ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. Dry skin of mild to moderate severity was the most frequently reported (>= 1%) treatment related adverse event. Erythema, scaling, dryness, burning/stinging were also seen during treatment. (6)To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L.P. at 1-866-735-4137 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.A total of 2141 subjects with acne vulgaris, 12 years and older, were treated once daily for 12 weeks. Of these, 1068 were exposed to DIFFERIN Lotion during the clinical trials. total of 1057 subjects completed at least one post treatment evaluation.Related adverse reactions that were reported in at least 1% of subjects treated with DIFFERIN Lotion or with the Vehicle Lotion are presented in Table 1.The majority of cases were transient, mild to moderate in severity and were managed with moisturizers.Table 1: Adverse Reactions Reported in Clinical Trials by At Least 1% of SubjectsSystem Organ Class/Preferred TermAdapalene Lotion 0.1%N 1068Vehicle LotionN 1073Subjects with Related AR(s)10.2%4.6% Dry Skin7.7%3.0% Skin irritation1.5%0.7% Skin burning/skin discomfort0.9%0.0% Sunburn0.6%0.6%Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials. Erythema, scaling, dryness, burning/stinging were assessed:Table 2: Incidence of Local Cutaneous Irritation, for Subjects Whose Irritation Score was Higher than Baseline, in Controlled Clinical Trials Adverse Reactions (DIFFERIN Lotion Group = 1057)Combined Trial and Trial 2Maximum Severity During Treatment(N 1057)Week 12 Treatment Severity(N 950)Local Cutaneous Irritation (skin irritation)MildModerateSevereMildModerateSevereErythema21.8%8.0%0.2%7.9%2.6%0.2%Scaling25.3%6.5%0.1%5.3%1.1%0%Dryness36.1%7.3%0.3%7.6%2.0%0%Stinging/burning22.1%7.0%0.9%4.6%1.0%0.4% Data from 11 subjects with missing data are not includedLocal tolerability scores for erythema, scaling, dryness, burning/stinging rose during the first two weeks of treatment and generally decreased thereafter.In an open label postmarketing pharmacokinetic trial of 13 adolescent subjects, the adverse reaction of pruritus was reported in out of 13 subjects.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity, mutagenicity and impairment of fertility studies were conducted with DIFFERIN Lotion. Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m2/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/m2/day). In terms of body surface area, the highest dose levels are 9.8 (mice) and 7.4 times (rats) the MRHD of grams of DIFFERIN Lotion. In the rat study, an increased incidence of benign and malignant pheochromocytomas in the adrenal medulla of male rats was observed. No photocarcinogenicity studies were conducted with adapalene. However, 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 sunlight. Although the significance of these findings to humans is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial irradiation sources. Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo (mouse micronucleus test). In rat oral studies, 20 mg adapalene/kg/day (120 mg/m2/day; 98 times the MRHD based on mg/m2/day comparison) did not affect the reproductive performance and fertility of F0 males and females, or growth, development and reproductive function of F1 offspring.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. 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 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.. 12.2 Pharmacodynamics. Pharmacodynamics of DIFFERIN Lotion is unknown.. 12.3 Pharmacokinetics. Systemic exposure of adapalene following 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 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 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 Cmax was 0.128 +- 0.049 ng/mL (range: <0.100 to 0.244 ng/mL) and the mean of AUC0-24hr 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.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 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 studies 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 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 and 95.7% of subjects had 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 12Trial 1DIFFERIN Lotion (N 533)Vehicle Lotion(N 542)IGA Success140 (26.3%)95 (17.3%)Total Lesions: Mean Absolute (Percent) Change37.9 (51.5%)26.7 (37.1%)Inflammatory Lesions: Mean Absolute (Percent) Change14.7 (54.9%)10.6 (40.3%)Non-inflammatory Lesions: Mean Absolute (Percent) Change23.2 (49.6%)16.1 (35.7%)Trial 2DIFFERIN Lotion (N 535)Vehicle Lotion(N 531)IGA Success129 (24.1%)87 (16.4%)Total Lesions: Mean Absolute (Percent) Change32.4 (44.6%)23.4 (32.8%)Inflammatory Lesions: Mean Absolute (Percent) Change12.7 (46.0%)10.2 (36.9%)Non-inflammatory Lesions: Mean Absolute (Percent) Change19.6 (43.1%)13.1 (30.2%).

