Introduction
Winlevi (clascoterone) 1% cream is a novel topical antiandrogen medication approved by the FDA in August 2020 for the treatment of acne vulgaris. It represents the first in its class of topical androgen receptor inhibitors specifically developed for dermatological use. This medication offers a unique mechanism of action distinct from other acne treatments, providing clinicians with an additional therapeutic option for patients with acne.
Mechanism of Action
Clascoterone competitively inhibits androgen binding to androgen receptors in the sebaceous gland and hair follicle. This action reduces the production of sebum, which plays a crucial role in acne pathogenesis. Unlike systemic antiandrogens, clascoterone is rapidly metabolized to cortexolone upon systemic absorption, minimizing systemic hormonal effects while maintaining local efficacy in the skin.
Indications
Winlevi is indicated for the topical treatment of acne vulgaris in patients 12 years and older. Clinical trials demonstrated efficacy in both inflammatory and non-inflammatory acne lesions. The medication is approved for use in all genders, making it particularly valuable for female patients who may not be candidates for systemic antiandrogen therapy.
Dosage and Administration
Standard dosing: Apply a thin layer of Winlevi 1% cream to affected areas twice daily (morning and evening) Application: Clean and dry affected areas before application. Use sparingly and rub in gently. Special populations: No dosage adjustment required for renal or hepatic impairment. Safety and effectiveness in pediatric patients below 12 years have not been established.Pharmacokinetics
Absorption: Minimal systemic absorption with topical application. Mean maximum plasma concentration (Cmax) of clascoterone and its active metabolite cortexolone are 0.76 ng/mL and 11.3 ng/mL, respectively. Distribution: Primarily local distribution in the skin with minimal systemic distribution. Metabolism: Rapidly metabolized to cortexolone by esterases in the skin and plasma. Elimination: Systemically eliminated metabolites are excreted primarily in urine.Contraindications
- Hypersensitivity to clascoterone or any component of the formulation
- Not contraindicated in pregnancy based on current labeling, but caution is advised
Warnings and Precautions
Hypothalamic-pituitary-adrenal (HPA) axis suppression: Although rare with topical use, potential for HPA axis suppression exists with prolonged use. Local reactions: May cause skin irritation, erythema, scaling, and dryness Pregnancy: No adequate human data available. Use caution in pregnant women. Pediatric use: May affect gonadal function with prolonged use. Monitor pediatric patients appropriately.Drug Interactions
No formal drug interaction studies have been conducted. However, theoretical interactions include:
- Potential increased systemic exposure when used with other topical products that increase skin permeability
- Possible interaction with systemic androgen inhibitors (though unlikely due to minimal systemic absorption)
Adverse Effects
Common adverse reactions (≥1%):- Erythema (6%)
- Pruritus (5%)
- Scaling (3%)
- Dryness (2%)
- Irritation (1%)
- HPA axis suppression (rare)
- Ocular irritation (if applied near eyes)
Monitoring Parameters
- Skin response and tolerance at treatment initiation and periodically thereafter
- Signs of HPA axis suppression in cases of prolonged use or excessive application
- Assessment of acne improvement using standardized acne grading scales
- Monitoring for local skin reactions and irritation
Patient Education
- Apply only to affected areas as directed by healthcare provider
- Avoid application in eyes, mouth, lips, and mucous membranes
- Use sunscreen as medication may increase sensitivity to sunlight
- Report any signs of skin irritation, rash, or worsening acne
- Do not cover treated areas with occlusive dressings
- Consistency in application is important for optimal results
- Results may take 8-12 weeks to become apparent
- Continue other acne medications as prescribed unless instructed otherwise
References
1. Hebert A, Thiboutot D, Stein Gold L, et al. Efficacy and safety of topical clascoterone cream, 1%, for treatment in patients with facial acne: Two phase 3 randomized clinical trials. JAMA Dermatol. 2020;156(6):621-630.
2. Eichenfield LF, Hebert A, Gold LS, et al. Open-label study of the safety and effectiveness of clascoterone cream 1% in the treatment of facial acne. J Drugs Dermatol. 2021;20(10):1045-1050.
3. Winlevi [package insert]. Irvine, CA: Cassiopea SpA; 2020.
4. Rosette C, Agan FJ, Mazzetti A, et al. Clascoterone cream 1%: A novel treatment for acne. SKIN J Cutan Med. 2019;3(6):421-426.
5. FDA Center for Drug Evaluation and Research. Approval letter for Winlevi. August 2020.
6. Thiboutot D, Anderson R, Cook-Bolden F, et al. Standard management options for rosacea: The 2019 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2020;82(6):1501-1510.
Note: This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical recommendations.