CONTRAINDICATIONS
Adapalene cream and gel should not be administered to individuals who are
hypersensitive to adapalene or any of the components in the cream vehicle or gel.
WARNINGS
Use of adapalene gel should be discontinued if hypersensitivity to any of the ingredients is
noted. Patients with sunburn should be advised not to use this product until fully
recovered.
PRECAUTIONS
General
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 2-4 weeks of treatment, are mostly mild to moderate in intensity, 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.
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 the 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 eyes, lips, angles of the nose, and mucous membranes. The product
should not be applied to cuts, abrasions, eczematous skin, or sunburned skin. As with
other retinoids, use of "waxing" as a depilatory method should be avoided on skin treated
with adapalene.
Information for the Patient
Patients using adapalene cream should receive the following information and instructions:
1. This medication is to be used only as directed by the physician.
2. It is for external use only.
3. Avoid contact with the eyes, lips, angles of the nose, and mucous membranes.
4. Cleanse area with a mild or soapless cleanser before applying this medication.
5. Moisturizers may be used if necessary; however, products containing alpha
hydroxy or glycolic acids should be avoided.
6. Exposure of the eye to this medication may result in reactions such as swelling,
conjunctivitis, and eye irritation.
7. This medication should not be applied to cuts, abrasions, eczematous or
sunburned skin.
8. Wax epilation should not be performed on treated skin due to the potential for
skin erosions.
9. 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 2 weeks of therapy, but at least 8 weeks are required to
obtain consistent beneficial effects.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
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 irridation 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 irridation 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.
Cream
Carcinogenicity 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 g adapalene 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.
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 F0 males or females. There were also no detectable effects on the growth,
development and subsequent reproductive function of the F1 generation.
Gel
Carcinogenicity studies 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.
Pregnancy, Teratogenic Effects, Pregnancy Category C
No teratogenic effects were seen in rats at oral doses of 0.15-5.0 mg/kg/day adapalene
(up to 20 times the MRHD based on mg/m2 comparisons). However, adapalene
administered orally at doses of ³25 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 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 is administered to a
nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 12 have not been
established.
Geriatric Use
Clinical studies of adapalene cream were conducted in patients 12-30 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.