PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Topical Retinoids for use for Acne

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Topical agent for the tx of acne vulgaris; causes less skin irritation and is more effective than the highest concentration of tretinoin gel (0.025%).

    COMMON BRAND NAMES

    Differin, Differin Pump, Plixda

    HOW SUPPLIED

    Adapalene/Differin Topical Cream: 0.1%
    Adapalene/Differin Topical Lotion: 0.1%
    Adapalene/Differin/Differin Pump Topical Gel: 0.1%, 0.3%
    Adapalene/Differin/Plixda Topical Sol: 0.1%

    DOSAGE & INDICATIONS

    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

    Adults

    Maximum dosage information is not available.

    Elderly

    Maximum dosage information is not available.

    Adolescents

    Maximum dosage information is not available.

    Children

    Safe and effective use has not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Topical Administration
    Cream/Ointment/Lotion Formulations

    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.

    STORAGE

    Differin:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Differin Pump:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Plixda:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Pregnancy

    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.

    Breast-feeding

    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.

    Eczema, skin abrasion, sunburn, sunlight (UV) exposure

    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.

    Children

    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.

    Geriatric

    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.

    ADVERSE REACTIONS

    Severe

    erythema / Early / 0-1.0
    xerosis / Delayed / 0-1.0

    Moderate

    contact dermatitis / Delayed / 0-1.0
    atopic dermatitis / Delayed / 0-1.0
    conjunctivitis / Delayed / 0-1.0

    Mild

    pruritus / Rapid / 10.0-40.0
    photosensitivity / Delayed / 0-2.0
    skin irritation / Early / 0-1.5
    skin discoloration / Delayed / 0-1.0
    acne vulgaris / Delayed / 0-1.0
    blepharedema / Early / 0-1.0
    rash / Early / 0-1.0

    DRUG INTERACTIONS

    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.
    Photosensitizing agents: (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
    Porfimer: (Moderate) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.
    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) Concomitant use of adapalene and photosensitizing agents may cause additive phototoxicity; use together with caution.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.  

    Topical 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.