`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
` These highlights do not include all the information
` needed to use ACZONE® Gel, 7.5% safely and
`
`
`effectively. See full prescribing information for
`ACZONE® Gel, 7.5%.
`
`
`
`
`
`
`
`ACZONE® (dapsone) Gel, 7.5%, for topical use
`
`Initial U.S. Approval: 1955
`
`__________
`INDICATIONS AND USAGE____________
`
`
`
`
`ACZONE® Gel, 7.5%, is a sulfone indicated for the topical
`
`treatment of acne vulgaris in patients 12 years of age and
`
`
`older (1).
`
`DOSAGE AND ADMINISTRATION_______
`_________
`
`• Apply once daily (2).
`
`
`• Apply approximately a pea-sized amount of ACZONE
`
`
`
`Gel, 7.5%, in a thin layer to the entire face. A thin layer can
`
`
`
`also be applied to other affected areas (2).
`
`• If there is no improvement after 12 weeks, treatment with
`
`
`
`
`ACZONE Gel, 7.5% should be reassessed (2).
`
`
`• For topical use only. Not for oral, ophthalmic, or
`
`
`intravaginal use (2).
`
`
`
`DOSAGE FORMS AND STRENGTHS_______
`_______
`
`
`
`Gel, 7.5% (3).
`
`CONTRAINDICATIONS_______________
`___________
`
`
`None (4).
`
`_________
`
` WARNINGS AND PRECAUTIONS________
` • Methemoglobinemia: Cases of methemoglobinemia have
`
`
`
` been reported. Discontinue ACZONE Gel if signs of
`
`
`
` methemoglobinemia occur (5.1).
`
`
` • Hemolysis: Some patients with Glucose-6-phosphate
`
` Dehydrogenase (G6PD) deficiency using topical dapsone
`
`
`
` developed laboratory changes suggestive of hemolysis
`
`
`
`
`(5.1)(8.6).
`ADVERSE REACTIONS_____________
`
`_____________
`Most common (incidence ≥ 0.9%) adverse reactions are
`
`
`
`
`
`application site dryness and pruritus (6.1).
`
`
`
`
`
`To report SUSPECTED ADVERSE REACTIONS,
`
`contact Allergan at 1-800-678-1605 or FDA at 1-800­
`
`
`
`FDA-1088 or www.fda.gov/medwatch.
`
`
`DRUG INTERACTIONS______________
`____________
`
`• Trimethoprim/sulfamethoxazole (TMP/SMX) increases
`
`the systemic level of dapsone and its metabolites (7.1).
`
`
`
`• Topical benzoyl peroxide used at the same time as
`
`ACZONE Gel, 7.5% may result in temporary local yellow
`
`
`
`or orange skin discoloration (7.2).
`
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION
`
`
`and FDA-approved patient labeling.
`
`
`
`Revised: 05/2018
`
`
`
`
`
`
`
`
`
`
`
` FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`
` 1
` INDICATIONS AND USAGE
`8 USE IN SPECIFIC POPULATIONS
`
`
`
` Pregnancy
`8.1
`
`
` 2 DOSAGE AND ADMINISTRATION
`
`
`
` Lactation
`8.2
`
` 3 DOSAGE FORMS AND STRENGTHS
`
`
`
` Pediatric Use
`8.4
`
` 4 CONTRAINDICATIONS
`
`
`
`
` Geriatric Use
`8.5
`
` 5 WARNINGS AND PRECAUTIONS
`5.1 Hematological Effects
`
`
`
`
`
`
`
`8.6 Glucose-6-phosphate Dehydrogenase (G6PD)
`5.2 Peripheral Neuropathy
`
`
`
`
`
`Deficiency
`5.3 Skin Reactions
`
`
`
`
`
`
`11 DESCRIPTION
`6 ADVERSE REACTIONS
`
`
`
`
`12 CLINICAL PHARMACOLOGY
`6.1 Clinical Studies Experience
`
`
`
`
`
`
`
`
`12.1 Mechanism of Action
`6.2 Experience with Oral Use of Dapsone
`
`
`
`
`
`
`
`12.3 Pharmacokinetics
`6.3 Postmarketing Experience
`
`
`
`
`
`
`12.4 Microbiology
`7 DRUG INTERACTIONS
`
`
`
`
`13 NONCLINICAL TOXICOLOGY
`7.1 Trimethoprim-Sulfamethoxazole
`
`
`
`
`
`
`13.1 Carcinogenesis, Mutagenesis,
`
`7.2 Topical Benzoyl Peroxide
`
`
`
`
`
`Impairment of Fertility
`
`7.3 Drug Interactions with Oral Dapsone
`
`
`
`
`
`
`14 CLINICAL STUDIES
`
`7.4 Concomitant Use with Drugs that Induce
`
`
`
`
`
`16 HOW SUPPLIED/STORAGE AND
`
`
`Methemoglobinemia
`
`
`HANDLING
`
`
`
`17 PATIENT COUNSELING INFORMATION
`
`
`
`
`* Sections or subsections omitted from the full prescribing
`
`
`information are not listed.
`
`
`
`
`
`
`
`
`
`Reference ID: 4265328
`
`

