Tapinarof is a topical aryl hydrocarbon receptor (AhR) agonist approved for the treatment of plaque psoriasis in adults. The drug is administered as a thin film once daily to the affected areas. Treatment with tapinarof has been associated with the development of headaches, dermatologic reactions (e.g., folliculitis, dermatitis, pruritus, urticaria), and respiratory tract reactions (e.g., congestion, infection, pharyngitis, rhinorrhea).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
Cream/Ointment/Lotion Formulations
-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.
Dermatologic adverse reactions reported by patients receiving treatment with tapinarof during clinical trials include folliculitis (20%), contact dermatitis and rash (7%), urticaria (0.3% to 1%), and drug eruption (0.7%). Pruritis, which included application site pruritis, generalized pruritus, and genital pruritis, was reported in 3% of patients.
During the tapinarof clinical trials, 11% of drug recipients experienced respiratory tract adverse reactions, including nasal congestion, pharyngitis, respiratory tract infection, rhinorrhea, and sinus congestion. Additionally, 2% of patients reported influenza or influenza-like illness.
Headaches, including migraine and tension headache, were reported by 4% of patients who received treatment with tapinarof during the clinical trials.
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.
For the treatment of plaque psoriasis:
Topical dosage:
Adults: Apply a thin layer of cream to affected areas once daily.
Maximum Dosage Limits:
-Adults
1 application per day topically.
-Geriatric
1 application per day topically.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Tapinarof products.
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
-Route-Specific Pharmacokinetics
Topical Route
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.