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`ACZONETM Gel 5% PACKAGE INSERT
`
`
`ACZONETM (dapsone) Gel, 5%
`FOR TOPICAL USE ONLY
`NOT FOR ORAL, OPHTHALMIC, OR INTRAVAGINAL USE
`
`
`DESCRIPTION
`
`ACZONETM Gel, 5%, contains dapsone, a sulfone, in an aqueous gel base for topical
`dermatologic use. ACZONETM Gel is a gritty, translucent material with visible drug
`substance particles. Chemically, dapsone has an empirical formula of C12H12N2O2S. It is
`a white, odorless crystalline powder that has a molecular weight of 248. Dapsone’s
`chemical name is 4,4'-diaminodiphenylsulfone and its structural formula is:
`
`
`Each gram of ACZONE™ (dapsone) Gel, 5%, contains 50 mg of dapsone, USP, in a gel
`of carbomer 980; diethylene glycol monoethyl ether, NF; methylparaben, NF; sodium
`hydroxide, USP; and purified water, USP.
`
`
`CLINICAL PHARMACOLOGY
`
`Mechanism of Action:
`The mechanism of action of dapsone gel in treating acne vulgaris is not known.
`
`Pharmacokinetics:
`An open-label study compared the pharmacokinetics of dapsone after ACZONETM Gel,
`5%, (110 ± 60 mg/day) was applied twice daily (~BSA 22.5%) for 14 days (n=18) with a
`single 100 mg dose of oral dapsone administered to a subgroup of patients (n=10) in a
`crossover design. On Day 14 the mean dapsone AUC0-24 h was 415 ± 224 ng•h/mL for
`ACZONETM Gel, 5%, whereas following a single 100 mg dose of oral dapsone the AUC0-
`infinity was 52,641 ± 36,223 ng•h/mL.
`
`Special Populations: In a clinical study, periodic blood samples were collected up to 12
`months to determine systemic exposure of dapsone and its metabolites in approximately
`500 patients. Based on the measurable dapsone concentrations from 408 patients
`(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).
`
`
`
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`AMN1010
`
`

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`MICROBIOLOGY
`
`In Vivo Activity: No microbiology or immunology studies were conducted during
`dapsone gel clinical trials.
`
`Drug Resistance: No dapsone resistance studies were conducted during dapsone gel
`clinical trials. Therapeutic resistance to dapsone has been reported for Mycobacterium
`leprae, when patients have been treated with oral dapsone.*
`
`*Matsuoka, M. A. Dec 2000. Mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and
`sparfloxacin. Int J Lepr Other Mycobact Dis. 68(4):452-5.
`
`
`CLINICAL STUDIES
`
`Two randomized, double blind, vehicle controlled, clinical studies were conducted to
`evaluate ACZONETM Gel, 5%, for the treatment of patients with acne vulgaris (N=1475
`and 1525). The studies were designed to enroll patients 12 years of age and older with 20
`to 50 inflammatory and 20 to 100 non-inflammatory lesions at baseline. In these studies
`patients applied either ACZONETM Gel, 5%, or vehicle control twice daily for up to 12
`weeks. Efficacy was evaluated in terms of success on the Global Acne Assessment
`Score (no or minimal acne) and in the percent reduction in inflammatory, non-
`inflammatory, and total lesions.
`
`The Global Acne Assessment Score was a 5-point scale as follows:
`0
`None: no evidence of facial acne vulgaris
`1
`Minimal: few non-inflammatory lesions (comedones) are present; a few
`inflammatory lesions (papules/pustules) may be present
`Mild: several to many non-inflammatory lesions (comedones) are present;
`a few inflammatory lesions (papules/pustules) are present
`Moderate: many non-inflammatory (comedones) and inflammatory lesions
`(papules/pustules) are present; no nodulo-cystic lesions are allowed
`Severe: significant degree of inflammatory disease; papules/pustules are a
`predominant feature; a few nodulo-cystic lesions may be present;
`comedones may be present.
`
`2
`
`3
`
`4
`
`
`The success rates on the Global Acne Assessment Score (no or minimal acne) at Week 12
`are presented in Table 1.
