DIFFERIN Lotion is indicated for the topical treatment of acne vulgaris in patients 12 years and older.

{ "type": "p", "children": [], "text": "DIFFERIN Lotion is indicated for the topical treatment of acne vulgaris in patients 12 years and older." }

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.

{ "type": "p", "children": [], "text": "Wash affected areas gently with a mild soapless cleanser. \n \n 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. \n \n Avoid application to the areas of skin around eyes, lips and mucous membranes. \n \n DIFFERIN Lotion is for topical use only and not for oral, ophthalmic, or intravaginal use.\n " }

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.

{ "type": "p", "children": [], "text": "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." }

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

{ "type": "p", "children": [], "text": "DIFFERIN Lotion is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of DIFFERIN Lotion [\n \n see WARNINGS AND PRECAUTIONS (\n \n 5.1)\n \n ]\n\n " }

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).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials 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. A 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.

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <caption> <span>Table 1: Adverse Reactions Reported in Clinical Trials by At Least 1% of Subjects</span> </caption> <col/> <col/> <col/> <tbody class="Headless HeadlessHeadless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">System Organ Class/Preferred Term</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Adapalene Lotion 0.1% <br/> N = 1068 </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle Lotion <br/> N = 1073 </span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Subjects with Related AR(s)</span></td><td align="center" class="Botrule Lrule Rrule Toprule">10.2%</td><td align="center" class="Botrule Lrule Rrule Toprule">4.6%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Dry Skin</td><td align="center" class="Botrule Lrule Rrule Toprule">7.7%</td><td align="center" class="Botrule Lrule Rrule Toprule">3.0%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Skin irritation</td><td align="center" class="Botrule Lrule Rrule Toprule">1.5%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.7%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">   Skin burning/skin discomfort</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.0%</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">   Sunburn</td><td align="center" class="Botrule Lrule Rrule Toprule">0.6%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.6%</td> </tr> </tbody> </table></div>

Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials. Erythema, scaling, dryness, burning/stinging were assessed:

<div class="scrollingtable"><table border="1" cellpadding="4"> <caption> <span>Table 2: Incidence of Local Cutaneous Irritation, for Subjects Whose Irritation Score was Higher than at Baseline, in Controlled Clinical Trials Adverse Reactions (DIFFERIN Lotion Group N = 1057*)</span> </caption> <col/> <col/> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule">Combined Trial 1 and Trial 2</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3">Maximum Severity During Treatment <br/> (N = 1057) </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3">Week 12 Treatment Severity <br/> (N = 950) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Local Cutaneous Irritation (skin irritation)</td><td align="center" class="Botrule Lrule Rrule Toprule">Mild</td><td align="center" class="Botrule Lrule Rrule Toprule">Moderate</td><td align="center" class="Botrule Lrule Rrule Toprule">Severe</td><td align="center" class="Botrule Lrule Rrule Toprule">Mild</td><td align="center" class="Botrule Lrule Rrule Toprule">Moderate</td><td align="center" class="Botrule Lrule Rrule Toprule">Severe</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Erythema</td><td align="center" class="Botrule Lrule Rrule Toprule">21.8%</td><td align="center" class="Botrule Lrule Rrule Toprule">8.0%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.2%</td><td align="center" class="Botrule Lrule Rrule Toprule">7.9%</td><td align="center" class="Botrule Lrule Rrule Toprule">2.6%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.2%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Scaling</td><td align="center" class="Botrule Lrule Rrule Toprule">25.3%</td><td align="center" class="Botrule Lrule Rrule Toprule">6.5%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.1%</td><td align="center" class="Botrule Lrule Rrule Toprule">5.3%</td><td align="center" class="Botrule Lrule Rrule Toprule">1.1%</td><td align="center" class="Botrule Lrule Rrule Toprule">0%</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Dryness</td><td align="center" class="Botrule Lrule Rrule Toprule">36.1%</td><td align="center" class="Botrule Lrule Rrule Toprule">7.3%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.3%</td><td align="center" class="Botrule Lrule Rrule Toprule">7.6%</td><td align="center" class="Botrule Lrule Rrule Toprule">2.0%</td><td align="center" class="Botrule Lrule Rrule Toprule">0%</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Stinging/burning</td><td align="center" class="Botrule Lrule Rrule Toprule">22.1%</td><td align="center" class="Botrule Lrule Rrule Toprule">7.0%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.9%</td><td align="center" class="Botrule Lrule Rrule Toprule">4.6%</td><td align="center" class="Botrule Lrule Rrule Toprule">1.0%</td><td align="center" class="Botrule Lrule Rrule Toprule">0.4%</td> </tr> </tbody> </table></div>

* Data from 11 subjects with missing data are not included

Local 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 8 out of 13 subjects.

The following adverse reactions have been identified during post approval use of adapalene: Immune system disorders:angioedema, face edema, lip swelling Skin disorders:application site pain Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

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 2comparison). 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 2comparison) 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, for topical use, contains adapalene in a white to off-white oil-in-water emulsion.

{ "type": "p", "children": [], "text": "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:

{ "type": "p", "children": [], "text": "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:

{ "type": "p", "children": [], "text": "Adapalene:" }

Molecular formula: C 28H 28O 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.

{ "type": "p", "children": [], "text": "Molecular formula: C\n \n 28H\n \n 28O\n \n 3                                                        Molecular weight: 412.5 \n 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.\n\n " }

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 maxwas 0.128 ± 0.049 ng/mL (range: <0.100 to 0.244 ng/mL) and the mean of AUC 0-24hrwas 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 2comparison. 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 2comparison) did not affect the reproductive performance and fertility of F 0males and females or the growth, development, or reproductive function of F 1offspring.

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.

