Winlevi

WINLEVI- clascoterone cream
Sun Pharmaceutical Industries, Inc.

1 INDICATIONS AND USAGE

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

2 DOSAGE AND ADMINISTRATION

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.

3 DOSAGE FORMS AND STRENGTHS

Cream 1%. Each gram of WINLEVI cream contains 10 mg of clascoterone in a white to almost white cream.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Local Skin Reactions

WINLEVI cream may induce local irritation (erythema/redness, pruritus, scaling/ dryness). Concomitant use with other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect and products with high concentrations of alcohol, astringents, spices or lime) should be limited.

The product should not be applied to cuts, abrasions, eczematous or sunburned skin.

5.2 Hypothalamic-pituitary-adrenal (HPA) Axis Suppression

Hypothalamic-pituitary-adrenal (HPA) axis suppression was observed and may occur during or after treatment with clascoterone. In the PK trial, all subjects returned to normal HPA axis function at follow-up 4 weeks after stopping treatment [see Clinical Pharmacology (12.2)]. Conditions which augment systemic absorption include use over large surface areas, prolonged use, and the use of occlusive dressings.

If HPA axis suppression develops, an attempt should be made to withdraw the drug.

Pediatric patients may be more susceptible to systemic toxicity.

6 ADVERSE REACTIONS

6.1 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 the12-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=674a)

Vehicle Cream(N=656a)

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%)

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.

The following adverse reactions associated with the use of WINLEVI cream were identified in clinical trials and long-term safety studies.

Metabolism: hyperkalemia [see Clinical Pharmacology (12.2) ]

Reproductive: polycystic ovaries, amenorrhea.

8 USE IN SPECIFIC POPULATIONS

8.1 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).

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