Adapalene

Adapalene is an Antiacne Agent belonging to pharmacology class of Retinoic Acid Derivative

Adapalene can be used in the treatment of Acne Vulgaris.

Adapalene is Minimal systemic absorption and get excreted Via bile with terminal elimination half-life of 7-51 hours

The common side effects associated with Adapalene include Hypersensitivity reactions (e.g. pruritus, face or eyelid oedema, lip swelling); photosensitivity

Adapalene is available in the form of Cream, gel.

The molecule is available in India, USA, Japan, Germany.

It is a retinoid like compound which is a modulator of cellular differentiation, keratinization, and inflammatory processes, all of which represent important features in the pathology of acne vulgaris.

Adapalene is available in Cream, gel.

Adapalene can be used in the treatment of Acne Vulgaris.

Adapalene is a retinoid-like compound that acts on the important features of acne vulgaris pathology by modulating cellular differentiation, keratinisation and inflammatory processes. It is also suggested to normalize the differentiation of follicular epithelial cells leading to decreased microcomedone formation.

Adapalene is approved for use in the following clinical indications:

Acne vulgaris: Treatment of acne vulgaris.

Although not approved there have been certain off labelled uses documented for Adapalene which includes:

Rosacea.

Acne vulgaris: Topical: Cream 0.1%; Gel 0.1%, 0.3%; Lotion 0.1%: Apply once daily. Consider starting with the lowest possible concentration to minimize skin irritation and increase potency as tolerated. For moderate to severe acne, may be used as part of an appropriate combination regimen. If irritation occurs, may reduce the frequency of application.

Rosacea (off-label use): Topical: 0.1% Gel: Apply to affected area once daily in the evening for up to 12 weeks.

Cream, gel

• 0.1%, 0.3%

Cream, Gel

Dose Adjustment in Pediatric Patient:

Acne vulgaris, treatment:

Children ≥7 years and Adolescents: Limited data available in ages <12 years : Topical: Apply once daily; cream, gel, or solution should be applied in the evening (at bedtime). Note: During the initial 2 weeks of therapy, it may appear that acne worsens; full effect may take up to 8 to 12 weeks of therapy.

Adapalene may be contraindicated in the following conditions:

Hypersensitivity to adapalene or any component of the formulation.

Concerns related to adverse effects:

• Hypersensitivity reactions: Reactions such as anaphylaxis, angioedema, urticaria, pruritus, face edema, eyelid edema, and lip swelling have been reported. Discontinue use immediately if allergic or anaphylactoid/anaphylactic reactions occur.

• Photosensitivity: Use is associated with increased susceptibility/sensitivity to UV light; avoid sunlamps or excessive sunlight exposure. Daily sunscreen use and other protective measures are recommended. Patients with sunburn should discontinue use until sunburn has healed.

• Skin irritation: Certain cutaneous signs and symptoms such as erythema, dryness, scaling, stinging/burning, or pruritus may occur during treatment; these are most likely to occur during the first 2 to 4 weeks and will usually lessen with continued use. Treatment can increase skin sensitivity to weather extremes of wind or cold. Concomitant topical medications (eg, medicated or abrasive soaps and cleansers, or cosmetics with a strong drying effect, products with high concentrations of alcohol, astringents, spices or limes) should be avoided due to increased skin irritation. Depending on the severity of irritation, use moisturizer, reduce the frequency of application, or discontinue use.

Other warnings/precautions:

• Appropriate use: For external use only; avoid contact with abraded, broken, eczematous, or sunburned skin, mucous membranes, eyes, lips, and angles of the nose. Wax depilation is not recommended.

There is no sufficient scientific evidence traceable regarding use and safety of Adapalene in concurrent use with alcohol.

It is not known if adapalene is present in breast milk.

Pregnancy Category (FDA): C

Teratogenic Effects. Pregnancy Category C. No teratogenic effects were seen in rats at oral doses of adapalene 0.15 to 5.0 mg/kg/day, up to 120 times the maximal daily human topical dose. Cutaneous route teratology studies conducted in rats and rabbits at doses of 0.6, 2.0, and 6.0 mg/kg/day, up to 150 times the maximal daily human topical dose exhibited no fetotoxicity and only minimal increases in supernumerary ribs in rats. There are no adequate and well-controlled studies in pregnant women. Adapalene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The adverse reactions related to Adapalene can be categorized as

Common Adverse effects:

Hypersensitivity reactions (e.g. pruritus, face or eyelid oedema, lip swelling); photosensitivity

Less Common Adverse effects:

local skin irritation (e.g. erythema, dryness, scaling, stinging/burning sensation, pruritus); may increase skin sensitivity to weather extremes (e.g. wind, cold).

Rare Adverse effects:

Exfoliation of skin, skin discomfort, sunburn.

The clinically relevant drug interactions of Adapalene is briefly summarized here

May cause additive local irritation with other topical products (e.g. medicated or abrasive soaps and cleansers, cosmetics with strong drying effect, peeling agents; products with high concentration of alcohol, astringents, spices, or lime).

The most common side effects of Adapalene includes: Hypersensitivity reactions (e.g. Pruritus, Face or Eyelid Oedema, Lip Swelling); Photosensitivity.

Pregnancy Category (FDA): C

Teratogenic Effects. Pregnancy Category C. No teratogenic effects were seen in rats at oral doses of adapalene 0.15 to 5.0 mg/kg/day, up to 120 times the maximal daily human topical dose. Cutaneous route teratology studies conducted in rats and rabbits at doses of 0.6, 2.0, and 6.0 mg/kg/day, up to 150 times the maximal daily human topical dose exhibited no fetotoxicity and only minimal increases in supernumerary ribs in rats. There are no adequate and well-controlled studies in pregnant women. Adapalene should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

There is no FDA guidance on use of Adapalene during labor and delivery.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when DIFFERIN Gel is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Geriatic Use

There is no FDA guidance on the use of Adapalene in geriatric settings.

Gender

There is no FDA guidance on the use of Adapalene with respect to specific gender populations.

Race

There is no FDA guidance on the use of Adapalene with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Adapalene in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Adapalene in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Adapalene in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Adapalene in patients who are immunocompromised.

Adapalene is intended for cutaneous use only. If the medication is applied excessively, no more rapid or better results will be obtained and marked redness, peeling, or discomfort may occur. The acute oral toxicity of Adapalene in mice and rats is greater than 10 mL/kg. Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of Vitamin A.

Pharmacodynamics:

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.

Pharmacokinetics:

Absorption: Minimal systemic absorption.

Excretion: Via bile. Terminal elimination half-life: 7-51 hours.

1. https://www.uptodate.com/contents/Adapalene -drug-information?search=Adapalene &source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F154338
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022352s017lbl.pdf
3. https://www.medicaid.nv.gov/Downloads/provider/Adapalene _2015-1215.pdf
4. https://www.mims.com/india/drug/info/Adapalene ?type=full&mtype=generic#mechanism-of-action