Epsolay - Benzoyl Peroxide cream prescribing information
INDICATIONS AND USAGE
EPSOLAY is indicated for the treatment of inflammatory lesions of rosacea in adults.
DOSAGE AND ADMINISTRATION
- Before initial use, prime the pump until the first drop of cream is released.
- Apply a pea-sized amount of EPSOLAY once daily in a thin layer to each area of the face (forehead, chin, nose, each cheek) on clean and dry skin. Avoid the eyes, lips and mouth.
- Wash hands after application.
- EPSOLAY may bleach hair or colored fabric.
- EPSOLAY is for topical use only. Not for oral, ophthalmic, or intravaginal use.
- Discard unused EPSOLAY 60 days after first use.
DOSAGE FORMS AND STRENGTHS
Cream, 5%. Each gram of EPSOLAY contains 50 mg of benzoyl peroxide in a white to off-white base.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
The systemic exposure of benzoyl peroxide is unknown. Based on the published literature, benzoyl peroxide is metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Hence, maternal use is not expected to result in fetal exposure to the drug. Animal reproductive studies have not been conducted with EPSOLAY or benzoyl peroxide.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, 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 is 2 to 4% and 15 to 20%, respectively.
Lactation
Risk Summary
There are no data on the presence of benzoyl peroxide in human milk, its effects on the breastfed infant or its effects on milk production. The systemic exposure of benzoyl peroxide is unknown. Based on the published literature, benzoyl peroxide is metabolized to benzoic acid (an endogenous substance), which is eliminated in the urine. Any amount of benzoyl peroxide excreted into human milk by a nursing mother would be expected to be metabolized by tissue and stomach esterases. Therefore, breastfeeding is not expected to result in exposure of the infant to EPSOLAY. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for EPSOLAY and any potential adverse effects on the breastfed child from EPSOLAY or from the underlying maternal condition.
Pediatric Use
Safety and effectiveness of EPSOLAY for the treatment of inflammatory lesions of rosacea have not been established in pediatric patients.
Geriatric Use
Of the 733 subjects in the clinical trials of EPSOLAY, 127 (17%) subjects were 65 and over, while 37 (3%) subjects were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
CONTRAINDICATIONS
EPSOLAY is contraindicated in patients with a history of hypersensitivity reactions to benzoyl peroxide or any components of the formulation in EPSOLAY [ see Warnings and Precautions (5.1) ].
WARNINGS AND PRECAUTIONS
- Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with the use of benzoyl peroxide products. (5.1 )
- Skin irritation/contact dermatitis: Erythema, scaling, dryness, stinging/burning, irritation and allergic contact dermatitis may occur with use of EPSOLAY and may necessitate discontinuation. (5.2 )
- Photosensitivity: Avoid or minimize exposure to natural or artificial sunlight and use sun protection measures. (5.3 )
Hypersensitivity
Hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria, have been reported with the use of benzoyl peroxide products. If a serious hypersensitivity reaction occurs, discontinue EPSOLAY immediately and initiate appropriate therapy.
Skin Irritation/Contact Dermatitis
Erythema, scaling, dryness and stinging/burning may be experienced with use of EPSOLAY. Irritation and contact dermatitis may occur. Apply a moisturizer and discontinue EPSOLAY if symptoms do not improve. Avoid application of EPSOLAY to cuts, abrasions, eczematous or sunburned skin.
Photosensitivity
Benzoyl peroxide may increase sensitivity to sunlight. Minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using EPSOLAY. Instruct the patient to implement sun protection measures (e.g., sunscreen and loose- fitting clothes) when sun exposure cannot be avoided. Discontinue EPSOLAY at the first evidence of sunburn.
ADVERSE REACTIONS
- Most common adverse reactions (incidence ≥ 1%) are application site reactions: pain, erythema, pruritis and edema. (6.1 )
To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Clinical Trials Experience
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.
In two randomized, double-blind, vehicle-controlled trials, adult subjects with rosacea applied EPSOLAY (N = 488) or vehicle (N = 234) once daily for 12 weeks. The majority of subjects were Caucasian (93%) and female (73%) with a mean age of 51 years.
Table 1 presents the most common adverse reactions occurring in ≥ 1% of subjects treated with EPSOLAY and more frequently than in subjects treated with vehicle.
| EPSOLAY N=488 | Vehicle N=234 | |
|---|---|---|
| Application site pain | 11 (2%) | 2 (1%) |
| Application site erythema | 11 (2%) | 2 (1%) |
| Application site pruritus | 6 (1%) | 1 (<1%) |
| Application site edema Application site edema includes: application site swelling and application site edema | 4 (1%) | 0 (0%) |
During the clinical trials, local tolerability evaluations were conducted at baseline and at each study visit by assessment of dryness, itching, scaling and stinging/burning. Table 2 presents the local tolerability assessments by severity grade at Week 12.
| Sign/Symptom | EPSOLAY N=455 Of the 488 subjects treated with EPSOLAY, 455 subjects had local tolerability assessments at Week 12. | ||
|---|---|---|---|
| Severity at Week 12 | |||
| Mild | Moderate | Severe | |
| Dryness | 25% | 7% | 0% |
| Itching | 24% | 6% | 0% |
| Scaling | 13% | 4% | 0% |
| Stinging/Burning | 20% | 3% | 1% |
In a 40-week open-label extension safety study (for a total of up to 52 weeks of treatment) the frequency and severity of local tolerability signs and symptoms at Week 52 were comparable to those reported at Week 12.
DESCRIPTION
EPSOLAY (benzoyl peroxide) cream is for topical use. Each gram of EPSOLAY contains 50 mg of benzoyl peroxide.
