Adapalene is a third-generation topical

retinoid The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout t ...

primarily used in the treatment of mild-moderate

acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

, and is also used

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although m ...

to treat

keratosis pilaris Keratosis pilaris (KP; also follicular keratosis, lichen pilaris, or colloquially chicken skin) is a common, autosomal- dominant, genetic condition of the skin's hair follicles characterized by the appearance of possibly itchy, small, goosefle ...

as well as other skin conditions. Studies have found adapalene is as effective as other retinoids, while causing less irritation. It also has several advantages over other retinoids. The adapalene molecule is more stable compared to

tretinoin Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth f ...

and

tazarotene Tazarotene, sold under the brand name Tazorac, among others, is a third-generation prescription topical retinoid. It is primarily used for the treatment of plaque psoriasis and acne. Tazarotene is also used as a therapeutic for photoaged and p ...

, which leads to less concern for photodegradation. It is also chemically more stable compared to the other two retinoids, allowing it to be used in combination with

benzoyl peroxide Benzoyl peroxide is a chemical compound (specifically, an organic peroxide) with structural formula , often abbreviated as (BzO)2. In terms of its structure, the molecule can be described as two benzoyl (, Bz) groups connected by a peroxide () ...

. Due to its effects on keratinocyte proliferation and differentiation, adapalene is superior to tretinoin for the treatment of comedonal acne and is often used as a first-line agent. The

Swiss Swiss may refer to: * the adjectival form of Switzerland * Swiss people Places * Swiss, Missouri * Swiss, North Carolina *Swiss, West Virginia * Swiss, Wisconsin Other uses *Swiss-system tournament, in various games and sports *Swiss Internation ...

company

Galderma Galderma S.A. is a Swiss pharmaceutical company specializing in dermatological treatments and skin care products. Formerly a subsidiary of L'Oréal and Nestlé, it has been held by a consortium of private institutional investors since 2019. Gal ...

sells adapalene under the brand-name product Differin.

Medical uses

Per the recommendations of the Global Alliance on Improving Outcomes of Acne,

retinoids The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout ...

such as adapalene are considered first-line therapy in acne treatment and are to be used either independently or in conjunction with

and/or an

antimicrobial agent An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...

, like

clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infec ...

, for maximum efficacy. Furthermore, adapalene, like other retinoids, increases the efficacy and penetration of other topical acne medications that are used in conjunction with topical retinoids as well as hastens the improvement of the post-inflammatory hyperpigmentation caused by acne. In the long term, it can be used as maintenance therapy.

Off-label uses

Adapalene has the unique ability to inhibit

keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...

differentiation and decrease

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...

deposition. This property makes adapalene an effective treatment for

and

callus A callus is an area of thickened and sometimes hardened skin that forms as a response to repeated friction, pressure, or other irritation. Since repeated contact is required, calluses are most often found on the feet and hands, but they may o ...

. It may be used by men undergoing

foreskin restoration Foreskin restoration is the process of expanding the skin on the penis to reconstruct an organ similar to the foreskin, which has been removed by circumcision or injury. Foreskin restoration is primarily accomplished by stretching the residual ski ...

to reduce excess keratin that forms a layer on the exterior of the

human penis The human penis is an external male intromittent organ that additionally serves as the urinary duct. The main parts are the root (radix); the body (corpus); and the epithelium of the penis including the shaft skin and the foreskin (prepuce) co ...

after

circumcision Circumcision is a surgical procedure, procedure that removes the foreskin from the human penis. In the most common form of the operation, the foreskin is extended with forceps, then a circumcision device may be placed, after which the foreskin ...

. Other non-FDA approved indications that have been reported in the literature include treatment of

warts Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the ...

molluscum contagiosum Molluscum contagiosum (MC), sometimes called water warts, is a viral infection of the skin that results in small raised pink lesions with a dimple in the center. They may become itchy or sore, and occur singularly or in groups. Any area of the sk ...

Darier disease Darier's disease (DAR) is an inherited skin disorder that presents with multiple greasy, crusting, thick brown bumps that merge into patches. It is an autosomal dominant disorder discovered by French dermatologist Ferdinand-Jean Darier. Darier's ...

photoaging Photoaging or photoageing (also known as "dermatoheliosis") is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure. Tretinoin is the best studied retinoid in the treatment of photoaging. The deterioration ...

, pigmentary disorders,

actinic keratoses Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic k ...

and

alopecia areata Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. Often, it results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are po ...

Side effects

Adapalene is known to cause mild adverse effects such as photosensitivity, irritation, redness, dryness, itching, and burning. It is common (between 1% and 10% of users) to experience a brief sensation of warmth or stinging, as well as dry skin, peeling and redness during the first 2–4 weeks of using the medication. These effects are considered mild and generally decrease over time. Any serious allergic reaction is rare. Furthermore, of the three topical retinoids, adapalene is often regarded as the most tolerable.