`

`
`CONTRAINDICATIONS
`
`
`
`FULL PRESCRIBING INFORMATION
`
`
`
`INDICATIONS AND USAGE
`1
`
`ACZONE® (dapsone) Gel, 7.5%, is indicated for the topical treatment of acne vulgaris in patients 12 years of
`
`
`
`
`
`
`age and older.
`
`
`
`DOSAGE AND ADMINISTRATION
`2
`
`
`
`For topical use only. Not for oral, ophthalmic, or intravaginal use.
`
`
`After the skin is gently washed and patted dry, apply approximately a pea-sized amount of ACZONE Gel,
`
`
`
`
`
`
`
`7.5%, in a thin layer to the entire face once daily. In addition, a thin layer may be applied to other affected areas
`
`once daily. Rub in ACZONE Gel, 7.5%, gently and completely.
`
`
`
`If there is no improvement after 12 weeks, treatment with ACZONE Gel, 7.5% should be reassessed (2).
`
`
`
`
`
`DOSAGE FORMS AND STRENGTHS
`3
`Gel, 7.5%. Each gram of ACZONE Gel, 7.5% contains 75 mg of dapsone in an off-white to yellow gel with
`
`
`
`
`
`
`
`
`
`
`suspended particles.
`
`
`4
`
`None.
`
`
`
`WARNINGS AND PRECAUTIONS
`5
`
`
`5.1 Hematological Effects
`
`Methemoglobinemia
`Cases of methemoglobinemia, with resultant hospitalization, have been reported postmarketing in association
`
`
`with twice daily dapsone gel, 5%, treatment. Patients with glucose-6-phosphate dehydrogenase deficiency or
`
`
`
`
`
`
`
`congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia. Avoid
`
`
`use of ACZONE Gel, 7.5% in those patients with congenital or idiopathic methemoglobinemia.
`
`
`
`
`
`Signs and symptoms of methemoglobinemia may be delayed some hours after exposure. Initial signs and
`
`
`
`symptoms of methemoglobinemia are characterized by a slate grey cyanosis seen in e.g., buccal mucous
`
`
`
`membranes, lips, and nail beds. Advise patients to discontinue ACZONE Gel, 7.5% and seek immediate
`
`
`
`
`
`
`medical attention in the event of cyanosis.
`
`
`Dapsone can cause elevated methemoglobin levels particularly in conjunction with methemoglobin-inducing
`
`agents [see Drug Interactions (7.4)].
`
`
`
`Hemolysis
`
` Oral dapsone treatment has produced dose-related hemolysis and hemolytic anemia. Individuals with glucose-6­
`
`
`
`
` phosphate dehydrogenase (G6PD) deficiency are more prone to hemolysis with the use of certain drugs. G6PD
` deficiency is most prevalent in populations of African, South Asian, Middle Eastern, and Mediterranean
`
`
`
` ancestry.
`
`In clinical trials, there was no evidence of clinically relevant hemolysis or hemolytic anemia in subjects treated
`
`
`
`
`with topical dapsone. Some subjects with G6PD deficiency using dapsone gel, 5 %, twice daily developed
`
`
`
`laboratory changes suggestive of hemolysis [see Use in Specific Populations (8.6)].
`
`
`
`
`Discontinue ACZONE Gel, 7.5%, if signs and symptoms suggestive of hemolytic anemia occur. Avoid use of
`
`
`
`ACZONE Gel, 7.5% in patients who are taking oral dapsone or antimalarial medications because of the
`
`
`potential for hemolytic reactions. Combination of ACZONE Gel, 7.5%, with trimethoprim/sulfamethoxazole
`
`
`
`
`
`Reference ID: 4265328
`
`

