Adapalene

Pharmacologic Category

Acne Products; Retinoic Acid Derivative; Topical Skin Product, Acne

Dosing: Adult

Acne vulgaris: Topical: Apply once daily in the evening before bedtime. 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 (Altinyazar 2005)

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

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.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Pediatric

Acne vulgaris, treatment: Children ≥7 years and Adolescents: Limited data available in ages <12 years (Eichenfield 2013): 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.

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely necessary due to low systemic absorption.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely necessary due to low systemic absorption.

Use: Labeled Indications

Acne vulgaris: Treatment of acne vulgaris.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

RosaceaLevel of Evidence [C]

Topical adapalene for the management of rosacea has been studied in a limited number of patients, with data suggesting it may be a useful alternative to topical metronidazole in patients with papulopustular rosacea Ref. Access Full Off-Label Monograph

Level of Evidence Definitions

Level of Evidence Scale

Clinical Practice Guidelines

Acne:

American Academy of Dermatology, "Guidelines of Care for the Management of Acne Vulgaris," May 2016

Administration: Topical

For topical external use only; not for oral, ophthalmic, or intravaginal use. Avoid contact with abraded, broken, eczematous, or sunburned skin, mucous membranes, eyes, lips, and angles of the nose. Moisturizers may be used if necessary; avoid alpha hydroxy or glycolic acid-containing products. A mild transitory sensation of warmth or slight stinging may occur shortly after application.

Cream/gel: Apply a thin film to clean/dry skin in the evening before bedtime; apply enough to cover entire affected area.

External pad: Remove pad from foil just prior to use. Before bedtime, wash and dry area to be treated, then apply pad containing topical solution to affected areas. Discard pad after single use.

Lotion: Apply after washing gently with a mild or soapless cleanser and then pat dry; dispense a nickel size amount (3 to 4 pump actuations) to cover entire face.

Administration: Pediatric

Topical: For topical external use only. Avoid contact with eyes, angles of the nose, lips, and mucous membranes. Do not apply to cuts, abrasions, eczematous, or sunburned skin. Shortly after application, a mild transitory sensation of warmth or slight stinging may occur. Moisturizers may be used if necessary; avoid moisturizers containing alpha hydroxy or glycolic acid-containing products. Wash hands after application.

Cream/gel: Cleanse affected area with a mild or soapless cleanser and pat dry; apply a thin film to skin in the evening before bedtime; apply enough to cover entire affected area.

External pad: Remove pad from foil just prior to use. Before bedtime, wash and dry area to be treated, then apply pad containing topical solution to affected areas. Discard pad after single use.

Lotion: Apply after washing gently with a mild or soapless cleanser and then pat dry; dispense a nickel size amount (3 to 4 pump actuations) to cover entire face.

Solution: External Pad (Plixda): Remove pad from foil just prior to use. Before bedtime, wash and dry area to be treated, then apply pad containing topical solution to affected areas. Discard pad after single use.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze. Protect from light.

Lotion: Protect from light and heat; do not refrigerate.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat pimples (acne).

Frequently reported side effects of this drug

• Redness

• Dry skin

• Itching

• Peeling

• Scaling

• Burning

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe skin irritation

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Contraindications

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.

Canadian labeling: Additional contraindications (not in US labeling): Patients with eczema or seborrheic dermatitis; women who are pregnant or planning to become pregnant.

Warnings/Precautions

Concerns related to adverse effects:

• 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.

* See Cautions in AHFS Essentials for additional information.

Warnings: Additional Pediatric Considerations

May cause mild hyperglycemia; more common in pediatric patients. Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).

Reproductive Considerations

In clinical trials, women of childbearing potential were required to have a negative pregnancy test prior to therapy.

Pregnancy Risk Factor

C

Pregnancy Considerations

Inadvertent exposure to a limited number of pregnant women occurred during premarketing studies. Published information related to adapalene exposure in pregnancy is limited (Autret 1997).

