/kg/day hydrocortisone butyrate were administered to pregnant female rabbits during gestation days 7 - 20. Increased abortion was noted at 0.3 mg/kg/day. In the absence of maternal toxicity, a dose-dependent decrease in fetal body weight was noted at doses ≥0.1 mg/kg/day. Embryofetal toxicities (reduction in litter size, decreased number of viable fetuses, and increased post-implantation loss) were noted at doses ≥0.2 mg/kg/day. Additional fetal effects included delayed ossification noted at doses ≥0.1 mg/kg/day and increased fetal malformations (primarily skeletal malformations) noted at doses ≥0.2 mg/kg/day. A dose at which no embryofetal toxicity or malformation was observed was not established in this study. Additional systemic embryofetal development studies were conducted in rats and mice. Subcutaneous doses of 0.1 and 9 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days 9 – 15. In the presence of maternal toxicity, an increase in fetal death and fetal resorption and an increase in ossification of caudal vertebrae were noted at 9 mg/kg/day. No treatment-related embryofetal toxicity or malformation was noted at 0.1 mg/kg/day. Subcutaneous doses of 0.2 and 1 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days 7 – 13. In the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at 1 mg/kg/day. No treatment-related embryofetal toxicity or malformation was noted at 1 and 0.2 mg/kg/day. No topical embryofetal development studies were conducted with hydrocortisone butyrate cream. However, topical embryofetal development studies were conducted in rats and rabbits with a hydrocortisone butyrate ointment formulation. Topical doses of 1% and 10% hydrocortisone butyrate ointment were administered to pregnant female rats during gestation days 6 – 15 or pregnant female rabbits during gestation days 6 -18. A dose-dependent increase in fetal resorption was noted in rabbits and fetal resorptions were noted in rats at the 10% hydrocortisone butyrate oi…

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Endocrine system adverse reactions [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 )] Ophthalmic adverse reactions [see Warnings and Precautions ( 5.2 )] Skin infections [see Warnings and Precautions ( 5.3 )] Allergic contact dermatitis [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥1%) are application site reactions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 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. The safety data derived from Hydrocortisone Butyrate Cream (lipid), 0.1% clinical trials reflect exposure to Hydrocortisone Butyrate Cream (lipid), 0.1% twice daily for up to 4 weeks in pediatric subjects 3 months of age and older with mild to moderate atopic dermatitis. Table 1. Frequency of Adverse Reactions in Pediatric Subjects 3 Months of Age and Older with Mild to Moderate Atopic Dermatitis Hydrocortisone Butyrate Cream (lipid), 0.1% (n=131) Vehicle (n=133) Application site folliculitis 1% 0.0% Application site irritation 1% 0.0% Acne 1% 0.0% 6.2 Postmarketing Experience The following adverse reactions have been reported during post approval use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%. Because these 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. Local Adverse Reactions: burning, itching, drying, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria. Ophthalmic Adverse Reactions: blurred vision, cataracts, glaucoma, and increased intraocular pressure. 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. The safety data derived from Hydrocortisone Butyrate Cream (lipid), 0.1% clinical trials reflect exposure to Hydrocortisone Butyrate Cream (lipid), 0.1% twice daily for up to 4 weeks in pediatric subjects 3 months of age and older with mild to moderate atopic dermatitis. Table 1. Frequency of Adverse Reactions in Pediatric Subjects 3 Months of Age and Older with Mild to Moderate Atopic Dermatitis Hydrocortisone Butyrate Cream (lipid), 0.1% (n=131) Vehicle (n=133) Application site folliculitis 1% 0.0% Application site irritation 1% 0.0% Acne 1% 0.0% 6.2 Postmarketing Experience The following adverse reactions have been reported during post approval use of topical corticosteroids, including Hydrocortisone Butyrate Cream (lipid), 0.1%. Because these 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. Local Adverse Reactions: burning, itching, drying, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria. Ophthalmic Adverse Reactions: blurred vision, cataracts, glaucoma, and increased intraocular pressure.