`
`Table 1 - Success (No or Minimal Acne) on the Global Acne Assessment Score at Week 12
`
`Study 1*
`Study 2*
`ACZONETM
`ACZONETM
`
`Vehicle
`Vehicle
`N=699
`N=687
`N=729
`N=738
`291 (42%)
`223
`253 (35%)
`206
`Subjects with No
`(32%)
`or Minimal Acne
`(28%)
`*Analysis excludes subjects classified with minimal acne at baseline
`
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`121
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`Study 2
`ACZONETM
`Vehicle
`N=761
`N=764
`48%
`40%
`30%
`21%
`37%
`29%
`
`
`Table 2 presents the mean percent reduction in inflammatory, non-inflammatory, and
`total lesions from baseline to Week 12.
`
`Table 2 - Percent Reduction in Lesions from Baseline to Week 12
`
`Study 1
`ACZONETM
`
`Vehicle
`N=745
`N=740
`46%
`42%
`31%
`24%
`38%
`32%
`
`Inflammatory
`Non-Inflammatory
`Total
`
`The clinical studies enrolled about equal proportions of male and female subjects.
`Female patients tended to have greater percent reductions in lesions and greater success
`on the Global Acne Assessment Score than males. The breakdown by race in the clinical
`studies was about 73% Caucasian, 14% Black, 9% Hispanic, and 2% Asian. Efficacy
`results were similar across the racial subgroups.
`
`
`INDICATIONS AND USAGE
`
`ACZONETM Gel, 5%, is indicated for the topical treatment of acne vulgaris.
`
`Glucose 6-phosphate dehydrogenase (G6PD) levels should be obtained prior to initiating
`therapy with ACZONETM Gel, 5%. In patients with a history of anemia and
`predisposition to increased hemolytic effect with dapsone (e.g., glucose-6-phosphate
`dehydrogenase deficiency), closer follow-up for blood hemoglobin levels and
`reticulocyte counts should be implemented (see PRECAUTIONS). Alternatively, other
`therapies for acne than ACZONETM Gel, 5%, may be considered.
`
`
`CONTRAINDICATIONS
`
`ACZONETM Gel, 5%, is contraindicated in persons with a hypersensitivity to dapsone or
`any other component of the formulation.
`
`
`PRECAUTIONS
`
`General
`
`Glucose 6-phosphate dehydrogenase levels should be obtained in all patients prior to
`initiating therapy with ACZONETM Gel, 5%. Baseline complete blood counts, including
`a reticulocyte count, should be obtained in patients who are G6PD deficient or with a
`history of anemia. Routine follow-up for complete blood count and reticulocyte count
`
`
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`should be implemented for patients at risk. If signs, symptoms or laboratory evidence of
`anemia develop during treatment, use of ACZONETM Gel, 5%, should be discontinued.
`Dose-related hemolysis is the most common adverse event seen in patients treated with
`oral Dapsone (with or without glucose-6-phosphate dehydrogenase deficiency).
`Hemolysis may be exaggerated in individuals with G6PD deficiency, methemoglobin
`reductase deficiency, or hemoglobin M.
`
`While clinical studies conducted did not demonstrate evidence of clinically significant
`anemia, an increased reticulocyte count and a decreased hemoglobin level were noted to
`be associated in a G6PD deficient patient treated with ACZONETM Gel, 5%, for acne
`vulgaris who had a complete blood count performed. Only 25 patients with low plasma
`glucose 6-phosphate dehydrogenase activity treated with ACZONETM Gel, 5%, were
`included in the clinical study program. Safety of ACZONETM Gel, 5%, has not been
`fully evaluated in patients with G6PD deficiency.
`
`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).
`
`In the clinical trials, a total of 12 out of 4032 patients were reported to have depression (3
`of 1660 treated with vehicle and 9 of 2372 treated with ACZONE™ Gel, 5%). Psychosis
`was reported in 2 of 2372 patients treated with ACZONE™ Gel, 5%, and in 0 of 1660
`patients treated with vehicle.
`
`Information for Patients
`
`1. Patients should use ACZONETM Gel, 5%, as directed by the physician. ACZONETM
`Gel, 5%, is for external topical use only. ACZONETM Gel, 5%, is not for oral,
`ophthalmic or intravaginal use.
