Trifarotene - Uses, Efficacy, Side Effects, Warnings, and Precautions

Overview

Trifarotene sorts with the class of medications called retinoids, more specifically with the fourth-generation selective Retinoid Acid Receptor (RAR)-r. In the United States, Trifarotene is indicated for its topical treatment of acne vulgaris in individuals of nine years and older. It is available as a topical cream that comes in a pump bottle. So, this medicine helps in clearing acne by keeping the skin pores clean and free from clogs.

Trifarotene was once granted as an orphan drug (a drug used to treat specific rare conditions) for congenital ichthyosis treatment by the European Medicine Agency (EMA) and the Food and Drug Administration (FDA). Then, it received approval for medicinal use in October 2019 in the United States and November 2019 in Canada. In December 2019, decentralized approval was given for its labeling and package leaflet information for about 16 European countries.

Uses of Trifarotene:

• Acne: Trifarotene is chiefly used to treat acne or acne vulgaris. Acne vulgaris is an inflammatory skin condition of the pilosebaceous unit that progresses a long-term course and is self-limiting. Acne vulgaris is the formation of papules, pustules, nodules, comedones, or cysts occurring as a result of the blockage and inflammation of pilosebaceous units. The topical medication Trifarotene might decrease the number, appearance, and severity of acne pimples.

• Acne Symptoms: To a certain extent, Trifarotene is also used in the treatment of acne symptoms such as blackheads and whiteheads.

• Off-Label Uses: Trifarotene is currently being studied in several clinical trials for the management of lamellar ichthyosis and early cutaneous T-cell lymphoma.

How Does Trifarotene Work?

Trifarotene medication is used to treat acne concerns. It treats all forms of acne, including blackheads, whiteheads, and pimples. It might diminish the number, size, and severity of acne pimples. It also increases the speed of the healing process of acne pimples in the development stage. Trifarotene sorts with a class of medications called retinoids. It works by influencing and blocking the growth of the cells involved in acne. As a result, there can be a significant reduction in swelling and inflammation. Subsequently, Trifarotene helps with the overall healing process of acne pimples.

Trifarotene and Its Form:

• It is available as topical cream with a strength of 0.005 percent of Trifarotene.

• Trifarotene cream comes in three packages, including 1.07 ounces, 1.61 ounces, and 2.68 ounces pump.

• Each gram of Trifarotene cream contains about 50 mcg of Trifarotene on the basis of white cream.

Dosage and Administration:

Trifarotene comes in a package of pump bottles. Trifarotene cream is only for topical use. So, it is not meant for oral, intravaginal, or ophthalmic use. It is generally recommended to apply a thin layer of Trifarotene cream on the affected areas of clean and pat dry skin once in the evening.

• One pump actuation can be sufficient to cover the face.

• Two pump actuation can be sufficient to cover the areas of the upper trunk, including the shoulders, upper back, and chest.

• One additional pump actuation can be required in addition to two pump actuation for the regions of the middle and lower back if there is acne.

For Patients,

What Factors Contribute to the Progression of Acne?

Acne or acne vulgaris is a long-term inflammatory skin condition that results when dead skin cells or oil clog the hair follicles. Acne has certain typical features, including whiteheads, blackheads, oily skin, pimples, open enlarged pores, and potential scarring. Though It can occur in any part of the skin, it primarily affects skin possessing an increased number of oil glands to a certain extent. So, it generally affects the face, the upper region of the chest, and the back. Acne is a profound concern among youngsters since its appearance can cause one to have a lack of confidence, fear, anxiety, low self-esteem, and other mood declines. It can even lead to depression and suicidal thoughts in severe extreme cases.

A mild or recently formed acne can progress into more severe degrees or forms. So, starting a few pimples would worsen into widespread blackheads and deep or painful acne. As the inflammation proceeds, the acne progresses by breakage of the wall of the widened pores resulting in the spread of the inflammation and exudation of pus. Hence, the popping of pimples or the constant rubbing of hair over the face is not advisable since such practices would irritate acne, inducing it to worsen further. Acne might leave a scar after the healing process if it worsens once.

Potential Causes of Acne Vulgaris:

Acne is formed as a result of the plugging of oil or dead cells in the hair follicles. There are a wide variety of causative factors attributing to the development of acne.

• Excess oil production.

• Bacterial infection.

• Inflammation.

