VTAMA

Topical Antipsoriasis Agents

For topical use only. DO NOT administer via the oral, ophthalmic, or intravaginal routes.
Apply as a thin layer to affected areas.
Wash hands after application, unless the hands are included as an area to be treated.

contact dermatitis / Delayed / 7.0-7.0
migraine / Early / 4.0-4.0

folliculitis / Delayed / 20.0-20.0
rhinorrhea / Early / 11.0-11.0
infection / Delayed / 11.0-11.0
nasal congestion / Early / 11.0-11.0
pharyngitis / Delayed / 11.0-11.0
rash / Early / 7.0-7.0
headache / Early / 4.0-4.0
pruritus / Rapid / 3.0-3.0
influenza / Delayed / 2.0-2.0
urticaria / Rapid / 0.3-1.0

VTAMA

Rx

Topical aryl hydrocarbon receptor agonist
For treatment of plaque psoriasis in adults
Headaches, dermatologic reactions, and respiratory tract reactions have been reported by drug recipients

Apply a thin layer of cream to affected areas once daily.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Tapinarof products.

VTAMA Topical Cream: 1%

1 application per day topically.

1 application per day topically.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Tapinarof is a topical aryl hydrocarbon receptor (AhR) agonist. AhR is a ligand-dependent transcription factor that regulates gene expression in immune and epithelial cells, and thus, plays a part in maintaining skin homeostasis. The exact mechanism by which tapinarof exerts its therapeutic action in plaque psoriasis patients is unknown; however, potential mechanisms of action include:
Immunomodulation: In a T-cell polarization assay, tapinarof decreased T-cell expansion and T helper cell (Th17) differentiation and reduced the production of interleukin-17 (IL-17). In a mouse model of psoriasis, tapinarof downregulated inflammatory cytokine expression in skin tissue, including IL-17A and IL-17F.
Reduce oxidative stress: Tapinarof induces the AhR-nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor pathway, causing expression of antioxidant enzyme genes (e.g., nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 and heme oxygenase-1) to reduce reactive oxygen species (ROS). Tapinarof also directly scavenges ROS, including superoxide anions and hydroxyl radicals.
Skin barrier normalization: Tapinarof induces the expression of skin barrier genes related to keratinocyte differentiation, including filaggrin and loricrin.

Tapinarof is administered topically. According to in vitro data, approximately 99% of tapinarof binds to human plasma proteins. The drug is metabolized by the liver via multiple pathways including oxidation, glucuronidation, and sulfation.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

In a study evaluating the pharmacokinetics of tapinarof, 21 subjects with moderate to severe plaque psoriasis were administered topical tapinarof at a mean daily dose of 5.23 grams applied to a mean body surface area involvement of 27.2% (range: 21% to 46%). The plasma concentrations of tapinarof were below the quantifiable limits (BQL) of the assay (i.e., 50 pg/mL) in 68% of the samples. On Day 1, the mean maximum plasma concentration (Cmax) and exposure (AUC) were 0.9 +/- 1.4 ng/mL and 4.1 +/- 6.3 ng x hour/mL, respectively. On Day 29, the mean Cmax and AUC were 0.12 +/- 0.15 ng/mL and 0.61 +/- 0.65 ng x hour/mL, respectively. No accumulation was observed with repeated topical application.

Data regarding the use of tapinarof during human pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. In animal reproduction studies, no significant adverse effects were observed following subcutaneous administration of tapinarof to pregnant rats and rabbits during organogenesis at doses 268- and 16-times the maximum recommended human dose (MRHD), respectively. In a prenatal and postnatal development study in pregnant rats, tapinarof doses at 45-times the MRHD were associated with decreased fetal survival and viability that resulted in reduced litter sizes and decreased fetal weights. No tapinarof-related effects on fetal survival and viability were noted at 6-times the MRHD, and no effects on postnatal development, neurobehavioral performance, or reproductive performance of the offspring were noted at doses 268-times the MRHD; however, an increased incidence of skeletal variations (incomplete ossification of nasal bones) was noted. In an embryofetal development study in rabbits, meternal toxicity, evidenced by decreased maternal body weight and increased post-implantation loss (embryolethality) was observed at tapinarof subcutaneous injection doses of 30-times the MRHD; no fetal malformations were observed at this dose.

No data are available regarding the presence of tapinarof in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding, the mother's clinical need for tapinarof, and any potential adverse effects on the breast-fed infant from tapinarof or the underlying maternal condition.