{ "type": "p", "children": [], "text": "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’.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "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." }

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <caption> <span>Table 3: Clinical Trial Primary Efficacy Results at Week 12</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="right" class="Botrule Lrule Rrule Toprule">Trial 1</td><td align="center" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule">DIFFERIN Lotion <br/> (N = 533) </td><td align="center" class="Botrule Lrule Rrule Toprule">Vehicle Lotion <br/> (N = 542) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">IGA Success</td><td align="center" class="Botrule Lrule Rrule Toprule">140 (26.3%)</td><td align="center" class="Botrule Lrule Rrule Toprule">95 (17.3%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Total Lesions: Mean Absolute (Percent) Change</td><td align="center" class="Botrule Lrule Rrule Toprule">37.9 (51.5%)</td><td align="center" class="Botrule Lrule Rrule Toprule">26.7 (37.1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Inflammatory Lesions: Mean Absolute (Percent) Change</td><td align="center" class="Botrule Lrule Rrule Toprule">14.7 (54.9%)</td><td align="center" class="Botrule Lrule Rrule Toprule">10.6 (40.3%)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Non-inflammatory Lesions: Mean Absolute (Percent) Change</td><td align="center" class="Botrule Lrule Rrule Toprule">23.2 (49.6%)</td><td align="center" class="Botrule Lrule Rrule Toprule">16.1 (35.7%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"4\" cellspacing=\"0\">\n<caption>\n<span>Table 3: Clinical Trial Primary Efficacy Results at Week 12</span>\n</caption>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"right\" class=\"Botrule Lrule Rrule Toprule\">Trial 1</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">DIFFERIN Lotion \n <br/> (N = 533)\n </td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Vehicle Lotion \n <br/> (N = 542)\n </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">IGA Success</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">140 (26.3%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">95 (17.3%)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">Total Lesions: Mean Absolute (Percent) Change</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">37.9 (51.5%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">26.7 (37.1%)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">Inflammatory Lesions: Mean Absolute (Percent) Change</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">14.7 (54.9%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">10.6 (40.3%)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">Non-inflammatory Lesions: Mean Absolute (Percent) Change</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">23.2 (49.6%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">16.1 (35.7%)</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <col/> <col/> <col/> <tbody class="Headless HeadlessHeadless"> <tr class="First"> <td align="right" class="Botrule Lrule Rrule Toprule">Trial 2</td><td align="center" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule">DIFFERIN Lotion <br/> (N = 535) </td><td align="center" class="Botrule Lrule Rrule Toprule">Vehicle Lotion <br/> (N = 531) </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">IGA Success</td><td align="center" class="Botrule Lrule Rrule Toprule">129 (24.1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">87 (16.4%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Total Lesions: Mean Absolute (Percent) Change</td><td align="center" class="Botrule Lrule Rrule Toprule">32.4 (44.6%)</td><td align="center" class="Botrule Lrule Rrule Toprule">23.4 (32.8%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Inflammatory Lesions: Mean Absolute (Percent) Change</td><td align="center" class="Botrule Lrule Rrule Toprule">12.7 (46.0%)</td><td align="center" class="Botrule Lrule Rrule Toprule">10.2 (36.9%)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Non-inflammatory Lesions: Mean Absolute (Percent) Change</td><td align="center" class="Botrule Lrule Rrule Toprule">19.6 (43.1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">13.1 (30.2%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"4\" cellspacing=\"0\">\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless HeadlessHeadless\">\n<tr class=\"First\">\n<td align=\"right\" class=\"Botrule Lrule Rrule Toprule\">Trial 2</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">DIFFERIN Lotion \n <br/> (N = 535)\n </td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Vehicle Lotion \n <br/> (N = 531)\n </td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">IGA Success</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">129 (24.1%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">87 (16.4%)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">Total Lesions: Mean Absolute (Percent) Change</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">32.4 (44.6%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">23.4 (32.8%)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">Inflammatory Lesions: Mean Absolute (Percent) Change</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">12.7 (46.0%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">10.2 (36.9%)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">Non-inflammatory Lesions: Mean Absolute (Percent) Change</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">19.6 (43.1%)</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">13.1 (30.2%)</td>\n</tr>\n</tbody>\n</table></div>" }

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.

{ "type": "p", "children": [], "text": "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:

{ "type": "p", "children": [], "text": "DIFFERIN Lotion is supplied as follows:" }

2 oz bottle pump NDC 0299-5912-02

{ "type": "p", "children": [], "text": "2 oz bottle pump\n \n NDC 0299-5912-02\n" }

Storage and handling

{ "type": "p", "children": [], "text": "Storage and handling" }

{ "type": "ul", "children": [ "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] \n \n", "Do not freeze.", "Do not refrigerate.", "Protect from light.", "Keep out of reach of children.", "Keep away from heat.", "Keep bottle tightly closed." ], "text": "" }

Patients using DIFFERIN Lotion should receive the following information and instructions:

{ "type": "p", "children": [], "text": "Patients using DIFFERIN Lotion should receive the following information and instructions:" }

{ "type": "ul", "children": [ "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.", "Do not apply to cuts, abrasions, eczematous, or sunburned skin. ", "Wax depilation should not be performed on treated skin due to the potential for skin erosions.", "DIFFERIN Lotion may cause irritation such as erythema, scaling, dryness, stinging or burning. 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 product is for external use only.", "Contact the doctor if skin rash, pruritus, hives, chest pain, edema, and shortness of breath occurs, as these may be signs of allergy or hypersensitivity.", "Lactation: Use DIFFERIN Lotion on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply DIFFERIN Lotion to areas with increased risk for potential ingestion by or ocular exposure to the breastfeeding child. [See\n \n Use in Specific Populations, Lactation (8.2)] \n \n" ], "text": "" }

Marketed by: GALDERMA LABORATORIES, L.P., Dallas, Texas 75201 USA Made in Canada. All trademarks are property of their respective owners. P51503-X

{ "type": "p", "children": [], "text": "Marketed by: \n GALDERMA LABORATORIES, L.P., Dallas, Texas 75201 USA \n \n Made in Canada. \n All trademarks are property of their respective owners. \n P51503-X\n " }

Patient Information DIFFERIN® (Dif-er-in) (adapalene) Lotion

{ "type": "p", "children": [], "text": "Patient Information \n DIFFERIN® (Dif-er-in) \n (adapalene) \n Lotion\n " }

Important:DIFFERIN Lotion is for use on the skin only (topical). Do not use DIFFERIN Lotion in or on your mouth, eyes, or vagina.

{ "type": "p", "children": [], "text": "\nImportant:DIFFERIN Lotion is for use on the skin only (topical). Do not use DIFFERIN Lotion in or on your mouth, eyes, or vagina.\n\n " }

What is DIFFERIN Lotion? DIFFERIN Lotion is a 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.

{ "type": "p", "children": [], "text": "\nWhat is DIFFERIN Lotion? \n \nDIFFERIN Lotion is a prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years of age and older. \n It is not known if DIFFERIN Lotion is safe and effective in children under 12 years of age.\n\n " }

Do not use DIFFERIN Lotion if youare allergic to adapalene or any of the ingredients in DIFFERIN Lotion. See the end of this Patient Information leaflet for a complete list of ingredients in DIFFERIN Lotion.

{ "type": "p", "children": [], "text": "\nDo not use DIFFERIN Lotion if youare allergic to adapalene or any of the ingredients in DIFFERIN Lotion. See the end of this Patient Information leaflet for a complete list of ingredients in DIFFERIN Lotion.\n\n " }

Before using DIFFERIN Lotion, tell your healthcare provider about all your medical conditions, including if you:

{ "type": "p", "children": [], "text": "\nBefore using DIFFERIN Lotion, tell your healthcare provider about all your medical conditions, including if you:\n" }

{ "type": "ul", "children": [ "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 child’s mouth or eyes." ], "text": "" }

Tell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins and herbal supplements.