• Hormones- rise in the hormone levels in the males and females during puberty results in enlargement and high production of sebum from the sebaceous gland under the skin.

• Hereditary concerns.

• Oil-based cosmetic products.

• Medications.

• Diet.

• Stress and anxiety.

Is Acne Curable?

Acne has no significant cure. Also, there is no way of preventing acne. Nevertheless, it can be successfully managed with treatments and medications. It might take several months or years to completely get clear of the acne issues. The treatment regimen prescribed by the doctors depends upon the age, type, and severity of the acne. The treatment options include oral medications and topical creams primarily. It includes anti-inflammatory, amniotic, topical antiseptics, and vitamin A derivatives. Doctors may also prescribe other treatments for severe acne and its scarring.

How Trifarotene Helps Treat Acne?

Trifarotene sorts with a class of medications called retinoids (vitamin A derivatives). This medicine is used to treat acne or acne vulgaris in adults and children of nine years and older. Trifarotene comes as a topical cream that is meant to be applied over the affected skin areas. This medication works by promoting the peeling process of affected skin regions, unclogging the pores, and preventing new pimples from their formation underneath the skin.

How to Use Trifarotene Cream?

Trifarotene is available as a cream to be applied to the skin. The dosing, frequency, and length of the Trifarotene therapy depend upon the type and severity of the condition of acne vulgaris. Follow conscientiously the directions addressed on the prescription label and according to the information provided by the healthcare professionals. So, one should use it exactly as the doctors direction. Do not use in less or more frequencies than advised. Doing it more often could cause certain degrees of skin irritation. Trifarotene cream is generally advised to use for several weeks or months to see the desired results.

Things to Consider and Inform the Doctor:

Here include certain things to inform the doctor before one starts using Trifarotene topical cream. The doctor might alter the dosage and frequency, taking risks and efficacy into consideration.

• Tell the doctor if one is allergic to Trifarotene or any vitamin-A-based medicines such as Tretinoin (retinoids).

• Talk to the doctor about the ingredients of the prescribed cream and convey if one has any past history of allergy to the included inactive and active ingredients.

• Tell the doctor if there are any general or underlying medical illnesses. Be certain to inform about the prevailing skin conditions, particularly eczema. Eczema is a skin condition that causes the skin to become itchy, inflamed, dry, and bumpy since the skin’s barrier function is weakened.

• Trifarotene medication can make one more sensitive to ultraviolet (UV) rays. So, inform the doctor if one is having high sun exposure every day or has instinctive sun sensitivity and get the protective measures.

• Inform the doctor and use it cautiously if one has used skin products constituting Resorcinol, Salicylic acid, or Sulfur in recent times.

• Convey the doctor if one is pregnant or has any further plans for pregnancy. The medication is prescribed after considering the possible risks and benefits.

• Tell the doctor if one is breastfeeding; the doctors might advise not to apply the cream on the areolas or nipples.

Directions to Use Trifarotene Topical Cream:

• Trifarotene topical cream comes in a pump bottle.

• The essential thing before applying is to wash the hands thoroughly with soap or a cleansing agent.

• Firstly, wash or cleanse the area to be treated with Trifarotene topical cream. Then, pat dry.

• Apply a thin layer of the cream to the face.

• It can also be used on the chest, back, arms, and shoulders.

• It is to be applied once in the evening on a daily basis.

• Avoid applying or contact with lips, eyes, nasolabial folds, vaginal area, and mucous membranes. If any contact happens, rinse the area well with water.

• One pump actuation is more than enough the covering the face, while two to three pump actuation can be used to cover the other areas of the upper trunk, middle back, and lower back if acne is seen.

• One should moisturize subsequently with this cream right from the initiation of the Trifarotene treatment.

• Do not use it more frequently or in a large quantity than the doctor’s recommendation.

Important Considerations:

• It is not recommended to use Trifarotene cream in conjugation with other medicated products, non-medicated cosmetics, alcohol-contains cleansers, abrasive products, and other irritants.

• One should avoid direct sun exposure. Also, consider using protective clothing and effective sunscreen when outdoors is unavoidable. Inform the doctor rightly if one gets sunburn or skin blisters.

• Moisturiser is a must with Trifarotene cream, so never fail to apply moisturizer cream over the treated areas.

• One should avoid waxing, electrolysis, and chemical depilatory methods for hair removal on the Trifarotene treated areas.

