These Highlights Do Not Include All The Information Needed To Use Dapsone Gel Safely And Effectively. See Full Prescribing Information For Dapsone Gel.

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 dapsone 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 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)].

Storage: Store at 20ºC to 25ºC (68ºF to 77ºF), excursions permitted to 15 ºC to 30 ºC (59 ºF to 86 ºF). [see USP Controlled Room Temperature]. Protect from freezing.

Dapsone Gel, 7.5%, contains dapsone, a sulfone, in an aqueous gel base for topical dermatologic use. Dapsone Gel, 7.5% is an off-white to yellow color homogeneous gel with suspended particles, no phase separation and sedimentation, free of lumps and foreign matter. Chemically, dapsone has an empirical formula of C₁₂H₁₂N₂O₂S. It is a White to creamy 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 dapsone gel, 7.5% contains 75 mg of dapsone, USP in a gel of diethylene glycol monoethyl ether, methylparaben, carbomer homopolymer type C, sodium hydroxide and purified water.

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 1,066 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.

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.

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.

The safety and efficacy of once daily use of dapsone gel, 7.5% was assessed in two 12 week multicenter, randomized, double-blind, vehicle-controlled trials. Efficacy was assessed in a total of 4,340 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, and were randomized to receive either dapsone 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.

None.

Most common (incidence ≥0.9 %) adverse reactions are application site dryness and pruritus (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No formal drug-drug interaction studies were conducted with dapsone gel, 7.5%.

In a pharmacokinetic study, male and female subjects 16 years of age or older with acne vulgaris (N=19) applied 2 grams of dapsone gel, 7.5% 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 (C_max) and area under the concentration-time curve from 0 to 24 hours post dose (AUC_0-24h) were 13.0 ± 6.8 ng/mL and 282 ± 146 ng∙h/mL, respectively. The systemic exposure from dapsone 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 dapsone 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 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.

Dapsone gel, 7.5% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

The mechanism of action of dapsone gel in treating acne vulgaris is not known.

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.

• Methemoglobinemia: Cases of methemoglobinemia have been reported. Discontinue dapsone 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)

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 dapsone 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 dapsone gel, 7.5%, gently and completely.

If there is no improvement after 12 weeks, treatment with dapsone gel, 7.5%, should be reassessed.

Gel, 7.5%. Each gram of dapsone gel, 7.5% contains 75 mg of dapsone in an off-white to yellow color homogeneous gel with suspended particles, no phase separation and sedimentation, free of lumps and foreign matter.

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).

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.

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 2,161 subjects were treated with dapsone 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 dapsone gel, 7.5% appear in Table 1 below.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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 dapsone gel, 7.5% is expected to be about 1% of that from the 100 mg oral dose, even when co-administered with TMP/SMX.

Dapsone Gel is an off-white to yellow color homogeneous gel with suspended particles; no phase separation and sedimentation; free of lumps and foreign matter. It is supplied in an airless polypropylene pump containing a polypropylene bottle with a high density polyethylene piston.

Dapsone Gel, 7.5% is supplied in the following sizes:

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).

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.

NDC 68308-342-60

Dapsone Gel, 7.5%

FOR TOPICAL USE ONLY

Rx Only

60 g

mayne pharma

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)].

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 dapsone 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 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 1,407 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.

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)].

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 dapsone 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 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)].

Storage: Store at 20ºC to 25ºC (68ºF to 77ºF), excursions permitted to 15 ºC to 30 ºC (59 ºF to 86 ºF). [see USP Controlled Room Temperature]. Protect from freezing.

Dapsone Gel, 7.5%, contains dapsone, a sulfone, in an aqueous gel base for topical dermatologic use. Dapsone Gel, 7.5% is an off-white to yellow color homogeneous gel with suspended particles, no phase separation and sedimentation, free of lumps and foreign matter. Chemically, dapsone has an empirical formula of C₁₂H₁₂N₂O₂S. It is a White to creamy 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 dapsone gel, 7.5% contains 75 mg of dapsone, USP in a gel of diethylene glycol monoethyl ether, methylparaben, carbomer homopolymer type C, sodium hydroxide and purified water.

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 1,066 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.

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.

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.

The safety and efficacy of once daily use of dapsone gel, 7.5% was assessed in two 12 week multicenter, randomized, double-blind, vehicle-controlled trials. Efficacy was assessed in a total of 4,340 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, and were randomized to receive either dapsone 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.

None.

Most common (incidence ≥0.9 %) adverse reactions are application site dryness and pruritus (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

No formal drug-drug interaction studies were conducted with dapsone gel, 7.5%.

In a pharmacokinetic study, male and female subjects 16 years of age or older with acne vulgaris (N=19) applied 2 grams of dapsone gel, 7.5% 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 (C_max) and area under the concentration-time curve from 0 to 24 hours post dose (AUC_0-24h) were 13.0 ± 6.8 ng/mL and 282 ± 146 ng∙h/mL, respectively. The systemic exposure from dapsone 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 dapsone 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 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.

Dapsone gel, 7.5% is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.

The mechanism of action of dapsone gel in treating acne vulgaris is not known.

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.

• Methemoglobinemia: Cases of methemoglobinemia have been reported. Discontinue dapsone 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)

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 dapsone 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 dapsone gel, 7.5%, gently and completely.

If there is no improvement after 12 weeks, treatment with dapsone gel, 7.5%, should be reassessed.

Gel, 7.5%. Each gram of dapsone gel, 7.5% contains 75 mg of dapsone in an off-white to yellow color homogeneous gel with suspended particles, no phase separation and sedimentation, free of lumps and foreign matter.

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).

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.

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 2,161 subjects were treated with dapsone 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 dapsone gel, 7.5% appear in Table 1 below.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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 dapsone gel, 7.5% is expected to be about 1% of that from the 100 mg oral dose, even when co-administered with TMP/SMX.

Dapsone Gel is an off-white to yellow color homogeneous gel with suspended particles; no phase separation and sedimentation; free of lumps and foreign matter. It is supplied in an airless polypropylene pump containing a polypropylene bottle with a high density polyethylene piston.

Dapsone Gel, 7.5% is supplied in the following sizes:

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).

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.

NDC 68308-342-60

Dapsone Gel, 7.5%

FOR TOPICAL USE ONLY

Rx Only

60 g

mayne pharma

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)].

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 dapsone 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 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 1,407 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.

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)].