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.. None. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. DIFFERIN (adapalene) Lotion, 0.1% for topical use, contains adapalene in white to off-white oil-in-water emulsion.Adapalene is naphthoic acid derivative with retinoid-like properties. The chemical name for adapalene is (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid). Adapalene has the following structural formula:Adapalene:Molecular formula: C28H28O3 Molecular weight: 412.5Each gram of DIFFERIN Lotion contains 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, PPG-12/SMDI copolymer, propylene glycol, propylparaben, purified water, sodium hydroxide, and stearyl alcohol.. differin structural Formula.

DOSAGE & ADMINISTRATION SECTION.

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

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Lotion, 0.1%. Each gram of the lotion contains mg of adapalene in white to off-white oil-in-water emulsion.. Lotion, 0.1% (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. Concomitant use of topical products with strong drying effect can increase skin irritation. Use with caution, especially in using preparations containing sulfur, resorcinol, or salicylic acid in combination with DIFFERIN Lotion. (7.1) . Concomitant topical acne therapy should be used with caution because possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. Caution should be exercised in using preparation containing sulfur, resorcinol or salicylic acid in combination with DIFFERIN Lotion. No formal drug-drug interaction studies were conducted with DIFFERIN Lotion.

GERIATRIC USE SECTION.

8.5 Geriatric Use. 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.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. DIFFERIN (adapalene) Lotion, 0.1%, is white to off-white liquid packaged in 2 oz (59 mL) bottle which is equipped with lotion dispensing pump.DIFFERIN Lotion is supplied as follows:2 oz bottle pump NDC 0299-5912-02 Storage and handlingStore at 20C to 25C (68F to 77F), excursions permitted between 15C and 30C (between 59F and 86F). [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.. Do not freeze.. Do not refrigerate.. Protect from light.. Keep out of reach of children.. Keep away from heat.. Keep bottle tightly closed.

INDICATIONS & USAGE SECTION.