In pregnancy

Use of topical adapalene in pregnancy has not been well studied, but has a theoretical risk of retinoid embryopathy. Thus far, there is no evidence that the cream causes problems in the baby if used during pregnancy. Use is at the consumer's own risk. According to the Drugs and Lactation Database, topical adapalene has poor systemic absorption and results in low blood levels (less than 0.025 mcg/L) despite long term use, suggesting that there is low risk of harm for a nursing infant. However, it is recommended that the topical medication should not be applied to the nipple or any other area that may come into direct contact with the infant's skin.

Interactions

Adapalene has been shown to enhance the efficacy of topical

, although adverse effects are also increased. Application of adapalene gel to the skin 3–5 minutes before application of clindamycin enhances penetration of clindamycin into the skin, which may enhance the overall efficacy of the treatment as compared to clindamycin alone.

Pharmacology

Unlike the retinoid

(Retin-A), adapalene has also been shown to retain its efficacy when applied at the same time as

due to its more stable chemical structure. Furthermore,

photodegradation Photodegradation is the alteration of materials by light. Commonly, the term is used loosely to refer to the combined action of sunlight and air, which cause oxidation and hydrolysis. Often photodegradation is intentionally avoided, since it destroy ...

of the molecule is less of a concern in comparison to tretinoin and

Pharmacokinetics

Absorption of adapalene through the skin is low. A study with six acne patients treated once daily for five days with two grams of adapalene cream applied to of skin found no quantifiable amounts, or less than 0.35 ng/mL of the drug, in the patients' blood plasma. Controlled trials of chronic users of adapalene have found drug levels in the patients' plasma to be 0.25 ng/mL.

Pharmacodynamics

Adapalene is highly lipophilic. When applied topically, it readily penetrates hair follicles and absorption occurs five minutes after topical application. After penetration into the follicle, adapalene binds to nuclear retinoic acid receptors (namely

retinoic acid receptor beta Retinoic acid receptor beta (RAR-beta), also known as NR1B2 (nuclear receptor subfamily 1, group B, member 2) is a nuclear receptor that in humans is encoded by the ''RARB'' gene. Function This gene encodes retinoic acid receptor beta, a memb ...

and

gamma Gamma (uppercase , lowercase ; ''gámma'') is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. In Ancient Greek, the letter gamma represented a voiced velar stop . In Modern Greek, this letter re ...

). These complexes then bind to the

retinoid X receptor The retinoid X receptor (RXR) is a type of nuclear receptor that is activated by 9-cis retinoic acid, which is discussed controversially to be of endogenous relevance, and 9-''cis''-13,14-dihydroretinoic acid, which is likely to be the major e ...

which induces

gene transcription Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...

by binding to specific DNA sites, thus modulating downstream keratinocyte proliferation and differentiation. This results in normalization of keratinocyte differentiation, allowing for decreased microcomedone formation, decreased clogging of pores, and increased exfoliation by increasing

cell turnover The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

. Adapalene is also regarded as an anti-inflammatory agent, as it suppresses the inflammatory response stimulated by the presence of ''

Cutibacterium acnes ''Cutibacterium acnes'' (formerly ''Propionibacterium acnes'') is the relatively slow-growing, typically aerotolerant Anaerobic organism, anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne vulgaris, acne; it can also ca ...

'', and inhibits both

lipoxygenase Lipoxygenases () are a family of (non-heme) iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into cell signaling agents that serve diverse roles as auto ...

activity and the oxidative metabolism of

arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...

into

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

. Adapalene selectively targets retinoic acid receptor beta and retinoic acid receptor gamma when applied to

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

such as those found in the skin. Its agonism of the gamma subtype is largely responsible for adapalene's observed effects. In fact, when adapalene is applied in conjunction with a retinoic acid receptor gamma antagonist, adapalene loses clinical efficacy. Retinization is a common temporary phenomenon reported by patients when initiating use of retinoids. Within the initial period of treatment, skin can become red, irritated, dry and may burn or itch from retinoid application; however, this tends to resolve within four weeks with once a day use.

History

Adapalene was a research product of the

company Galderma's French subsidiary Galderma Laboratories. Adapalene was approved in 1996 by the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) for use in the treatment of acne.

Research

A study has concluded that adapalene can be used to treat

plantar wart A plantar wart, or verruca vulgaris, is a wart occurring on the sole (foot), bottom of the foot or toes. Its color is typically similar to that of the skin. Small black dots often occur on the surface. One or more may occur in an area. They may r ...

s and may help clear lesions faster than

cryotherapy Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...

. Computational study claims that the adapalene can be used as a potential entry inhibitor for Omicron variant of SARS-CoV2.Fidan, O., Mujwar, S. & Kciuk, M. Discovery of adapalene and dihydrotachysterol as antiviral agents for the Omicron variant of SARS-CoV-2 through computational drug repurposing. Mol Divers (2022). https://doi.org/10.1007/s11030-022-10440-6

References

External links

* {{Portal bar , Medicine Anti-acne preparations Retinoids Naphthoic acids Adamantanes 4-Hydroxybiphenyl ethers French inventions