WINLEVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WINLEVI (WINLEVI).
WINLEVI (clascoterone) is a topical androgen receptor inhibitor. It binds to the androgen receptor, preventing androgen-mediated signaling in sebocytes and inflammatory cells, thereby reducing sebum production and inflammation.
| Metabolism | Clascoterone is metabolized primarily by CYP3A4 and CYP2C8 to its major metabolite, cortexolone. It undergoes extensive first-pass metabolism if absorbed systemically. |
| Excretion | Primarily fecal (approximately 84% of the dose) and renal (approximately 2.5% of the dose) following intravenous administration. Unchanged drug accounts for less than 1% in urine and feces. |
| Half-life | Terminal elimination half-life is approximately 7.3 hours following topical application of clascoterone 1% cream. This supports twice-daily dosing for maintaining therapeutic drug levels. |
| Protein binding | Approximately 72% bound to plasma proteins (mainly albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Following intravenous administration, volume of distribution is approximately 1.8 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Systemic bioavailability is minimal after topical application of clascoterone 1% cream, with plasma concentrations typically below the limit of quantitation; the exact percentage is not determined, but systemic exposure is negligible (<1% of applied dose). |
| Onset of Action | Clinical improvement may be observed as early as 2 weeks of twice-daily topical application, with maximum effect typically by 12 weeks. |
| Duration of Action | Effects persist over the course of twice-daily application; after discontinuation, clinical benefit may wane over 2–4 weeks based on lesion count rebound in trials. |
WINLEVI (clascoterone) topical cream 1%: Apply a thin layer to the affected skin areas twice daily, in the morning and evening.
| Dosage form | CREAM |
| Renal impairment | No dosage adjustment required for renal impairment, as systemic absorption is minimal. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Approved for patients aged 12 years and older. Same dosing as adults: apply a thin layer of 1% cream twice daily to affected areas. Safety and efficacy in children under 12 years have not been established. |
| Geriatric use | No specific dosage adjustment needed. However, elderly patients may have more sensitive skin; monitor for local irritation. Systemic exposure is minimal. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WINLEVI (WINLEVI).
| Breastfeeding | It is not known whether clascoterone is excreted in human milk after topical application. Systemically absorbed clascoterone is minimal; however, it is lipophilic and may partition into breast milk. No M/P ratio is available. Due to potential for serious adverse reactions in nursing infants, advise patients to avoid application to the breast area and to discontinue nursing or drug, taking into account importance of drug to mother. |
| Teratogenic Risk | WINLEVI (clascoterone) is a topical androgen receptor inhibitor. No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm was observed following topical administration of clascoterone during organogenesis at doses up to 2.5 mg/kg/day in rats (systemic exposure ~27 times the MRHD based on AUC) and 50 mg/kg/day in rabbits (systemic exposure 4 times the MRHD). However, because systemic absorption is minimal, the risk is considered low. Per FDA labeling, use during pregnancy only if clearly needed. No known fetal risks by trimester; avoid use on large areas of broken skin. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to clascoterone or any component of the formulation."]
| Precautions | ["Local skin reactions including erythema, pruritus, and scaling may occur. Avoid contact with eyes, mouth, and mucous membranes. Not for oral, ophthalmic, or intravaginal use. Discontinue if signs of systemic toxicity or hypersensitivity develop. Use in pregnancy only if clearly needed; no adequate and well-controlled studies exist."] |
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| Fetal Monitoring | No specific maternal or fetal monitoring required beyond routine prenatal care. Monitor for signs of local skin reactions (erythema, scaling, pruritus) and if used on large areas, consider monitoring for systemic effects (e.g., HPA axis suppression) due to potential absorption. No fetal monitoring indicated. |
| Fertility Effects | Animal studies (rats) at topical doses up to 2.5 mg/kg/day (27 times MRHD) showed no impairment of male or female fertility. However, as an androgen receptor inhibitor, theoretical potential exists for hormonal interference; no human data available. Effects on fertility are considered unlikely given minimal systemic absorption. |