`

`
`
`
`
`
`
`
` (TMP/SMX) may increase the likelihood of hemolysis in patients with G6PD deficiency [see Drug Interactions
`
` (7.1)].
`
`
`
`5.2
`Peripheral Neuropathy
`Peripheral neuropathy (motor loss and muscle weakness) has been reported with oral dapsone treatment. No
`
`
`
` events of peripheral neuropathy were observed in clinical trials with topical dapsone treatment.
`
`
`
`
`5.3
`Skin Reactions
`
`
`Skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions,
`
`
`bullous and exfoliative dermatitis, erythema nodosum, and urticaria) have been reported with oral dapsone
`
`
`
`treatment. These types of skin reactions were not observed in clinical trials with topical dapsone treatment.
`
`
`
`6
`ADVERSE REACTIONS
`
`
`6.1
`Clinical Studies 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.
`
`A total of 2161 subjects were treated with ACZONE Gel, 7.5%, for 12 weeks in 2 controlled clinical trials. The
`
`
`
`
`
`
`
`
`
`population ranged in age from 12 to 63 years, was 56% female, and 58% Caucasian. Adverse drug reactions
`that were reported in at least 0.9% of subjects treated with ACZONE Gel, 7.5% appear in Table 1 below.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Table 1. Adverse Reactions Occurring in at Least 0.9% of Subjects with Acne Vulgaris in 12-week
`
`
`
`Controlled Clinical Trials
`
` ACZONE Gel, 7.5%
`
`
` (N=2161)
`
` 24 (1.1%)
`
`
` 20 (0.9%)
`
`
`
`
`
` Application Site Dryness
`
` Application Site Pruritus
`
`
`
` Vehicle
`
`
` (N=2175)
` 21 (1.0%)
`
`
` 11 (0.5%)
`
`
`
`
`
`
`
` Experience with Oral Use of Dapsone
`
`6.2
`
`
`
`
` Although not observed in the clinical trials with topical dapsone, serious adverse reactions have been reported
`with oral use of dapsone, including agranulocytosis, hemolytic anemia, peripheral neuropathy (motor loss and
`
` muscle weakness), and skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and
`
`
` scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria).
`
` Postmarketing Experience
` 6.3
`
`
` Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to
`
`
`
` reliably estimate their frequency or establish a causal relationship to drug exposure.
`
`The following adverse reactions have been identified during post-approval use of topical dapsone:
`
`
`
`methemoglobinemia, rash (including erythematous rash, application site rash) and swelling of face (including
`
`
`
`
`
`lip swelling, eye swelling).
`
`
`7
`DRUG INTERACTIONS
`
`
`No formal drug-drug interaction studies were conducted with ACZONE Gel, 7.5%.
`
`
`
`
`
`
`
`Reference ID: 4265328
`
`