{ "type": "p", "children": [], "text": "\nTell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins and herbal supplements.\n\n " }

How should I use DIFFERIN Lotion?

{ "type": "p", "children": [], "text": "\nHow should I use DIFFERIN Lotion?\n" }

{ "type": "ul", "children": [ "Use DIFFERIN Lotion exactly as your healthcare provider tells you to use it. ", "Apply DIFFERIN Lotion 1 time a day." ], "text": "" }

Applying DIFFERIN Lotion:

{ "type": "p", "children": [], "text": "\nApplying DIFFERIN Lotion:\n" }

{ "type": "ul", "children": [ "Wash the area where DIFFERIN Lotion will be applied gently with a mild soapless cleanser and pat dry.", "DIFFERIN Lotion comes in a pump. Dispense a nickel size amount of DIFFERIN Lotion (3 to 4 pumps) and apply a thin layer over the entire face and any other affected area of the skin.\n \n Do notapply DIFFERIN Lotion on areas of the skin around your eyes, lips, nose and mouth.\n \n ", "Wash your hands after applying DIFFERIN Lotion." ], "text": "" }

What should I avoid while using DIFFERIN Lotion?

{ "type": "p", "children": [], "text": "\nWhat should I avoid while using DIFFERIN Lotion?\n" }

{ "type": "ul", "children": [ "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 a 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. ", "\nDo notapply DIFFERIN Lotion to cuts, abrasions, sunburned skin, or skin that is dry, itchy or red. \n \n ", "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 a hair removal method on skin treated with DIFFERIN Lotion." ], "text": "" }

What are the possible side effects of DIFFERIN Lotion? DIFFERIN Lotion may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of DIFFERIN Lotion? \n DIFFERIN Lotion may cause serious side effects, including:\n \n" }

{ "type": "ul", "children": [ "\nAllergic 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:\n \n \nskin rash, itching or hives \ntrouble breathing or chest pain \nswelling of your face, eyes, lips, tongue or throat \n\n", "\nSkin 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 2 weeks of treatment, and usually lessen with continued use of DIFFERIN Lotion. Your healthcare provider may tell you to use a moisturizer, decrease how often you use DIFFERIN Lotion, or stop treatment with DIFFERIN Lotion if you get any skin reactions. If you use a moisturizer, you should avoid moisturizers that contain alpha hydroxy or glycolic acid. Ask your healthcare provider or pharmacist if you are not sure. \n \n" ], "text": "" }

The most common side effects of DIFFERIN Lotion includedry skin and skin irritation. These are not all the possible side effects of DIFFERIN Lotion.

{ "type": "p", "children": [], "text": "\nThe most common side effects of DIFFERIN Lotion includedry skin and skin irritation. \n These are not all the possible side effects of DIFFERIN Lotion.\n\n " }

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.

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. \n You may also report side effects to Galderma Laboratories, L.P. at 1-866-735-4137.\n " }

How should I store DIFFERIN Lotion?

{ "type": "p", "children": [], "text": "\nHow should I store DIFFERIN Lotion?\n" }

{ "type": "ul", "children": [ "Store DIFFERIN Lotion at room temperature between 68° F to 77° F (20° C to 25° C).", "\nDo notfreeze or refrigerate DIFFERIN Lotion. \n \n ", "Keep DIFFERIN Lotion out of light and away from heat. ", "Keep the DIFFERIN Lotion bottle tightly closed." ], "text": "" }

Keep DIFFERIN Lotion and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep DIFFERIN Lotion and all medicines out of the reach of children.\n" }

General information about the safe and effective use of DIFFERIN Lotion. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use DIFFERIN Lotion for a 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.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of DIFFERIN Lotion.\n Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use DIFFERIN Lotion for a 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.\n\n " }

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.

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in DIFFERIN Lotion? \n \nActive ingredient:adapalene \n \nInactive 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.\n\n " }

Marketed by: GALDERMA LABORATORIES, L.P., Dallas, Texas 75201 USA Made in Canada. GALDERMA is a registered trademark. P51503-X This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 04/2023 

{ "type": "p", "children": [], "text": "Marketed by: GALDERMA LABORATORIES, L.P., Dallas, Texas 75201 USA \n Made in Canada. \n GALDERMA is a registered trademark. \n P51503-X \n \n This Patient Information has been approved by the U.S. Food and Drug Administration. \n Issued: 04/2023 \n " }

Rx Only NDC0299-5912-02 Differin® (adapalene) Lotion 0.1% For External Use Only 2 FL OZ (59 mL) GALDERMA For external use only. Not for ophthalmic, oral or intravaginal use. Usual dosage:Apply a thin film on the entire face and other affected areas of the skin once daily. See package insert for complete prescribing information. Each gram contains:adapalene 1 mg (0.1%) in an aqueous based lotion consisting of 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, sodium hydroxide, stearyl alcohol, and purified water. Storage:Store at controlled room temperature 68° - 77°F (20° - 25°C) with excursions permitted between 59° - 86°F (15° - 30°C). Do not freeze or refrigerate. Marketed by: GALDERMA LABORATORIES, L.P. Dallas, TX 75201 Made in Canada. All trademarks are the property of their respective owners. P51638-5

{ "type": "p", "children": [], "text": "\nRx Only\n\n\nNDC0299-5912-02 \n \n Differin® \n (adapalene) Lotion 0.1% \n \n For External \n Use Only \n \n 2 FL OZ \n (59 mL) \n \n GALDERMA \n \n\nFor external use only.\n\n\nNot for ophthalmic, oral or intravaginal use.\n\n\nUsual dosage:Apply a thin film on the entire face and other affected areas of the skin once daily. See package insert for complete prescribing information. \n \n\nEach gram contains:adapalene 1 mg (0.1%) in an aqueous based lotion consisting of the following inactive ingredients: \n carbomer 941, disodium edetate, medium chain triglycerides, methylparaben, phenoxyethanol, poloxamer 124, polyoxyl-6-polyoxyl-32 palmitostearate, PPG-12/SMDI copolymer, propylene glycol, propylparaben, sodium hydroxide, stearyl alcohol, and purified water. \n \n\nStorage:Store at controlled room temperature 68° - 77°F (20° - 25°C) with excursions permitted between 59° - 86°F (15° - 30°C). Do not freeze or refrigerate. \n \n Marketed by: \n GALDERMA LABORATORIES, L.P. \n Dallas, TX 75201 \n Made in Canada. \n All trademarks are the property of their respective owners. \n P51638-5\n\n " }

Adapalene Gel, 0.3% is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

{ "type": "p", "children": [], "text": "Adapalene Gel, 0.3% is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older." }

Wash affected areas gently with a non-medicated soap. Apply a thin film of Adapalene Gel, 0.3% to the entire face and any other affected areas of the skin once daily in the evening. Avoid application to the areas of skin around eyes, lips, and mucous membranes. A mild transitory sensation of warmth or slight stinging may occur shortly after the application of Adapalene Gel, 0.3%.

