HOW SUPPLIED SECTION.

HOW SUPPLIED Hydrocortisone Butyrate Ointment, 0.1% is supplied in tubes containing: 15 (NDC 68682-271-15) 45 (NDC 68682-271-45).

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE Hydrocortisone Butyrate Ointment, 0.1% is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS The following local adverse reactions are 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, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria.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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility Note: The animal multiples of human exposure calculations in this label were based on body surface area comparisons for an adult (i.e., mg/m2/day dose comparisons) assuming 100% human percutaneous absorption of maximum topical human dose (MTHD) for hydrocortisone butyrate ointment (25 g).In 2-year dermal rat carcinogenicity study with LOCOID(R) lotion, hydrocortisone butyrate was administered to Sprague-Dawley rats at topical doses of 0.05, 0.15, and 0.3 mg/kg/day in males and 0.1, 0.25, and 0.5 mg/kg/day in females (0.1% lotion). No drug-related tumors were noted in this study up to the highest doses evaluated in this study of 0.3 mg/kg/day in males (0.1X MTHD) and 0.5 mg/kg/day in females (0.2X MTHD).Hydrocortisone butyrate revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitrogenotoxicity tests (Ames test and L5178Y/TK+/- mouse lymphoma assay) and one in vivogenotoxicity test (mouse micronucleus assay).No evidence of impairment of fertility or effect on mating performance was observed in fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to and including 1.8 mg/kg/day (0.7X MTHD). Mild effects on maternal animals, such as reduced food consumption and subsequent reduction in body weight gain, were seen at doses >=0.6 mg/kg/day (0.2X MTHD).

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY Topical corticosteroids share anti-inflammatory, anti-pruritic, and vasoconstrictive actions. The mechanism of anti-inflammatory activity of topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of topical corticosteroids. There is some evidence to suggest that recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS None.

DESCRIPTION SECTION.

DESCRIPTION. Hydrocortisone Butyrate Ointment, 0.1% contains the topical corticosteroid, hydrocortisone butyrate, non-fluorinated hydrocortisone ester. It has the chemical name: 11,17,21-Trihydroxypregn-4-ene-3,20-dione 17-butyrate; the molecular formula: C25H36O6; the molecular weight: 432.54; and the CAS registry number: 13609-67-1.Its structural formula is:Each gram of Hydrocortisone Butyrate Ointment contains mg of hydrocortisone butyrate in base consisting of mineral oil and polyethylene.. hydrocortisone-butyrate-figure-1-hydrocortisonebutyratestructure.jpg.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION Hydrocortisone Butyrate Ointment, 0.1% should be applied to the affected areas as thin layer or times daily depending on the severity of the condition. Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions.If an infection develops, the use of occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.

GENERAL PRECAUTIONS SECTION.

General Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushings syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings.Therefore, patients receiving large dose of potent topical corticosteroid applied to large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA-axis suppression by using adrenocorticotropic hormone (ACTH) stimulation tests.If HPA-axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute less potent corticosteroid.Recovery of HPA-axis function is generally prompt and complete upon discontinuation of the drug.Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids.Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. [See PRECAUTIONS, Pediatric Use.]If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

INFORMATION FOR PATIENTS SECTION.

Information for Patients Patients using topical corticosteroids should receive the following information and instructions:1.This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.2.Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.3.The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.4.Patients should report any signs of local adverse reactions especially under occlusive dressing.5.Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on child being treated in the diaper area, as these garments may constitute occlusive dressings.. 1.This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.. 2.Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.. 3.The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.. 4.Patients should report any signs of local adverse reactions especially under occlusive dressing.. 5.Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on child being treated in the diaper area, as these garments may constitute occlusive dressings.

NURSING MOTHERS SECTION.

Nursing Mothers It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk, in quantities not likely to have deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 45 CartonNDC 68682-271-45Rx onlyHYDROCORTISONE BUTYRATE OINTMENT0.1%For topical use only. Not for ophthalmic use.Net Wt. 45 gOCEANSIDEPHARMACEUTICALS. carton45g.

PEDIATRIC USE SECTION.

Pediatric Use Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA-axis suppression and Cushings syndrome than mature patients because of larger skin-surface-area-to-body-weight ratio.Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushings syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids.Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

PHARMACOKINETICS SECTION.

Pharmacokinetics. The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids.Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

PRECAUTIONS SECTION.