`

` Trimethoprim-Sulfamethoxazole
` 7.1
`
`
`
`
`
`
`
` A drug-drug interaction study evaluated the effect of the use of dapsone gel, 5% in combination with double
`
` strength (160 mg/800 mg) trimethoprim-sulfamethoxazole (TMP/SMX). During co-administration, systemic
` levels of TMP and SMX were essentially unchanged, however, levels of dapsone and its metabolites increased
`
`
` in the presence of TMP/SMX. The systemic exposure from ACZONE Gel, 7.5% is expected to be about 1% of
`
`
`
` that from the 100 mg oral dose, even when co-administered with TMP/SMX.
`
`
`
`
`Topical Benzoyl Peroxide
`7.2
`
`
`
`
`
`
`Topical application of dapsone gel followed by benzoyl peroxide in patients with acne vulgaris may result in a
`
`
`
`temporary local yellow or orange discoloration of the skin and facial hair.
`
`
`
`
`7.3
`Drug Interactions with Oral Dapsone
`
`
`Certain concomitant medications (such as rifampin, anticonvulsants, St. John’s wort) may increase the
`
`
`formation of dapsone hydroxylamine, a metabolite of dapsone associated with hemolysis. With oral dapsone
`
`treatment, folic acid antagonists such as pyrimethamine have been noted to possibly increase the likelihood of
`
`hematologic reactions.
`
`
`7.4 Concomitant Use with Drugs that Induce Methemoglobinemia
`
`Concomitant use of ACZONE Gel, 7.5% with drugs that induce methemoglobinemia such as sulfonamides,
`
`
`
`
`acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites,
`
`
`
`
` USE IN SPECIFIC POPULATIONS
`
` Pregnancy
`
`
`
`nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para‐aminosalicylic acid, phenacetin, phenobarbital,
`
`
`
`phenytoin, primaquine, and quinine may increase the risk for developing methemoglobinemia [see Warnings
`
`
`
`
`
`and Precautions (5.1)].
`
`
` 8
`
` 8.1
`
` Risk Summary
`
` There are no available data on ACZONE Gel, 7.5%, use in pregnant women to inform a drug-associated risk for
`
`
`
`
` adverse developmental outcomes. In animal reproduction studies, oral doses of dapsone administered to pregnant
` rats and rabbits during organogenesis that resulted in systemic exposures more than 400 times the systemic exposure
`
`
`
` at the maximum recommended human dose (MRHD) of ACZONE Gel, 7.5%, resulted in embryocidal effects.
`
`
` When orally administered to rats from the onset of organogenesis through the end of lactation at systemic exposures
`
`
` approximately 500 times the exposure at the MRHD, dapsone resulted in increased stillbirths and decreased pup
`
`weight [see Data].
`
` The estimated background risks of major birth defects and miscarriage for the indicated population are
`
`
`
`
` unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage
` in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
`
`
`Data
`
`Animal Data
`
`
`Dapsone has been shown to have an embryocidal effect in rats and rabbits when administered orally daily to
`
`
`females during organogenesis at dosages of 75 mg/kg/day and 150 mg/kg/day, respectively. These dosages
`
`
`resulted in systemic exposures that represented approximately 1407 times [rats] and 425 times [rabbits] the
`systemic exposure observed in human females as a result of use of the MRHD of ACZONE Gel, 7.5%, based
`
`
`
`
`
`
`on AUC comparisons. These effects were probably secondary to maternal toxicity.
`
`
`Dapsone was assessed for effects on perinatal/postnatal pup development and postnatal maternal behavior and
`
`
`function in a study in which dapsone was orally administered to female rats daily beginning on the seventh day
`
`of gestation and continuing until the twenty-seventh day postpartum. Maternal toxicity (decreased body weight
`
`and food consumption) and developmental effects (increase in stillborn pups and decreased pup weight) were
`
`
`
`
`
`Reference ID: 4265328
`
`

