Trifarotene

Breast Feeding; Lactation; Dermatologic Agents; Retinoids

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Warning

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

P203, P260, P261, P263, P264, P264+P265, P270, P271, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

D - Dermatologicals

QD - Dermatologicals

Trifarotene exerts its effects via agonism at retinoid receptors - these receptors function to alter DNA transcription, resulting in downstream modulation of the expression of various genes involved in acne pathogenesis. It may be associated with skin irritation and should not be applied to cuts, abrasions, or otherwise damaged skin. As trifarotene may result in photosensitivity, patients should be cautioned to avoid excess sun exposure and to use sunscreen and/or protective clothing if exposure is unavoidable.

Trifarotene is a potent and selective agonist of retinoic acid receptor-γ (RAR-γ). It has significantly less activity at RAR-β and RAR-α (16- and 65-fold lower than activity at RAR-γ, respectively), and has no activity at retinoid X receptors (RXRs). Agonism at retinoic acid receptors results in dimerization, and the resulting receptor-ligand dimer binds to specific DNA regulatory sequences (retinoic acid response elements, or RAREs) in the promotor regions of retinoid-responsible genes. Downstream alterations to gene expression induced by binding to these regions is the principle mechanism through which trifarotene exerts its comedolytic, anti-inflammatory, and depigmenting effects. Like other retinoids, trifarotene influences the expression of a number of genes involved in retinoid metabolism, epidermal differentiation/proliferation, and epidermal response to stress. In addition, trifarotene appears to modulate retinoid-mediated pathways involved in proteolysis, skin hydration, and cell adhesion - modulation of these additional pathways has not been observed with other retinoids and may therefore be unique to trifarotene.

Trifarotene is rapidly metabolized in human hepatocytes - its observed half-life in human keratinocytes is >24 hours, whereas half-life in human liver microsomes is approximately 5 minutes. Metabolism of trifarotene is catalyzed primarily by CYP2C9, CYP3A4, CYP2C8, and, to a lesser extent, CYP2B6.