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

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Apply thin film of DIFFERIN Lotion to the affected areas of the skin once daily, after washing gently with mild soapless cleanser. Dispense nickel size amount of DIFFERIN Lotion (3-4 actuations of the pump) to cover the entire face. Avoid application to the areas of skin around eyes, lips and mucous membranes. DIFFERIN Lotion may cause irritation such as erythema, scaling, dryness, stinging or burning.Advise patients to cleanse the area to be treated with mild or soapless cleanser; pat dry. Apply DIFFERIN Lotion to the entire face or other acne affected areas as thin layer, avoiding the eyes, lips and mucous membranes.Exposure of the eye to this medication may result in reactions such as swelling, conjunctivitis and eye irritation.Patients should be advised not to use more than the recommended amount and not to apply more than once daily as this will not produce faster results, but may increase irritation.Advise patients to minimize exposure to sunlight including sunlamps. Recommend the use of sunscreen products and protective apparel (e.g., hat) when exposure cannot be avoided.Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided.This medication should not be applied to cuts, abrasions, eczematous, or sunburned skin.Wax depilation should not be performed on treated skin due to the potential for skin erosions.This product is for external use only.Marketed by:GALDERMA LABORATORIES, L.P., Fort Worth, Texas 76177 USAManufactured by:G Production Inc., Baie dUrfe, QC, H9X 3S4 CanadaMade in Canada.GALDERMA is registered trademark.P51503-2. Apply thin film of DIFFERIN Lotion to the affected areas of the skin once daily, after washing gently with mild soapless cleanser. Dispense nickel size amount of DIFFERIN Lotion (3-4 actuations of the pump) to cover the entire face. Avoid application to the areas of skin around eyes, lips and mucous membranes. DIFFERIN Lotion may cause irritation such as erythema, scaling, dryness, stinging or burning.. Advise patients to cleanse the area to be treated with mild or soapless cleanser; pat dry. Apply DIFFERIN Lotion to the entire face or other acne affected areas as thin layer, avoiding the eyes, lips and mucous membranes.. Exposure of the eye to this medication may result in reactions such as swelling, conjunctivitis and eye irritation.. Patients should be advised not to use more than the recommended amount and not to apply more than once daily as this will not produce faster results, but may increase irritation.. Advise patients to minimize exposure to sunlight including sunlamps. Recommend the use of sunscreen products and protective apparel (e.g., hat) when exposure cannot be avoided.. Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided.. This medication should not be applied to cuts, abrasions, eczematous, or sunburned skin.. Wax depilation should not be performed on treated skin due to the potential for skin erosions.. This product is for external use only.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. 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 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.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity, mutagenicity and impairment of fertility studies were conducted with DIFFERIN Lotion. Carcinogenicity studies with adapalene have been conducted in mice at topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m2/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/m2/day). In terms of body surface area, the highest dose levels are 9.8 (mice) and 7.4 times (rats) the MRHD of grams of DIFFERIN Lotion. In the rat study, an increased incidence of benign and malignant pheochromocytomas in the adrenal medulla of male rats was observed. No photocarcinogenicity studies were conducted with adapalene. However, 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 sunlight. Although the significance of these findings to humans is not clear, patients should be advised to avoid or minimize exposure to either sunlight or artificial irradiation sources. Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo (mouse micronucleus test). In rat oral studies, 20 mg adapalene/kg/day (120 mg/m2/day; 98 times the MRHD based on mg/m2/day comparison) did not affect the reproductive performance and fertility of F0 males and females, or growth, development and reproductive function of F1 offspring.

NURSING MOTHERS SECTION.

8.3 Nursing Mothers. It is not known whether adapalene is excreted in human milk following use of DIFFERIN Lotion. Because many drugs are excreted in human milk, caution should be exercised when DIFFERIN Lotion is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL 2 FL OZ CARTON.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. Safety and effectiveness of DIFFERIN Lotion in pediatric patients under the age of 12 have not been established.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Pharmacodynamics of DIFFERIN Lotion is unknown.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Systemic exposure of adapalene following 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 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 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 Cmax was 0.128 +- 0.049 ng/mL (range: <0.100 to 0.244 ng/mL) and the mean of AUC0-24hr 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.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Category C. There are no well-controlled trials in pregnant women treated with DIFFERIN Lotion. Therefore, DIFFERIN Lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproduction studies have not been conducted with DIFFERIN Lotion. Furthermore, such studies are not always predictive of human response.Human DataIn clinical trials involving DIFFERIN Lotion, 0.1% in the treatment of acne vulgaris, women of childbearing potential initiated treatment only after negative pregnancy test. Two women became pregnant while using DIFFERIN Lotion, 0.1%. One patient delivered healthy full term baby and the other patient electively terminated her pregnancy.Animal DataNo teratogenic effects were observed in rats treated with oral doses of 0.15 to 5.0 mg adapalene/kg/day, up to 25 times (mg/m2/day) the maximum recommended human dose (MRHD) of grams of DIFFERIN Lotion. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of >= 25 mg adapalene/kg/day representing 123 and 246 times MRHD, respectively. Findings included cleft palate, microphthalmia, encephalocele and skeletal abnormalities in rats; and umbilical hernia, exophthalmos and kidney and skeletal abnormalities in rabbits.Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day [25-59 times (mg/m2) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.Systemic exposure (AUC 0-24h) to adapalene at topical doses (6.0 mg/kg/day) in rats represented 101 times the exposure to adapalene in patients with acne treated with DIFFERIN Lotion applied to the face, chest and back (2 grams applied to 1000 cm2 of acne-involved skin).

