educe the frequency of application or discontinue use.
Drug Interactions:
As DIFFERIN Gel 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) should be approached with caution. Particular caution should be exercised in using preparations containing sulfur, resorcinol, or salicylic acid in combination with DIFFERIN Gel. If these preparations have been used, it is advisable not to start therapy with DIFFERIN Gel until the effects of such preparations in the skin have subsided.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Carcinogenicity studies with adapalene 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.
No photocarcinogenicity studies were conducted. Animal studies have shown an increased tumorigenic risk 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.
In a series of in vivo and in vitro studies, adapalene did not exhibit mutagenic or genotoxic activities.
Pregnancy:
Teratogenic Effects. Pregnancy Category C. No teratogenic effects were seen in rats at oral doses of adapalene 0.15 to 5.0 mg/kg/day, up to 120 times the maximal daily human topical dose. Cutaneous route teratology studies conducted in rats and rabbits at doses of 0.6, 2.0, and 6.0 mg/kg/day, up to 150 times the maximal daily human topical dose 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 DIFFERIN Gel is administered to a nursing woman.
Pediatric Use:
Safety and effectiveness in pediatric patients below the age of 12 have not been established.
ADVERSE REACTIONS:
Some adverse effects such as erythema, scaling, dryness, pruritus, and burning will occur in 10-40% of patients. Pruritus or burning immediately after application also occurs in approximately 20% of patients. The following additional adverse experiences were reported in approximately 1% or less of patients: skin irritation, burning/stinging, erythema, sunburn, and acne flares. These are most commonly seen during the first month of therapy and decrease in frequency and severity thereafter. All adverse effects with use of DIFFERIN Gel during clinical trials were reversible upon discontinuation of therapy.
OVERDOSAGE:
DIFFERIN Gel is intended for cutaneous use only. If the medication is applied excessively |
