General
Certain cutaneous signs and symptoms of treatment such as
erythema, dryness, scaling, burning, or pruritus may be experienced with use of
DIFFERIN® Cream. These are most likely to occur during
the first two to four weeks of treatment, are mostly mild to moderate in
intensity, and usually lessen with continued use of the medication. Depending
upon the severity of these side effects, patients should be instructed to reduce
the frequency of application or discontinue use.
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 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 or sunburned
skin. As with other retinoids, use of “waxing” as a depilatory method should be
avoided on skin treated with adapalene.
Information for Patients
Patients using DIFFERIN® Cream should
receive the following information and instructions:
- This medication is to be used only as directed by the physician.
- It is for external use only.
- Avoid contact with the eyes, lips, angles of the nose, and mucous membranes.
- Cleanse area with a mild or soapless cleanser before applying this
medication.
- Moisturizers may be used if necessary; however, products containing alpha
hydroxy or glycolic acids should be avoided.
- Exposure of the eye to this medication may result in reactions such as
swelling, conjunctivitis, and eye irritation.
- This medication should not be applied to cuts, abrasions, eczematous or
sunburned skin.
- Wax epilation should not be performed on treated skin due to the potential
for skin erosions.
- During the early weeks of therapy, an apparent exacerbation of acne may
occur. This is due to the action of this medication on previously unseen lesions
and should not be considered a reason to discontinue therapy. Overall clinical
benefit may be noticed after two weeks of therapy, but at least eight weeks are
required to obtain consistent beneficial effects.
Drug InteractionsAs DIFFERIN® Cream 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 rind) should be
approached with caution. Particular caution should be exercised in using
preparations containing sulfur, resorcinol, or salicylic acid in combination
with DIFFERIN® Cream. If these preparations have been
used, it is advisable not to start therapy with DIFFERIN®
Cream until the effects of such preparations in the skin have subsided.
Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenicity studies with adapalene have been conducted in
mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day, and in rats at oral doses
of 0.15, 0.5, and 1.5 mg/kg/day. These doses are up to 8 times (mice) and 6
times (rats) in terms of mg/m2/day the maximum potential
exposure at the recommended topical human dose (MRHD), assumed to be 2.5 grams
DIFFERIN® Cream, which is approximately 1.5 mg/m2 adapalene. In the oral study, increased incidence of benign
and malignant pheochromocytomas in the adrenal medullas of male rats was
observed.
No photocarcinogenicity studies were conducted. Animal studies have shown an
increased risk of skin neoplasms 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.
Adapalene did not exhibit mutagenic or genotoxic effects in vivo (mouse micronucleous test) and in vitro (Ames test, Chinese hamster ovary cell assay,
mouse lymphoma TK assay) studies.
Reproductive function and fertility studies were conducted in rats
administered oral doses of adapalene in amounts up to 20 mg/kg/day (up to 80
times the MRHD based on mg/m2 comparisons). No effects of
adapalene were found on the reproductive performance or fertility of the FO males or females. There were also no detectable effects on
the growth, development and subsequent reproductive function of the F1 generation.
PregnancyTeratogenic effects. Pregnancy Category
C. No teratogenic effects were seen in rats at oral doses of 0.15 to 5.0
mg/kg/day adapalene (up to 20 times the MRHD based on mg/m2 comparisons). However, adapalene administered orally at doses
of ≥ 25 mg/kg, (100 times the MRHD for rats or 200 times MRHD for rabbits) has
been shown to be teratogenic. Cutaneous teratology studies in rats and rabbits
at doses of 0.6, 2.0, and 6.0 mg/kg/day (24 times the MRHD for rats or 48 times
the MRHD for rabbits) 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 MothersIt is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when
DIFFERIN® Cream is administered to a nursing woman.
Pediatric UseSafety and effectiveness in pediatric patients below the age of
12 have not been established.
Geriatric UseClinical studies of DIFFERIN® Cream were
conducted in patients 12 to 30 years of age with acne vulgaris and therefore did
not include subjects 65 years and older to determine whether they respond
differently than younger subjects. Other reported clinical experience has not
identified differences in responses between the elderly and younger
patients.