In general, topical products are recommended for the treatment of acne in pregnancy due to lower systemic exposure. However, because adapalene may share the characteristic of teratogenicity with other retinoids, agents other than adapalene are preferred. Avoid applying large amounts over prolonged periods of time to decrease the potential for systemic absorption (Akhavan 2003; Kong 2013; Leechman 2006).

Breast-Feeding Considerations

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

In general, the use of topical agents is preferred over systemic agents for the treatment of acne in females who are breastfeeding.

Although the manufacturer recommends caution when administering adapalene to breastfeeding females, the use of topical agents is generally preferred over systemic agents for the treatment of acne in women who are breastfeeding. Topical adapalene may be compatible with breastfeeding; however, specific studies are not available. Avoid applying large amounts over prolonged periods of time to decrease the potential for systemic absorption (Kong 2013; Leechman 2006). Mothers should wash hands following application. Because topical agents can be transferred to a breastfeeding infant, avoid direct skin-to-skin contact with treated areas (Anderson 2018). Use of alternative agents or postponement of therapy may also be considered (Zip 2002).

Briggs' Drugs in Pregnancy & Lactation

• Adapalene

Adverse Reactions

>10%: Dermatologic: Xeroderma (≤45%), exfoliation of skin (≤44%), erythema (≤38%), burning sensation of skin (≤29%), stinging of the skin (≤29%)

1% to 10%: Dermatologic: Skin abnormalities (1% to 6%; discomfort), desquamation (2%), pruritus (≤2%), skin irritation (1% to 2%), sunburn (1% to 2%)

≤1%, postmarketing, and/or case reports: 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)

* See Cautions in AHFS Essentials for additional information.

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Risk X: Avoid combination

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Risk X: Avoid combination

Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Risk X: Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

Differin: 0.1% (45 g)

Generic: 0.1% (45 g)

Gel, External:

Differin: 0.1% (15 g, 45 g); 0.3% (45 g) [contains edetate disodium, methylparaben, propylene glycol]

Differin: 0.1% (15 g, 45 g) [fragrance free, oil free; contains edetate disodium, methylparaben, propylene glycol]

Generic: 0.1% (45 g); 0.3% (45 g)

Lotion, External:

Differin: 0.1% (59 mL) [contains methylparaben, propylene glycol, propylparaben]

Generic: 0.1% (59 mL [DSC])

Pad, External:

Generic: 0.1% (14 ea)

Solution, External:

Generic: 0.1% (60 mL)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Cream, External:

Differin: 0.1% (2 g, 15 g, 45 g, 60 g) [contains edetate disodium, methylparaben, propylparaben, trolamine (triethanolamine)]

Gel, External:

Differin: 0.1% (2 g, 15 g, 45 g, 60 g) [contains edetate disodium, methylparaben, propylene glycol]

Differin XP: 0.3% (2 g, 60 g) [contains edetate disodium, methylparaben, propylene glycol]

Anatomic Therapeutic Chemical (ATC) Classification

• D10AD03

Generic Available (US)

Yes

Pricing: US

Cream (Adapalene External)

0.1% (per gram): $6.03 - $6.55

Cream (Differin External)

0.1% (per gram): $14.11

Gel (Adapalene External)

0.1% (per gram): $4.37

0.3% (per gram): $6.60 - $6.88

Gel (Differin External)

0.1% (per gram): $0.78

0.3% (per gram): $14.64

Lotion (Differin External)

0.1% (per mL): $9.86

Pads (Adapalene External)

0.1% (per each): $105.00

Solution (Adapalene External)

0.1% (per mL): $18.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Onset of action: 8 to 12 weeks

Absorption: Topical: Minimal; only trace amounts have been measured in serum after chronic application

Half-life elimination, terminal: 7 to 51 hours (gel)

Excretion: Bile

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

FDA Approval Date

May 31, 1996

References

Adapalene Topical Solution (adapalene) [prescribing information]. Canton, MS: Allegis Holdings, LLC; May 2019.[PubMed 12814337]

Akhavan A, Bershad S. Topical acne drugs: review of clinical properties, systemic exposure, and safety. Am J Clin Dermatol. 2003;4(7):473-492.