`2. Patients should not use this medication for any disorder other than that for which it
`was prescribed.
`3. Patients should tell their physician if they have any history of anemia or an enzyme
`deficiency (such as G6PD deficiency).
`4. Patients should be informed as to the need for laboratory evaluation prior to starting
`ACZONETM Gel, 5%.
`5. Patients should report any signs of adverse reactions to their physician.
`6. Protect ACZONETM Gel, 5%, from freezing and light. Return to the original carton
`after application to protect from light.
`7. See Patient Information for additional information on safety, efficacy, general use,
`and storage of ACZONETM Gel, 5%.
`Laboratory Tests
`
`
`
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`Glucose 6-phosphate dehydrogenase levels should be obtained in all patients prior to
`initiating therapy with ACZONETM Gel, 5%. Baseline complete blood counts, including
`a reticulocyte count, should be obtained in patients who are G6PD deficient or with a
`history of anemia. Routine follow-up for complete blood count and reticulocyte count
`should be implemented for patients at risk.
`
`Drug Interactions
`A drug-drug interaction study evaluated the effect of the use of ACZONE 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. Systemic exposure (AUC0-12) of dapsone and N-acetyl-dapsone
`(NAD) were increased by about 40% and 20% respectively in presence of TMP/SMX.
`Notably, systemic exposure (AUC0-12) of dapsone hydroxylamine (DHA) was more than
`doubled in the presence of TMP/SMX. Exposure from the proposed topical dose is about
`1% of that from the 100 mg oral dose, even when co-administered with TMP/SMX.
`
`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.
`
`Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`Dapsone was not mutagenic in a bacterial reverse mutation assay (Ames test) using
`S. typhimurium and E. coli, with and without metabolic activation and was negative in a
`micronucleus assay conducted in mice. Dapsone increased both numerical and structural
`aberrations in a chromosome aberration assay conducted with Chinese hamster ovary
`(CHO) cells.
`
`In studies conducted for ACZONE Gel, 5%, 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 160 times the systemic exposure observed in human males
`and 300 times the systemic exposure observed in human females as a result of use of the
`maximum recommended topical dose, based on AUC comparisons).
`
`No evidence of potential to induce carcinogenicity was obtained 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.
`
`ACZONE Gel, 5%, did not increase the rate of formation of ultra violet light-induced
`skin tumors when topically applied to hairless mice in a 12-month photocarcinogenicity
`study.
`
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`The effects of dapsone on fertility and general reproduction performance were assessed in
`male and female rats following oral (gavage) dosing. Dapsone reduced sperm motility at
`dosages of 3 mg/kg/day or greater (approximately 17 times the systemic exposure
`observed in human males as a result of use of the maximum recommended topical dose,
`based on AUC comparisons). 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 70 times the systemic exposure
`observed in human males as a result of use of the maximum recommended topical dose,
`based on AUC comparisons), presumably due to reduced numbers or effectiveness of
`sperm, indicating impairment of fertility. Dapsone had no effect on male fertility at
`dosages of 2 mg/kg/day or less (approximately 13 times the systemic exposure observed
`in human males as a result of use of the maximum recommended topical dose, based on
`AUC comparisons). When administered to female rats at a dosage of 75 mg/kg/day
`(approximately 800 times the systemic exposure observed in human females as a result of
`use of the maximum recommended topical dose, 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 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 seen at a dapsone dose of 30 mg/kg/day (approximately 500 times the
`systemic exposure observed in human females as a result of use of the maximum
`recommended topical dose, based on AUC comparisons). No effects were observed on
`the viability, physical development, behavior, learning ability, or reproductive function of
`surviving pups.
`
`Pregnancy:
`Teratogenic Effects: Pregnancy Category C
`
`Dapsone has been shown to have an embryocidal effect in rats and rabbits when given in
`doses of 75 mg/kg/day and 150 mg/kg/day (approximately 800 and 500 times the
`systemic exposure observed in human females as a result of use of the maximum
`recommended topical dose, based on AUC comparisons), respectively. These effects
`were probably secondary to maternal toxicity. There are no adequate and well controlled
`studies in pregnant women. ACZONE Gel, 5%, should be used during pregnancy only if
`the potential benefit justifies the potential risk to the fetus.
