Adapalene + Benzoyl peroxide

Uses

Adapalene + Benzoyl peroxide is used for the topical treatment of acne vulgaris.

Adapalene + Benzoyl peroxide is also used to associated treatment for these conditions: Acne VulgarisAcne, Acne Vulgaris, Inflammatory Acne Vulgaris

How Adapalene + Benzoyl peroxide works

Adapalene is used for the treatment/maintenance of mild-to-severe acne (acne vulgaris). Acne is a multifactorial condition, and evidence exists to support multiple mechanisms of action for adapalene. Adapalene binds to retinoic acid receptor (RAR)-beta and RAR-gamma; this complex subsequently binds to one of three retinoid X receptors (RXRs), which as a complex is capable of binding DNA to modulate transcriptional activity. Although the full extent of transcriptional modulation is not described, retinoid activation is generally known to affect cellular proliferation and differentiation, and adapalene has been shown to inhibit HeLa cell proliferation and human keratinocyte differentiation. These effects primarily account for adapalene's comedolytic and anticomedogenic properties.

In addition, adapalene modulates the immune response by down-regulating toll-like receptor 2 (TLR-2) expression and inhibiting the transcription factor activator protein 1 (AP-1). TLR-2 recognizes Cutibacterium acnes (formerly Propionibacterium acnes), the bacterium primarily associated with acne. TLR-2 activation causes nuclear translocation of AP-1 and downstream pro-inflammatory gene regulation. Therefore, adapalene has a general anti-inflammatory effect, which reduces inflammation-mediated acne symptoms.

When used with benzoyl peroxide, which possesses free radical-mediated bactericidal effects, the combination acts synergistically to reduced comedones and inflammatory lesions.

Acne vulgaris is caused by inflammation in the pilosebaceous gland. Acne is generally caused by increased excretion of sebum from pilosebaceous glands, endocrine factors such as androgenic hormones, keratin developing around follicles, bacterial growth, and inflammation. These factors contribute to the formation of comedones (whiteheads and blackheads).

The peroxide bond of benzoyl peroxide is cleaved to form 2 benzoyloxy radicals. These radicals interact nonspecifically with bacterial proteins, interfering with their function, and survival of the bacteria. Over time, free radical interactions with bacterial proteins lead to decreased keratin and sebum around follicles.

Benzoyl peroxide can also increase the turnover rate of epithelial cells, leading to skin peeling, and breaking down comedones.

Dosage

Adapalene + Benzoyl peroxide dosage

Persons 12 years of age and older apply a thin film of Adapalene + Benzoyl peroxide to affected areas of the face and/or trunk once daily after washing. Use a pea-sized amount for each area of the face (e.g. forehead, chin, each cheek). Avoid the eyes, lips and mucous membranes. Adapalene + Benzoyl peroxide is not for oral, ophthalmic, or intravaginal use.

Pediatric Use: Safety and effectiveness of Adapalene + Benzoyl peroxide in pediatric patients under the age of 12 have not been established.

Side Effects

Adapalene + Benzoyl peroxide is usually a well tolerated preparation. But the local adverse reactions that may be observed are dry skin, erythema, pruritus of skin, skin scaling, skin rash etc.

Toxicity

Toxicity information regarding adapalene is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as redness, scaling, and skin discomfort. Symptomatic and supportive measures are recommended.

Adapalene has an acute oral LD₅₀ in S-D rats and CD-1 mice of over 5000 mg/kg. The LD₅₀ of 0.3% applied topically to Credo OF1 mice is over 10 ml/kg (30 mg/kg). No systemic or local toxicity was observed in rats treated topically with 6 mg/kg/day of 0.3% adapalene.

Data regarding overdoses of benzoyl peroxide are not readily available. During an overdose patients may experience and increased risk or severity of adverse effects such as skin itching, burning, peeling, inflammation, and erythema.

The oral LD₅₀ in rats is 490 mg/kg.

Precaution

Exposure to sunlight (ultraviolet ray), including sunlamps, should be minimized during the use of this preparation. Use of sunscreen products and protective apparel, (e.g. hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with Adapalene + Benzoyl peroxide.

Interaction

Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. No formal drug-drug interaction studies were conducted.

Elimination Route

Adapalene is applied topically and absorbed through the skin. In one clinical study treating patients once per day with 2g of 0.3% gel applied to 2 mg/cm² of skin, 15 patients had detectable blood plasma adapalene levels (0.1 ng/ml) resulting in a mean C_max of 0.553 ± 0.466 ng/ml and a mean AUC of 8.37 ± 8.46 ng*h/ml on day 10.

In a sample of excised skin, 1.9% of a radiolabelled topical dose fully penetrates the skin, and 2.6% remains in the skin. The radiolabelled dose that fully penetrates the skin is recovered as benzoic acid, while the dose in the skin is approximately half benzoic acid and half benzoyl peroxide. 95.5% of a radiolabelled dose is not absorbed or metabolized after 8 hours.

Half Life

In one clinical study, after ten days of treatment with 2g of 0.3% cream or gel, the terminal half-life was between 7 and 51 hours, with a mean of 17.2 ± 10.2.

Clearance

Adapalene is rapidly cleared from blood plasma, typically undetectable after 72 hours following topical application.

Elimination Route

Adapalene is primarily excreted by the biliary route at about 30 ng/g of the topically applied amount. Approximately 75% of the drug remains unchanged.

Benzoyl peroxide's metabolite benzoic acid, is eliminated in the urine. Data regarding fecal elimination is not readily available.

Pregnancy & Breastfeeding use

Pregnancy: Pregnancy category C. There are no well-controlled trials in pregnant women treated with Adapalene + Benzoyl peroxide.

Lactating mother: It is not known whether Adapalene or Benzoyl peroxide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Adapalene + Benzoyl peroxide is administered to a lactating mother.

Contraindication

Should not be administered to individuals who are hypersensitive to any of its component.

Special Warning

Safety and effectiveness of Adapalene and Benzoyl peroxide gel in pediatric patients under the age of 12 years have not been established.

Acute Overdose

No available data are found.

Interaction with other Medicine

Particular caution should be exercised in using preparations containing sulfur, resorcinol or salicylic acid in combination with this preparation. If these preparations have been used, it is advisable not to start therapy with Adapalene + Benzoyl peroxide until the effects of such preparations in the skin have subsided.

Warning: Adapalene + Benzoyl peroxide should be discontinued if hypersensitivity to any of the ingredients is noted. Patients with sunburn should be advised not to use the product until fully recovered.

Storage Condition

Store in a cool (below 25°C) and dry place protected from light and moisture. Keep out of the reach of children. Keep the tube tightly closed after use.

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