Adapalene is a third-generation topical retinoid with anticomedogenic, anticomedolytic, and anti-inflammatory properties used to treat acne in adolescents and adults.
ATC code: D10AD03
Pharmaceutical category: Skin, anti-acne
Dosage form: cream and gel
Available dosages: 0.1 percent
Brand name: Aknalen
Uses: Acne
Pharmacodynamics
Adapalene is anticomedogenic and prevents the formation of new comedones and inflammatory lesions, and also works to reduce inflammation by modulating the innate immune response.
Mechanism of action
Acne is a multifactorial condition, and there is evidence to support multiple mechanisms of action for adapalene. Adapalene binds to the retinoic acid receptor (RAR)-beta and gamma. This complex subsequently binds to one of three retinoid X receptors (RXR), which as a complex is capable of binding DNA to modulate transcriptional activity. Although the full extent of transcriptional modulation has not been described, retinoid activation generally affects cell proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation. These effects are primarily attributable to the comedolytic and anticomedogenic properties of adapalene.
In addition, adapalene modulates the immune response by reducing the expression of the TLR-2 receptor and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes Cutibacterium acnes (a bacterium primarily associated with acne). Activation of TLR-2 causes nuclear translocation of AP-1 and downregulation of downstream proinflammatory genes. Therefore, adapalene has a general anti-inflammatory effect that reduces the symptoms of acne caused by inflammation.
Adapalene, when used with benzoyl peroxide, which has free radical-mediated bactericidal effects, works synergistically to reduce comedones and inflammatory lesions.
Pharmacokinetics
Attract
Bioavailability: low, dermal
Onset of effect: 8 to 12 weeks
Distribution
Adapalene molecules are distributed in the epidermis and dermis.
Metabolism
Information on the metabolism of adapalene in humans is not available, although it is known to accumulate in the liver. The main products of metabolism are glucuronides. Approximately 25% of adapalene is metabolized, with the remainder excreted unchanged.
Excretion
Half-life: The terminal half-life is 7 to 51 hours.
Excretion: Adapalene is excreted mainly via the biliary tract.
Uses
This medication is used to treat acne vulgaris. It may reduce the number and severity of acne and promote faster healing.
Contraindications
Hypersensitivity to adapalene or any of the drug’s components.
Warnings
- Avoid using the medicine on eyes, lips, and mucous membranes (for external use only)
- Minimize exposure to UV light during the period of use.
- Cold weather may cause skin irritation.
- The risk of side effects is highest in the first month of treatment. It generally subsides with use.
- Do not apply the product to scratches or cuts, or to eczematous or sunburned skin.
- Skin irritation: Use moisturizer, reduce frequency of use, or discontinue use.
- Avoid waxing the treated area and do not use topical products that may further irritate the skin.
- Anaphylaxis, angioedema, urticaria, facial edema, eyelid edema, lip swelling, and pruritus, sometimes requiring medical treatment, have been reported during post-marketing use of adapalene. If allergic or anaphylactoid/anaphylactic reactions occur during treatment, the drug should be discontinued and a physician consulted.
Side effects
> 10%
- Dryness (1-45%)
- Scaly skin (1-44%)
- Burning (4-29%)
- Erythema (0.5-26%)
1-10%
- Skin discomfort (6 percent)
- Itching (2 percent)
- Scaling (2 percent)
- Sunburn (1 percent)
<1%
- Acne flare-ups
- Conjunctivitis
- Contact dermatitis
- Eczema
- Erythema
- Eyelid edema
- Hives
- Skin discoloration
Postmarketing reports
- Immune system disorders: angioedema, facial edema, lip swelling
- Skin disorders: application site pain
Drug interactions
- Aminoleucine acid
- Topical aminolevulinic acid
- Topical benzoyl peroxide
- Topical klaskotron
- Isotretinoin
- Methoxsalen
- Topical methylaminogluconate
- Porfimer
- Topical resorcinol
- Topical salicylic acid
- Topical sulfur
- Verteporfin