`
`Nursing Mothers:
`
`Although systemic absorption of dapsone following topical application of ACZONETM
`Gel, 5%, is minimal relative to oral dapsone administration, it is known that dapsone is
`excreted in human milk. Because of the potential for oral dapsone to cause adverse
`
`
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`
`reactions in nursing infants, a decision should be made whether to discontinue nursing or
`to discontinue ACZONETM Gel, 5%, taking into account the importance of the drug to the
`mother.
`
`Pediatric Use:
`
`Safety and efficacy was evaluated in 1169 children aged 12-17 years old treated with
`ACZONE Gel, 5%, in the clinical studies. The adverse event rate for ACZONETM Gel,
`5%, was similar to the vehicle control group. Safety and efficacy was not studied in
`pediatric patients less than 12 years of age, therefore ACZONETM Gel, 5%, is not
`recommended for use in this age group.
`
`Geriatric Use:
`
`Clinical studies of ACZONETM Gel, 5%, did not include sufficient number of patients
`aged 65 and over to determine whether they respond differently from younger patients.
`
`
`ADVERSE REACTIONS
`
`While clinical studies conducted with ACZONE Gel, 5%, for acne vulgaris did not
`demonstrate evidence of clinically significant anemia, an increased reticulocyte count and
`a decreased hemoglobin level were found in a G6PD deficient patient who had a
`complete blood count performed. Only 25 patients with low plasma glucose 6-phosphate
`dehydrogenase activity treated with ACZONE Gel, 5%, were included in the clinical
`study program.
`
`Serious adverse events reported in patients treated with ACZONE Gel, 5%, during
`clinical trials included but were not limited to the following:
`Nervous system/Psychiatric – Suicide attempt, tonic clonic movements.
`Gastrointestinal – Abdominal pain, severe vomiting, pancreatitis.
`Other – Severe pharyngitis
`
`Combined contact sensitization/irritation studies with ACZONE Gel, 5%, in 253 healthy
`subjects resulted in at least 3 subjects with moderate erythema. ACZONETM Gel, 5%,
`did not induce phototoxicity or photoallergy in human dermal safety studies.
`
`ACZONETM Gel, 5%, was evaluated for 12 weeks in four controlled studies for local
`cutaneous events in 1819 patients. The most common events reported from these studies
`include oiliness/peeling, dryness, and erythema. These data are shown by severity in
`Table 3 below.
`
`
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`Table 3 - Application Site Adverse Events by Maximum Severity from Four 12-Week, Vehicle-Controlled
`Studies
`
`Application Site
`Event
`Erythema
`Dryness
`Oiliness/Peeling
`
`Vehicle
`ACZONE™
`(N=1660)
`(N=1819)
`Mild Moderate Severe Mild Moderate Severe
`9%
`5%
`<1%
`9%
`6%
`<1%
`14%
`3%
`<1%
`14%
`4%
`<1%
`13%
`6%
`<1%
`15%
`6%
`<1%
`
`
`There were no significant differences in the adverse event rates between ACZONETM
`Gel, 5%, and vehicle control treated patients. The adverse events occurring in at least 1%
`of patients in either arm in the four vehicle controlled studies are presented in Table 4.
`
`Table 4 – Adverse Events Occurring in at least 1% of Patients in Four Vehicle Controlled Studies
`
`ACZONE™
`Vehicle
`N=1819
`N=1660
`18%
`20%
`16%
`17%
`13%
`14%
`1%
`2%
`1%
`1%
`1%
`1%
`5%
`6%
`3%
`3%
`2%
`1%
`1%
`1%
`2%
`2%
`2%
`2%
`1%
`1%
`4%
`4%
`
`Application Site Reaction NOS
`Application Site Dryness
`Application Site Erythema
`Application Site Burning
`Application Site Pruritus
`Pyrexia
`Nasopharyngitis
`Upper Respiratory Tract Inf. NOS
`Sinusitis NOS
`Influenza
`Pharyngitis
`Cough
`Joint Sprain
`Headache NOS
`
`One patient treated with topical dapsone in the clinical trials had facial swelling which
`led to discontinuation of medication.
