of cushing’s syndrome, hyperglycemia, and glucosuria. studies conducted in pediatric subjects demonstrated reversible hpa axis suppression after use of hydrocortisone butyrate cream. pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of hydrocortisone butyrate cream due to their larger skin surface-to-body-mass ratios [see use in specific populations (8.4)] . patients applying a topical corticosteroid to a large surface area or to areas under occlusion should be considered for periodic evaluation of the hpa axis. this may be done by using cosyntropin (acth1-24) stimulation testing (cst). minimize systemic corticosteroid effects by mitigating the risk factors for increased systemic absorption and using hydrocortisone butyrate cream as recommended [see dosage and administration (2)] . if hpa axis suppression is noted, the frequency of application should be reduced or the drug should be withdrawn, or a less potent corticosteroid should be substituted. signs and symptoms of glucocorticosteroid insufficiency may occur, requiring supplemental systemic corticosteroids [see adverse reactions (6)] . 5.2 concomitant skin infections if skin infections are present or develop, an appropriate antifungal, antibacterial or antiviral agent should be used. if a favorable response does not occur promptly, use of hydrocortisone butyrate cream should be discontinued until the infection has been adequately controlled [see adverse reactions (6)] . 5.3 allergic contact dermatitis allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. such an observation should be corroborated with appropriate patch testing. discontinue hydrocortisone butyrate cream if the diagnosis is established [see adverse reactions (6)] .

(lipophilic) with occlusive dressings unless directed by a physician. avoid use in the diaper area, as diapers or plastic pants may constitute occlusive dressings. hydrocortisone butyrate cream, 0.1% (lipophilic) is not for oral, ophthalmic, or intravaginal use. • apply a thin layer to the affected skin areas two or three times daily for corticosteroid-responsive dermatoses in adults. ( 2 ) • apply a thin layer to the affected skin areas two times daily for atopic dermatitis in patients 3 months of age and older. ( 2 ) • rub in gently. ( 2 ) • discontinue hydrocortisone butyrate cream, 0.1% (lipophilic) when control is achieved. ( 2 ) • reassess diagnosis if no improvement is seen within 2 weeks. before prescribing for more than 2 weeks, any additional benefits of extending treatment to 4 weeks should be weighed against the risk of hpa axis suppression and local adverse events. safety and efficacy of hydrocortisone butyrate cream, 0.1% (lipophilic) has not been established beyond 4 weeks of use. ( 2 ) • avoid use under occlusion or in the diaper area. ( 2 ) • hydrocortisone butyrate cream, 0.1% (lipophilic) is not for oral, ophthalmic, or intravaginal use. ( 2 )

ta derived from hydrocortisone butyrate cream clinical trials reflect exposure to hydrocortisone butyrate cream twice daily for up to four weeks in separate clinical trials involving pediatric subjects 3 months to 18 years of age with mild to moderate atopic dermatitis. adverse reactions shown in the table below include those for which there is some basis to believe there is a causal relationship to hydrocortisone butyrate cream. table 1. frequency of adverse reactions in pediatric subjects with mild to moderate atopic dermatitis hydrocortisone butyrate cream (n=131) vehicle (n=133) application site reactions, including application site folliculitis, irritation, dermatitis, erythema 1.5% 1.5% acne 0.8% 0% telangiectasia 0% 0.8% 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. the following additional local adverse reactions have been reported infrequently with topical corticosteroids but may occur more frequently with the use of occlusive dressings. these reactions are listed in an approximate decreasing order of occurrence: burning, itching, drying, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.

