Differin

Topical Retinoids for Acne

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.

xerosis / Delayed / 0-1.0
erythema / Early / 0-1.0
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

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

pruritus / Rapid / 10.0-40.0
photosensitivity / Delayed / 0-2.0
skin irritation / Early / 0-1.5
rash / Early / 0-1.0
blepharedema / Early / 0-1.0
acne vulgaris / Delayed / 0-1.0
skin discoloration / Delayed / 0-1.0
application site reaction / Early / Incidence not known
urticaria / Rapid / Incidence not known

Differin, Differin Pump, Plixda

Rx, OTC

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%).

Apply a thin layer topically to the affected skin area(s) once daily in the evening.

Apply a thin layer topically to the affected skin area(s) once daily in the evening.

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

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/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%

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.

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.

Available data regarding the use of adapalene during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. 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/kg/day representing 40- and 81-times the maximum recommended human dose (MRHD), respectively, of the adapalene 0.3% gel and 122- and 243-times the MRHD, respectively, of the adapalene lotion. These teratogenic changes included cleft palate, microphthalmia, exophthalmos, encephalocele, skeletal abnormalities, umbilical hernia, and kidney abnormalities. Dermal adapalene embryofetal development studies in rats and rabbit at doses up to 6 mg/kg/day (9.7- and 19.5-times the MRHD, respectively, of the adapalene 0.3% gel and 29- and 58-times the MRHD, respectivley, of the adapalene lotion) showed no fetotoxicity and only minimal increases in skeletal variations (i.e., supernumerary ribs in both species and delayed ossification in rabbits).

There are no data on the presence of topical adapalene or its metabolite in human milk, the effects on the breast-fed infant, or the effects on milk production. Adapalene is poorly absorbed through human intact skin and has low systemic exposure; however, it is possible that topical administration of large amounts of drug could result in sufficient systemic absorption to produce detectable quantities in human milk. To minimize potential exposure to the breast-fed infant via breast milk, use adapalene on the smallest area of skin and for the shortest duration possible while breast-feeding. Avoid application to areas with increased risk for potential ingestion by or ocular exposure to the breast-fed infant. 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, health care providers are encouraged to report the adverse effect to the FDA.