Winlevi

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.

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

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

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.

• Local Irritation: Pruritus, burning, skin redness or peeling may be experienced with WINLEVI cream. If these effects occur, discontinue or reduce the frequency of application of WINLEVI cream. (
  
  
  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.
  )
  
• Hypothalamic-pituitary-adrenal (HPA) axis suppression may occur during or after treatment with clascoterone. (
  
  
  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.
  )
  
• Attempt to withdraw use if HPA axis suppression develops. (
  
  
  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.
  )
  
• Pediatric patients may be more susceptible to systemic toxicity. (
  
  
  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.
  ,
  
  
  8.4 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

  [see

  Clinical Studies (14)

  ].

  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

  [see

  Clinical Pharmacology (12.2)

  ].

  Children may be more susceptible to systemic toxicity when treated with clascoterone

  [see

  Pharmacodynamics (12.2)

  ].
  )
  
• Hyperkalemia: Elevated potassium levels were observed in some subjects during the clinical trials. (
  
  
  12.2 Pharmacodynamics

  Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

  HPA axis suppression was evaluated in adult (n=20) and adolescent (n=22) subjects with acne vulgaris following twice daily application of WINLEVI cream for 2 weeks in the pharmacokinetic study described in Section 12.3. HPA axis suppression indicated by 30-minute post-stimulation serum cortisol level of ≤18 mcg/dL was observed in 1/20 (5%) of adult subjects and 2/22 (9%) of adolescent subjects at Day 14. All subjects returned to normal HPA axis function at follow-up 4 weeks after the end of treatment.

  Potassium

  Shifts from normal to elevated potassium levels were observed in 5% of clascoterone-treated subjects and 4% of vehicle-treated subjects.

  Cardiac Electrophysiology

  At approximately 2-times the systemic exposure observed with the maximum dose, WINLEVI cream does not prolong the QT interval to any clinically relevant extent.
  )