Locoid Information
Locoid (Hydrocortisone) Indications And Usage
Locoid (Hydrocortisone) Lotion is a corticosteroid indicated for the topical treatment of mild to moderate atopic dermatitis in patients 3 months of age and older.
Locoid (Hydrocortisone) Dosage And Administration
Locoid (Hydrocortisone) Lotion is not for oral, ophthalmic, or intravaginal use.
Apply a thin layer to the affected skin areas two times daily. Rub in gently.
Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. The safety of Locoid (Hydrocortisone) Lotion has not been established beyond 4 weeks of use.
Locoid (Hydrocortisone) Lotion should not be used with occlusive dressings or applied in the diaper area unless directed by a physician.
Locoid (Hydrocortisone) Dosage Forms And Strengths
Lotion, 0.1% (1 mg/g), supplied in bottles of 2 fl. oz. and 4 fl. oz.
Locoid (Hydrocortisone) Contraindications
Locoid (Hydrocortisone) Warnings And Precautions
Systemic effects of topical corticosteroids may include reversible HPA axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria.
Studies conducted in pediatric subjects demonstrated reversible HPA axis suppression after use of Locoid (Hydrocortisone) Lotion. Pediatric patients may be more susceptible than adults to systemic toxicity from equivalent doses of Locoid (Hydrocortisone) Lotion due to their larger skin surface-to-body-mass ratios [].
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 (ACTH) stimulation testing (CST).
If HPA axis suppression is noted, the frequency of application should be reduced or the drug should be withdrawn, or a less potent corticosteroid should be substituted.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.
Locoid (Hydrocortisone) Lotion may cause local skin adverse reactions [].
If irritation develops, Locoid (Hydrocortisone) Lotion should be discontinued and appropriate therapy instituted. 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.
Locoid (Hydrocortisone) Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Locoid (Hydrocortisone) Drug Interactions
There are no known drug interactions with Locoid (Hydrocortisone) Lotion.
Locoid (Hydrocortisone) Use In Specific Populations
Pregnancy Category C. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.
There are no adequate and well-controlled studies in pregnant women. Therefore, Locoid (Hydrocortisone) Lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Note: The animal multiples of human exposure calculations in this label were based on body surface area comparisons for an adult (i.e., mg/m/day dose comparisons) assuming 100% human percutaneous absorption of a maximum topical human dose (MTHD) for hydrocortisone butyrate lotion (25 g lotion).
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 (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 mg/kg/day 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– 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 embyrofetal 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 – 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 – 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 lotion. 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 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 embyrofetal toxicity were noted at the 1% hydrocortisone butyrate ointment dose in rats (8 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 – 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.
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. They are therefore also at a greater risk of glucocorticosteroid insufficiency after withdrawal of treatment and of Cushing’s syndrome while on treatment.
Eighty-four (84) pediatric subjects (3 months to less than 18 years of age) with moderate to severe atopic dermatitis affecting at least 25% of body surface area (BSA) treated with Locoid (Hydrocortisone) Lotion three times daily for up to 4 weeks were assessed for HPA axis suppression. The disease severity (moderate to severe atopic dermatitis) and the dosing regimen (three times daily) in this HPA axis study were different from the subject population (mild to moderate atopic dermatitis) and the dosing regimen (two times daily) for which Locoid (Hydrocortisone) lotion is indicated. Seven of the 82 evaluable subjects (8.5%) demonstrated laboratory evidence of suppression, where the sole 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 1 to 12 years and, at the time of enrollment, had 35% to 90% BSA involvement. These subjects did not develop any other signs or symptoms 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 the second post treatment visit, 55 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.
Locoid (Hydrocortisone) Description
Locoid (Hydrocortisone) Lotion contains hydrocortisone butyrate, a non-fluorinated hydrocortisone ester [Pregn-4-ene-3, 20-dione, 11, 21-dihydroxy-17- [(1-oxobutyl) oxy (11β)-] for topical dermatologic use. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents.
Chemically, hydrocortisone butyrate is CHO. It has the following structural formula:
Hydrocortisone butyrate is a white to practically white powder with a molecular weight of 432.56. It is practically insoluble in water, slightly soluble in ether, soluble in methanol, in alcohol, and in acetone, and freely soluble in chloroform.
Each gram of Locoid (Hydrocortisone) Lotion contains 1 mg hydrocortisone butyrate in a base consisting of water, light mineral oil, cetostearyl alcohol, white petrolatum, ceteth-20, citric acid, sodium citrate, safflower oil and butylated hydroxytoluene (BHT), with propylparaben and butylparaben as preservatives.
Locoid (Hydrocortisone) Clinical Pharmacology
No studies were conducted to determine the pharmacokinetics of Locoid (Hydrocortisone) Lotion.
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 through normal intact skin. Inflammation and/or other disease processes in the skin, occlusive dressings, or widespread application may increase percutaneous absorption.
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.
Locoid (Hydrocortisone) Clinical Studies
In a multicenter, randomized, vehicle-controlled trial of 284 pediatric subjects 3 months to 18 years of age with mild to moderate atopic dermatitis, Locoid (Hydrocortisone) Lotion or vehicle was applied twice daily for up to four weeks. Treatment success was assessed at day 29 (after 28 days of treatment) and was defined as the proportion of patients who achieved both “clear” or “almost clear” and at least a two grade improvement from baseline on a 5-point Physician’s Global Assessment (PGA) scale.
Study results are shown in Table 3.
Another multicenter, randomized, double-blind study compared twice daily treatment with Locoid (Hydrocortisone) Lotion (n=151) to vehicle (n=150) for three or four weeks in adult subjects (ages 18 years or older), including those mild or moderate atopic dermatitis. Results favored Locoid (Hydrocortisone) Lotion over vehicle.
Locoid (Hydrocortisone) How Supplied/storage And Handling
Locoid (Hydrocortisone) Lotion, 0.1% is supplied in bottles of 2 fl. oz. (NDC 0496-0872-02) and 4 fl. oz. (NDC 0496-0872-04).
Locoid (Hydrocortisone) Patient Counseling Information
Patients using Locoid (Hydrocortisone) Lotion should receive the following information and instructions:
Ferndale Laboratories, Inc. Ferndale MI 48220