`
`In addition, 486 patients were evaluated in a 12 month safety study. The adverse event
`profile in this study was consistent with that observed in the vehicle-controlled studies.
`
`
`OVERDOSAGE
`
`ACZONETM Gel, 5%, is not for oral use. If oral ingestion occurs, medical advice should
`be sought.
`
`DOSAGE AND ADMINISTRATION
`
`
`
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`Product Code 500503
`
`After the skin is gently washed and patted dry, apply approximately a pea-sized amount
`of ACZONETM Gel, 5%, in a thin layer to the acne affected areas twice daily. Rub in
`ACZONETM Gel, 5%, gently and completely. ACZONETM Gel, 5%, is gritty with visible
`drug substance particles present. Wash hands after application of ACZONETM Gel, 5%.
`
`If there is no improvement after 12 weeks, appropriateness of treatment with ACZONETM
`Gel, 5%, should be reassessed.
`
`
`HOW SUPPLIED:
`
`ACZONE™ (dapsone) Gel, 5%, is supplied in the following size tubes:
`
`Professional Sample
`5 % NDC 0469-5005-03
`3 gram laminate tube
`
`Commercially Available as:
`5 % NDC 0469-5005-30
`30 gram plastic tube
`
`KEEP OUT OF THE REACH OF CHILDREN LESS THAN 12 YEARS OLD.
`
`Storage conditions:
`Store at controlled room temperature, 20-25 °C (68-76 °F), excursions permitted to 15–
`30 ºC (59–86 ºF). Protect from freezing and light. Return to the original carton after
`application.
`
`Rx Only
`
`Manufactured by QLT USA, Inc., Fort Collins, CO 80525
`
`
`
`Product Code 500530
`
`
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`PATIENT INFORMATION
`
`
`ACZONE™ (dapsone) Gel 5%
`
`
`Read this important information before you start using ACZONE™ (AK-zōn) Gel and
`each time you refill your prescription. There may be new information that you need to
`know. This summary is not meant to take the place of your doctor’s advice. If you have
`any questions or want more information about ACZONE™ Gel, ask your doctor or
`pharmacist.
`
`What is ACZONE™ Gel?
`ACZONE™ Gel is a prescription skin use (topical) medicine used to help treat acne in
`people 12 years and older.
`
`ACZONE™ Gel has not been studied in children under 12 years of age.
`
`Who should not use ACZONE™ Gel?
`Do not use ACZONE™ Gel if you are allergic any of the ingredients in ACZONE™
`Gel. Ask your doctor or pharmacist for a list of these ingredients. The active ingredient
`is dapsone. See the end of this leaflet for a complete list of ingredients in ACZONE™
`Gel.
`
`What should I tell my doctor before using ACZONE™ Gel?
`Tell your doctor about all of your medical conditions, including if you:
`• are pregnant or planning to become pregnant. It is not known if ACZONE Gel
`may harm your unborn baby.
`• are breastfeeding. ACZONE™ Gel passes into your milk and may harm your
`baby. You should choose either to use ACZONE™ Gel, or breastfeed, but not
`both. Talk to you doctor about the best way to feed your baby while using
`ACZONE™ Gel.
`• have a history of anemia or have been diagnosed with glucose-6-phosphate
`dehydrogenase deficiency
`
`
`Tell your doctor about all the medicines you are taking including prescription and
`nonprescription medicines, vitamins and herbal supplements. Especially, tell your
`doctor if you are using any other medicines applied to the skin.
`
`How do I use ACZONE™ Gel?
`• Use ACZONE™ Gel exactly as prescribed by your doctor. ACZONE™ Gel is
`usually used on your affected skin twice a day, once in the morning and once in the
`evening.
`• Wash the areas of your skin where you will apply ACZONE™ Gel. Gently pat your
`skin dry with a clean towel.
`• Apply a thin layer of ACZONE™ Gel to the areas of your skin that have acne. A pea-
`sized amount of ACZONE™ Gel will usually be enough.