ts during gestation days 6 to 17. in the presence of maternal toxicity, fetal effects noted at 5.4 mg/kg/day (2x mthd) included an increased incidence of ossification variations and unossified sternebra. no treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of 5.4 and 1.8 mg/kg/day, respectively (2x mthd and 0.7x mthd, 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 to 20. an increased incidence of abortion was noted at 0.3 mg/kg/day (0.2x mthd). in the absence of maternal toxicity, a dose-dependent decrease in fetal body weight was noted at doses ≥0.1 mg/kg/day (0.1x mthd). additional indicators of embryofetal toxicity (reduction in litter size, decreased number of viable fetuses, increased post-implantation loss) were noted at doses ≥0.2 mg/kg/day (0.2x mthd). additional fetal effects noted in this study included delayed ossification noted at doses ≥0.1 mg/kg/day and an increased incidence of fetal malformations (primarily skeletal malformations) noted at doses ≥0.2 mg/kg/day. a dose at which no treatment-related effects on embryofetal toxicity or teratogenicity were 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 to 15. in the presence of maternal toxicity, an increase in fetal deaths and fetal resorptions and an increase in the number of ossifications in caudal vertebrae were noted at a dose of 9 mg/kg/day (3x mthd). no treatment-related effects on embryofetal toxicity or teratogenicity were noted at 0.1 mg/kg/day (0.1x mthd). subcutaneous doses of 0.2 and 1 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days 7 to 13. in the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at a dose of 1 mg/kg/day (0.2x mthd). no treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of 1 and 0.2 mg/kg/day, respectively (0.2x mthd and 0.1x mthd, respectively). 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 to 15 or pregnant female rabbits during gestation days 6 to 18. a dose-dependent increase in fetal resorptions was noted in rabbits (0.2 to 2x mthd) and fetal resorptions were noted in rats at the 10% hydrocortisone butyrate ointment dose (80x mthd). no treatment-related effects on embryofetal toxicity were noted at the 1% hydrocortisone butyrate ointment dose in rats (8x mthd). a dose at which no treatment-related effects on embryofetal toxicity were observed in rabbits after topical administration of hydrocortisone butyrate ointment was not established in this study. no treatment-related effects on teratogenicity were noted at a dose of 10% hydrocortisone butyrate ointment in rats or rabbits (80x mthd and 2x mthd, respectively). a peri- and post-natal development study was conducted in rats. subcutaneous doses of 0.6, 1.8 and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats from gestation day 6 to lactation day 20. in the presence of maternal toxicity, a dose-dependent decrease in fetal weight was noted at doses ≥1.8 mg/kg/day (0.7x mthd). no treatment-related effects on fetal toxicity were noted at 0.6 mg/kg/day (0.2x mthd). a delay in sexual maturation was noted at 5.4 mg/kg/day (2x mthd). no treatment-related effects on sexual maturation were noted at 1.8 mg/kg/day. no treatment-related effects on behavioral development or subsequent reproductive performance were noted at 5.4 mg/kg/day. 8.3 nursing mothers systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. it is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. because many drugs are excreted in human milk, caution should be exercised when hydrocortisone butyrate cream is administered to a nursing woman. 8.4 pediatric use safety and efficacy in pediatric patients below 3 months of age have not been established. because of higher skin surface-to-body-mass ratios, pediatric patients are at a greater risk than adults of hpa axis suppression when they are treated with topical corticosteroids [see warnings and precautions (5.1)] . they are therefore also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of cushing’s syndrome while on treatment. eighty-six (86) pediatric subjects (between 5 months and 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (bsa) treated with hydrocortisone butyrate cream three times daily for up to 4 weeks were assessed for hpa axis suppression in two separate studies. the disease severity (moderate to severe atopic dermatitis) and the dosing regimen (three times daily) in these hpa axis studies were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (two times daily) for which hydrocortisone butyrate cream is indicated in this population. five of the 82 evaluable subjects (6.1%) demonstrated evidence of suppression, where the criterion for defining hpa axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter after cosyntropin stimulation. suppressed subjects ranged in age from 5 months to 16 years and, at the time of enrollment, had 25% to 95% bsa involvement. these subjects did not demonstrate any clinical signs or symptoms despite evidence of hpa axis suppression. at the first follow up visit, approximately one month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. this last subject recovered adrenal function by 65 days post-treatment. cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have also been reported in pediatric patients receiving topical corticosteroids. manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an absence of response to acth stimulation. manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. 8.5 geriatric use clinical studies of hydrocortisone butyrate cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