{ "type": "p", "children": [], "text": "Wash affected areas gently with a non-medicated soap. Apply a thin film of Adapalene Gel, 0.3% to the entire face and any other affected areas of the skin once daily in the evening. Avoid application to the areas of skin around eyes, lips, and mucous membranes. A mild transitory sensation of warmth or slight stinging may occur shortly after the application of Adapalene Gel, 0.3%." }

Instruct patients to minimize sun exposure and to use moisturizers for relief of dry skin or irritation.

{ "type": "p", "children": [], "text": "Instruct patients to minimize sun exposure and to use moisturizers for relief of dry skin or irritation." }

If therapeutic results are not noticed after 12 weeks of treatment, therapy should be re-evaluated. For topical use only. Not for ophthalmic, oral or intravaginal use.

{ "type": "p", "children": [], "text": "If therapeutic results are not noticed after 12 weeks of treatment, therapy should be re-evaluated. For topical use only. Not for ophthalmic, oral or intravaginal use." }

Each gram of Adapalene Gel, 0.3% contains 3 mg adapalene in an off-white aqueous gel.

{ "type": "p", "children": [], "text": "Each gram of Adapalene Gel, 0.3% contains 3 mg adapalene in an off-white aqueous gel." }

Adapalene Gel, 0.3% is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of Adapalene Gel, 0.3% [see WARNINGS AND PRECAUTIONS (5.1)] .

{ "type": "p", "children": [], "text": "Adapalene Gel, 0.3% is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of Adapalene Gel, 0.3%\n \n [see\n \n WARNINGS AND PRECAUTIONS (5.1)]\n \n .\n\n " }

Adverse reactions including anaphylaxis angioedema, 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 Adapalene Gel, 0.3% and seek medical attention if experiencing allergic or anaphylactoid/anaphylactic reactions during treatment.

Exposure to sunlight, including sunlamps, should be minimized during use of Adapalene Gel, 0.3%. 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 Gel, 0.3%.

Cutaneous signs and symptoms such as erythema, scaling, dryness, and stinging/burning were reported with use of Adapalene Gel, 0.3%. These were most likely to occur during the first four weeks of treatment, were mostly mild to moderate in intensity, and usually lessened with continued use of the medication.

Depending upon the severity of these side effects, patients should be instructed to either use a moisturizer, reduce the frequency of application of Adapalene Gel, 0.3% or discontinue use.

Avoid application 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.

As adapalene gel has the potential to induce 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.

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In the multi-center, controlled clinical trial, signs and symptoms of local cutaneous irritation were monitored in 258 acne subjects who used Adapalene Gel, 0.3% once daily for 12 weeks. Of the subjects who experienced cutaneous irritation (erythema, scaling, dryness, and/or burning/stinging), the majority of cases were mild to moderate in severity, occurred early in treatment and decreased thereafter. The incidence of local cutaneous irritation with Adapalene Gel, 0.3% from the controlled clinical trial is provided in the following table:

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 1: Physician assessed local cutaneous irritation with Adapalene Gel, 0.3% Incidence of Local Cutaneous Irritation with Adapalene Gel, 0.3% (N = 253 <a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a>) Maximum Severity Scores Higher Than Baseline </span> </caption> <col align="left" valign="middle" width="25%"/> <col align="center" valign="middle" width="25%"/> <col align="center" valign="middle" width="25%"/> <col align="center" valign="middle" width="25%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule"></th><th align="center" class="Rrule">Mild</th><th align="center" class="Rrule">Moderate</th><th align="center" class="Rrule">Severe</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Total number of subjects with local cutaneous data for at least one post-Baseline evaluation.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Erythema</td><td align="center" class="Rrule">66 (26.1%)</td><td align="center" class="Rrule">33 (13%)</td><td align="center" class="Rrule">1 (0.4%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Scaling</td><td align="center" class="Rrule">110 (43.5%)</td><td align="center" class="Rrule">47 (18.6%)</td><td align="center" class="Rrule">3 (1.2%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Dryness</td><td align="center" class="Rrule">113 (44.7%)</td><td align="center" class="Rrule">43 (17%)</td><td align="center" class="Rrule">2 (0.8%)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Burning/Stinging</td><td align="center" class="Rrule">72 (28.5%)</td><td align="center" class="Rrule">36 (14.2%)</td><td align="center" class="Rrule">9 (3.6%)</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 2: Patient reported local cutaneous adverse reactions with Adapalene Gel, 0.3%</span> </caption> <col align="left" valign="top" width="34%"/> <col align="center" valign="top" width="33%"/> <col align="center" valign="top" width="33%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="2"></th><th align="center" class="Rrule" valign="middle">Adapalene Gel, 0.3%</th><th align="center" class="Rrule" valign="middle">Vehicle Gel</th> </tr> <tr class="Last"> <th align="center" class="Rrule">N=258</th><th align="center" class="Rrule">N=134</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Selected adverse reactions defined by investigator as Possibly, Probably or Definitely Related</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule">Related <a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a>Adverse Reactions </td><td align="center" class="Rrule">57 (22.1%)</td><td align="center" class="Rrule">6 (4.5%)</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Dry Skin</td><td align="center" class="Rrule">36 (14%)</td><td align="center" class="Rrule">2 (1.5%)</td> </tr> <tr> <td align="left" class="Lrule Rrule">  Skin Discomfort</td><td align="center" class="Rrule">15 (5.8%)</td><td align="center" class="Rrule">0 (0%)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Desquamation</td><td align="center" class="Rrule">4 (1.6%)</td><td align="center" class="Rrule">0 (0%)</td> </tr> </tbody> </table></div>

The following adverse reactions occurred in less than 1% of subjects: acne flare, contact dermatitis, eyelid edema, conjunctivitis, erythema, pruritus, skin discoloration, rash, and eczema.

In a one-year, open-label safety trial of 551 subjects with acne who received Adapalene Gel, 0.3%, the pattern of adverse reactions was similar to the 12-week controlled study.