Altinyazar HC, Koca R, Tekin NS, Eştürk E. Adapalene vs. metronidazole gel for the treatment of rosacea. Int J Dermatol. 2005;44(3):252-255.[PubMed 15807740]

American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Anderson PO. Topical drugs in nursing mothers. Breastfeed Med. 2018;13(1):5-7.[PubMed 29298085]

Autret E, Berjot M, Jonville-Bera AP, Aubry MC. Moraine C. Anophthalmia and agenesis of optic chiasma associated with adapalene gel in early pregnancy. Lancet. 1997;350(9074):339.[PubMed 9251645]

Chien AL, Qi J, Rainer B, Sachs DL, Helfrich YR. Treatment of acne in pregnancy. J Am Board Fam Med. 2016;29(2):254-262.[PubMed 26957383]

Differin (adapalene) [product monograph]. Thornhill, Ontario, Canada: Galderma Canada Inc; December 2018.

Differin Cream (adapalene) [prescribing information]. Fort Worth, TX: Galderma; June 2004.

Differin Cream (adapalene) [prescribing information]. Fort Worth, TX: Galderma; November 2015.

Differin Gel 0.1% (adapalene) [prescribing information]. Fort Worth, TX: Galderma; June 2018.

Differin Gel 0.3% (adapalene) [prescribing information]. Fort Worth, TX: Galderma; December 2013.

Differin Gel 0.3% (adapalene) [prescribing information]. Fort Worth, TX: Galderma; February 2018.

Differin Lotion (adapalene) [prescribing information]. Fort Worth, TX: Galderma; April 2013.

Differin Lotion (adapalene) [prescribing information]. Fort Worth, TX: Galderma; July 2014.

Eichenfield LF, Krakowski AC, Piggott C, et al, "Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric Acne," Pediatrics, 2013, (131 Suppl 3):S163-86.[PubMed 23637225]

Kong YL, Tey HL. Treatment of acne vulgaris during pregnancy and lactation. Drugs. 2013;73(8):779-787.[PubMed 23657872]

Leachman SA, Reed BR. The use of dermatologic drugs in pregnancy and lactation. Dermatol Clin. 2006;24(2):167-197.[PubMed 16677965]

Plixda (adapalene) [prescribing information]. Charleston, SC: Marnel Pharmaceuticals; July 2018.

Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.[PubMed 19188870]

Zip C. Common sense dermatological drug suggestions for women who are breast-feeding. Skin Therapy Lett. 2002;7(3):5-7.

Brand Names: International

Aclear (HK); Aclene (IN, KR, LK); Acnelene (PK); Acnescave (EG); Acure (TW); Adaferin (CR, DO, GR, GT, HN, IN, MX, NI, PA, SV); Adaferin Gel (IL); Adagel (EG); Adaklin (RU); Adapco (LK); Adapel (BD); Adgar (BD); Adiamil (PY); Adolin (QA, SA); Beautyface (TW); Butipalen (KR); Clenzit (RU); Deriva (LK, ZW); Deriva MS (MY); Differin (AE, AR, AU, BB, BH, BR, CL, CN, CO, EE, FI, HK, HU, IS, JO, KR, KW, LT, LU, MY, NL, NO, NZ, PE, PH, PL, PT, PY, QA, RU, SA, SG, SI, TH, TR, TW, UY, VE, VN, ZA); Differin Gel (AT, BE, CH, DE, GB, IE, IL, IT, SE); Differine (CZ, ES, FR, LB, MT, SK); Doulishu (TW); Easy Acne (TW); Ellia (HK); Evalen (ID); Fona (BD); Klenzit (PH); Klenzit-MS (PH); Leneda (CR, DO, GT, HN, NI, PA, SV); Marpalene (EG); Opalen (LK); Palexil (TR); Panalene (AR); Redap (DK); Rozac (IN); Sona (HR); Sure Cure (QA); Surecure (JO); T3ADA (MY); Watene (SA); Yunneco (CR, DO, GT, HN, NI, PA, SV); Zudenina (CO, EC); Zudenina F (CO)

Last Updated 4/10/20