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 dapsone gel, 7.5% with drugs that induce methemoglobinemia such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, 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) ].

es, lips, and nail beds. advise patients to discontinue dapsone 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 dapsone gel, 7.5%, if signs and symptoms suggestive of hemolytic anemia occur. avoid use of dapsone gel, 7.5% in patients who are taking oral dapsone or antimalarial medications because of the potential for hemolytic reactions. combination of dapsone gel, 7.5%, with trimethoprim/sulfamethoxazole (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.

nical trials dapsone gel, 7.5% (n=2161) vehicle (n=2175) application site dryness 24 (1.1%) 21 (1.0%) application site pruritus 20 (0.9%) 11 (0.5%) 6.2 experience with oral use of dapsone 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). 6.3 postmarketing experience 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).

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 dapsone gel, 7.5% with drugs that induce methemoglobinemia such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, 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) ].

e unknown. 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. 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 dapsone 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 seen at a dapsone dose of 30 mg/kg/day (approximately 563 times the systemic exposure that is associated with the mrhd of dapsone 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. 8.2 lactation 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 low relative to oral dapsone administration. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for dapsone gel, 7.5% and any potential adverse effects on the breastfed child from dapsone gel, 7.5% or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of dapsone gel, 7.5% for the topical treatment of acne vulgaris have been established in patients 9 years of age and older. use of dapsone gel, 7.5% in patients 9 to 11 years of age for this indication is supported by evidence from adequate and well-controlled clinical trials in 1066 subjects 12 years of age and older and with additional pharmacokinetic and safety data in pediatric subjects 9 to 11 years of age from an open label study of 100 subjects with acne [see adverse reactions (6.1) , and clinical pharmacology (12.3) ] . the safety profile for dapsone gel, 7.5% in clinical trials was similar to the vehicle control group. safety and effectiveness of dapsone gel, 7.5%, have not been established in pediatric patients below the age of 9 years. 8.5 geriatric use clinical trials of dapsone 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) ]. dapsone 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 dapsone 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) ].

population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 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 dapsone 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 seen at a dapsone dose of 30 mg/kg/day (approximately 563 times the systemic exposure that is associated with the mrhd of dapsone 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.

ne 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 to 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. in an open label safety and pharmacokinetic study in pediatric subjects 9 to 11 years of age with acne vulgaris, a subset of subjects (n=16) received once daily topical application of approximately 2 grams of dapsone gel, 7.5%, to the entire face, shoulders, upper chest and upper back for 8 days. on day 8, the systemic concentrations were at or near steady state and the mean ± sd systemic concentration of dapsone at 10 hours post dose was 20 ± 12.5 ng/ml. 12.4 microbiology in vivo activity: no microbiology or immunology studies were conducted during dapsone gel, 7.5% clinical studies. drug resistance: no dapsone resistance studies were conducted during dapsone gel clinical studies therefore 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.

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 to 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. in an open label safety and pharmacokinetic study in pediatric subjects 9 to 11 years of age with acne vulgaris, a subset of subjects (n=16) received once daily topical application of approximately 2 grams of dapsone gel, 7.5%, to the entire face, shoulders, upper chest and upper back for 8 days. on day 8, the systemic concentrations were at or near steady state and the mean ± sd systemic concentration of dapsone at 10 hours post dose was 20 ± 12.5 ng/ml.

ssed 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 dapsone 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 dapsone 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 dapsone 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.

ts 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 dapsone 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 dapsone 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 dapsone 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.

. 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 dapsone gel at week 12 in subjects with acne vulgaris trial 1 trial 2 dapsone gel, 7.5% (n=1044) vehicle (n=1058) dapsone gel, 7.5% (n=1118) vehicle (n=1120) global acne assessment score gaas success (score 0 or 1) 30% 21% 30% 21% inflammatory lesions mean absolute reduction 16.1 14.3 15.6 14.0 mean percent reduction 56% 49% 54% 48% non-inflammatory lesions mean absolute reduction 20.7 18.0 20.8 18.7 mean percent reduction 45% 39% 46% 41%

el, 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 dapsone 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 dapsone gel, 7.5%? use dapsone gel, 7.5% exactly as your doctor tells you to use it. apply dapsone gel, 7.5% one time a day. gently wash and pat dry the areas of your skin where you will apply dapsone gel, 7.5%. apply a pea-sized amount of dapsone 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 dapsone gel, 7.5% in gently and completely. wash your hands after applying dapsone gel, 7.5%. if your acne does not get better after using dapsone gel, 7.5% for 12 weeks, talk to your doctor about continuing treatment. what are the possible side effects of dapsone gel, 7.5%? dapsone 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 dapsone 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 dapsone gel, 7.5% may develop mild hemolytic anemia. stop using dapsone gel, 7.5% and tell your doctor right away if you get any of the following signs and symptoms: back pain dark brown urine shortness of breath fever tiredness or weakness yellow or pale skin the most common side effects of dapsone gel, 7.5% include dryness and itching of the skin being treated. these are not all of the possible side effects of dapsone 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 dapsone gel, 7.5%? store dapsone gel, 7.5%, at room temperature 68°f to 77°f (20°c to 25°c). protect dapsone gel, 7.5% from freezing. keep dapsone gel, 7.5% and all medicines out of the reach of children. general information about the safe and effective use of dapsone gel, 7.5%. medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use dapsone gel, 7.5% for a condition for which it was not prescribed. do not give dapsone 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 dapsone gel, 7.5% that is written for health professionals. what are the ingredients in dapsone gel, 7.5%? active ingredient: dapsone inactive ingredients: carbomer homopolymer type c, diethylene glycol monoethyl ether, light mineral oil, methylparaben, polysorbate 80, purified water, sodium hydroxide, and sorbitan monooleate. manufactured by: taro pharmaceuticals inc. brampton, ontario, canada l6t 1c1 distributed by: taro pharmaceuticals u.s.a., inc. hawthorne, ny 10532 for more information, call 1-866-923-4914