`

`seen at a dapsone dose of 30 mg/kg/day (approximately 563 times the systemic exposure that is associated with
`the MRHD of ACZONE Gel, 7.5%, based on AUC comparisons). No effects were observed on the viability,
`
`
`
`physical development, behavior, learning ability, or reproductive function of surviving pups.
`
`
`
`
` Lactation
` 8.2
`
`
` Risk Summary
`There is no information regarding the presence of topical dapsone in breastmilk, the effects on the breastfed
`
`
`
`
`infant or the effects on milk production. Orally administered dapsone appears in human milk and could result in
`
`
`hemolytic anemia and hyperbilirubinemia especially in infants with G6PD deficiency. Systemic absorption of
`
`
`
`
`dapsone following topical application is minimal relative to oral dapsone administration; however, it is known
`that dapsone is present in human milk following administration of oral dapsone.
`
`
`
`
`
`Pediatric Use
`8.4
`
`
`Safety and efficacy was evaluated in 1066 subjects aged 12-17 years old treated with ACZONE Gel, 7.5% in
`
`
`
`
`
`
`the clinical trials. The safety profile for ACZONE Gel, 7.5%, was similar to the vehicle control group. Safety
`
`
`
`
`
`and effectiveness of ACZONE Gel, 7.5%, have not been established in pediatric patients below the age of 12
`
`
`
`
`
`years.
`
`
`8.5 Geriatric Use
`
`
`Clinical trials of ACZONE Gel, 7.5% did not include sufficient numbers of subjects aged 65 years and over to
`
`
`
`
`determine whether they respond differently from younger subjects.
`
`
`
`
`8.6 Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency
`
`
`
`Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more prone to
`
`methemoglobinemia and hemolysis [see Warnings and Precautions (5.1)].
`
`
`
`
`
`
`ACZONE Gel, 5% and vehicle were evaluated in a randomized, double-blind, cross-over design clinical study
`
`
`of 64 subjects with G6PD deficiency and acne vulgaris. Subjects were Black (88%), Asian (6%), Hispanic (2%)
`
`
`or of other racial origin (5%). Blood samples were taken at Baseline, Week 2, and Week 12 during both vehicle
`
`
`
`
`
`and ACZONE Gel, 5% treatment periods. Some of these subjects developed laboratory changes suggestive of
`
`
`hemolysis, but there was no evidence of clinically significant hemolytic anemia in this study [see Warnings and
`
`
`
`
`
`Precautions (5.1)].
`
`DESCRIPTION
`11
`
`
`ACZONE (dapsone) Gel, 7.5%, contains dapsone, a sulfone, in an aqueous gel base for topical dermatologic
`
`
`
`
`
`use. ACZONE Gel, 7.5% is an off-white to yellow gel with suspended particles. Chemically, dapsone has an
`
`
`
`
`
`empirical formula of C12H12N2O2S. It is a white or slightly yellow-white, crystalline powder that has a
`
`
`
`
`molecular weight of 248.30. Dapsone’s chemical name is 4-[(4-aminobenzene) sulfonyl] aniline and its
`
`
`
`
`
`structural formula is:
`
`
`
`
`
`Each gram of ACZONE Gel, 7.5%, contains 75 mg of dapsone, USP, in a gel of diethylene glycol monoethyl
`
`
`
`
`
`
`
`
`ether, methylparaben, acrylamide/sodium acryloyldimethyl taurate copolymer, isohexadecane, polysorbate 80,
`
`
`and purified water.
`
`
`CLINICAL PHARMACOLOGY
`12
`
`
`12.1 Mechanism of Action
`
`
`The mechanism of action of dapsone gel in treating acne vulgaris is not known.
`
`
`
`
`12.3 Pharmacokinetics
`
`
`
`Reference ID: 4265328
`
`

`

`
`
` In a pharmacokinetic study, male and female subjects 16 years of age or older with acne vulgaris (N=19)
`
`
`
`
`
` received 2 grams of ACZONE Gel, 7.5%, topically to the face, upper chest, upper back and shoulders once
`
`
`
` daily for 28 days. Steady state for dapsone was reached within 7 days of dosing. On Day 28, the mean dapsone
`
` maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 24 hours post
`
`
`
` dose (AUC0-24h) were 13.0 ± 6.8 ng/mL and 282 ± 146 ng∙h/mL, respectively. The systemic exposure from
`
`
` ACZONE Gel, 7.5% is expected to be about 1% of that from a 100 mg oral dose.
