DailyMed Label: Differin

DailyMed Label: Differin

2023

DailyMed Prescription

Differin

adapalene

Galderma Laboratories, L.P.

NDC: 0299-5912

NDC: 0299-5912

NDC: 0299-5912

DIFFERIN (adapalene) Lotion, for topical use, contains adapalene in a white to off-white oil-in-water emulsion. Adapalene is a naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene is (6-[3-(1-adamantyl)-4methoxyphenyl]- 2-naphthoic acid). Adapalene has the following structural formula: Adapalene: Molecular formula: C 28 H 28 O 3                                                         Molecular weight: 412.5 Each gram of DIFFERIN Lotion contains 1 mg of adapalene. The lotion also contains the following inactive ingredients: carbomer 941, disodium edetate, medium chain triglycerides, methylparaben, phenoxyethanol, poloxamer 124, polyoxyl-6-polyoxyl-32 palmitostearate, PPG12/SMDI copolymer, propylene glycol, propylparaben, purified water, sodium hydroxide, and stearyl alcohol. differin structural Formula

DIFFERIN Lotion is indicated for the topical treatment of acne vulgaris in patients 12 years and older. DIFFERIN Lotion is a retinoid product indicated for the topical treatment of acne vulgaris in patients 12 years and older.. (1)

Wash affected areas gently with a mild soapless cleanser. Dispense a nickel size amount of DIFFERIN Lotion (3-4 actuations of the pump) and apply a thin film to the entire face and other affected areas of the skin once daily. Avoid application to the areas of skin around eyes, lips and mucous membranes. DIFFERIN Lotion is for topical use only and not for oral, ophthalmic, or intravaginal use. Apply once daily, after washing gently with a mild soapless cleanser. ( 2 ) Dispense a nickel size amount of DIFFERIN Lotion (3-4 actuations of the pump) to cover the entire face and other affected areas of the skin. ( 2 ) Avoid application to the areas of skin around eyes, lips and mucous membranes. ( 2 ) For topical use only and not for oral, ophthalmic, or intravaginal use. ( 2 )

Lotion, 0.1%. Each gram of the lotion contains 1 mg of adapalene in a white to off-white oil-in-water emulsion. DIFFERIN Lotion is available in 2 oz bottle with pump. Lotion, 0.1% in 2 oz bottle with pump.  (3)

DIFFERIN Lotion is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of DIFFERIN Lotion [ see WARNINGS AND PRECAUTIONS ( 5.1 ) ] Contraindicated in patients with known hypersensitivity to adapalene or any excipient of DIFFERIN Lotion. ( 4 )

Allergic/ Hypersensitivity Reactions: Allergy/hypersensitivity reactions include anaphylaxis, angioedema, urticaria, and pruritis. Discontinue DIFFERIN Lotion in the event of an allergic/hypersensitivity reaction. ( 5.1 ) Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight and sunlamps. Wear sunscreen when sun exposure cannot be avoided. ( 5.2 ) Local Cutaneous reactions: Erythema, scaling, dryness, and stinging/burning may occur with use of DIFFERIN Lotion. Avoid application of DIFFERIN Lotion to cuts, abrasions, eczematous or sunburned skin. Avoid concomitant use of other potentially irritating topical products (abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes). ( 5.3 ) Anaphylaxis, angioedema, urticaria, face edema, eyelid edema, lip swelling, and pruritus that sometimes required medical treatment have been reported during postmarketing use of adapalene. Advise a patient to stop using DIFFERIN Lotion and seek medical attention if experiencing allergic or anaphylactoid/anaphylactic reactions during treatment. Avoid exposure to sunlight, including sunlamps, during the use of DIFFERIN Lotion. Patients with high levels of sun exposure and those with inherent sensitivity to sun should be warned to exercise caution. Use of sunscreen products and protective apparel (e.g., hat) are recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, may be irritating to patients under treatment with DIFFERIN Lotion.. Signs and symptoms of local skin irritation (such as erythema, scaling, dryness, stinging/burning) may be experienced with use of DIFFERIN Lotion. These are most likely to occur during the first 2 weeks of treatment, are mostly mild to moderate in severity, and usually lessen with continued use of DIFFERIN Lotion. Depending upon the severity of these side effects, patients should be instructed to use a moisturizer, reduce the frequency of the application of DIFFERIN Lotion or discontinue use. Avoid application of DIFFERIN Lotion 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 DIFFERIN Lotion. Avoid concomitant use of other potentially irritating topical products (abrasive soaps and cleansers, soaps and cosmetics that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes).

Risk Summary Available data from clinical trials with DIFFERIN Lotion use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of adapalene to pregnant rats and rabbits during organogenesis at dose exposures 122 and 243 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 2 g resulted in fetal skeletal and visceral malformations ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data No malformations were observed in rats treated with oral adapalene doses of 0.15 to 5.0 mg/kg/day, up to 24 times the MRHD based on a mg/m2 comparison. However, malformations were observed in rats and rabbits when treated with oral doses of ≥ 25 mg/kg/day adapalene (122 and 243 times the MRHD, respectively, based on a mg/m 2 comparison). Findings included cleft palate, microphthalmia, encephalocele, and skeletal abnormalities in rats and umbilical hernia, exophthalmos, and kidney and skeletal abnormalities in rabbits. Dermal adapalene embryofetal development studies in rats and rabbits at doses up to 6.0 mg/kg/day (29 and 58 times the MRHD, respectively, based on a mg/m 2 comparison) exhibited no fetotoxicity and only minimal increases in skeletal variations (supernumerary ribs in both species and delayed ossification in rabbits). Risk Summary There are no data on the presence of topical adapalene lotion or its metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, adapalene is present in rat milk with oral administration of the drug. When a drug is present in animal milk, it is likely that the drug will be present in human milk. It is possible that topical administration of large amounts of adapalene could result in sufficient systemic absorption to produce detectable quantities in human milk ( see Clinical Considerations ). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DIFFERIN Lotion and any potential adverse effects on the breastfed child from DIFFERIN Lotion or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breastmilk, use DIFFERIN Lotion on the smallest area of skin and for the shortest duration possible while breastfeeding. Avoid application of DIFFERIN Lotion to areas with increased risk for potential ingestion by or ocular exposure to the breastfeeding child. Safety and effectiveness of DIFFERIN Lotion in pediatric patients under the age of 12 have not been established. Clinical studies of DIFFERIN Lotion did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