The chemical name for benzoyl peroxide is benzoyl benzenecarboperoxoate. It has the following structural formula:
 | |
| Molecular Formula: C 14 H 10 O 4 | Molecular Weight: 242.23 |
The benzoyl peroxide in EPSOLAY is in a solid form that is incorporated into a microcapsule composed of silicon dioxide, cetrimonium chloride and polyquaternium-7.
EPSOLAY contains anhydrous citric acid, cetrimonium chloride, cetyl alcohol, cyclomethicone, edetate disodium, glycerin, hydrochloric acid, lactic acid, macrogol stearate Type I, mono and di-glycerides, phenoxyethanol, polyquaternium-7, purified water, silicon dioxide and sodium hydroxide as inactive ingredients.
CLINICAL PHARMACOLOGY
Mechanism of Action
Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action in the treatment of rosacea is unknown.
Pharmacodynamics
The pharmacodynamics of EPSOLAY in the treatment of rosacea are unknown.
Pharmacokinetics
Benzoyl peroxide is absorbed by the skin where it is converted to benzoic acid, an endogenous substance, which is eliminated in the urine. The systemic exposure of benzoyl peroxide following the application of EPSOLAY was not assessed.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and impairment of fertility studies were not conducted with EPSOLAY.
The role of benzoyl peroxide as a tumor promoter has been well established in several animal species. However, the significance of this finding in humans is unknown.
No significant increase in tumor formation was observed in rats treated topically with a 15 to 25% benzoyl peroxide carbopol gel (3 to 5 times the concentration of benzoyl peroxide in EPSOLAY) for two years. Similar results were obtained in mice topically treated with 25% benzoyl peroxide gel for 56 weeks followed by intermittent treatment with 15% benzoyl peroxide gel for rest of the 2 years study period and in mice topically treated with 5% benzoyl peroxide gel for two years.
Bacterial mutagenicity assays (Ames test) conducted with benzoyl peroxide have provided mixed results; mutagenic potential was observed in a few studies but not in a majority of investigations. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types and to cause sister chromatid exchanges in Chinese hamster ovary cells.
Fertility studies were not conducted with benzoyl peroxide.
CLINICAL STUDIES
The safety and efficacy of EPSOLAY was evaluated in two multicenter, randomized, double-blind, vehicle-controlled trials (Trial 1 [NCT03448939] and Trial 2 [NCT03564119]) in subjects with moderate-to-severe papulopustular rosacea. The trials were conducted in 733 subjects, aged 18 years and older. Subjects were treated once daily for 12 weeks with either EPSOLAY or vehicle cream.
Subjects were required to have a minimum of 15 to 70 total inflammatory lesions (papules and/or pustules) and no more than 2 nodules (where a nodule was defined as a papule or pustule greater than 5 mm in diameter) and an Investigator Global Assessment (IGA) score of 3 ("moderate") or 4 ("severe") at baseline. Overall, 93% of subjects were Caucasian, 73% were female, and the mean age was 51 years (ranged from 18 to 85 years). At baseline, subjects had a mean inflammatory lesion count of 27.5, 89% were scored as moderate (IGA=3), and 11% scored as severe (IGA=4).
The co-primary efficacy endpoints in both trials were the proportion of subjects with treatment success at Week 12, defined as an IGA score of 0 ("clear") or 1 ("almost clear") with at least a two-grade reduction from baseline, and the absolute change from baseline in inflammatory lesion counts at Week 12. The results at Week 12 are presented in Table 3. EPSOLAY was more effective than vehicle cream on the co-primary efficacy endpoints starting from 4 weeks of treatment in both trials, see Figure 1 through Figure 4.
| Trial 1 | Trial 2 | |||
|---|---|---|---|---|
| Epsolay (N=243) | Vehicle (N=118) | Epsolay (N=250) | Vehicle (N=122) | |
| IGA Treatment Success Investigator Global Assessment (IGA) success was defined as an IGA score of 0 ("clear") or 1 ("almost clear") with at least a two-grade reduction from baseline. | 47.4% | 20.7% | 49.2% | 28.2% |
| Difference from Vehicle (95% Cl) | 26.7% (16.7%, 36.8%) | 21.0% (10.7%, 31.3%) | ||
| Inflammatory Lesions | ||||
| Mean Means presented in table are Least Square (LS) Means. Absolute Change | -17.4 | -9.5 | -20.3 | -13.3 |
| Difference from Vehicle (95% Cl) | -7.9 (-10.0, -5.9) | -6.9 (-9.0, -4.9) | ||
| MeanPercent Change | -68.2% | -38.3% | -69.4% | -46.0% |
| Difference from Vehicle (95% Cl) | -29.9% (-37.8%, -22.0%) | -23.4% (-30.5%, -16.3%) | ||
| Figure 1: IGA Success Rate Over Time in Trial 1 | Figure 2: IGA Success Rate Over Time in Trial 2 |
|---|---|
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| Figure 3: Mean Absolute Change in Inflammatory Lesion Counts fromBaseline Over Time in Trial 1 | Figure 4: Mean Absolute Change in Inflammatory Lesion Counts from Baseline Over Time in Trial 2 |
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HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
EPSOLAY is a white to off-white cream supplied in an airless pump as follows: 30 gram pump: NDC 51862-772-30
Storage and Handling
- Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
- Keep away from heat.
- Do not freeze.
- Discard unused cream 60 days after first use.
Mechanism of Action
Benzoyl peroxide is an oxidizing agent with bactericidal and keratolytic effects but the precise mechanism of action in the treatment of rosacea is unknown.