`
`
`
`
`
`
` Long-term safety studies were not conducted with ACZONE Gel, 7.5%, however, in a long-term clinical study
`
`
`
`
`
`
`
`
` of dapsone gel, 5% treatment (twice daily), periodic blood samples were collected up to 12 months to determine
`systemic exposure of dapsone and its metabolites in approximately 500 subjects. Based on the measurable
`dapsone concentrations from 408 subjects (M=192, F=216), obtained at Month 3, neither gender nor race
`
`
`appeared to affect the pharmacokinetics of dapsone. Similarly, dapsone exposures were approximately the same
`between the age groups of 12-15 years (N=155) and those greater than or equal to 16 years (N=253). There was
`
`
`
`
`no evidence of increasing systemic exposure to dapsone over the study year in these subjects.
`
`
`
`12.4 Microbiology
`
`
`In Vivo Activity: No microbiology or immunology studies were conducted during ACZONE Gel, 7.5% clinical
`
`
`
`
`
`
`
`studies.
`
`
`Drug Resistance: No dapsone resistance studies were conducted during dapsone gel clinical studies. Because no
`
`such studies were done, there are no data available as to whether dapsone treatment may have resulted in
`
`decreased susceptibility of Propionibacterium acnes, an organism associated with acne, or to other
`
`
`
`
`antimicrobials that may be used to treat acne. Therapeutic resistance to dapsone has been reported for
`
`
`
`Mycobacterium leprae, when patients have been treated with oral dapsone.
`
`
`NONCLINICAL TOXICOLOGY
`13
`
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`
`Dapsone was not carcinogenic to rats when orally administered to females for 92 weeks or males for 100 weeks
`
`
`
`
`at dose levels up to 15 mg/kg/day (approximately 340 times the systemic exposure observed in humans as a
`
`
`result of use of the MRHD of ACZONE Gel, 7.5%, based on AUC comparisons).
`
`
`
`
`
`No evidence of potential to induce carcinogenicity was observed in a dermal study in which dapsone gel was
`
`
`
`
`
`topically applied to Tg.AC transgenic mice for approximately 26 weeks. Dapsone concentrations of 3%, 5%,
`
`and 10% were evaluated; 3% material was judged to be the maximum tolerated dosage.
`
`
`
`Dapsone was negative in a bacterial reverse mutation assay (Ames test), and was negative in a micronucleus
`
`
`
`
`
`assay conducted in mice. Dapsone was positive (clastogenic) in a chromosome aberration assay conducted with
`
`
`
`Chinese hamster ovary (CHO) cells.
`
`
`
`The effects of dapsone on fertility and general reproductive performance were assessed in male and female rats
`
`
`
`following oral dosing. Dapsone reduced sperm motility at dosages of 3 mg/kg/day or greater (approximately 22
`
`times the systemic exposure that is associated with the MRHD of ACZONE Gel, 7.5%, based on AUC
`
`
`
`
`comparisons) when administered daily beginning 63 days prior to mating and continuing through the mating
`
`
`
`period. The mean numbers of embryo implantations and viable embryos were significantly reduced in untreated
`females mated with males that had been dosed at 12 mg/kg/day or greater (approximately 187 times the
`
`
`
`
`
`systemic exposure that is associated with the MRHD of ACZONE Gel, 7.5%, based on AUC comparisons),
`
`
`
`presumably due to reduced numbers or effectiveness of sperm, indicating impairment of fertility. When
`
`
`administered to female rats at a dosage of 75 mg/kg/day (approximately 1407 times the systemic exposure that
`
`is associated with the MRHD of ACZONE Gel, 7.5%, based on AUC comparisons) for 15 days prior to mating
`
`
`
`
`and for 17 days thereafter, dapsone reduced the mean number of implantations, increased the mean early
`
`
`resorption rate, and reduced the mean litter size. These effects probably were secondary to maternal toxicity.
`
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`
`
`
`
`Reference ID: 4265328
`
`