SPL UNCLASSIFIED SECTION.

5.1 Ultraviolet Light and Environmental Exposure. Exposure to sunlight, including sunlamps, should be avoided 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.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Pregnancy Category C. There are no well-controlled trials in pregnant women treated with DIFFERIN Lotion. Therefore, DIFFERIN Lotion should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproduction studies have not been conducted with DIFFERIN Lotion. Furthermore, such studies are not always predictive of human response.Human DataIn clinical trials involving DIFFERIN Lotion, 0.1% in the treatment of acne vulgaris, women of childbearing potential initiated treatment only after negative pregnancy test. Two women became pregnant while using DIFFERIN Lotion, 0.1%. One patient delivered healthy full term baby and the other patient electively terminated her pregnancy.Animal DataNo teratogenic effects were observed in rats treated with oral doses of 0.15 to 5.0 mg adapalene/kg/day, up to 25 times (mg/m2/day) the maximum recommended human dose (MRHD) of grams of DIFFERIN Lotion. However, teratogenic changes were observed in rats and rabbits when treated with oral doses of >= 25 mg adapalene/kg/day representing 123 and 246 times MRHD, respectively. Findings included cleft palate, microphthalmia, encephalocele and skeletal abnormalities in rats; and umbilical hernia, exophthalmos and kidney and skeletal abnormalities in rabbits.Dermal teratology studies conducted in rats and rabbits at doses of 0.6-6.0 mg adapalene/kg/day [25-59 times (mg/m2) the MRHD] exhibited no fetotoxicity and only minimal increases in supernumerary ribs in both species and delayed ossification in rabbits.Systemic exposure (AUC 0-24h) to adapalene at topical doses (6.0 mg/kg/day) in rats represented 101 times the exposure to adapalene in patients with acne treated with DIFFERIN Lotion applied to the face, chest and back (2 grams applied to 1000 cm2 of acne-involved skin).. 8.3 Nursing Mothers. It is not known whether adapalene is excreted in human milk following use of DIFFERIN Lotion. Because many drugs are excreted in human milk, caution should be exercised when DIFFERIN Lotion is administered to nursing woman.. 8.4 Pediatric Use. Safety and effectiveness of DIFFERIN Lotion in pediatric patients under the age of 12 have not been established.. 8.5 Geriatric Use. 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight and sunlamps. Wear sunscreen when sun exposure cannot be avoided. (5.1) Erythema, scaling, dryness, and stinging/burning may occur with use of DIFFERIN Lotion. (5.2) 5.1 Ultraviolet Light and Environmental Exposure. Exposure to sunlight, including sunlamps, should be avoided 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.. 5.2 Local Cutaneous Reactions. 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 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 moisturizer, reduce the frequency of the application of DIFFERIN Lotion 0.1%, or discontinue use. DIFFERIN Lotion should not be applied to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of waxing as 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).

LABOR & DELIVERY SECTION.

8.2 Lactation. 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 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 mothers clinical need for DIFFERIN Lotion and any potential adverse effects on the breastfed child from DIFFERIN Lotion or from the underlying maternal condition.Clinical ConsiderationsTo 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.

PATIENT MEDICATION INFORMATION SECTION.