`
`
`
`13
`
`10
`
`

`

`402
`403
`404
`405
`406
`407
`408
`409
`410
`411
`412
`413
`414
`415
`416
`417
`418
`419
`420
`421
`422
`423
`424
`425
`426
`427
`428
`429
`430
`431
`432
`433
`434
`435
`
`•
`
`• Rub the medicine in gently and completely
`• Make sure to put the cap back on the ACZONE™ Gel tube. Close it tightly and put
`the tube back in its original box.
`• Wash your hands after applying ACZONE™ Gel.
`• Keep ACZONE™ Gel away from your mouth and eyes. Do not swallow
`ACZONE™ Gel. If you swallow ACZONE™ Gel, call your doctor or poison control
`center right away.
`If your acne does not get better after using ACZONE™ for 12 weeks, talk to your
`doctor about other treatments for acne.
`
`
`What are the possible side effects of ACZONE™ Gel?
`Like all medicines, ACZONE™ Gel can cause some side effects. These side effects are
`usually mild. The most common side effects of ACZONE™ Gel are dryness, redness,
`oiliness and peeling of the skin being treated.
`Call your doctor if you have excessive tiredness or any side effects that do not go away or
`bother you. This is not a complete list of all the side effects. If you have any questions,
`ask your doctor or pharmacist.
`
`How should I store ACZONE™ Gel?
`Store ACZONE™ Gel at room temperature 68 to 76 ºF. Do not freeze ACZONE™ Gel.
`Protect ACZONE™ Gel tube from light. Store in original box after using it.
`
`Keep ACZONE™ Gel out of the reach of children less than 12 years of age.
`
`Where can I find more information about ACZONE™ Gel?
`If you have any questions or want more information about ACZONE™ Gel, ask your
`doctor or pharmacist. Your doctor or pharmacist can also give you a copy of the
`ACZONE™ Gel Package Insert written for health professionals. Ask them to explain
`anything you do not understand.
`
`You may call 1-800-727-7003 to obtain more information about ACZONE™ Gel.
`
`
`
`
`
`
`14
`
`11
`
`

`

`OPEN END
`
`BACK PANEL
`CENTER LINE
`
`FRONT PANEL
`CENTER LINE
`
`2 3/8 inches
`
`OVER
`
`Side Seam – Overlap
`
`OVER
`
`Exp.
`
`FOR TOPICAL USE ONLY: Not for oral, ophthalmic or intravaginal use. Rx only
`Each gram of ACZONE™ (dapsone) Gel, 5% contains 50 mg of dapsone, USP, in a gel of
`carbomer 980; diethylene glycol monoethyl ether, NF; methylparaben, NF; sodium hydroxide,
`USP; and purified water, USP. See package insert for dosage information. Store at controlled
`room temperature 20° to 25°C (68°-76°F), excursions permitted to 15°-30°C (59°-86°F).
`Protect from freezing.
`Manufactured by QLT USA, Inc., Fort Collins, CO 80525
`for Astellas Pharma US, Inc., Deerfield, IL 60015-2548
`
`TEXT/ARTWORK AREA
`
`02110 Rev. 2 6/05
`
`NDC 0469-5005-03
`
`ACZONEp
`(dapsone)
`5%
`Gel,
`
`5
`
`PROFESSIONAL SAMPLE - NOT FOR SALE
`
`CAP END
`
`5 mm
`
`4 mm
`
`6.97 mm
`
`9.97 mm
`
`9.97 mm
`
`9.97 mm
`
`4.2 mm
`
`UNDER
`
`Side Seam – Overlap
`
`UNDER
`
`3/16”
`
`1/4”
`
`1/8”
`
`PMS265C
`
`Black
`
`Astellas logo
`Red: 193C
`Gray Cool gray 9C
`Overlap: 193C + Cool Gray 9C (40%)
`
`m
`
`CrossTech–46871–Proof A9
`Form M01
`Astellas Pharma US, Inc.–P.O. 21321–Job No. 02110–
`6/30/05–am–Q4.1
`
`Fonts: Helvetica (A)
`Typesmiths Pi Font
`
`12
`
`

`

`03208 Rev. 1 6/05
`
`3
`
`5
`
`5
`Gel,
`
`dapsone
`ACZONEp
`
`Black
`
`PMS2756C
`
`PMS265C
`
`Astellas logo
`Red: 193C
`Gray Cool gray 9C
`Overlap: 193C + Cool Gray 9C (40%)
`
`NDC 0469-5005-03
`
`ACZONEp
`
`dapsone
`5
`Gel,
`
`FOR TOPICAL USE ONLY.