The following adverse reactions have been identified during post approval use of adapalene:

Immune system disorders:angioedema, face edema, lip swelling

Skin disorders:application site pain

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Risk Summary

Available data from clinical trials with Adapalene Gel, 0.3% 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 40 and 81 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 mg/kg/day, up to 8 times the MRHD based on a mg/m 2comparison. However, malformations were observed in rats and rabbits when treated with oral doses of ≥ 25 mg/kg/day adapalene (40 and 81 times the MRHD, respectively, based on a mg/m 2comparison). 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 mg/kg/day (9.7 and 19.5 times the MRHD, respectively, based on a mg/m 2comparison) 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 gel 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 Adapalene Gel, 0.3% and any potential adverse effects on the breastfed child from Adapalene Gel, 0.3%, or from the underlying maternal condition.

Clinical Considerations

To minimize potential exposure to the breastfed infant via breastmilk, use Adapalene Gel, 0.3% on the smallest area of skin and for the shortest duration possible while breastfeeding. Avoid application of Adapalene Gel, 0.3% to areas with increased risk for potential ingestion by or ocular exposure to the breastfeeding child.

Safety and effectiveness have not been established in pediatric patients below the age of 12.

Clinical studies of Adapalene Gel, 0.3% did not include subjects 65 years of age and older to determine whether they respond differently than younger subjects. Safety and effectiveness in geriatric patients age 65 and above have not been established.

Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of vitamin A.

{ "type": "p", "children": [], "text": "Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of vitamin A." }

Adapalene Gel, 0.3% contains adapalene 0.3% (3 mg/g) in a topical aqueous gel for use in the treatment of acne vulgaris, consisting of carbomer homopolymer type C, edetate disodium, methylparaben, poloxamer 182, propylene glycol, purified water and sodium hydroxide.

{ "type": "p", "children": [], "text": "Adapalene Gel, 0.3% contains adapalene 0.3% (3 mg/g) in a topical aqueous gel for use in the treatment of acne vulgaris, consisting of carbomer homopolymer type C, edetate disodium, methylparaben, poloxamer 182, propylene glycol, purified water and sodium hydroxide." }

The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid. It is a white to off-white powder, which is soluble in tetrahydrofuran, very slightly soluble in ethanol, and practically insoluble in water. The molecular formula is C 28H 28O 3and molecular weight is 412.53. Adapalene is represented by the following structural formula.

{ "type": "p", "children": [], "text": "The chemical name of adapalene is 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid. It is a white to off-white powder, which is soluble in tetrahydrofuran, very slightly soluble in ethanol, and practically insoluble in water. The molecular formula is C\n \n 28H\n \n 28O\n \n 3and molecular weight is 412.53. Adapalene is represented by the following structural formula.\n\n " }

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.

Clinical pharmacodynamic studies have not been conducted for Adapalene Gel, 0.3%.

Systemic exposure of adapalene following topical application of Adapalene Gel, 0.3% was evaluated in a clinical trial. Sixteen acne subjects were treated once daily for 10 days with 2 grams of Adapalene Gel, 0.3% applied to the face, chest and back, corresponding to approximately 2 mg/cm 2. Fifteen subjects had quantifiable (LOQ = 0.1 ng/mL) adapalene levels resulting in a mean C maxof 0.553 ± 0.466 ng/mL on Day 10 of treatment. The mean AUC 0-24hrwas 8.37 ± 8.46 ng∙h/mL as determined in 15 of the 16 subjects on Day 10. The terminal apparent half-life, determined in 15 of 16 subjects, ranged from 7 to 51 hours, with a mean of 17.2 ± 10.2 hours. Adapalene was rapidly cleared from plasma and was not detected 72 hours after the last application for all but one subject. Exposure of potential circulating metabolites of adapalene was not measured. Excretion of adapalene appears to be primarily by the biliary route.

In another clinical trial in subjects with moderate to moderately severe acne, Adapalene Gel, 0.3% or Adapalene Gel, 0.1% was applied to the face and optionally to the trunk, once daily for 12 weeks. Seventy-eight (78) subjects had plasma adapalene levels evaluated at Weeks 2, 8, and 12. Of the 209 plasma samples analyzed, adapalene concentrations were below the limit of detection (LOD = 0.15 ng/mL) of the method in all samples but three. For the three samples, traces of adapalene below the limit of quantification (LOQ = 0.25 ng/mL) of the method were found. One of these samples was taken at Week 12 from a male subject treated with Adapalene Gel, 0.3% who treated the face and the trunk for eight weeks (thereafter, only the face was treated). The second and third samples were from the Week 2 and 12 visits of a female subject treated with Adapalene Gel, 0.1% who treated only the face for 12 weeks. In this study, the average daily usage of product was 1 g/day.

No carcinogenicity, genotoxicity, or impairment of fertility studies were conducted with Adapalene Gel, 0.3%.

Carcinogenicity studies with adapalene were conducted in mice at topical doses of 0.4, 1.3, and 4 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, and 9.0 mg/m 2/day). The highest dose levels are 3.2 (mice) and 2.4 (rats) times the MRHD based on a mg/m 2comparison. In the rat study, an increased incidence of benign and malignant pheochromocytomas reported 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 (32 times the MRHD based on a mg/m 2comparison) did not affect the reproductive performance and fertility of F 0males and females or the growth, development, or reproductive function of F 1offspring.

The safety and efficacy of once daily use of Adapalene Gel, 0.3% for treatment of acne vulgaris were assessed in one 12 week, multi-center, controlled, clinical trial, conducted in a total of 653 subjects 12 to 52 years of age with acne vulgaris of mild to moderate severity. All female subjects of child-bearing potential enrolled in the trial were required to have a negative urine pregnancy test at the beginning of the trial and were required to practice a highly effective method of contraception during the trial. Female subjects who were pregnant, nursing or planning to become pregnant were excluded from the trial.

