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Trifarotene

Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: 4-[3-(3-tert-butyl-4-pyrrolidin-1-ylphenyl)-4-(2-hydroxyethoxy)phenyl]benzoic acid
Molecular Formula: C29H33NO4
CAS Number: 895542-09-3
Brands: Aklief

Medically reviewed by Drugs.com. Last updated on Oct 28, 2019.

Introduction

Trifarotene is a skin or mucous membrane agent.

Uses for Trifarotene

Trifarotene has the following uses:

Trifarotene cream is a retinoid indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.1

Trifarotene Dosage and Administration

General

Trifarotene is available in the following dosage form(s) and strength(s):

Cream: 0.005% trifarotene.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration
  • For topical use only. Not for oral, ophthalmic, or intravaginal use.1

  • Apply a thin layer of trifarotene cream to the affected areas once daily, in the evening, on clean and dry skin.1 Avoid contact with the eyes, lips, paranasal creases, mucous membranes.1

  • One pump actuation should be enough to cover the face (i.e., forehead, cheeks, nose, and chin).1

  • 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.1

  • The use of a moisturizer is recommended as frequently as needed from the initiation of treatment. 1

Adults

Dosage and Administration
  • For topical use only. Not for oral, ophthalmic or intravaginal use. 1

  • Apply a thin layer of trifarotene cream to the affected areas once daily, in the evening, on clean and dry skin. Avoid contact with the eyes, lips, paranasal creases, and mucous membranes.1

  • One pump actuation should be enough to cover the face (i.e., forehead, cheeks, nose, and chin).1

  • 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.1

  • The use of a moisturizer is recommended as frequently as needed from the initiation of treatment. 1

Cautions for Trifarotene

Contraindications

None.1

Warnings/Precautions

Skin Irritation

Patients using trifarotene 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 trifarotene cream, or suspend use temporarily. If severe reactions persist the treatment may be discontinued.1

Avoid application of trifarotene to cuts, abrasions, or eczematous or sunburned skin. Use of “waxing” as a depilatory method should be avoided on skin treated with trifarotene cream.1

Ultraviolet Light And Environmental Exposure

Minimize unprotected exposure to ultraviolet rays (including sunlight and sunlamps) during treatment with trifarotene. 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.1

Specific Populations

Pregnancy

Risk Summary: Available data from clinical trials with trifarotene cream 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 case reports do not establish a pattern or association with retinoid-related embryopathy.1

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 trifarotene cream resulted in adverse fetal effects, including fetal deaths and external, visceral, and skeletal malformations. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

Animal Data: Oral administration of trifarotene to pregnant rats during the period of organogenesis at doses that resulted in systemic exposures greater than 1600 times those in humans at the MRHD of trifarotene cream resulted in adverse fetal effects, including fetal deaths, reduced mean fetal weight, and external, visceral, and skeletal malformations.1

Oral administration of trifarotene to pregnant rabbits during the period of organogenesis at doses that resulted in systemic exposures at least 800 times those in humans at the MRHD of trifarotene cream resulted in adverse fetal effects, including defects of the tail, limbs, urogenital organs, and vertebral column.1

Trifarotene administered orally to female rats from gestation Day 6 to lactation Day 20, at doses that resulted in systemic exposures up to 594 times those in humans at the MRHD of trifarotene cream, had no effect on maternal function or behavior, including gestation, delivery, pup-rearing, lactation and nursing, or survival or development of pups. There were no effects of maternal treatment on behavior, learning, memory, or reproductive function of pups.1

Lactation

Risk Summary: There are no data on the presence of trifarotene in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, trifarotene was present in rat milk with oral administration of the drug. When a drug is present in animal milk, it is likely that the drug will be present in human milk. It is possible that topical administration of large amounts of trifarotene could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for trifarotene cream and any potential adverse effects on the breastfed infant from trifarotene cream or from the underlying maternal condition.1

Clinical Considerations: To minimize potential exposure to the breastfed infant via breastmilk, use trifarotene cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply trifarotene cream directly to the nipple and areola to avoid direct infant exposure.1

Pediatric Use

Safety and effectiveness of trifarotene cream for the topical treatment of acne vulgaris have been established in pediatric patients age 9 years to 17 years based on evidence from well-controlled clinical trials, a long-term safety trial, and a pharmacokinetic trial. A total of 897 pediatric subjects aged 9 to 17 years received trifarotene cream in the clinical trials.1

Safety and effectiveness of trifarotene cream have not been established in pediatric subjects under the age of 9 years.1

Geriatric Use

Clinical trials of trifarotene cream did not include any subjects aged 65 years and over to determine whether they respond differently than younger subjects.1 1

Common Adverse Effects

Most common adverse reactions (incidence ≥ 1%) in patients treated with trifarotene cream were application site irritation, application site pruritus, and sunburn. 1 1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Topical application of trifarotene cream is not expected to affect the circulating concentrations of oral hormonal contraceptives containing ethinyl estradiol and levonorgestrel.1

Actions

Mechanism of Action

Trifarotene is an agonist of retinoic acid receptors (RAR), with particular activity at the gamma subtype of RAR. Stimulation of RAR results in modulation of target genes which are associated with various processes, including cell differentiation and mediation of inflammation. The exact process by which trifarotene ameliorates acne is unknown.1

Advice to Patients

Patient Counseling Information

See FDA-approved patient labeling (Patient Information).1

Cleanse the area to be treated; pat dry. Apply trifarotene cream as a thin layer once daily in the evening to the face, avoiding the eyes, lips, nasolabial folds, and mucous membranes. A thin layer of trifarotene cream may also be applied to the chest, shoulders, and back.1

Avoid applying trifarotene cream to damaged skin (such as cuts, abrasions), eczematous areas, and sunburned skin.1

Reduce the risk of such irritation, use a moisturizer from the start of treatment, and, if appropriate, reduce the frequency of application of trifarotene cream or suspend use temporarily. Trifarotene cream may cause irritation such as erythema, scaling, dryness, and stinging or burning.1

Minimize exposure to sunlight, including sunlamps and phototherapy devices.1

Use sunscreen products and protective apparel (e.g., hat) over treated areas when exposure to sunlight cannot be avoided.1

Avoid concomitant use of other potentially irritating topical products (medicated or not).1

Use trifarotene cream on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply trifarotene cream directly to the nipple and areola to avoid direct infant exposure.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Trifarotene

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

0.005% (30, 45, and 75 g)

Aklief

Galderma Laboratories L.P.

AHFS Drug Information. © Copyright 2021, Selected Revisions October 28, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Galderma Laboratories, L.P. AKLIEF (trifarotene) TOPICAL prescribing information. 2019 Oct. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=62d910db-85a6-4696-b69b-4bd2f3080cfc