Adapalene is a topical retinoid-like drug for the treatment of mild to moderate acne vulgaris. Unlike tretinoin, adapalene is a naphtholic acid derivative and causes less skin irritation. Adapalene is more effective than tretinoin gel (0.025%) in the treatment of acne vulgaris. Adapalene is commercially available as a cream, lotion, or gel and is reported to be cosmetically appealing to most patients, according to clinical trial data. The drug was approved by the FDA June 3, 1996.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-For topical administration only. Not for oral, ophthalmic, or intravaginal use.
-Administered topically in the evening before going to bed. Instruct patient to wash face with a non-medicated soap, then apply a thin film of the cream, lotion, or gel to cover the entire face; avoid eyes, lips, and mucous membranes.
Local cutaneous adverse reactions may occur with adapalene therapy. Erythema, skin scaling, dryness of skin (xerosis), burning, and pruritus occur in 10-40% of patients using adapalene gel. Pruritus or burning immediately after application occurs in 20% of patients using adapalene gel. The frequency and severity (mild, moderate, or severe) of local cutaneous irritations were reported for patients using adapalene cream in clinical trials. Mild and moderate xerosis were reported in 42% and 9% of patients, respectively. Erythema was reported as mild in 38% of patients and moderate in 10% of patients. Mild scaling was reported in 35% of patients; moderate scaling was reported in 6% of patients. Persistent pruritus was reported as mild in 21% of patients and moderate in 4% of patients. Persistent burning and/or stinging was reported as mild in 24% of patients and moderate in 4% of patients. Erythema, scaling, dryness, persistent pruritus, and persistent burning/stinging were all reported as severe in < 1% of patients. Photosensitivity (sunburn) occurred in 2% of patients using adapalene cream and <= 1% of patients using the gel. Skin irritation and discomfort were reported rarely (<= 1%) among patients using the gel or cream. Acne vulgaris flares occur in patients receiving adapalene gel (<= 1%) and cream (< 1%). Additional adverse events reported in < 1% of patients using adapalene cream include dermatitis and contact dermatitis, blepharedema (eyelid edema), conjunctivitis, skin discoloration, rash (unspecified), and atopic dermatitis (as eczema). Among patients receiving adapalene lotion in clinical trials, 7.7% reported dry skin, 1.5% reported skin irritation, 0.9% reported skin burning and discomfort, and 0.6% reported sunburn. For patients whose irritation scores were higher while on therapy compared to baseline, mild, moderate, and severe erythema occurred in 21.8%, 8%, and 0.2% of patients, respectively. Mild scaling occurred in 25.3% of patients; moderate and severe scaling were reported in 6.5% and 0.1% of patients, respectively. Dry skin was reported as mild in 36.1% of patients, moderate in 7.3% of patients, and severe in 0.3% of patients. Stinging and/or burning of the skin was reported as mild, moderate, and severe in 22.1%, 7%, and 0.9% of patients, respectively. In an open-label post-marketing study of 13 adolescent subjects, 8 out of 13 reported incidents of pruritus. The local cutaneous adverse reactions seen with use of adapalene are most common during the first 2-4 weeks of treatment, decrease in frequency and severity over time, and are reversible with discontinuation of therapy. Depending upon the severity of cutaneous adverse reactions, patients should be instructed to use moisturizer, reduce the frequency of application of adapalene, or discontinue use.
According to the manufacturer, adapalene should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. There are no adequate and well controlled studies in pregnant women. Further, during clinical trials women of childbearing potential initiated treatment only after negative pregnancy tests were obtained. However, 2 women receiving the topical lotion and 6 women receiving the topical gel became pregnant during adapalene clinical trials. Pregnancy outcomes for these 8 women were: 3 healthy full term deliveries, 2 premature deliveries, 2 elective pregnancy terminations, and 1 lost to follow-up. In animal studies, teratogenic changes were observed in rats and rabbits receiving oral doses of more than 25 mg adapalene/kg/day representing 123- and 246-times the maximum recommended human dose. These teratogenic changes included cleft palate, microphthalmia, exophthalmos, encephalocele, skeletal abnormalities, umbilical hernia, and kidney abnormalities.
According to the manufacturer, it is not known whether adapalene distributes into breast milk. Because adapalene is poorly absorbed through human intact skin, the amount of drug excreted into the breast milk is expected to be low , and therefore risk to the nursing infant is also expected to be low. Do not apply near the nipple area, and be careful to avoid direct contact between the infant and the treated area. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Topical adapalene is for external use only. Avoid contact with the eyes, lips, angles of the nose and other mucous membranes. Apply only to affected areas; accidental exposure to unaffected skin may cause irritation. Do not apply to skin that is cut or is affected with seborrheic dermatitis, eczema, a skin abrasion, or sunburn. As with other retinoids, avoid the use of waxing as a depilatory method. Avoid the use of other potentially irritating topical products. If sun exposure cannot be avoided during topical adapalene therapy, sunscreen products and physical sun blocks (protective clothing, hats) are recommended for protection of treated areas. Sunlight (UV) exposure may potentiate the effects of adapalene. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using topical adapalene. Weather extremes, such as wind or cold, also may be irritating to patients receiving adapalene.
No information is available on the relationship of age to the effects of adapalene in pediatric patients. Safety and efficacy in children less than 12 years of age have not been established.
Clinical studies of adapalene were mainly conducted in patients aged 12 to 30 years, and did not include a sufficient number of geriatric patients (>= 65 years) to determine any differences in response as compared to younger patients. Other reported clinical experience has not identified differences in responses between elderly and younger patients.
For the treatment of acne vulgaris:
Topical dosage (0.1% cream, lotion, or gel; 0.3% gel):
Adults, Adolescents, and Children 12 years and older: Apply to affected areas once daily in the evening before going to bed.
Maximum Dosage Limits:
Maximum dosage information is not available.
Maximum dosage information is not available.
Maximum dosage information is not available.
Safe and effective use has not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Aminolevulinic Acid: (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
Methoxsalen: (Moderate) Use methoxsalen and adapalene together with caution; the risk of severe burns or phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Photosensitizing agents (topical): (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
Porfimer: (Major) Avoid coadministration of porfimer with adapalene due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like adapalene may increase the risk of a photosensitivity reaction.
Salicylic Acid: (Moderate) Concomitant use of other potentially irritating topical products with adapalene should be done cautiously because of additive local irritation. Particular caution should be exercised in using adapalene in combination with preparations containing salicylic acid. If these preparations have been used, it is advisable not to start therapy with adapalene until the effects of such preparations in the skin have subsided.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Concomitant use of other potentially irritating topical products with adapalene should be done cautiously because of additive local irritation. Particular caution should be exercised in using adapalene in combination with preparations containing salicylic acid. If these preparations have been used, it is advisable not to start therapy with adapalene until the effects of such preparations in the skin have subsided.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with adapalene is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like adapalene may increase the risk of a photosensitivity reaction.
Adapalene binds to specific retinoic acid nuclear receptors but does not bind to the cytosolic receptor protein. Adapalene reportedly penetrates deeply into the hair follicle. As a result of its actions, adapalene modulates cell differentiation and keratinization. Adapalene also possesses potent antiinflammatory and comedolytic properties.
Adapalene is applied topically to the skin. The distribution and metabolism of absorbed adapalene is unknown. Excretion appears to be primarily by the biliary route.
Following application, absorption through human skin is low. Trace amounts (< 0.25 ng/mL) of the parent compound have been found in the plasma of acne patients after chronic topical application in controlled clinical trials.