{ "type": "p", "children": [], "text": "The safety and efficacy of once daily use of Adapalene Gel, 0.3% for treatment of acne vulgaris were assessed in one 12 week, multi-center, controlled, clinical trial, conducted in a total of 653 subjects 12 to 52 years of age with acne vulgaris of mild to moderate severity. All female subjects of child-bearing potential enrolled in the trial were required to have a negative urine pregnancy test at the beginning of the trial and were required to practice a highly effective method of contraception during the trial. Female subjects who were pregnant, nursing or planning to become pregnant were excluded from the trial." }

Subjects enrolled in the trial were Caucasian (72%), Hispanic (12%), African-American (10%), Asian (3%), and other (2%). An equal number of males (49.5%) and females (50.5%) enrolled. Success was defined as "Clear" or "Almost Clear" in the Investigator's Global Assessment (IGA). The success rate, mean reduction, and percent reduction in acne lesion counts from Baseline after 12 weeks of treatment are presented in the following table:

{ "type": "p", "children": [], "text": "Subjects enrolled in the trial were Caucasian (72%), Hispanic (12%), African-American (10%), Asian (3%), and other (2%). An equal number of males (49.5%) and females (50.5%) enrolled. Success was defined as \"Clear\" or \"Almost Clear\" in the Investigator's Global Assessment (IGA). The success rate, mean reduction, and percent reduction in acne lesion counts from Baseline after 12 weeks of treatment are presented in the following table:" }

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 3: Clinical study primary efficacy results at Week 12</span> </caption> <col align="left" valign="top" width="28%"/> <col align="center" valign="top" width="24%"/> <col align="center" valign="top" width="24%"/> <col align="center" valign="top" width="24%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="2"></th><th align="center" class="Rrule">Adapalene Gel, 0.3%</th><th align="center" class="Rrule">Adapalene Gel, 0.1%</th><th align="center" class="Rrule">Vehicle Gel</th> </tr> <tr class="Last"> <th align="center" class="Rrule">N=258</th><th align="center" class="Rrule">N=261</th><th align="center" class="Rrule">N=134</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">IGA Success Rate</td><td align="center" class="Rrule">53 (21%)</td><td align="center" class="Rrule">41 (16%)</td><td align="center" class="Rrule">12 (9%)</td> </tr> <tr> <td align="left" class="Lrule Rrule">Inflammatory Lesions</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Mean Baseline Count</td><td align="center" class="Botrule Rrule" valign="middle">27.7</td><td align="center" class="Botrule Rrule" valign="middle">28.1</td><td align="center" class="Botrule Rrule" valign="middle">27.2</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean Absolute (%) Reduction</td><td align="center" class="Rrule">14.4 (51.6%)</td><td align="center" class="Rrule">13.9 (49.7%)</td><td align="center" class="Rrule">11.2 (40.7%)</td> </tr> <tr> <td align="left" class="Lrule Rrule">Non-inflammatory Lesions</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Mean Baseline Count</td><td align="center" class="Botrule Rrule" valign="middle">39.4</td><td align="center" class="Botrule Rrule" valign="middle">41</td><td align="center" class="Botrule Rrule" valign="middle">40</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">  Mean Absolute (%) Reduction</td><td align="center" class="Rrule">16.3 (39.7%)</td><td align="center" class="Rrule">15.2 (35.2%)</td><td align="center" class="Rrule">10.3 (27.2%)</td> </tr> <tr> <td align="left" class="Lrule Rrule">Total Lesions</td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td><td align="center" class="Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule">  Mean Baseline Count</td><td align="center" class="Botrule Rrule" valign="middle">67.1</td><td align="center" class="Botrule Rrule" valign="middle">69.1</td><td align="center" class="Botrule Rrule" valign="middle">67.2</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">  Mean Absolute (%) Reduction</td><td align="center" class="Rrule">30.6 (45.3%)</td><td align="center" class="Rrule">29 (41.8%)</td><td align="center" class="Rrule">21.4 (33.7%)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"90%\">\n<caption>\n<span>Table 3: Clinical study primary efficacy results at Week 12</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"28%\"/>\n<col align=\"center\" valign=\"top\" width=\"24%\"/>\n<col align=\"center\" valign=\"top\" width=\"24%\"/>\n<col align=\"center\" valign=\"top\" width=\"24%\"/>\n<thead>\n<tr class=\"Botrule First\">\n<th align=\"left\" class=\"Lrule Rrule\" rowspan=\"2\"></th><th align=\"center\" class=\"Rrule\">Adapalene Gel, 0.3%</th><th align=\"center\" class=\"Rrule\">Adapalene Gel, 0.1%</th><th align=\"center\" class=\"Rrule\">Vehicle Gel</th>\n</tr>\n<tr class=\"Last\">\n<th align=\"center\" class=\"Rrule\">N=258</th><th align=\"center\" class=\"Rrule\">N=261</th><th align=\"center\" class=\"Rrule\">N=134</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\">IGA Success Rate</td><td align=\"center\" class=\"Rrule\">53 (21%)</td><td align=\"center\" class=\"Rrule\">41 (16%)</td><td align=\"center\" class=\"Rrule\">12 (9%)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Inflammatory Lesions</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">  Mean Baseline Count</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">27.7</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">28.1</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">27.2</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">  Mean Absolute (%) Reduction</td><td align=\"center\" class=\"Rrule\">14.4 (51.6%)</td><td align=\"center\" class=\"Rrule\">13.9 (49.7%)</td><td align=\"center\" class=\"Rrule\">11.2 (40.7%)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Non-inflammatory Lesions</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">  Mean Baseline Count</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">39.4</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">41</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">40</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">  Mean Absolute (%) Reduction</td><td align=\"center\" class=\"Rrule\">16.3 (39.7%)</td><td align=\"center\" class=\"Rrule\">15.2 (35.2%)</td><td align=\"center\" class=\"Rrule\">10.3 (27.2%)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Total Lesions</td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">  Mean Baseline Count</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">67.1</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">69.1</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"middle\">67.2</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\">  Mean Absolute (%) Reduction</td><td align=\"center\" class=\"Rrule\">30.6 (45.3%)</td><td align=\"center\" class=\"Rrule\">29 (41.8%)</td><td align=\"center\" class=\"Rrule\">21.4 (33.7%)</td>\n</tr>\n</tbody>\n</table></div>" }

S torage:Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].

Protect from freezing. Keep out of reach of children.

Information for Patients

Patients using Adapalene Gel, 0.3% should receive the following information and instructions:

Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1 Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532

{ "type": "p", "children": [], "text": "Mfd. by: Taro Pharmaceuticals Inc., \n Brampton, Ontario, Canada L6T 1C1 \n Dist. by:\n \n Taro Pharmaceuticals U.S.A., Inc., \n Hawthorne, NY 10532\n\n " }