Important Note:

Do not apply Trifarotene cream in scraped, cut, irritated, sunburned and eczematous areas.

In Case of Missed Dose:

If one misses the dose, apply the missed dose of Trifarotene cream as soon as one has the thought. But, if it is nearly the time of the subsequent dose, then skip the missed one and continue with the regular dosing schedule. Be cautious that one should not apply extra Trifarotene cream to compensate for the missed dose.

In Case of Emergency:

Overdose of Trifarotene does not cause any significant harm since it is a topical agent. But, if one swallows Trifarotene cream, reach out to the emergency services or other healthcare helplines.

Storage of Trifarotene Cream:

Store the Trifarotene medication in an airtight closed container keeping it at room temperature away from moisture and heat. So, the medicine is to be stored at a temperature between 20 and 25 degree Celsius. Trifarotene medication is quite flammable, so avoid its exposure to fire, flame, smoke, and heat. Subsequently, it is essential to keep any medication away from the reach of children and pets.

Dispensal Method of Trifarotene Cream:

One should safely get rid of unused and expired medications. Reach out to the community disposal technique or any take-back program nearing the location for the disposal of Trifarotene cream. In case one cannot reach such programs, then the medication can be disposed of as per the directions available on the label or package.

What Are the Side Effects of Trifarotene?

Trifarotene induces certain common reactions during the first four weeks of the treatment. These effects can be reduced with the continued usage of cream. Moisturiser is required along with Trifarotene cream to reduce these side effects. Tell the doctor or other healthcare providers if those reactions last or get worse with time. The doctors might recommend reduced dosage or discontinuation of treatment either temporarily or permanently. The common reaction occurring with Trifarotene cream in the first four weeks include:

• Skin redness.

• Scaling.

• Itching.

• Mild stinging or burning.

• Dryness.

Serious Side Effects:

The doctors prescribe the Trifarotene medication considering the potential risks and benefits for every individual. So, serious side effects are unlikely or less likely to occur with this cream. Though, in any case, inform the healthcare providers straight away if one encounters any of the following serious side effects.

• Redness or irritation in the skin.

• Eye redness.

• Conjunctivitis (red and watery eyes).

• Skin discoloration.

• Eyelid swelling.

Allergic Reaction:

Serious allergic reactions associated with Trifarotene cream are very rare. Nevertheless, one should seek professional help rightly if any of the following symptoms are noticed.

• Rashes.

• Itching.

• Swelling of face, tongue, or throat.

• Difficulty breathing.

• Severe dizziness.

For Doctors,

Clinical Data of Trifarotene:

Drug Name: Trifarotene.

Other Names: CD5789.

Drug Class: Retinoids or skin and mucous membrane agents.

Route of Administration: Topical.

Chemical Formula: C29H33NO4.

Molecular Mass: 459.586 g.mol-1.

Indication:

The drug Trifarotene is indicated for the acne vulgaris treatment in individuals of nine years and above.

Associated condition:

• Acne vulgaris.

Pharmacology of Trifarotene

Pharmacodynamics:

Trifarotene exerts its action through agnostic at the retinoid receptors. These receptors function to modify the DNA transcription that culminates in a consequent modulation of the expression of distinct genes involved in the pathogenesis of acne.

Trifarotene should not be applied for certain other concerns like abrasions, cut, and otherwise irritated skin since the drug might be attributed to skin irritations. Individuals using this topical cream should avoid excess degrees of sun exposure because it may induce photosensitivity reactions. So it is advisable to use either sunscreen or protective clothing in case exposure is inevitable.

Mechanism of Action:

Trifarotene is a significantly potent and exacting agonist of the Retinoid Acid Receptor-r (RAR-r). It possesses minimal activity at RAR-a and RAR-B while no activity at retinoid X receptors. The agonism potency of the drug at retinoid acid receptors culminates in dimerization, where the subsequent receptor-ligand dimer binds to DNA regulatory sequences of distinct types in the aspects of retinoid-responsible genes. Binding to these regions induces the downstream modification of gene expression, whereas this is the basic mechanism by which Trifarotene employs its effect of anti-inflammatory, comedolytic, and depigmentation.

Trifarotene exerts its action similar to other retinoids. Trifarotene fundamentally affects the number of expressed genes associated with certain mechanisms, including retinoid metabolism, epidermal response to stimulus (stress), and epidermal differentiation and proliferation. Trifarotene also possesses another unique way of approach, which is not usually observed in other retinoids. So, Trifarotene has been known to influence retinoid-mediated pathways concerning skin hydration, cell adhesion, and proteolysis.