PRECAUTIONS General Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushings syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings.Therefore, patients receiving large dose of potent topical corticosteroid applied to large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA-axis suppression by using adrenocorticotropic hormone (ACTH) stimulation tests.If HPA-axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute less potent corticosteroid.Recovery of HPA-axis function is generally prompt and complete upon discontinuation of the drug.Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids.Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. [See PRECAUTIONS, Pediatric Use.]If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.. Information for Patients Patients using topical corticosteroids should receive the following information and instructions:1.This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.2.Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.3.The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.4.Patients should report any signs of local adverse reactions especially under occlusive dressing.5.Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on child being treated in the diaper area, as these garments may constitute occlusive dressings.. 1.This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.. 2.Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.. 3.The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.. 4.Patients should report any signs of local adverse reactions especially under occlusive dressing.. 5.Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on child being treated in the diaper area, as these garments may constitute occlusive dressings.. Carcinogenesis, Mutagenesis, Impairment of Fertility Note: The animal multiples of human exposure calculations in this label were based on body surface area comparisons for an adult (i.e., mg/m2/day dose comparisons) assuming 100% human percutaneous absorption of maximum topical human dose (MTHD) for hydrocortisone butyrate ointment (25 g).In 2-year dermal rat carcinogenicity study with LOCOID(R) lotion, hydrocortisone butyrate was administered to Sprague-Dawley rats at topical doses of 0.05, 0.15, and 0.3 mg/kg/day in males and 0.1, 0.25, and 0.5 mg/kg/day in females (0.1% lotion). No drug-related tumors were noted in this study up to the highest doses evaluated in this study of 0.3 mg/kg/day in males (0.1X MTHD) and 0.5 mg/kg/day in females (0.2X MTHD).Hydrocortisone butyrate revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitrogenotoxicity tests (Ames test and L5178Y/TK+/- mouse lymphoma assay) and one in vivogenotoxicity test (mouse micronucleus assay).No evidence of impairment of fertility or effect on mating performance was observed in fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to and including 1.8 mg/kg/day (0.7X MTHD). Mild effects on maternal animals, such as reduced food consumption and subsequent reduction in body weight gain, were seen at doses >=0.6 mg/kg/day (0.2X MTHD).. Teratogenic Effects Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.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 - 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 - 20. An increased incidence of abortion was noted at 0.3 mg/kg/day (0.2X MTHD). In the absence of maternal toxicity, dose-dependent decrease in fetal body weight was noted at doses >=0.1 mg/kg/day (0.1X MTHD). Additional indicators of embryofetal toxicity (i.e., 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. 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 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days - 15. In the presence of maternal toxicity, an increase in fetal deaths, fetal resorptions and an increase in the number of ossifications in caudal vertebrae were noted at dose of 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 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days - 13. In the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at dose of mg/kg/day (0.2X MTHD). No treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of and 0.2 mg/kg/day, respectively (0.2X MTHD and 0.1X MTHD, respectively).Topical embryofetal development studies were conducted in rats and rabbits with hydrocortisone butyrate ointment formulation. Topical doses of 1% and 10% hydrocortisone butyrate ointment were administered to pregnant female rats during gestation days - 15 or pregnant female rabbits during gestation days - 18. dose-dependent increase in fetal resorptions was noted in rabbits (0.2 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). 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 dose of 10% hydrocortisone butyrate ointment in rats or rabbits (80X MTHD and 2X MTHD, respectively).A peri- and postnatal 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 to lactation day 20. In the presence of maternal toxicity, 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.. Nursing Mothers It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk, in quantities not likely to have deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to nursing woman.. Pediatric Use Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA-axis suppression and Cushings syndrome than mature patients because of larger skin-surface-area-to-body-weight ratio.Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushings syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids.Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

PREGNANCY SECTION.

Teratogenic Effects Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.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 - 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 - 20. An increased incidence of abortion was noted at 0.3 mg/kg/day (0.2X MTHD). In the absence of maternal toxicity, dose-dependent decrease in fetal body weight was noted at doses >=0.1 mg/kg/day (0.1X MTHD). Additional indicators of embryofetal toxicity (i.e., 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. 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 mg/kg/day hydrocortisone butyrate were administered to pregnant female rats during gestation days - 15. In the presence of maternal toxicity, an increase in fetal deaths, fetal resorptions and an increase in the number of ossifications in caudal vertebrae were noted at dose of 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 mg/kg/day hydrocortisone butyrate were administered to pregnant female mice during gestation days - 13. In the absence of maternal toxicity, an increased number of cervical ribs and one fetus with clubbed legs were noted at dose of mg/kg/day (0.2X MTHD). No treatment-related effects on embryofetal toxicity or teratogenicity were noted at doses of and 0.2 mg/kg/day, respectively (0.2X MTHD and 0.1X MTHD, respectively).Topical embryofetal development studies were conducted in rats and rabbits with hydrocortisone butyrate ointment formulation. Topical doses of 1% and 10% hydrocortisone butyrate ointment were administered to pregnant female rats during gestation days - 15 or pregnant female rabbits during gestation days - 18. dose-dependent increase in fetal resorptions was noted in rabbits (0.2 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). 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 dose of 10% hydrocortisone butyrate ointment in rats or rabbits (80X MTHD and 2X MTHD, respectively).A peri- and postnatal 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 to lactation day 20. In the presence of maternal toxicity, 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.

STORAGE AND HANDLING SECTION.

STORAGE. Store at controlled temperature between to 30C (36 to 86F).Distributed by:Oceanside Pharmaceuticals, division ofBausch Health US, LLCBridgewater, NJ 08807 USAManufactured by:Ferndale Laboratories, Inc.Ferndale, MI 48220 USALOCOID is trademark of Leo Pharma A/S used under license. (C) 2020 Bausch Health Companies Inc. or its affiliates9491001Revised: 12/2020.