PATIENT MEDICATION INFORMATION SECTION. Patient InformationDIFFERIN(R) (Dif-er-in) (adapalene) LotionImportant: DIFFERIN Lotion is for use on the skin only (topical). Do not use DIFFERIN Lotion in or on your mouth, eyes, or vagina.What is DIFFERIN Lotion DIFFERIN Lotion is prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years of age and older. It is not known if DIFFERIN Lotion is safe and effective in children under 12 years of age.Do not use DIFFERIN Lotion if you are allergic to adapalene or any of the ingredients in DIFFERIN Lotion. See the end of this Patient Information leaflet for complete list of ingredients in DIFFERIN Lotion.Before using DIFFERIN Lotion, tell your healthcare provider about all your medical conditions, including if you:have other skin problems, including cuts, abrasions, sunburn, or skin that is dry, itchy or redare pregnant or plan to become pregnant. It is not known if DIFFERIN Lotion can harm your unborn babyare breastfeeding or plan to breastfeed. It is not known if DIFFERIN Lotion passes into your breast milk and if it can harm your baby. Talk to your healthcare provider about the best way to feed your baby if you use DIFFERIN Lotion. If you use DIFFERIN Lotion while breastfeeding, use DIFFERIN Lotion on the smallest area of the skin and for the shortest time needed. Do not apply DIFFERIN Lotion to areas that may increase the risk of getting DIFFERIN Lotion in your childs mouth or eyes.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.How should use DIFFERIN LotionUse DIFFERIN Lotion exactly as your healthcare provider tells you to use it. Apply DIFFERIN Lotion time day.Applying DIFFERIN Lotion:Wash the area where DIFFERIN Lotion will be applied gently with mild soapless cleanser and pat dry.DIFFERIN Lotion comes in pump. Dispense nickel size amount of DIFFERIN Lotion (3 to pumps) and apply thin layer over the entire face and any other affected area of the skin. Do not apply DIFFERIN Lotion on areas of the skin around your eyes, lips, nose and mouth.Wash your hands after applying DIFFERIN Lotion.What should avoid while using DIFFERIN LotionAvoid spending time in sunlight, including sunlamps. DIFFERIN Lotion can make your skin sensitive to the sun and the light from sunlamps. Use sunscreen and wear hat and clothes that cover the areas treated with DIFFERIN Lotion if you have to be in sunlight. Cold weather and wind may irritate your skin treated with DIFFERIN Lotion. Do not apply DIFFERIN Lotion to cuts, abrasions, sunburned skin, or skin that is dry, itchy or red. Avoid skin products that may dry or irritate your skin such as harsh soaps or cleansers, soaps and cosmetics that make your skin dry, and products that contain high levels of alcohol, astringents, spices, or limes. Avoid the use of waxing as hair removal method on skin treated with DIFFERIN Lotion.What are the possible side effects of DIFFERIN Lotion DIFFERIN Lotion may cause serious side effects, including:Allergic reactions. DIFFERIN Lotion may cause serious allergic reactions that sometimes may require medical treatment. Stop using DIFFERIN Lotion and tell your healthcare provider or get medical help right away if you have any of these symptoms of an allergic reaction: skin rash, itching or hives trouble breathing or chest pain swelling of your face, eyes, lips, tongue or throat Skin reactions at the treated site. DIFFERIN Lotion may cause skin reactions including redness, scaling, dryness, stinging, or burning. These skin reactions are most likely to happen during the first weeks of treatment, and usually lessen with continued use of DIFFERIN Lotion. Your healthcare provider may tell you to use moisturizer, decrease how often you use DIFFERIN Lotion, or stop treatment with DIFFERIN Lotion if you get any skin reactions. If you use moisturizer, you should avoid moisturizers that contain alpha hydroxy or glycolic acid. Ask your healthcare provider or pharmacist if you are not sure. The most common side effects of DIFFERIN Lotion include dry skin and skin irritation. These are not all the possible side effects of DIFFERIN Lotion. