Clascoterone is a topical cream approved for the treatment of acne vulgaris in males and females 12 years of age and older. The drug is a first-in-class androgen receptor inhibitor. Although the exact mechanism of action is unknown, it is theorized that clascoterone competes with dihydrotestosterone for binding to androgen receptors located in sebocytes. By blocking dihydrotestosterone from binding to these receptors, clascoterone limits transcription of genes that modulate sebum production and inflammation. Adverse events associated with the use of clascoterone include local cutaneous adverse reactions (e.g., erythema, pruritus, scaling, and xerosis) and hypothalamic-pituitary-adrenal (HPA) axis suppression.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations
-For topical administration only. Not for oral, ophthalmic, or intravaginal use.
-Instruct the patient to gently wash the affected area(s) and pat dry.
-After the skin is dry, apply a thin uniformed layer to the affected area(s).
-Avoid contact with eyes, mouth, or other mucous membranes.
-Do not apply to cuts, abrasions, or eczematous or sunburned skin.
-Limit concurrent use with other potentially irritating topical products.
In a pharmacodynamic study involving 20 adults and 22 adolescents with acne vulgaris, hypothalamic-pituitary-adrenal (HPA) suppression (indicated by a 30-minute post-stimulation serum cortisol concentrations of 18 mcg/dL or less) was observed in 1 adult (5%) and 2 adolescents (9%) at day 14 of clascoterone treatment. All 3 of the affected patients returned to normal HPA axis function at follow-up 4 weeks after stopping treatment.
During clinical trials, patients receiving treatment with clascoterone cream developed local skin reactions at a similar percentage to those who were treated with the vehicle cream. The incidence of specific adverse reactions in patients who received clascoterone and the vehicle cream, respectively, were edema (3.6% vs. 3.5%), erythema (12.2% vs. 15.4%), pruritus (7.7% vs. 8.2%), skin atrophy (1.6% vs. 2.6%), striae rubrae (2.5% vs. 1.5%), telangiectasia (1.2% vs. 1.8%), and xerosis (10.5% vs. 10.4%). Skin irritation, including stinging and burning, occurred in 4.2% and 4.3% of patients who received clascoterone and the vehicle cream, respectively.
Adverse reactions associated with clascoterone treatment that were identified during clinical trials and long-term safety studies include polycystic ovaries and amenorrhea.
During clinical trials, hyperkalemia occurred in 5% and 4% of patients who received clascoterone and the vehicle cream, respectively.
Clascoterone is approved for topical administration to the skin. Do not give via oral or vaginal administration, and ensure steps are taken to avoid accidental ocular exposure. If contact with a mucous membrane occurs, rinse the area thoroughly with water.
Topical clascoterone cream is for external use only. Do not apply the cream to skin that is cut or affected by eczema, skin abrasion, or sunburn. Clascoterone may cause local skin irritation at the application site; when possible, avoid concurrent use with other potentially irritating topical products (e.g., medicated or abrasive soaps or cleansers; soaps and cosmetics with a strong drying effect; products with high concentrations of alcohol, astringents, spices, or lime).
Hypothalamic-pituitary-adrenal (HPA) suppression has been associated with the use of clascoterone. In a pharmacodynamic study involving 20 adults and 22 adolescents with acne vulgaris, HPA suppression (indicated by a 30-minute post-stimulation serum cortisol concentrations of 18 mcg/dL or less) was observed in 1 adult (5%) and 2 adolescents (9%) at day 14 of clascoterone treatment. All 3 of the affected patients returned to normal HPA axis function at follow-up 4 weeks after stopping treatment. Conditions that increase systemic absorption and the risk for HPA suppression include use over large surface areas, prolonged use, and the use of an occlusive dressing. Pediatric patients may also be at increased risk for HPA suppression. If HPA axis suppression is noted, an attempt should be made to withdraw the drug.
Safety and efficacy of clascoterone have not been established in pediatric patients younger than 12 years of age (i.e., neonates, infants, and children). Pediatric patients may be more susceptible to the systemic toxicity of clascoterone.
There are no human data available regarding the use of clascoterone during pregnancy to determine a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. In animal studies, subcutaneous doses (at 8- to 39-times the maximum recommended human dose) administered during organogenesis to pregnant rats and rabbits increased malformations (rats) and post-implantation loss and resorptions (rabbits). Malformations observed in rats included omphalocele, thin skin, decreased size, protruding tongue, and severe dilation of the lateral and third cerebral ventricles.
There are no data available regarding the excretion of clascoterone or its metabolite into human milk, the effects on a breast-fed infant, or the effects on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
For the treatment of acne vulgaris:
Topical dosage:
Adults: Apply a thin layer topically to the affected skin area(s) twice daily.
Children and Adolescents 12 to 17 years: Apply a thin layer topically to the affected skin area(s) twice daily.
Maximum Dosage Limits:
-Adults
2 applications per day topically.
-Geriatric
2 applications per day topically.
-Adolescents
2 applications per day topically.
-Children
12 years: 2 applications per day topically.
1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Clascoterone products.
Clascoterone a first-in-class androgen receptor inhibitor. The exact mechanism of action is unknown; however, data from in vitro studies indicate clascoterone competes with dihydrotestosterone for binding to androgen receptors located in sebocytes. Due to a higher binding affinity, clascoterone blocks dihydrotestosterone from binding to these receptors; thereby reducing transcription of androgen-responsive genes that modulate sebum production and inflammation.
Clascoterone is administered topically to the skin. Once absorption, clascoterone is 84% to 89% bound to plasma proteins, with the binding being independent of drug concentrations. Data from an in vitro study using cryopreserved hepatocytes found clascoterone is metabolized to cortexolone (possible primary metabolite) and other unidentified metabolites, including conjugated metabolites. Drug excretion and the elimination half-life have not been determined.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4
At a half-maximal inhibitory concentration (IC50) over 40 microMolar, clascoterone inhibits CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4; however, no clinically meaningful effect on the pharmacokinetics of drugs metabolized by these enzymes is expected. Studies evaluating the drug interaction potential of clascoterone have not been conducted.
-Route-Specific Pharmacokinetics
Topical Route
Following topical application of approximately 6 grams of clascoterone twice daily for 2 weeks to adults with moderate to severe acne vulgaris, steady-state drug concentrations were achieved by treatment day 5. On day 14, the mean maximum plasma concentration (Cmax), mean drug exposure (AUC), and mean average plasma concentration (Cavg) were 4.5 +/- 2.9 ng/mL, 37.1 +/- 22.3 hour x ng/mL, and 3.1 +/- 1.9 ng/mL, respectively.
-Special Populations
Pediatrics
Data from a study involving 22 adolescent patients (ages 12 to 17 years) found the systemic exposure of clascoterone to be similar to those observed in adults. In both adults and adolescents, steady-state drug concentrations were achieved by treatment day 5.