Source: FDA, National Drug Code (US) Revision Year: 2021
Topical corticosteroids share anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical corticosteroids is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 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 A2.
No studies were conducted to determine the pharmacokinetics of LOCOID 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.
In a 2-year dermal rat carcinogenicity study with LOCOID 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 vivo genotoxicity test (mouse micronucleus assay).
No evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to and I ncluding 1.8 mg/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).
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 Lotion or vehicle was applied twice daily for up to 4 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 2-grade improvement from baseline on a 5-point Physician’s Global Assessment (PGA) scale. Study results are shown in Table 3.
Table 3. Efficacy results at Day 29 in pediatric subjects:
| LOCOID Lotion (n=139) | Vehicle (n=145) | |
|---|---|---|
| Number (%) successes | 68 (49%) | 35 (24%) |
Another multicenter, randomized, double-blind study compared twice-daily treatment with LOCOID Lotion (n=151) to vehicle (n=150) for 3 or 4 weeks in adult subjects (ages 18 years or older) having atopic dermatitis, including those with mild or moderate severity. Results favored LOCOID Lotion over vehicle.
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