`Not for oral, ophthalmic, or intravaginal use.
`
`500503
`
`Each gram of ACZONE™ (dapsone) Gel, 5%,
`contains 50 mg of dapsone, USP, in a gel of
`carbomer 980; diethylene glycol monoethyl
`ether, NF; methylparaben, NF; sodium
`hydroxide, USP; and purified water, USP.
`
`Dosage: Apply twice daily. See package insert
`for dosage information.
`
`WARNING: Keep out of the reach of children.
`Rx only
`
`Storage: Store at controlled room temperature
`20˚-25˚C (68˚-76˚F), excursions permitted to
`15˚-30˚C (59˚-86˚F). Protect from freezing.
`For Lot and Exp.: See crimp of tube.
`P R O F E S S I O N A L S A M P L E S - N O T F O R S A L E
`
`5
`
`5
`
`3
`
`ACZONEp
`dapsone
`
`5
`Gel,
`
`101.6x76.2x50.8
`
`5
`
`Manufactured
`by QLT USA, Inc.,
`Fort Collins, CO 80525
`for Astellas Pharma US, Inc.,
`Deerfield, IL 60015-2548
`
`CrossTech–46874–Proof A7
`Form M01
`Astellas Pharma US, Inc.–P.O. 21321–Job No. 03208
`Aczone Gel 5%
`6/29/05–jc–Q4.11
`
`m
`
`13
`
`

`

`Cap End
`
`3
`
`quiet zone
`
`Open end
`
`FOR TOPICAL USE ONLY: Not for oral, ophthalmic or
`intravaginal use.
`WARNING: Keep out of reach of children.
`Rx only
`Each gram of ACZONE™ (dapsone) Gel, 5%, contains 50 mg of
`dapsone, USP, in a gel of carbomer 980; diethylene glycol
`monoethyl ether, NF; methylparaben, NF; sodium hydroxide,
`USP; and purified water, USP.
`Dosage: Apply twice daily. See package insert for dosage
`information.
`
`5
`Storage: Store at controlled room temperature 20° to 25°C
`(68°-76°F), excursions permitted to 15°-30°C (59°-86°F).
`Protect from freezing and light. Return to the original
`carton after application.
`
`NO PRINT AREA
`
`For Lot and Exp.: See crimp.
`
`Manufactured by: QLT USA, Inc., Fort Collins, CO 80525
`for Astellas Pharma US, Inc., Deerfield, IL 60015-2548
`
`NDC 0469-5005-30
`
`02109 Rev. 2 6/05
`
`ACZONEp
`(dapsone)
`5%
`Gel,
`
`30g
`
`4
`
`1/
`
`Height
`Print
`Actual
`
`“
`
`2. 1/2
`
`All copy must be below the eye-mark
`
`NO PRINT AREA
`
`4
`
`1/
`
`if full wrap is desired
`Bleed1/8”for overlap only
`
`3gx0.03%.AI Rev 4
`Astellas Red (PMS 193C)
`Red:
`Dark Red: Astellas Red+Astellas Gray (PMS 193C + Cool Gray 9C @40%)
`Gray:
`Astellas Gray (PMS Cool Gray 9C)
`Purple:
`PMS 265C
`Black
`
`m
`
`CrossTech–46870–Proof A9
`Form M01
`Astellas Pharma, US, Inc.–P.O. 21321—Job No. 02109–Job
`6/30/05–am –Q4.1
`
`Fonts: Helvetica (A)
`Typesmiths Pi Font
`
`GTIN (01)00304695005303
`
`14
`
`

`

`Black
`
`PMS265C
`
`Astellas logo
`Red: 193C
`Gray Cool gray 9C
`Overlap: 193C + Cool Gray 9C (40%)
`
`03207 Rev. 1 6/05
`
`ACZONEp
`dapsone
`5
`Gel,
`
`ACZONEp
`dapsone
`5Gel,
`
`NDC 0469-5005-30
`
`5
`
`30
`
`Each gram of ACZONE™
`(dapsone) Gel, 5%, contains
`50 mg of dapsone, USP, in a
`gel of carbomer 980;
`diethylene glycol monoethyl
`ether, NF; methylparaben,
`NF; sodium hydroxide, USP;
`and purified water, USP.