Absorption:

• Trifarotene is known to possess selective action, and systemic absorption is generally unquantifiable in most cases.

• So, the systemic absorption is minimal.

• According to a pharmacokinetic study including 19 subjects, the systemic concentrations showed quantifiable steady-state C max, ranging from less than 5 pg/mL to 10 pg/mL. The AUC was found to be within the range of 75 to 104 pg.h/mL.

Distribution:

• The protein binding of Tritfaratene to plasma is about 99.9 percent.

Metabolism:

• Trifarotene undergoes well and rapid metabolism in human hepatocytes.

• Its detected half-life is about greater than 24 hours in human keratinocytes, whereas nearly five minutes in human liver microsomes.

• The metabolism is chiefly catalyzed by CYP2C8, CYP2C9, and CYP3A4. It is also catalyzed by CYP2B6 to a lesser extent.

Elimination:

• Trifarotene is chiefly eliminated in the feces.

• The terminal half-life lies between two and nine hours.

Toxicity:

• Trifarotene on standard doses does not possess any risk of carcinogenesis.

• The systemic exposure after both oral and topical administration in mice was about 162 times greater than with humans (maximal human dose).

• Addedly, the systemic concentrations did not culminate in notable carcinogenic effects.

Adverse Reactions:

The most common adverse reactions of Trifarotene topical application include the following.

Adversities (1 to 10 percent)

• Application site pruritus.

• Application site irritation.

• Sunburn.

• Severe erythema.

• Severe degrees of burning, scaling, dryness, or erythema.

Adversities (greater than 10 percent)

This involves mild to moderate degrees of the following reactions.

• Dryness.

• Scaling.

• Stinging.

• Dryness.

• Erythema

What Are the Cautions and Warnings for Trifarotene?

1. Ultraviolet Light and Environmental Exposure:

• As Trifarotene can significantly induce photosensitivity reactions, so unprotected sun exposure should be minimized during Trifarotene treatment.

• Address extra caution in individuals who generally are prone to high degrees of sun exposure and those individuals having inherent sun sensitivity.

• When exposure is inevitable, advise patients to use sunscreen and protective clothing to cover the Trifarotene-treated regions.

2. Skin Irritation:

• Individuals with Trifarotene treatment might encounter scaling, dryness, stinging, burning, or erythema reactions. Also, the heightened severity of these reactions is generally developed in the first four weeks of Triafarotene treatment.

• So, subsequent application of moisturizer or reduction of the frequency of Trifarotene application should be considered according to the severity of the reactions.

• Discontinuation of Trifarotene treatment should be considered if the severe reactions still persist.

3. Others:

• Trifarotene application is not recommended to use for any abrasion, cut, sunburned, or eczematous areas of skin.

• The depilatory method of waxing should be avoided in the Trifarotene-treated areas.

Drug Interactions of Trifarotene:

The topical Trifarotene is known to interact with 12 other medications. Of all interactions, eleven were moderate, and one was major. In contrast, Trifarotene shows no minor interactions. The following are the drugs that can potentially interact with Trifarotene.

• Aminolevulinic acid.

• Topical Aminolevulinic acid.

• Topical Clascoterone.

• Topical Benzoyl peroxide.

• Isotretinoin.

• Methoxsalen.

• Porfimer.

• Methyl aminolevulinate- topical.

• Topical Sulfur.

• Verteporfin.

• Topical Salicylic acid.

• Topical Resorcinol.

How Far Have Clinical Trials Proven the Efficacy of the Drug Trifarotene?

There were several clinical trials experimented on to prove and validate the safety and efficacy profile of Trifarotene. One clinical trial experimented on the long-term safety and efficacy of the topical Trifarotene of 50 mu/g cream in facial and truncal acne. So, here it was, a multicentre and open-label 52-week study in which the individuals with moderate degrees of facial and truncal acne received topical Trifarotene cream. After the completion of the study, the outcomes were absolutely favorable, showing that Trifarotene was safe, effective, and well-tolerated in the case of moderate facial and truncal acne. The adverse events during the intervention were reported in about 12.6 percent of individuals. Nevertheless, these were mostly cutaneous and possibly happened in the first three months of treatment. Local irritation increased in the first week in the face, and that has diminished in the subsequent weeks.