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AKLIEF
Classes
Topical Retinoids for Acne
Administration
For topical administration only. Not for oral, ophthalmic, or intravaginal use.
Administered topically once daily, in the evening. Instruct patient to wash affected areas and pat dry, then apply a thin layer. Avoid contact with eyes, lips, paranasal creases, and mucous membranes.
One pump actuation should provide enough cream to cover the entire face (forehead, cheeks, nose, and chin). Two pump actuations should be enough to cover the upper back, including upper back, shoulders and chest; an additional pump may be used for middle and lower back if acne is present.
Do not apply to cuts, abrasions, or eczematous or sunburned skin.
Minimize exposure to ultraviolet rays (i.e., sunlight and sunlamps). Use sunscreen products and protective clothing when exposure cannot be avoided.
Avoid use of wax for hair removal on skin treated with trifarotene.
Adverse Reactions
edema / Delayed / 0-1.0
skin erosion / Delayed / 0-1.0
erythema / Early / 0-1.0
skin irritation / Early / 4.2-7.5
photosensitivity / Delayed / 2.6-5.5
pruritus / Rapid / 2.4-4.6
skin discoloration / Delayed / 0-1.0
acne vulgaris / Delayed / 0-1.0
rash / Early / 0-1.0
xerosis / Delayed / 0-1.0
Common Brand Names
AKLIEF
Dea Class
Rx
Description
Retinoic acid receptor (RAR) agonist with specific activity at the gamma subtype of RAR
For topical treatment of acne vulgaris in patients 9 years of age and older
Local cutaneous adverse reactions may occur, and are most severe within the first 4 weeks of treatment
Dosage And Indications
Apply a thin layer to affected areas once daily, in the evening, on clean and dry skin. Approximate doses are as follows: 1 pump actuation to cover the face (i.e., forehead, cheeks, nose, and chin) and 2 pump actuations to cover the upper trunk (i.e., reachable upper back, shoulders, and chest); 1 additional pump actuation may be needed to cover the middle and lower back.
Apply a thin layer to affected areas once daily, in the evening, on clean and dry skin. Approximate doses are as follows: 1 pump actuation to cover the face (i.e., forehead, cheeks, nose, and chin) and 2 pump actuations to cover the upper trunk (i.e., reachable upper back, shoulders, and chest); 1 additional pump actuation may be needed to cover the middle and lower back.
Dosing Considerations
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.
Drug Interactions
Adapalene; Benzoyl Peroxide: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Aminolevulinic Acid: (Moderate) Concomitant use of trifarotene and photosensitizing agents may cause additive phototoxicity; use together with caution. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Benzoyl Peroxide: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Benzoyl Peroxide; Clindamycin: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Benzoyl Peroxide; Erythromycin: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Benzoyl Peroxide; Sulfur: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Methoxsalen: (Moderate) Use methoxsalen and trifarotene together with caution; the risk of severe burns or phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Photosensitizing agents (topical): (Moderate) Concomitant use of trifarotene and photosensitizing agents may cause additive phototoxicity; use together with caution. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Porfimer: (Major) Avoid coadministration of porfimer with trifarotene due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like trifarotene may increase the risk of a photosensitivity reaction.
Salicylic Acid: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as salicylic acid.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as salicylic acid.
Tretinoin; Benzoyl Peroxide: (Moderate) Avoid concurrent use of trifarotene with other topical products that may dry or irritate the skin, such as benzoyl peroxide.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with trifarotene is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like trifarotene may increase the risk of a photosensitivity reaction.
How Supplied
AKLIEF Topical Cream: 0.005%
Maximum Dosage
Maximum dosage information is not available.
Maximum dosage information is not available.
Maximum dosage information is not available.
9 to 12 years: Maximum dosage information is not available.
1 to 8 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Mechanism Of Action
Trifarotene is a retinoic acid receptor (RAR) agonist, with specific activity at the gamma subtype of RAR. By binding to and activating RAR, trifarotene causes transcription of retinoic acid-responsive genes which are associated with various processes, including cell differentiation and mediation of inflammation. The exact mechanism by which trifarotene treats acne is uncertain; however, topical retinoids (such as trifarotene) are known to influence proliferation and differentiation of cells, increase follicular epithelial turnover, and accelerate the shedding of corneocytes. These actions result in an expulsion of mature comedones and suppression of microcomedo formation. Additionally, the restoration of normal cornification produces an aerobic environment that is inhospitable to the growth of Propionibacterium acnes.
Pharmacokinetics
Trifarotene is administered topically to the skin. Once absorbed into systemic circulation, the drug is approximately 99.9% bound to human plasma proteins. Metabolism occurs via the hepatic enzymes CYP2C9, CYP3A4, CYP2C8, and to a lesser extent CYP2B6 (in vitro). Trifarotene is primarily excreted by the feces and has a terminal half-life ranging from 2 to 9 hours.
Affected cytochrome P450 isoenzymes and transporters: none
Trifarotene is minimally absorbed through human skin. In a pharmacokinetic study, quantifiable systemic drug concentrations were observed in only 7 of 19 adults who received 2 weeks of once daily treatment. The steady-state maximum drug concentration (Cmax) ranged from below the limits of quantification (less than 5 pg/mL) to 10 pg/mL, and drug exposure (AUC) ranged from 75 to 104 pg x hour/mL. Based on this data, no drug accumulation is expected with long-term use.
Pregnancy And Lactation
Data from clinical trials have not associated the use of trifarotene during human pregnancy with an increased risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. However, there are case reports of major birth defects in pregnant women exposed to other topical retinoids, but these case reports do not establish a pattern or association with retinoid-related embryopathy. In animal studies, adverse fetal effects (i.e., fetal deaths and external, visceral and skeletal malformations) were observed in the off-spring of pregnant rats and rabbits who received oral dose of trifarotene during organogenesis that resulted in systemic exposures more than 800-times the systemic exposures at the maximum recommended human dose (MRHD) of the topical cream.
There are no data regarding the presence of trifarotene in human breast milk, effects on the nursing infant, or effects on milk production. Trifarotene is poorly absorbed through human intact skin; however, it is possible that applying large amounts of the cream could result in enough systemic absorption to produce detectable quantities in human milk. To minimize potential drug exposure to the breast-fed infant, instruct lactating women to use the smallest amount of drug possible while breast-feeding (i.e., smallest area of skin for the shortest duration). Also, advise breast-feeding women not to apply directly to the nipple and areola area. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.