Winlevi Drug Information

(clascoterone) cream is an androgen receptor inhibitor indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. WINLEVI (clascoterone) cream is an androgen receptor inhibitor indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

Cleanse the affected area gently. After the skin is dry, apply a thin uniform layer of WINLEVI cream twice per day, in the morning and the evening, to the affected area. Avoid accidental transfer of WINLEVI cream into eyes, mouth or other mucous membranes.

If contact with mucous membranes occurs, rinse thoroughly with water. WINLEVI cream is for topical use only. WINLEVI cream is not for ophthalmic, oral or vaginal use.

Apply a thin layer (approximately 1 gram) to affected area twice daily (morning and evening). Avoid contact with eyes, mouth, and mucous membranes. Not for ophthalmic, oral or vaginal use.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two identical multicenter, randomized, double-blind, vehicle-controlled trials, 1421 subjects 12 years and older with facial acne vulgaris applied WINLEVI cream or vehicle twice daily for 12 weeks. Overall, 62% of the subjects were female, and 38% were male, 91% of the patients were Caucasian, and the mean age was 19.7 years.

Local skin reactions (edema, erythema/redness, pruritus, scaling/dryness, skin atrophy, stinging/burning, striae rubrea, telangiectasia) were observed during the 12-week treatment and occurred in a similar percentage of subjects treated with vehicle. Local skin reactions reported by ≥ 1% of subjects treated with WINLEVI cream are shown in the following table. Table 1. Incidence of New or Worsening Local Skin Reactions Reported by ≥ 1% of Subjects Treated with WINLEVI Cream After Day 1 in 12-Week Controlled Clinical Trials WINLEVI Cream 1% (N=674 a ) Vehicle Cream (N=656 a ) a The denominators for calculating the percentages were the 674 of 709 subjects treated with WINLEVI cream and 656 of 712 subjects treated with vehicle in these trials who had local skin reaction results reported after Day 1. Edema 24 (3.6%) 23 (3.5%) Erythema/redness 82 (12.2%) 101 (15.4%) Pruritus 52 (7.7%) 54 (8.2%) Scaling/dryness 71 (10.5%) 68 (10.4%) Skin atrophy 11 (1.6%) 17 (2.6%) Stinging/burning 28 (4.2%) 28 (4.3%) Striae rubrae 17 (2.5%) 10 (1.5%) Telangiectasia 8 (1.2%) 12 (1.8%) The following adverse reactions associated with the use of WINLEVI cream were identified in clinical trials and long-term safety studies.

Metabolism: hyperkalemia Reproductive: polycystic ovaries, amenorrhea.

Pregnancy Risk Summary There are no available data on WINLEVI cream use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneous administration of clascoterone to pregnant rats and rabbits during organogenesis at doses 8 or 39 times the maximum recommended human dose (MRHD), respectively, increased malformations in rats and post-implantation loss and resorptions in rabbits (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryofetal development study, clascoterone was administered subcutaneously to pregnant rats at doses of 1, 5, or 25 mg/kg/day during the period of organogenesis. No clascoterone-related maternal toxicity or effects on uterine parameters were noted at doses up to 25 mg/kg/day (336 times the MRHD based on AUC comparison). Clascoterone-related malformations were noted at all dose levels, without a dose relationship.

Omphalocele was noted in a single fetus at each dose level. External and visceral malformations (severe dilation of the lateral and third cerebral ventricles; thin skin, small size, and protruding tongue) were noted in two additional fetuses at 1 mg/kg/day (8 times the MRHD based on AUC comparison). In an embryofetal development study, clascoterone was administered subcutaneously to pregnant rabbits at doses of 0.1, 0.4, or 1.5 mg/kg/day during the period of organogenesis. Post-implantation loss and resorptions were increased at 1.5 mg/kg/day (39 times the MRHD based on AUC comparison). No developmental toxicity was noted at doses up to 0.4 mg/kg/day (12 times the MRHD based on AUC comparison). No clascoterone-related maternal toxicity or fetal malformations were noted at doses up to 1.5 mg/kg/day (39 times the MRHD based on AUC comparison). In a prenatal and postnatal development study, clascoterone was administered subcutaneously to pregnant rats at doses of 0.5, 2.5, and 12.5 mg/kg/day beginning on gestation day 6 and continuing through lactation day 20. No significant maternal or developmental toxicity was observed at doses up to 12.5 mg/kg/day (163 times the MRHD based on AUC comparison).

Pediatric Use Safety and effectiveness of WINLEVI cream for the topical treatment of acne vulgaris have been established in 641 pediatric patients, aged 12 to 18 years in two identical multicenter, randomized, double-blind, vehicle-controlled, 12-week trials and 2 open-label pharmacokinetic studies. Safety and effectiveness of WINLEVI cream for the topical treatment of acne vulgaris has not been established in pediatric patients under 12 years of age. Hypothalamic-pituitary-adrenal (HPA) axis suppression was observed in 2/22 (9%) adolescent subjects.

All subjects returned to normal HPA axis function at follow-up 4 weeks after stopping the treatment. Children may be more susceptible to systemic toxicity when treated with clascoterone.