Adapalene

D10A - Anti-acne preparations for topical use ATC D10AD03 Small molecule approved 1996 Topical Natural product

JFDA label: Differin Gel

Mechanism of Action

Agonist of Retinoic acid receptor — Retinoic acid receptor agonist

Target	Action	Gene / class
Retinoic acid receptor efficacy	AGONIST

Indications

Approved

Acne vulgaris

Off-label

Rosacea

Contraindications

Source: Lexicomp

Hypersensitivity to adapalene or any component of the formulation. Lotion: There are no contraindications listed in the manufacturer's labeling. OTC labeling: When used for self-medication, do not use on damaged skin (cuts, abrasions, eczema, sunburn). Documentation of allergenic cross-reactivity for retinoids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Other (22)

Very Common burning sensation of skin · Dermatologic: Xeroderma · erythema · exfoliation of skin · stinging of the skin

Common Dermatologic: Skin abnormalities · desquamation · pruritus · skin irritation · sunburn

Not Known Acne flare · angioedema (gel) · application site pain (gel) · conjunctivitis · contact dermatitis · dermatitis · eczema · eyelid edema · facial edema (gel) · skin discoloration · skin rash (cream/gel) · swelling of lips (gel)

Dosing

Source: Lexicomp

Acne vulgaris: Topical: Apply once daily; use cream and gel in the evening before bedtime Rosacea (off-label use): Topical: 0.1% Gel: Apply to affected area once daily in the evening for up to 12 weeks (Altinyazar 2005)

(For additional information see "Adapalene: Pediatric drug information") Acne vulgaris: Children ≥12 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling; however, systemic absorption is not extensive, making the need for a dose adjustment unlikely.

Warnings & Precautions

Source: Lexicomp

Hypersensitivity reactions

Reactions such as pruritus, face edema, eyelid edema, and 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.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse effects were observed in animal reproduction studies. Retinoids may cause harm when administered during pregnancy. A case report described maternal use of adapalene 1 month prior to pregnancy and through 13 weeks' gestation; cerebral and ocular malformations were reported in the exposed fetus which resulted in termination of pregnancy (Autret 1997). In clinical trials, women of childbearing potential were required to have a negative pregnancy test prior to therapy.

Lactation

It is not known if adapalene is present in breast milk. The manufacturer recommends that caution be exercised when administering adapalene to breastfeeding women.

Chemistry & Properties

Formula	C28H28O3
Molecular weight	412.53 g/mol
IUPAC name	6-[3-(1-adamantyl)-4-methoxyphenyl]naphthalene-2-carboxylic acid
CAS	106685-40-9
PubChem CID	60164
InChIKey	`LZCDAPDGXCYOEH-UHFFFAOYSA-N`
logP	6.68 (XLogP 7.7)
Polar surface area	46.53 Å²
H-bond acceptors / donors	2 / 1
Drug-likeness (QED)	0.52
Lipinski violations	1

SMILES

COc1ccc(-c2ccc3cc(C(=O)O)ccc3c2)cc1C12CC3CC(CC(C3)C1)C2

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Substrate	—
CYP2C19	Inhibitor	—
CYP2C8	Inhibitor	—
CYP2C9	Substrate	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—

Receptor binding (top 3)

Target	Action	Affinity
Retinoic acid receptor-β (RARB)	Agonist	pKi 7.5
Retinoic acid receptor-γ (RARG)	Agonist	pKi 6.9
Retinoic acid receptor-α (RARA)	Agonist	pKi 6.0

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT2 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (8)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
SureCure 0.1% W/W Gel	Gel 0.1 %	30 g tube	شركة مستودع ادوية الايمان	2.650
Acnipare	Cream Adapalene 0.1 %WW	(30 GM) / TUB	Pella Pharmaceuticals Co. Ltd.	3.140
Acnex Gel	Gel 0.1 %	30 GM	JERASH PHARMACEUTICALS LTD.CO/JORDAN	3.200
Differin Gel	Gel 0.1 %	30 g tube pack varies	IBN CINA DRUG STORE	3.780
Differin Cream	Cream 0.1 %	30gm pack varies	IBN CINA DRUG STORE	3.870
Acne Mafee Cream	Cream 0.1 %	30 gm	Amman Pharmaceutical Indusries	4.010
Adacline Gel	Gel 0.75 g, 0.03 g	30 GM/1 UNT	PELLA PHARMACEUTICALS CO.LTD/JORDAN	6.550
Epiduo Gel	Gel 2.5 %, 0.1 %	30 GM	IBN CINA DRUG STORE	12.780