`

` 14
` CLINICAL STUDIES
`
`
`
` The safety and efficacy of once daily use of ACZONE Gel, 7.5%, was assessed in two 12-week multicenter,
`
`
`
`
`
` randomized, double-blind, vehicle-controlled trials. Efficacy was assessed in a total of 4340 subjects 12 years
`
`
`
`
`
`
`
`
` of age and older. The majority of the subjects had moderate acne vulgaris, 20 to 50 inflammatory and 30 to 100
` non-inflammatory lesions at baseline, who were randomized to receive either ACZONE Gel, 7.5% or vehicle.
`
`
`
`
`
`
`
`
`
`
`
`Treatment response was defined at Week 12 as the proportion of subjects who were rated “none” or “minimal”
`
`
`
`with at least a two-grade improvement from baseline on the Global Acne Assessment Score (GAAS), and mean
`
`
`
`
`absolute change from baseline in both inflammatory and non-inflammatory lesion counts. A GAAS score of
`
`
`“none” corresponded to no evidence of facial acne vulgaris. A GAAS score of “minimal” corresponded to a few
`
`
`
`
`non-inflammatory lesions (comedones) being present and to a few inflammatory lesions (papules/pustules) that
`
`
`may be present.
`
`
`The GAAS success rate, mean reduction, and percent reduction in acne lesion counts from baseline after 12
`
`
`weeks of treatment are presented in the following table.
`
`
`
`
`
`Table 2. Clinical Efficacy of ACZONE® Gel at Week 12 in Subjects with Acne Vulgaris
`
`
`
` Trial 2
` Trial 1
`
`
`
`
` ACZONE® Gel,
`
` ACZONE® Gel,
`
`
` 7.5%
` 7.5%
`
` (N=1044)
` (N=1118)
`
`
` Global Acne Assessment Score
` 30%
`
` GAAS Success
`
`
` (Score 0 or 1)
` Inflammatory Lesions
`Mean absolute
`
` reduction
`
` Mean percent
`
` reduction
` Non-inflammatory Lesions
`Mean absolute
`
` reduction
`
` Mean percent
`
` reduction
`
`
` Vehicle
`
` (N=1058)
`
`
`
`
`
` 21%
`
`
`
` 14.3
`
`
`
` 49%
`
`
`
` 18.0
`
`
`
` 39%
`
`
`
` 30%
`
`
`
` 15.6
`
`
`
` 54%
`
`
`
` 20.8
`
`
`
` 46%
`
`
` Vehicle
`
` (N=1120)
`
`
`
`
`
` 21%
`
`
`
` 14.0
`
`
`
` 48%
`
`
`
` 18.7
`
`
`
` 41%
`
`
`
`
`
`
`
` 16.1
`
`
`
` 56%
`
`
`
` 20.7
`
`
`
` 45%
`
`
` 16
` HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
` ACZONE Gel is an off-white to yellow gel with suspended particles. It is supplied in an airless pump
`
`
`
`
` containing a polypropylene bottle with a high density polyethylene piston.
`
` ACZONE (dapsone) Gel, 7.5%, is supplied in the following sizes:
`
`
`
`
`NDC 0023-5206-30
`
`
`
`
`
`
`
`
`
`30 gram pump
`
`
`
`
`
`
`
`
`
`
`
`NDC 0023-5206-60
`
`
`
`NDC 0023-5206-90
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`60 gram pump
`
`
`
`90 gram pump
`
`
`
`
`
`Storage: Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30ºC (59°F-86ºF) [see USP Controlled
`
`
`
`Room Temperature]. Protect from freezing.
`
`
`17
`
`
`PATIENT COUNSELING INFORMATION
`
`
`Reference ID: 4265328
`
`

