Clascoterone

Approved Indications:

• Acne Vulgaris:
  Treatment of acne vulgaris in patients aged 12 years and older. It is approved for topical use to reduce inflammatory and non-inflammatory acne lesions on the face and trunk.

Clinically Accepted Off-Label Uses (under investigation or emerging evidence):

• Androgenetic Alopecia (Male and Female Pattern Hair Loss):
  Topical clascoterone is being studied for its potential use in treating androgen-driven hair loss due to its local antiandrogenic activity.
• Seborrheic Dermatitis:
  Potential utility due to its antiandrogenic and anti-inflammatory properties in sebaceous gland-related conditions.
• Hirsutism (Facial):
  Though not formally approved, topical antiandrogens such as clascoterone may offer benefit in managing excessive facial hair growth in women.

Adults and Adolescents (≥12 years):

• Recommended Dose for Acne Vulgaris:
  Apply a thin layer of 1% clascoterone cream to the affected area twice daily, in the morning and evening.
• Application Area:
  Typically applied to facial and truncal acne sites.
  Avoid application to mucous membranes, eyes, or open wounds.

Pediatrics (<12 years):

• Not established.
  Safety and efficacy have not been confirmed for use in children under 12 years.

Elderly:

• Although acne is less common, dosing is the same if used. Safety data in this population are limited.

Renal or Hepatic Impairment:

• No dose adjustment is currently recommended.
  Systemic absorption is minimal; however, caution is advised in patients with severe hepatic impairment due to potential accumulation of metabolites.

Route of Administration:
Topical (cutaneous use only)

Duration of Therapy:
Visible improvement may be seen after 4–8 weeks. Continue therapy as directed, typically for at least 12 weeks, or as advised by the healthcare provider.

Clascoterone is a topical androgen receptor (AR) antagonist. It competes with dihydrotestosterone (DHT) and testosterone for binding to androgen receptors in the skin, particularly in sebaceous gland cells. By blocking androgen signaling, it reduces sebum production and inflammation—two major contributors to acne pathogenesis. Unlike systemic antiandrogens, clascoterone acts locally within the skin with minimal systemic absorption, thus limiting hormonal side effects.

• Absorption:
  Minimal systemic absorption when applied topically. Blood concentrations are low and transient even with repeated use.
• Distribution:
  Primarily local action in skin tissues. Systemic distribution is negligible in therapeutic use.
• Metabolism:
  Rapidly hydrolyzed in the skin to cortexolone, an inactive metabolite, via esterases.
• Excretion:
  Excreted mainly in urine as inactive metabolites.
• Onset of Action:
  Clinical improvement may begin within 2–4 weeks, with maximal results often seen by 8–12 weeks.
• Half-life:
  Systemic half-life is short due to rapid metabolism; exact value not clinically significant.
• Bioavailability:
  Negligible systemic bioavailability due to rapid local metabolism and low absorption.

• Pregnancy:
  Not assigned an FDA pregnancy category under the current labeling system. Animal studies have not shown teratogenic effects at typical topical doses. However, due to the lack of controlled human data, clascoterone should be used during pregnancy only if clearly needed.
• Lactation:
  Unknown if clascoterone or its metabolites are excreted into human breast milk. Systemic exposure is expected to be minimal.
  Recommendation: Use with caution in lactating individuals. Avoid direct application to the breast area to prevent infant exposure.
• Caution:
  Limited data on human use in pregnancy and breastfeeding; benefits should clearly outweigh potential risks.

• Primary Therapeutic Class: Topical Antiandrogen
• Subclass: Non-steroidal androgen receptor antagonist (structurally related to cortexolone 17α-propionate)

• Known hypersensitivity to clascoterone or any component of the formulation
• Not for ophthalmic, oral, or intravaginal use
• Use on open wounds or damaged skin (risk of increased systemic absorption)

• Hormonal Effects:
  Though minimal, systemic absorption could theoretically affect hormonal balance; monitor if signs of hormonal side effects appear.
• Local Skin Reactions:
  Possible irritation, erythema, or dryness at the application site.
• Hyperkalemia Risk:
  Rare cases of elevated serum potassium have been observed in clinical trials. Use caution in patients with renal impairment or those on potassium-sparing medications.
• Use in Pregnancy/Lactation:
  Use with caution due to limited human safety data.
• Monitoring:
• Monitor for local skin reactions.
• Periodic serum potassium may be considered in high-risk patients.

Common:

• Dermatologic (Local):
• Erythema
• Scaling
• Dryness
• Burning or stinging
• Itching at the application site

Less Common:

• Acne worsening (initial flare)
• Folliculitis
• Application site irritation

Rare/Serious:

• Hyperkalemia (reported in <1% of patients)
• Allergic contact dermatitis
• Hypersensitivity reactions

Onset & Severity:

• Local effects typically occur within the first few weeks of use.
• Most side effects are mild to moderate and self-limiting.

• Topical Drug Interactions:
  No significant known interactions when used with other topical acne medications. However, combining with other irritants (e.g., benzoyl peroxide, retinoids) may increase skin irritation.
• Systemic Drug Interactions:
  Due to negligible systemic absorption, drug-drug interactions are highly unlikely.
• CYP Enzyme Involvement:
  Not metabolized via the CYP450 system; no known CYP interactions.
• Drug–Cosmetic Interaction:
  Avoid applying cosmetics or other skin products immediately after clascoterone unless advised by a healthcare provider.

• FDA Approval:
  Clascoterone 1% cream (Winlevi®) was approved by the U.S. FDA in August 2020, making it the first topical androgen receptor inhibitor for acne.
• Guideline Integration:
  Recent acne management guidelines (e.g., American Academy of Dermatology) now mention clascoterone as a novel option for patients with inflammatory acne, particularly in hormone-driven cases or those seeking non-antibiotic alternatives.
• Pipeline Expansion:
  Clinical trials are ongoing for androgenetic alopecia and seborrheic dermatitis.

• Storage Temperature:
  Store at 20°C to 25°C (68°F to 77°F).
  Excursions permitted between 15°C and 30°C.
• Protection Requirements:
• Protect from excessive heat and freezing.
• Keep container tightly closed.
• Handling Instructions:
• Do not freeze.
• Avoid contact with eyes, mucous membranes, or broken skin.
• Wash hands after application (unless hands are the treatment site).
• Shelf Life & Use:
  Refer to the product label for expiration. Do not use beyond expiry. No reconstitution required.