Revised: 6/2024

{ "type": "p", "children": [], "text": "Revised: 6/2024" }

5251769 28

{ "type": "p", "children": [], "text": "5251769 28" }

Adapalene (a dap` a leen) Gel, 0.3%

{ "type": "p", "children": [], "text": "\nAdapalene (a dap` a leen) Gel, 0.3%\n" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="55%"/> <col align="right" valign="top" width="45%"/> <tfoot> <tr class="First Last"> <td align="left" valign="top">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="right" valign="top">Revised: June 2024</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Important:</span>Adapalene Gel, 0.3% is for use on the skin only (topical). Do not use Adapalene Gel, 0.3% in or on your mouth, eyes, or vagina. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What is Adapalene Gel, 0.3%?</span> <br/> Adapalene Gel, 0.3% is a prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years of age and older. <br/> It is not known if Adapalene Gel, 0.3% is safe and effective in children under 12 years of age or in people 65 years of age and older. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Do not use Adapalene Gel, 0.3% if you</span>are allergic to adapalene or any of the ingredients in Adapalene Gel, 0.3%. See the end of this Patient Information leaflet for a complete list of ingredients in Adapalene Gel, 0.3%. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Before using Adapalene Gel, 0.3% tell your healthcare provider about all your medical conditions, including if you:</span> <ul class="Disc"> <li>have other skin problems, including cuts, abrasions, sunburn, or skin that is dry, itchy, or red.</li> <li>are pregnant or plan to become pregnant. It is not known if Adapalene Gel, 0.3%, can harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. It is not known if adapalene 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 Adapalene Gel, 0.3%. If you use Adapalene Gel, 0.3% while breastfeeding, use Adapalene Gel, 0.3% on the smallest area of the skin and for the shortest time needed. Do not apply Adapalene Gel, 0.3% to areas that may increase the risk of getting Adapalene Gel, 0.3% in your child's mouth or eyes.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">How should I use Adapalene Gel, 0.3%?</span> <ul class="Disc"> <li>Use Adapalene Gel, 0.3% exactly as your healthcare provider tells you to use it.</li> <li>Apply Adapalene Gel, 0.3% 1 time a day in the evening.</li> <li>Tell your healthcare provider if you do not notice a difference in your acne after using Adapalene Gel, 0.3% for 12 weeks.</li> </ul> <span class="Bold">Applying Adapalene Gel, 0.3%:</span> <ul class="Disc"> <li>Wash the area where Adapalene Gel, 0.3% will be applied with a mild soap that does not contain a medicine and pat dry.</li> <li>Adapalene Gel, 0.3% comes in a tube and a pump. If you have been prescribed the: <ul class="Circle"> <li>Tube: Squeeze a small amount onto your fingertips and spread a thin layer over the entire face and any other affected areas.</li> <li>Pump: Depress the pump to dispense a small amount of Adapalene Gel, 0.3% and spread a thin layer over the entire face and any other affected area.</li> <li> <span class="Bold">Do not</span>apply Adapalene Gel, 0.3% on areas of the skin around your eyes, lips, nose, and mouth. </li> </ul> </li> <li>Wash your hands after applying Adapalene Gel, 0.3%.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What should I avoid while using Adapalene Gel, 0.3%?</span> <ul class="Disc"> <li>Avoid spending time in sunlight, including sunlamps. Adapalene Gel, 0.3% 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 Adapalene Gel, 0.3% if you have to be in sunlight.</li> <li>Cold weather and wind may irritate your skin treated with Adapalene Gel, 0.3%.</li> <li> <span class="Bold">Do not</span>apply Adapalene Gel, 0.3% to cuts, abrasions, sunburned skin, or skin that is dry, itchy, or red. </li> <li>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.</li> <li>Avoid the use of "waxing" as a hair removal method on skin treated with Adapalene Gel, 0.3%.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What are the possible side effects of Adapalene Gel, 0.3%? <br/> Adapalene Gel, 0.3% may cause serious side effects including: </span> <ul class="Disc"> <li> <span class="Bold">Allergic reactions.</span>Adapalene Gel, 0.3% may cause serious allergic reactions that sometimes may require medical treatment. Stop using Adapalene Gel, 0.3% and tell your healthcare provider or get medical help right away if you have any of these symptoms of an allergic reaction: <ul class="Circle"> <li>skin rash, itching or hives</li> <li>trouble breathing or chest pain</li> <li>swelling of your face, eyes, lips, tongue or throat</li> </ul> </li> <li> <span class="Bold">Skin reactions at the treated site.</span>Adapalene Gel, 0.3% may cause skin reactions including redness, scaling, dryness, stinging, and burning. These skin reactions are most likely to happen during the first 4 weeks of treatment, and usually lessen with continued use of Adapalene Gel, 0.3%. Your healthcare provider may tell you to use a moisturizer, decrease how often you use Adapalene Gel, 0.3%, or stop treatment with Adapalene Gel, 0.3%, if you get any skin reactions. If you use a moisturizer, you should avoid moisturizers that contain alpha hydroxy or glycolic acid. Ask your healthcare provider or pharmacist if you are not sure. </li> </ul> <span class="Bold">The most common side effects of Adapalene Gel, 0.3% include</span>dry skin, skin pain, itching, and skin peeling. <br/> These are not all the possible side effects of Adapalene Gel, 0.3% . <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. <br/> You may also report side effects to Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914. <br/> <span class="Bold">How should I store Adapalene Gel, 0.3%?</span> <ul class="Disc"> <li>Store Adapalene Gel, 0.3% at room temperature between 68° F to 77° F (20° C to 25° C).</li> <li> <span class="Bold">Do not</span>freeze Adapalene Gel, 0.3% </li> </ul> <span class="Bold">Keep Adapalene Gel, 0.3% and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">General information about the safe and effective use of Adapalene Gel, 0.3%</span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Adapalene Gel, 0.3% for a condition for which it was not prescribed. Do not give Adapalene Gel, 0.3% to other people, even if they have the same symptoms you have. It may harm them. You can also ask your pharmacist or healthcare provider for information about Adapalene Gel, 0.3% that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What are the ingredients in Adapalene Gel, 0.3%?</span> <br/> <span class="Bold">Active ingredient</span>: adapalene <br/> <span class="Bold">Inactive ingredients:</span>carbomer homopolymer type C, edetate disodium, methylparaben, poloxamer 182, propylene glycol, purified water and sodium hydroxide <br/> Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1 <br/> Dist. by: <span class="Bold">Taro Pharmaceuticals U.S.A., Inc.</span>, Hawthorne, NY 10532 </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"55%\"/>\n<col align=\"right\" valign=\"top\" width=\"45%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" valign=\"top\">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" valign=\"top\">Revised: June 2024</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Important:</span>Adapalene Gel, 0.3% is for use on the skin only (topical). Do not use Adapalene Gel, 0.3% in or on your mouth, eyes, or vagina.