`

`Advise the patient to read the FDA-approved patient labeling (Patient Information).
`
`
`
`
`Hematological Effects
`
`Inform patients that methemoglobinemia can occur with topical dapsone treatment. Advise patients to
`
`
`
`•
`seek immediate medical attention if they develop cyanosis [see Warnings and Precautions (5.1)].
`
`
`
`Inform patients who have G6PD deficiency that hemolytic anemia may occur with topical dapsone
`
`
`
`
`treatment. Advise patients to seek medical attention if they develop signs and symptoms suggestive of
`
`
`hemolytic anemia [see Warnings and Precautions (5.1)].
`
`
`
`
`•
`
`
`Important Administration Instructions
`
`
`• Advise patients to apply ACZONE Gel, 7.5%, once daily to the entire face [see Dosage and
`
`
`
`
`
`
`Administration (2)].
`
`
`• ACZONE Gel, 7.5% is for topical use only.
`
`
`
`
`• Do not apply ACZONE Gel, 7.5% to eyes, mouth, or mucous membranes.
`
`
`
`
`
`
`Distributed by: Allergan USA, Inc.
`
`
`
`
`Madison, NJ 07940
`
`
`
`© 2018 Allergan. All rights reserved.
`
`
`
`All trademarks are the property of their respective owners.
`
`
`Patented. See: www.allergan.com/patents
`
`
`
`
`
`
`
`
`
`-------Cut Here ---------------------------------------------------------------------------------------------------------------­
`
`
`
`
`
`Reference ID: 4265328
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Patient Information
`
`
` ACZONE® (AK-zōn) (dapsone) Gel, 7.5%
`
`
` Important: For use on skin only (topical use). Do not use ACZONE Gel, 7.5% in your mouth, eyes, or vagina.
`
`
`
`
`
`
` What is ACZONE Gel, 7.5%?
`
`
`
` ACZONE Gel, 7.5%, is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older.
`
`
`
` ACZONE Gel, 7.5%, has not been studied in children under 12 years of age.
`
`
` Before you use ACZONE Gel, 7.5%, tell your doctor about all of your medical conditions, including if you:
`
`
`
`
`
` • have a glucose-6-phosphate dehydrogenase deficiency (G6PD)
`
`
`
`
` • have higher than normal levels of methemoglobin in your blood (methemoglobinemia)
`
`
`
`
` • are pregnant or plan to become pregnant. It is not known if ACZONE Gel, 7.5% will harm your unborn baby.
`
`
`
`
` • are breastfeeding or plan to breastfeed. ACZONE Gel, 7.5% can pass into your breast milk and may harm your
`
`
`
`
`
`
`
` baby. You and your doctor should decide if you will use ACZONE Gel, 7.5%, or breastfeed. You should not do
`
`
`
`
`
`
` both.
` Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins,
`
`
`
`
`
` and herbal supplements. Especially, tell your doctor if you are using acne medicines that contain benzoyl peroxide. Use
`
`
`
` of benzoyl peroxide with ACZONE Gel, 7.5% at the same time may cause your skin or facial hair to temporarily turn
`
`
`
`yellow or orange at the site of application.
`
`
` How do I use ACZONE Gel, 7.5%?
`
` • Use ACZONE Gel, 7.5% exactly as your doctor tells you to use it.
`
`
`
` • Apply ACZONE Gel, 7.5% one time a day.
`
`
`
`
`
`
`
` • Gently wash and pat dry the areas of your skin where you will apply ACZONE Gel, 7.5%.
`
`
`
`
` • Apply a pea-sized amount of ACZONE Gel, 7.5% in a thin layer to the entire face. A thin layer may also be applied
`
`
`
`
` to other affected areas as instructed by your doctor.
`
`
`
`
` • Rub ACZONE Gel, 7.5% in gently and completely.
`
`
`
`
`
` • Wash your hands after applying ACZONE Gel, 7.5%.
`
`
`
` If your acne does not get better after using ACZONE Gel, 7.5% for 12 weeks, talk to your doctor about continuing
`
`
`•
`
`treatment.
` What are the possible side effects of ACZONE Gel, 7.5%?
`
`
`
` ACZONE Gel, 7.5% may cause serious side effects, including:
`
`
`
`
` • Decrease of oxygen in your blood caused by a certain type of abnormal red blood cell
`
`
`
`(methemoglobinemia). Stop using ACZONE Gel, 7.5% and get medical help right away if your lips, nail beds, or
`
`
`
`
` the inside of your mouth turns grey or blue.
`
`
`
`• Breakdown of red blood cells (hemolytic anemia). Some people with G6PD deficiency using ACZONE Gel,
`
`
`
`
` 7.5% may develop mild hemolytic anemia. Stop using ACZONE Gel, 7.5% and tell your doctor right away if you get
`
`
`
`
`
` any of the following signs and symptoms:
`
`
`o tiredness or weakness
`o back pain
`o shortness of breath
`
`
`
`
`
`
`
`o yellow or pale skin
`o dark brown urine
`o fever
`
`
`
`
`
`
`
`
`
` The most common side effects of ACZONE Gel, 7.5% include dryness and itching of the skin being treated.
` These are not all of the possible side effects of ACZONE Gel, 7.5%. Call your doctor for medical advice about side
`
`
`
`
`
`
`
`
`
`
`
` effects. You may report side effects to FDA at 1-800-FDA-1088.
` How should I store ACZONE Gel, 7.5%?
`
`
` • Store ACZONE Gel, 7.5%, at room temperature 68ºF to 77ºF (20ºC to 25ºC).
`
`
`
` • Protect ACZONE Gel, 7.5% from freezing.
`
`
`
`
` Keep ACZONE Gel, 7.5% and all medicines out of the reach of children.
`
`
`
` General information about the safe and effective use of ACZONE Gel, 7.5%.
`
`
`
` Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use
`
`
`
` ACZONE Gel, 7.5% for a condition for which it was not prescribed. Do not give ACZONE Gel, 7.5% to other people,
`
`
`
`
`
`
` even if they have the same symptoms you have. It may harm them. You can ask your doctor or pharmacist for
`
`
`
`
`
`
` information about ACZONE Gel, 7.5% that is written for health professionals.
`
`
`
`
`
` What are the ingredients in ACZONE Gel, 7.5%?
`
`
`
`Active ingredient: dapsone
`
`
`Inactive ingredients: diethylene glycol monoethyl ether, methylparaben, acrylamide/sodium acryloyldimethyl taurate
`
`
` copolymer, isohexadecane, polysorbate 80, and purified water.
`
`
`
`
`
`
` Distributed by: Allergan USA, Inc.
`
`
` Madison, NJ 07940
`
` © 2018 Allergan. All rights reserved.
`
`
`
`
`
`All trademarks are the property of their respective owners.
`
`
`Patented. See: www.allergan.com/patents
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4265328
`
`

`

`
`
` For more information, call 1-800-678-1605
`
`
`
`
`
`
`
`
`This Patient Information has been approved by the U.S. Food and Drug Administration.
`
`
`
`
`
`
`
`
`
`Issued: 05/2018
`
`Reference ID: 4265328
`
`
`