Topical clascoterone for acne: a practical prescribing guide

Clascoterone (Winlevi) is the first topical acne treatment to directly target androgen signalling within the skin, reducing androgen-driven sebum production.

Androgens contribute to acne through effects on the pilosebaceous unit, including sebum production and inflammation. Clascoterone competes with androgens at local androgen receptors. The exact mechanism by which this improves acne is not fully understood.

For mild-to-moderate acne, clascoterone can be used alone or added to other topical treatments, providing a different therapeutic target from retinoids, benzoyl peroxide and antibiotics. It may be particularly useful when inflammatory and comedonal lesions coexist, when the response to an existing topical regimen is incomplete, or when the patient wishes to avoid systemic treatment.

It can also be considered when systemic anti-androgen treatment is unsuitable or undesirable, or where acne has a lower-face/jawline distribution or fluctuates with the menstrual cycle. A “hormonal” pattern is not required, and its use is not restricted to females.

How effective is it?

Two phase III randomised, double-blind trials included 1,440 patients with moderate-to-severe facial acne.

Approximately 1g of clascoterone 1% cream was applied to the whole face twice daily for 12 weeks.

At week 12, treatment success (clear/almost clear with at least a two-grade improvement in Investigator Global Assessment score) occurred in approximately:

• 18–20% with clascoterone 
• 7–9% with vehicle placebo

Both inflammatory and non-inflammatory lesion counts improved significantly¹.

Improvement is gradual. Response should be assessed at 12 weeks.

Clascoterone is applied twice daily, morning and evening, as a field treatment over the entire acne-prone area rather than to individual lesions. In the main clinical trials, approximately 1g was used per whole-face application.

Apply to clean, dry skin, avoiding the eyes, lips and other mucosal surfaces, as well as broken, sunburnt, significantly inflamed or eczematous skin.

Allow the cream to absorb before applying other skincare products and avoid occlusion.

Clascoterone should not delay systemic treatment for severe inflammatory, nodulocystic or scarring acne, including extensive inflammatory truncal disease or patients with significant negative psychosocial impact from acne.

Winlevi and topical retinoids target different components of acne pathogenesis and can be used together synergistically.

For example, a patient whose comedonal acne has improved with adapalene but who continues to develop inflammatory lesions should continue adapalene when clascoterone is introduced.

A small open-label study evaluating clascoterone 1% twice daily with adapalene 0.3% once daily reported encouraging efficacy and tolerability, although evidence for combination treatment remains limited⁴.

Clascoterone can be layered with common topical acne treatments, including:
•    adapalene
•    tretinoin
•    benzoyl peroxide-containing preparations
•    azelaic acid.

Combining topical treatments may increase cumulative dryness and irritation, so the regimen should be adjusted according to individual tolerance.

A practical combination regimen would look like:

Emerging evidence supports concurrent use with oral isotretinoin.

A small multicenter retrospective study of 82 patients with severe/nodular acne found a higher proportion achieved clear/almost clear skin at 24 weeks with isotretinoin plus clascoterone than with isotretinoin alone (92.1% vs 72.7%), without a significant increase in xerosis.

However, lesion-count reductions did not differ significantly between groups, and prospective randomised studies are needed⁵. 

Routine laboratory monitoring is not required. Potassium monitoring is not recommended, although it may be considered in patients at increased risk of hyperkalaemia. In clinical studies involving patients aged 12–64 years, elevated potassium occurred at similar rates with clascoterone (3.7%) and vehicle (3.9%)^6,7. 

Maximum-use studies provide reassurance regarding systemic safety. Adults and larger adolescents applied approximately 6 g twice daily to the face, shoulders, upper chest and upper back for two weeks. Biochemical HPA-axis suppression occurred in 1/20 (5%) adults and 2/22 (9%) adolescents. Suppression was generally minimal and resolved in all affected participants within four weeks of stopping treatment^2,3.

The 6 g twice-daily regimen was designed to assess systemic exposure under maximum-use conditions and is not a recommended dose for truncal acne.

Winlevi is not approved for children under 12 years.

The main adverse effects are local skin reactions, including erythema, dryness or scaling, pruritus, stinging or burning, and oedema. Most reactions in clinical trials were mild.

If irritation develops, review the entire skincare regimen before attributing it to clascoterone. Common contributors include topical retinoids, benzoyl peroxide, salicylic or glycolic acids, exfoliating toners, scrubs, astringents, alcohol-containing products and some ‘natural’ skincare products.

Simplify the regimen, review concomitant topical treatments, reduce unnecessary irritants and recommend a bland, non-comedogenic moisturiser. Adjust the timing or frequency of other active treatments if needed. Supporting the skin barrier may allow effective acne treatment to continue, but persistent or significant irritation should prompt treatment review.

• Hypersensitivity: Avoid in patients with known hypersensitivity to clascoterone or any excipient; see the NZ data sheet for the full list.
• Pregnancy: Do not use during pregnancy. Human data are insufficient, and developmental toxicity has been demonstrated in animal studies. Discontinue if pregnancy occurs. Topical retinoids require separate pregnancy counselling.
• Breastfeeding:  Insufficient data.
• Children <12 years

Clascoterone should not delay systemic treatment for severe inflammatory, nodulocystic or scarring acne, including extensive inflammatory truncal disease or patients with significant negative psychosocial impact from acne.

Clinical studies to date have not identified systemic anti-androgenic adverse effects or a safety signal relating to pubertal development.

Systemic exposure following usual topical application is low.

Josh is 15 and has moderate facial acne with inflammatory papules and comedones.

He and his mother have heard that Winlevi acts on androgen receptors and ask whether this means it will cause harm to male hormone development.

A simple explanation for adolescents and parents is:
This medicine works mainly on the skin, where it reduces one of the signals that contributes to oil production and acne. It is approved for acne in both boys and girls from age 12.

Content created by Dr Danuta Amelung, BHB, MbChB, FRNZCGP, AFRACMA, Dip. Paed, PGCertWHlth, PGDipTrvMed, with expert review by Dr Peggy Chen, Specialist Dermatologist, MB ChB 2008 Otago; FRACP 2015 - Dermatology.