These highlights do not include all the information needed to use adapalene lotion safely and effectively. See full prescribing information for adapalene lotion. Adapalene lotion, 0.1%For topical use Initial U.S. Approval: 1996
Drug Labeling and Warnings
Drug Details [pdf]
ADAPALENE- adapalene lotion
Owen Laboratories, Inc.
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use adapalene lotion safely and effectively. See full prescribing information for adapalene lotion.
Adapalene lotion, 0.1% For topical use Initial U.S. Approval: 1996 INDICATIONS AND USAGEAdapalene lotion is a retinoid product indicated for the topical treatment of acne vulgaris in patients 12 years and older. (1) DOSAGE AND ADMINISTRATIONApply a thin layer of adapalene lotion to the entire face and other affected areas of the skin once daily, after washing gently with a mild soapless cleanser. Dispense a nickel size amount of adapalene 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) adapalene lotion is for topical use only and not for oral, ophthalmic, or intravaginal use. (2) DOSAGE FORMS AND STRENGTHSLotion, 0.1%. (3) CONTRAINDICATIONSNone. (4) WARNINGS AND PRECAUTIONSADVERSE REACTIONSDry 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 DRUG INTERACTIONSConcomitant use of topical products with a strong drying effect can increase skin irritation. Use with caution, especially in using preparations containing sulfur, resorcinol, or salicylic acid in combination with adapalene lotion. (7.1) See 17 for PATIENT COUNSELING INFORMATION. Revised: 7/2014 |
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
Adapalene lotion is indicated for the topical treatment of acne vulgaris in patients 12 years and older.
2 DOSAGE AND ADMINISTRATION
Apply a thin layer of adapalene lotion to the entire face and other affected areas of the skin once daily, after washing gently with a mild soapless cleanser. Dispense a nickel size amount of adapalene 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.
Adapalene lotion is for topical use only and not for oral, ophthalmic, or intravaginal use.
3 DOSAGE FORMS AND STRENGTHS
Lotion, 0.1%. Each gram of the lotion contains 1 mg of adapalene in a white to off-white oil-in-water emulsion.
5 WARNINGS AND PRECAUTIONS
5.1 Ultraviolet Light and Environmental Exposure
Exposure to sunlight, including sunlamps, should be avoided during the use of adapalene 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 adapalene 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 adapalene 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 adapalene lotion. Depending upon the severity of these side effects, patients should be instructed to use a moisturizer, reduce the frequency of the application of adapalene lotion 0.1%, or discontinue use. Adapalene lotion should not be applied 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 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).
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a 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 adapalene 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 adapalene 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.
Local tolerability evaluations, presented in Table 2, were conducted at each study visit in clinical trials. Erythema, scaling, dryness, burning/
stinging were assessed:
*Date 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.
7 DRUG INTERACTIONS
7.1 Concomitant Topical Medications
Concomitant topical acne therapy should be used with caution because a 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 adapalene lotion.
No formal drug-drug interaction studies were conducted with adapalene lotion.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C. There are no well-controlled trials in pregnant women treated with adapalene lotion. Therefore, adapalene 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 adapalene lotion. Furthermore, such studies are not always predictive of human response.
Human Data
In clinical trials involving adapalene lotion, 0.1% in the treatment of acne vulgaris, women of childbearing potential initiated treatment only after a negative pregnancy test. Two women became pregnant while using adapalene lotion, 0.1%. One patient delivered a healthy full term baby and the other patient electively terminated her pregnancy.
Animal Data
No 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 2 grams of adapalene 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 (AUC0-24h) 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 adapalene 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 adapalene lotion. Because many drugs are excreted in human milk, caution should be exercised when adapalene lotion is administered to a nursing woman.
11 DESCRIPTION
Adapalene lotion, 0.1% 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)-4-methoxyphenyl]-2-naphthoic acid).
Adapalene has the following structural formula:
Adapalene:
Molecular formula: C28H28O3 Molecular weight: 412.5
Each gram of adapalene 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, PPG-12/SMDI copolymer, propylene glycol, propylparaben, purified water, sodium hydroxide, and stearyl alcohol.
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 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.
12.3 Pharmacokinetics
Systemic exposure of adapalene following a topical application of adapalene 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 adapalene lotion applied once daily applied 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 adapalene 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 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.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity, mutagenicity and impairment of fertility studies were conducted with adapalene 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 2 grams of adapalene 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.
14 CLINICAL STUDIES
The safety and efficacy of adapalene lotion applied once daily for the treatment of acne vulgaris were assessed in two 12-week, multicenter, controlled clinical trials of similar design, comparing adapalene lotion to the lotion vehicle in acne subjects.
In Trial 1, 1075 subjects were randomized to adapalene 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 adapalene 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.
16 HOW SUPPLIED/STORAGE AND HANDLING
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.
Adapalene lotion is supplied as follows:
2 oz bottle pump NDC: 69007-912-02
Storage and handling
- Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F). [see USP Controlled Room temperature]
- Do not freeze.
- Do not refrigerate.
- Protect from light.
- Keep out of reach of children.
- Keep away from heat.
- Keep bottle tightly closed.
17 PATIENT COUNSELING INFORMATION
- Apply a thin layer of adapalene lotion to the affected areas of the skin once daily, after washing gently with a mild soapless cleanser. Dispense a nickel size amount of adapalene 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. Adapalene lotion may cause irritation such as erythema, scaling, dryness, stinging or burning.
- Advise patients to cleanse the area to be treated with a mild or soapless cleanser; pat dry. Apply adapalene lotion to the entire face or other acne affected areas as a 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.
Distributed by:
Owen Laboratories, Inc., a Galderma Company
Fort Worth, Texas 76177 USA
GALDERMA is a registered trademark.
P52442-0
Package
NDC: 69007-912-02
Rx only
Adapalene Lotion, 0.1%
OWEN
For External Use Only
2 FL OZ
(59 mL)
For external use only. Not for ophthalmic, oral or intravaginal use.
Usual dosage: Apply a thin layer 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, purified water, sodium hydroxide, and stearyl alcohol.
Storage: Store at controlled room temperature 68°F to 77°F (20°C to 25°C) with excursions permitted between 59°F and 86°F (15°C and 30°C). Do not freeze or refrigerate.
Distributed by:
Owen Laboratories, Inc.,
a Galderma Company
Fort Worth, Texas 76177 USA
Galderma is a registered trademark.
Made in Canada
P52441-0
| ADAPALENE
adapalene lotion |
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| Labeler - Owen Laboratories, Inc. (079337004) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| G Production, Inc. | 251676961 | manufacture(69007-912) | |