Adapalene

Name: Adapalene

What brand names are available for adapalene?

Differin

Actions

  • Actions similar to those of other retinoids (e.g., isotretinoin, tretinoin) but more potent anti-inflammatory activity in vitro and in vivo.1 4 5 6 9 13 15 16 17 19 23 24 31

  • Relatively selective affinity for specific nuclear retinoic acid receptor (RAR) proteins (e.g., RARβ, RARγ) that appear to enhance gene transcription.5 6 7 23 24

  • Exact mechanism(s) of action not elucidated.1 4 5 6 9 13 15 16 17 19 31 Appears to affect expression of genes that modulate follicular keratinization5 19 22 and cell (e.g., epithelial) differentiation,1 4 5 6 9 10 13 15 19 22 23 31 which result in inhibition of corneocyte accumulation and cohesion and reduction in inflammatory and noninflammatory acne lesions.1 6 11 12 22 23 24 31

Advice to Patients

  • Importance of clinicians instructing patients about proper use of the drug.1 31 32

  • Importance of continuing therapy in early weeks, even if acne initially appears to worsen.1 31 32

  • Risk of photosensitivity; importance of using sunscreens and wearing protective clothing over treated areas.1 31 32

  • Importance of avoiding contact with eyes, lips, angles of nose, or mucous membranes.1 31 32

  • Importance of not applying adapalene to cuts, abrasions, or eczematous or sunburned skin.1 31 32

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1 31 32

  • Importance of patients informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 31 32

  • Importance of informing patients of other important precautionary information.1 31 32 (See Cautions.)

How do I store and/or throw out Adapalene?

  • Store at room temperature. Do not freeze.
  • Protect from heat.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Precautions

General

If a reaction suggesting sensitivity or chemical irritation occurs, use of the medication should be discontinued. Exposure to sunlight, including sunlamps, should be minimized during the use of Adapalene. Patients who normally experience high levels of sun exposure, and those with inherent sensitivity to sun, should be warned to exercise caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with Adapalene. Avoid contact with the eyes, lips, angles of the nose, and mucous membranes. The product should not be applied to cuts, abrasions, eczematous skin, or sunburned skin.

Certain cutaneous signs and symptoms such as erythema, dryness, scaling, burning, or pruritus may be experienced during treatment. These are most likely to occur during the first two to four weeks and will usually lessen with continued use of the medication. Depending upon the severity of adverse events, patients should be instructed to reduce the frequency of application or discontinue use.

Drug Interactions

As Adapalene gel has the potential to produce local irritation in some patients, concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices, or lime) should be approached with caution. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid in combination with Adapalene gel. If these preparations have been used, it is advisable not to start therapy with Adapalene gel until the effects of such preparations in the skin have subsided.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies with Adapalene have been conducted in mice at topical doses of 0.3, 0.9, and 2.6 mg/kg/day and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day, approximately 4-75 times the maximal daily human topical dose. In the oral study, positive linear trends were observed in the incidence of follicular cell adenomas and carcinomas in the thyroid glands of female rats, and in the incidence of benign and malignant pheochromocytomas in the adrenal medullas of male rats.

No photocarcinogenicity studies were conducted. Animal studies have shown an increased tumorigenic risk with the use of pharmacologically similar drugs (e.g., retinoids) when exposed to UV irradiation in the laboratory or to sunlight. Although the significance of these studies to human use is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial UV irradiation sources.

In a series of in vivo and in vitro studies, Adapalene did not exhibit mutagenic or genotoxic activities.

Pregnancy

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.

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 Adapalene gel is administered to a nursing woman.

Pediatric Use

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

Brand Names U.S.

  • Differin
  • Differin [OTC]

Onset of Action

8 to 12 weeks

Half-Life Elimination

Terminal: 7 to 51 hours (gel)

Use Labeled Indications

Acne vulgaris: Treatment of acne vulgaris.

Contraindications

Hypersensitivity to adapalene or any component of the formulation.

Lotion: There are no contraindications listed in the manufacturer's labeling.

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.

Dosing Pediatric

Acne vulgaris: Children ≥12 years and Adolescents: Refer to adult dosing.

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% (Limited to important or life-threatening): 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)

Pharmacology

Mechanism of Action

Binds to specific retinoic-acid nuclear receptors and modulates cellular differentiation, keratinization, and inflammatory processes; exact mechanism of action for treatment of acne is unknown

Elimination

Excretion: Bile

Usual Pediatric Dose for Acne

12 years and older:
-Usual dose: Apply a thin layer to the affected area once a day at bedtime

Comments:
-The affected area should be thoroughly washed and dried before application.
-Patients may experience a transient warming or stinging sensation after application of the cream formulation.
-An apparent exacerbation of acne may occur during the first weeks of treatment, and should not be a reason to discontinue treatment.

Use: Topical treatment of acne vulgaris

Renal Dose Adjustments

Data not available

Precautions

Safety and efficacy have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

Adapalene Levels and Effects while Breastfeeding

Summary of Use during Lactation

Topical adapalene has not been studied during breastfeeding. Because it is poorly absorbed after topical application,[1] and blood levels are less than 0.25 mcg/L with long-term use, it is probably a low risk to the nursing infant. Do not apply to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[2]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Benzoyl Peroxide, Tretinoin

References

1. Akhavan A, Bershad S. Topical acne drugs: review of clinical properties, systemic exposure, and safety. Am J Clin Dermatol. 2003;4:473-92. PMID: 12814337

2. Noti A, Grob K, Biedermann M et al. Exposure of babies to C(15)-C(45) mineral paraffins from human milk and breast salves. Regul Toxicol Pharmacol. 2003;38:317-25. PMID: 14623482

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