DIFFERIN (adapalene) Lotion, 0.1%, is a white to off-white liquid packaged in a 2 oz (59 mL) bottle which is equipped with a lotion dispensing pump. DIFFERIN Lotion is supplied as follows: 2 oz bottle pump NDC 0299-5912-02 Storage and handling Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F). [see USP Controlled Room Temperature] Do not freeze. Do not refrigerate. Protect from light. Keep out of reach of children. Keep away from heat. Keep bottle tightly closed.

Adapalene binds to specific retinoic acid nuclear receptors but does not bind to cytosolic receptor protein. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization and inflammatory processes. However, the significance of these findings with regard to the mechanism of action of adapalene for the treatment of acne is unknown. Pharmacodynamics of DIFFERIN Lotion is unknown. Systemic exposure of adapalene following a topical application of DIFFERIN Lotion was studied in two pharmacokinetic (PK) clinical trials. The first trial was conducted in 14 adult subjects 18 to 29 years of age with severe acne and the second trial was conducted in 13 adolescent subjects 12 to 17 years of age with moderate to severe acne. In each trial, subjects were treated with 2 g of DIFFERIN Lotion applied once daily to approximately 1000 cm² of acne involved skin for 28 days (adolescent subjects) or 30 days (adult subjects). Serial plasma samples were collected at 24 or 72 hours following application on days 1, 15 and 28/30. Daily topical application of DIFFERIN Lotion resulted in low systemic exposure to adapalene in the two populations (adult and adolescent subjects). In the adult population, all plasma concentrations in 12 out of 14 subjects were below the limit of quantification (LOQ=0.1 ng/mL). One subject had one sample above LOQ at day 30 and the other subject had four plasma samples above LOQ on both days 1 and 15, which ranged from 0.102 and 0.131 ng/mL. In the adolescent population, plasma concentrations were quantifiable (>0.1 ng/mL) in five subjects. On Day 28, the mean C max was 0.128 ± 0.049 ng/mL (range: <0.100 to 0.244 ng/mL) and the mean of AUC 0-24hr was 3.07 ± 1.21 ng.hr/mL (range: 1.86 to 4.93 ng.hr/mL). Adapalene plasma concentrations in all subjects were below the limit of quantification (<0.1 ng/mL) 48 hours after the last application on Day 28.

No carcinogenicity, genotoxicity, or impairment of fertility studies were conducted with DIFFERIN Lotion. Carcinogenicity studies with adapalene were conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m 2 /day) and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day (0.9, 3.0, and 9.0 mg/m 2 /day). The highest dose levels are 9.8 (mice) and 7.4 (rats) times the MRHD based on a mg/m 2 comparison. In the rat study, an increased incidence of benign and malignant pheochromocytomas in the adrenal medulla of male rats was observed. Adapalene was not mutagenic or genotoxic in vitro (Ames test, Chinese hamster ovary cell assay, or mouse lymphoma TK assay) or in vivo (mouse micronucleus test). In rat oral studies, 20 mg/kg/day adapalene (97 times the MRHD based on a mg/m 2 comparison) did not affect the reproductive performance and fertility of F 0 males and females or the growth, development, or reproductive function of F 1 offspring.

The safety and efficacy of DIFFERIN Lotion applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical trials of similar design, comparing DIFFERIN Lotion to the lotion vehicle in acne subjects. In Trial 1, 1075 subjects were randomized to DIFFERIN Lotion or vehicle. The median age of these subjects was 16.7 years old and 53.1% were females. At baseline subjects had between 20 to 50 inflammatory lesions and 30 to 100 non-inflammatory lesions. The majority of subjects (91.0%) had a baseline IGA score of ‘Moderate’. In Trial 2, 1066 subjects were randomized to DIFFERIN Lotion or vehicle. The median age of subjects was 16.7 years old and 53.7% were females. At baseline subjects had the same inclusion criteria as in Trial 1 and 95.7% of subjects had a baseline IGA score of ‘Moderate’. The outcome of the two trials is presented in Table 3. Table 3: Clinical Trial Primary Efficacy Results at Week 12 Trial 1 DIFFERIN Lotion (N = 533) Vehicle Lotion (N = 542) IGA Success 140 (26.3%) 95 (17.3%) Total Lesions: Mean Absolute (Percent) Change 37.9 (51.5%) 26.7 (37.1%) Inflammatory Lesions: Mean Absolute (Percent) Change 14.7 (54.9%) 10.6 (40.3%) Non-inflammatory Lesions: Mean Absolute (Percent) Change 23.2 (49.6%) 16.1 (35.7%) Trial 2 DIFFERIN Lotion (N = 535) Vehicle Lotion (N = 531) IGA Success 129 (24.1%) 87 (16.4%) Total Lesions: Mean Absolute (Percent) Change 32.4 (44.6%) 23.4 (32.8%) Inflammatory Lesions: Mean Absolute (Percent) Change 12.7 (46.0%) 10.2 (36.9%) Non-inflammatory Lesions: Mean Absolute (Percent) Change 19.6 (43.1%) 13.1 (30.2%)