`Dosage: Apply twice daily.
`See package insert for
`dosage information.
`
`5
`
`Storage: Store at controlled room temperature 20˚-25˚C
`(68˚-76˚F), excursions permitted to 15˚-30˚C (59˚-86˚F).
`Protect from freezing and light.
`Return to the original carton after application.
`FOR TOPICAL USE ONLY. Not for oral, ophthalmic
`or intravaginal use.
`WARNING: Keep out of the reach of children.
`Rx only
`For Lot and Exp.: See End Flap.
`
`30
`
`04695 00530
`
`3
`
`3N
`
`ACZONEp
`dapsone
`5
`Gel,
`
`Manufactured
`by QLT USA, Inc.,
`Fort Collins, CO 80525
`for Astellas Pharma US, Inc.,
`Deerfield, IL 60015-2548
`
`305
`
`ACZONEp
`apsone
`Gel,
`
`5
`
`30
`
`n
`
`5 d
`
`
`
`CrossTech–46872–Proof A9
`Form M01
`Astellas Pharma US, Inc.–P.O. 21321–Job No. 03207
`Aczone Gel 5%
`6/30/05–am–Q4.11
`GTIN 304695005303
`
`m
`
`15
`
`

`

`30
`
`5
`
`For Lot and Exp: See Top Flap.
`
`carton after application.
`light. Return to the original
`Protect from freezing and
`(59˚-86˚F).
`permitted to 15˚-30˚C
`(68˚-76˚F), excursions
`room temperature 20˚-25˚C
`Storage: Store at controlled
`
`Black
`
`PMS265C
`
`Astellas logo
`Red: 193C
`Gray Cool gray 9C
`Overlap: 193C + Cool Gray 9C (40%)
`
`m
`
`GTIN (01)2030469500530C
`6/30/05–am–Q4.11
`Aczone Gel 5%
`Astellas Pharma US, Inc.–P.O. 21321–Job No. 03200
`Form M01
`CrossTech–46868–Proof A3
`
`NDC 0469-5005-30ACZONEp
`dapsone
`5
`Gel,
`
`30g x 12
`
`500530
`
`30
`
`5
`
`30g x 12
`
`ACZONEp
`dapsone
`5
`Gel,
`Storage: Store at controlled room temperature 20˚-25˚C
`(68˚-76˚F), excursions permitted to 15˚-30˚C (59˚-86˚F).
`Protect from freezing and light. Return to the original
`carton after application.
`
`30
`
`03209 Rev. 1 6/05
`
`NDC 0469-5005-30
`
`ACZONEp
`dapsone
`5
`Gel,
`
`30g x 12
`500530
`
`FOR TOPICAL USE ONLY. Not for oral, ophthalmic, or intravaginal use.
`WARNING: Keep out of the reach of children.
`Each gram of ACZONE™ (dapsone) Gel, 5%, contains 50 mg of dapsone,
`USP, in a gel of carbomer 980; diethylene glycol monoethyl ether, NF;
`methylparaben, NF; sodium hydroxide, USP; and purified water, USP.
`Dosage: Apply twice daily. See package insert for dosage information.
`
`Rx only
`
`5
`
`(01) 2 0304695 00530 7
`
`30
`
`5
`
`5
` Gel,
`dapsone
`ACZONEp
`NDC 0469-5005-30ACZONEp
`dapsone
`5
`Gel,
`
`30g x 12
`
`500530
`
`30
`
`30g x 12
`
`ACZONEp
`dapsone
`5
`Gel,
`
`Manufactured
`by QLT USA, Inc.
`Fort Collins, CO 80525
`for Astellas Pharma US, Inc.
`Deerfield, IL 60015-2548
`
`5
`
`5
`
`30
`
`16
`
`