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What is Adapalene Gel, 0.3%?</span>\n<br/> Adapalene Gel, 0.3% is a prescription medicine used on the skin (topical) to treat acne vulgaris in people 12 years of age and older. \n <br/> It is not known if Adapalene Gel, 0.3% is safe and effective in children under 12 years of age or in people 65 years of age and older.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Do not use Adapalene Gel, 0.3% if you</span>are allergic to adapalene or any of the ingredients in Adapalene Gel, 0.3%. See the end of this Patient Information leaflet for a complete list of ingredients in Adapalene Gel, 0.3%.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Before using Adapalene Gel, 0.3% tell your healthcare provider about all your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have other skin problems, including cuts, abrasions, sunburn, or skin that is dry, itchy, or red.</li>\n<li>are pregnant or plan to become pregnant. It is not known if Adapalene Gel, 0.3%, can harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if adapalene 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 Adapalene Gel, 0.3%. If you use Adapalene Gel, 0.3% while breastfeeding, use Adapalene Gel, 0.3% on the smallest area of the skin and for the shortest time needed. Do not apply Adapalene Gel, 0.3% to areas that may increase the risk of getting Adapalene Gel, 0.3% in your child's mouth or eyes.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">How should I use Adapalene Gel, 0.3%?</span>\n<ul class=\"Disc\">\n<li>Use Adapalene Gel, 0.3% exactly as your healthcare provider tells you to use it.</li>\n<li>Apply Adapalene Gel, 0.3% 1 time a day in the evening.</li>\n<li>Tell your healthcare provider if you do not notice a difference in your acne after using Adapalene Gel, 0.3% for 12 weeks.</li>\n</ul>\n<span class=\"Bold\">Applying Adapalene Gel, 0.3%:</span>\n<ul class=\"Disc\">\n<li>Wash the area where Adapalene Gel, 0.3% will be applied with a mild soap that does not contain a medicine and pat dry.</li>\n<li>Adapalene Gel, 0.3% comes in a tube and a pump. If you have been prescribed the:\n \n <ul class=\"Circle\">\n<li>Tube: Squeeze a small amount onto your fingertips and spread a thin layer over the entire face and any other affected areas.</li>\n<li>Pump: Depress the pump to dispense a small amount of Adapalene Gel, 0.3% and spread a thin layer over the entire face and any other affected area.</li>\n<li>\n<span class=\"Bold\">Do not</span>apply Adapalene Gel, 0.3% on areas of the skin around your eyes, lips, nose, and mouth.\n \n </li>\n</ul>\n</li>\n<li>Wash your hands after applying Adapalene Gel, 0.3%.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What should I avoid while using Adapalene Gel, 0.3%?</span>\n<ul class=\"Disc\">\n<li>Avoid spending time in sunlight, including sunlamps. Adapalene Gel, 0.3% 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 Adapalene Gel, 0.3% if you have to be in sunlight.</li>\n<li>Cold weather and wind may irritate your skin treated with Adapalene Gel, 0.3%.</li>\n<li>\n<span class=\"Bold\">Do not</span>apply Adapalene Gel, 0.3% to cuts, abrasions, sunburned skin, or skin that is dry, itchy, or red.\n \n </li>\n<li>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.</li>\n<li>Avoid the use of \"waxing\" as a hair removal method on skin treated with Adapalene Gel, 0.3%.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What are the possible side effects of Adapalene Gel, 0.3%? \n <br/> Adapalene Gel, 0.3% may cause serious side effects including:\n </span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Allergic reactions.</span>Adapalene Gel, 0.3% may cause serious allergic reactions that sometimes may require medical treatment. Stop using Adapalene Gel, 0.3% and tell your healthcare provider or get medical help right away if you have any of these symptoms of an allergic reaction:\n \n <ul class=\"Circle\">\n<li>skin rash, itching or hives</li>\n<li>trouble breathing or chest pain</li>\n<li>swelling of your face, eyes, lips, tongue or throat</li>\n</ul>\n</li>\n<li>\n<span class=\"Bold\">Skin reactions at the treated site.</span>Adapalene Gel, 0.3% may cause skin reactions including redness, scaling, dryness, stinging, and burning. These skin reactions are most likely to happen during the first 4 weeks of treatment, and usually lessen with continued use of Adapalene Gel, 0.3%. Your healthcare provider may tell you to use a moisturizer, decrease how often you use Adapalene Gel, 0.3%, or stop treatment with Adapalene Gel, 0.3%, if you get any skin reactions. If you use a moisturizer, you should avoid moisturizers that contain alpha hydroxy or glycolic acid. Ask your healthcare provider or pharmacist if you are not sure.\n \n </li>\n</ul>\n<span class=\"Bold\">The most common side effects of Adapalene Gel, 0.3% include</span>dry skin, skin pain, itching, and skin peeling. \n <br/> These are not all the possible side effects of Adapalene Gel, 0.3% . \n <br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. \n <br/> You may also report side effects to Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914. \n <br/>\n<span class=\"Bold\">How should I store Adapalene Gel, 0.3%?</span>\n<ul class=\"Disc\">\n<li>Store Adapalene Gel, 0.3% at room temperature between 68° F to 77° F (20° C to 25° C).</li>\n<li>\n<span class=\"Bold\">Do not</span>freeze Adapalene Gel, 0.3%\n \n </li>\n</ul>\n<span class=\"Bold\">Keep Adapalene Gel, 0.3% and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">General information about the safe and effective use of Adapalene Gel, 0.3%</span>\n<br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Adapalene Gel, 0.3% for a condition for which it was not prescribed. Do not give Adapalene Gel, 0.3% to other people, even if they have the same symptoms you have. It may harm them. You can also ask your pharmacist or healthcare provider for information about Adapalene Gel, 0.3% that is written for health professionals.\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What are the ingredients in Adapalene Gel, 0.3%?</span>\n<br/>\n<span class=\"Bold\">Active ingredient</span>: adapalene \n <br/>\n<span class=\"Bold\">Inactive ingredients:</span>carbomer homopolymer type C, edetate disodium, methylparaben, poloxamer 182, propylene glycol, purified water and sodium hydroxide \n <br/> Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1 \n <br/> Dist. by:\n \n <span class=\"Bold\">Taro Pharmaceuticals U.S.A., Inc.</span>, Hawthorne, NY 10532\n \n </td>\n</tr>\n</tbody>\n</table></div>" }

45 g

{ "type": "p", "children": [], "text": "\n45 g\n" }

NDC 51672-1377-9

{ "type": "p", "children": [], "text": "\nNDC 51672-1377-9\n" }

Adapalene Gel 0.3%

{ "type": "p", "children": [], "text": "\nAdapalene \n Gel 0.3%\n \n" }

PUMP

{ "type": "p", "children": [], "text": "\nPUMP\n" }

FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL OR INTRAVAGINAL USE.

{ "type": "p", "children": [], "text": "\nFOR TOPICAL USE ONLY.\n NOT FOR OPHTHALMIC, \n ORAL OR INTRAVAGINAL USE.\n\n " }

Keep this and all medications out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep this and all \n medications out of the \n reach of children.\n \n" }

Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

TARO

{ "type": "p", "children": [], "text": "\nTARO\n" }