17. in the presence of maternal toxicity, fetal effects noted at 5.4 mg/kg/day (2x mthd) included an increased incidence of ossification variations and unossified sternebra. no treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of 5.4 and 1.8 mg/kg/day, respectively (2x mthd and 0.7x mthd, 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 to 20. an increased incidence of abortion was noted at 0.3 mg/kg/day (0.2x mthd). in the absence of maternal toxicity, a dose-dependent decrease in fetal body weight was noted at doses ≥0.1 mg/kg/day (0.1x mthd). additional indicators of embryofetal toxicity (reduction in litter size, decreased number of viable fetuses, increased post-implantation loss) were noted at doses ≥0.2 mg/kg/day (0.2x mthd). additional fetal effects noted in this study included delayed ossification noted at doses ≥0.1 mg/kg/day and an increased incidence of fetal malformations (primarily skeletal malformations) noted at doses ≥0.2 mg/kg/day. a dose at which no treatment-related effects on embryofetal toxicity or teratogenicity were 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 to 15. in the presence of maternal toxicity, an increase in fetal deaths and fetal resorptions and an increase in the number of ossifications in caudal vertebrae were noted at a dose of 9 mg/kg/day (3x mthd). no treatment-related effects on embryofetal toxicity or teratogenicity were noted at 0.1 mg/kg/day (0.1x mthd). subcutaneous doses of 0.2 and 1 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days 7 to 13. in the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at a dose of 1 mg/kg/day (0.2x mthd). no treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of 1 and 0.2 mg/kg/day, respectively (0.2x mthd and 0.1x mthd, respectively). 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 to 15 or pregnant female rabbits during gestation days 6 to 18. a dose-dependent increase in fetal resorptions was noted in rabbits (0.2 to 2x mthd) and fetal resorptions were noted in rats at the 10% hydrocortisone butyrate ointment dose (80x mthd). no treatment-related effects on embryofetal toxicity were noted at the 1% hydrocortisone butyrate ointment dose in rats (8x mthd). a dose at which no treatment-related effects on embryofetal toxicity were observed in rabbits after topical administration of hydrocortisone butyrate ointment was not established in this study. no treatment-related effects on teratogenicity were noted at a dose of 10% hydrocortisone butyrate ointment in rats or rabbits (80x mthd and 2x mthd, respectively). a peri- and post-natal development study was conducted in rats. subcutaneous doses of 0.6, 1.8 and 5.4 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats from gestation day 6 to lactation day 20. in the presence of maternal toxicity, a dose-dependent decrease in fetal weight was noted at doses ≥1.8 mg/kg/day (0.7x mthd). no treatment-related effects on fetal toxicity were noted at 0.6 mg/kg/day (0.2x mthd). a delay in sexual maturation was noted at 5.4 mg/kg/day (2x mthd). no treatment-related effects on sexual maturation were noted at 1.8 mg/kg/day. no treatment-related effects on behavioral development or subsequent reproductive performance were noted at 5.4 mg/kg/day.

itis) and the dosing regimen (two times daily) for which hydrocortisone butyrate cream is indicated in this population. five of the 82 evaluable subjects (6.1%) demonstrated evidence of suppression, where the criterion for defining hpa axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter after cosyntropin stimulation. suppressed subjects ranged in age from 5 months to 16 years and, at the time of enrollment, had 25% to 95% bsa involvement. these subjects did not demonstrate any clinical signs or symptoms despite evidence of hpa axis suppression. at the first follow up visit, approximately one month after the conclusion of treatment, cosyntropin stimulation results of all subjects had returned to normal, with the exception of one subject. this last subject recovered adrenal function by 65 days post-treatment. cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have also been reported in pediatric patients receiving topical corticosteroids. manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an absence of response to acth stimulation. manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

in, occlusive dressings, or widespread application may increase percutaneous absorption and increase the risk of hpa axis suppression. the vasoconstrictor assay showed that hydrocortisone butyrate cream, 0.1% (lipohilic) had a more pronounced skin blanching effect than hydrocortisone butyrate cream, 0.1%, suggesting greater percutaneous absorption from the former. once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.

/kg/day (0.7x mthd). mild effects on maternal animals, such as reduced food consumption and a subsequent reduction in body weight gain, were seen at doses ≥0.6 mg/kg/day (0.2x mthd).

effects on maternal animals, such as reduced food consumption and a subsequent reduction in body weight gain, were seen at doses ≥0.6 mg/kg/day (0.2x mthd).

ream on the face, underarms, or groin areas unless directed by physician. • if no improvement is seen within 2 weeks, contact physician. • do not use other corticosteroid-containing products while using hydrocortisone butyrate cream without first consulting physician. rx only