trifarotene (Rx)

>10%

Mild dryness, face (39%)

Mild scaling, face (37.5%)

Mild stinging/burning, face (36.5%)

Mild dryness, trunk (32.9%)

Mild erythema, face (30.6%)

Moderate dryness, face (29.7%)

Mild scaling, trunk (29.7%)

Moderate erythema, face (28.4%)

Moderate scaling, face (27.1%)

Mild erythema, trunk (26.5%)

Mild stinging/burning, trunk (26.1%)

Moderate dryness, trunk (16.1%)

Moderate erythema, trunk (18.7%)

Moderate scaling, trunk (13.7%)

Moderate stinging/burning, face (20.6%)

Moderate stinging/burning, trunk (10.9%)

1-10%

Application site irritation (4.2-7.5%)

Severe erythema, face (6.2%)

Severe stinging/burning, face (5.9%)

Sunburn (2.6-5.5%)

Severe erythema, trunk (5.2%)

Severe scaling, face (4.9%)

Severe dryness, face (4.8%)

Severe scaling, trunk (4.3%)

Application site pruritus (2.4-4.6%)

Severe dryness, trunk (1.8%)

Severe scaling, trunk (1.7%)

Contraindications

None

Cautions

Minimize unprotected exposure to ultraviolet rays (including sunlight and sunlamps) during treatment; exercise caution in patients who normally experience high levels of sun exposure and those with inherent sensitivity to sun; use sunscreen products and protective clothing over treated areas when exposure cannot be avoided

Skin irritation

• 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
• Advise to use a moisturizer, reduce the frequency of application, or suspend use temporarily
• If severe reactions persist, consider discontinuing treatment

Pregnancy

Available data from clinical trials with use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

There are case reports of major birth defects similar to those seen in fetuses exposed to oral retinoids in pregnant women exposed to other topical retinoids, but these reports do not establish a pattern or association with retinoid-related embryopathy

Animal data

• In animal reproduction studies, oral doses of trifarotene administered to pregnant rats and rabbits during organogenesis that resulted in systemic exposures more than 800 times the systemic exposure at the maximum recommended human dose (MRHD) of topical cream resulted in adverse fetal effects, including fetal deaths and external, visceral, and skeletal malformations

Lactation

There are no data on the presence of trifarotene in human milk, the effects on the breastfed infant, or the effects on milk production

Trifarotene was present in rat milk with oral administration of the drug

When present in animal milk, it is likely that the drug will be present in human milk; topical administration of large amounts of trifarotene may result in sufficient systemic absorption to produce detectable quantities in human milk

Consider the developmental and health benefits of breastfeeding, along with the mother’s clinical need and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Clinical considerations

• To minimize potential exposure to the breastfed infant via breastmilk, use on the smallest area of skin and for the shortest duration possible while breastfeeding
• Advise breastfeeding women not to apply directly to the nipple and areola to avoid direct infant exposure

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

An agonist of retinoic acid receptors (RARs), with particular activity at the gamma subtype of RAR

Stimulation of RAR results in modulation of target genes that are associated with various processes, including cell differentiation and mediation of inflammation

Exact process by which trifarotene ameliorates acne is unknown

Absorption

Peak plasma concentration (steady-state): <10 pg/mL (adults); 5-9 pg/mL (children and adolescents)

AUC: 70-104 pg·hr/mL (adults); 5-9 pg·hr/mL (children and adolescents)

Steady-state achieved in children and adolescents within 2 weeks of topical administration

Distribution

Protein bound (99.9%)

Metabolism

Primarily metabolized by CYP2C9, CYP3A4, CYP2C8, and to a lesser extent by CYP2B6

Elimination

Excretion: Feces

Topical Administration

Topical use only; not for oral, ophthalmic, or intravaginal use

One pump actuation should be enough to cover the face (ie, forehead, cheeks, nose, and chin)

Two actuations of the pump should be enough to cover the upper trunk (ie, reachable upper back, shoulders, and chest)

May use 1 additional pump actuation for middle and lower back if acne is present

Use of a moisturizer is recommended as frequently as needed from the start of treatment

Avoid contact with the eyes, lips, paranasal creases, and mucous membranes

Avoid application to cuts, abrasions, or eczematous or sunburned skin

Avoid use of “waxing” as a depilatory method on treated skin

Storage

Store at 20-25ºC (68-77ºF) with excursions permitted to 15-30ºC (59- 86ºF)

Keep away from heat

Keep out of reach of children