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Galderma Laboratories, L.P. at 1-866-735-4137.How should store DIFFERIN LotionStore DIFFERIN Lotion at room temperature between 68 to 77 (20 to 25 C).Do not freeze or refrigerate DIFFERIN Lotion. Keep DIFFERIN Lotion out of light and away from heat. Keep the DIFFERIN Lotion bottle tightly closed.Keep DIFFERIN Lotion and all medicines out of the reach of children.General information about the safe and effective use of DIFFERIN Lotion.Medicines are sometimes prescribed for purposes other than those listed in Patient Information Leaflet. Do not use DIFFERIN Lotion for condition for which it was not prescribed. Do not give DIFFERIN Lotion to other people, even if they have the same symptoms you have. It may harm them. You can also ask your healthcare provider or pharmacist for information about DIFFERIN Lotion that is written for health professionals.What are the ingredients in DIFFERIN Lotion Active ingredient: adapalene Inactive ingredients: carbomer 941, disodium edetate, medium chain triglycerides, methylparaben, phenoxyethanol, poloxamer 124, polyoxyl-6-polyoxyl-32 palmitostearate, PPG-12/SMDI copolymer, propylene glycol, propylparaben, purified water, sodium hydroxide, and stearyl alcohol.Marketed by: GALDERMA LABORATORIES, L.P., Dallas, Texas 75201 USA Made in Canada. GALDERMA is registered trademark. P51503-X This Patient Information has been approved by the U.S. Food and Drug Administration.Issued: 04/2023 have other skin problems, including cuts, abrasions, sunburn, or skin that is dry, itchy or red. are pregnant or plan to become pregnant. It is not known if DIFFERIN Lotion can harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if DIFFERIN Lotion passes into your breast milk and if it can harm your baby. Talk to your healthcare provider about the best way to feed your baby if you use DIFFERIN Lotion. If you use DIFFERIN Lotion while breastfeeding, use DIFFERIN Lotion on the smallest area of the skin and for the shortest time needed. Do not apply DIFFERIN Lotion to areas that may increase the risk of getting DIFFERIN Lotion in your childs mouth or eyes.. Use DIFFERIN Lotion exactly as your healthcare provider tells you to use it. Apply DIFFERIN Lotion time day.. Wash the area where DIFFERIN Lotion will be applied gently with mild soapless cleanser and pat dry.. DIFFERIN Lotion comes in pump. Dispense nickel size amount of DIFFERIN Lotion (3 to pumps) and apply thin layer over the entire face and any other affected area of the skin. Do not apply DIFFERIN Lotion on areas of the skin around your eyes, lips, nose and mouth.. Wash your hands after applying DIFFERIN Lotion.. Avoid spending time in sunlight, including sunlamps. DIFFERIN Lotion can make your skin sensitive to the sun and the light from sunlamps. Use sunscreen and wear hat and clothes that cover the areas treated with DIFFERIN Lotion if you have to be in sunlight. Cold weather and wind may irritate your skin treated with DIFFERIN Lotion. Do not apply DIFFERIN Lotion to cuts, abrasions, sunburned skin, or skin that is dry, itchy or red. Avoid skin products that may dry or irritate your skin such as harsh soaps or cleansers, soaps and cosmetics that make your skin dry, and products that contain high levels of alcohol, astringents, spices, or limes. Avoid the use of waxing as hair removal method on skin treated with DIFFERIN Lotion.. Allergic reactions. DIFFERIN Lotion may cause serious allergic reactions that sometimes may require medical treatment. Stop using DIFFERIN Lotion and tell your healthcare provider or get medical help right away if you have any of these symptoms of an allergic reaction: skin rash, itching or hives trouble breathing or chest pain swelling of your face, eyes, lips, tongue or throat skin rash, itching or hives trouble breathing or chest pain swelling of your face, eyes, lips, tongue or throat Skin reactions at the treated site. DIFFERIN Lotion may cause skin reactions including redness, scaling, dryness, stinging, or burning. These skin reactions are most likely to happen during the first weeks of treatment, and usually lessen with continued use of DIFFERIN Lotion. Your healthcare provider may tell you to use moisturizer, decrease how often you use DIFFERIN Lotion, or stop treatment with DIFFERIN Lotion if you get any skin reactions. If you use moisturizer, you should avoid moisturizers that contain alpha hydroxy or glycolic acid. Ask your healthcare provider or pharmacist if you are not sure. Store DIFFERIN Lotion at room temperature between 68 to 77 (20 to 25 C).. Do not freeze or refrigerate DIFFERIN Lotion. Keep DIFFERIN Lotion out of light and away from heat. Keep the DIFFERIN Lotion bottle tightly closed.