New Release: Alpha testing version has been released.

Trifarotene

D10A - Anti-acne preparations for topical use ATC D10AD06 Small molecule approved 2019 Topical Natural product

JFDA label: AKLIEF 50mcg/g Cream

Mechanism of Action

Agonist of Retinoic acid receptor gamma — Retinoic acid receptor gamma agonist

TargetActionGene / class
Retinoic acid receptor gamma efficacy AGONIST RARG

Indications

Approved

  • Acne Vulgaris — acne

Off-label

  • Ichthyosis, Lamellar

Contraindications

Source: openFDA

  • None None ( 4 ) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Skin and subcutaneous tissue disorders (1)

Common For The Entire Trial Were Application Site Pruritus

General disorders and administration site conditions (2)

Common And Sunburn · Application Site Irritation

Dosing

Source: openFDA

Apply a thin layer of AKLIEF Cream to the affected areas once daily, in the evening, on clean and dry skin. One pump actuation should be enough to cover the face (i.e., forehead, cheeks, nose, and chin). Two actuations of the pump should be enough to cover the upper trunk (i.e., reachable upper back, shoulders and chest). One additional pump actuation may be used for middle and lower back if acne is present. The use of a moisturizer is recommended as frequently as needed from the initiation of treatment. Avoid contact with the eyes, lips, paranasal creases, mucous membranes. AKLIEF Cream is for topical use only. Not for oral, ophthalmic, or intravaginal use. For topical use only. Not for oral, ophthalmic or intravaginal use. Apply a thin layer of AKLIEF Cream to the affected areas of the face and/or trunk once a day, in the evening, on clean and dry skin. Avoid contact with the eyes, lips, paranasal creases, and mucous membranes. ( 2 )

Warnings & Precautions

Source: openFDA

Warnings & Precautions

Skin irritation: Erythema, scaling, dryness, and stinging/burning may be experienced with use of AKLIEF Cream. Use a moisturizer from the initiation of treatment, and, if appropriate, reduce the frequency of application of AKLIEF Cream, suspend or discontinue use. ( 5.1 ) Ultraviolet Light and Environmental Exposure: Minimize exposure to sunlight and sunlamps. Use sunscreen and protective clothing over treated areas when exposure cannot be avoided. ( 5.2 )

Skin Irritation Patients using AKLIEF Cream may experience erythema, s

Skin Irritation Patients using AKLIEF Cream may experience erythema, scaling, dryness, and stinging/burning. Maximum severity of these reactions typically occurred within the first 4 weeks of treatment, and severity decreased with continued use of the medication. Depending upon the severity of these adverse reactions, instruct patients to use a moisturizer, reduce the frequency of application of AKLIEF Cream, or suspend use temporarily. If severe reactions persist the treatment may be discontinued. Avoid application of AKLIEF Cream to cuts, abrasions, or eczematous or sunburned skin. Use of “waxing” as a depilatory method should be avoided on skin treated with AKLIEF Cream.

Ultraviolet Light and Environmental Exposure Minimize unprotected expo

Ultraviolet Light and Environmental Exposure Minimize unprotected exposure to ultraviolet rays (including sunlight and sunlamps) during treatment with AKLIEF Cream. Warn patients who normally experience high levels of sun exposure and those with inherent sensitivity to sun to exercise caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided.

Pregnancy & Lactation

Lactation

Probably Compatible Hale L2

Because it is poorly absorbed after topical application, it is a low risk to the nursing infant.

Chemistry & Properties

2D structure
FormulaC29H33NO4
Molecular weight459.59 g/mol
IUPAC name4-[3-(3-tert-butyl-4-pyrrolidin-1-ylphenyl)-4-(2-hydroxyethoxy)phenyl]benzoic acid
CAS895542-09-3
PubChem CID11518241
InChIKeyMFBCDACCJCDGBA-UHFFFAOYSA-N
logP5.99 (XLogP 6.3)
Polar surface area70.0 Ų
H-bond acceptors / donors4 / 2
Drug-likeness (QED)0.45
Lipinski violations1
SMILESCC(C)(C)c1cc(-c2cc(-c3ccc(C(=O)O)cc3)ccc2OCCO)ccc1N1CCCC1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability70.0%
Half-life1.225 h
Volume of distribution0.416 L/kg
Protein binding98.3%
BBB penetrantNo

Enzyme interactions

EnzymeRoleDetail
CYP2B6Inhibitor
CYP2B6Substrate
CYP2C19Inhibitor
CYP2C8Inhibitor
CYP3A4Substrate

Receptor binding (top 3)

TargetActionAffinity
Retinoic acid receptor-&gamma; (RARG) Agonist pEC50 8.1
Retinoic acid receptor-&beta; (RARB) Agonist pEC50 6.9
Retinoic acid receptor-&alpha; (RARA) Agonist pEC50 6.3

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (1)

BrandForm / strengthPackAgentCitizen (JOD)
AKLIEF 50mcg/g Cream Cream 50 mcg/1 g 75 GM Pump IBN CINA DRUG STORE 32.560