Dapsone is a sulfone derivative that has long been established as an effective oral agent for the treatment of leprosy and neutrophilic dermatoses, most notably dermatitis herpetiformis. Pharmacologic properties of dapsone include anti-inflammatory activities, among which are suppression of neutrophil recruitment, migration and release of lysosomal enzymes.1
In the pre-isotretinoin era, oral dapsone was sometimes used to treat severe, refractory, inflammatory acne vulgaris, most frequently when conventional topical and systemic antibiotic therapies proved unsuccessful. Use of oral dapsone warrants pre-treatment evaluation of patients to screen for the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency, an uncommon genetic state that predisposes patients to hemolytic anemia.1
Recently, a topical formulation of dapsone as a 5% gel has been extensively evaluated regarding efficacy and safety in patients with facial acne vulgaris. In two pivotal multicenter, randomized, double-blind, placebo-controlled Phase III trials inclusive of 3,010 patients, 1,506 study participants were actively treated with topical dapsone 5% gel twice daily.2
Additional studies have examined the use of dapsone 5% gel in combination with other topical agents for treating acne vulgaris.3 Collectively, these trials have demonstrated consistent results in terms of efficacy, favorable tolerability, and safety, with no evidence of clinically relevant hematologic or systemic abnormalities, and no reported cases of hemolytic anemia. The following is a review of available data on dapsone 5% gel.
Pharmacokinetic Properties
Due to potential toxicity concerns related to oral administration of dapsone, systemic bioavailability after application of dapsone 5% gel has been evaluated in 15-day and 52-week pharmacokinetic studies.4,5 After a single oral dose of dapsone 100 mg, the mean peak plasma dapsone level was 1375 ng/ml. After topical application of dapsone 5% gel, the mean peak plasma dapsone level through day 14 was 19.7 ng/ml (see Figure 1).4 Further continued application of dapsone 5% gel over 52 weeks demonstrated no increase in plasma dapsone concentrations over time with levels ranging from 7.4 ng/ml to 11.3 ng/ml.5
These studies demonstrated the following:
• Dapsone was minimally absorbed after topical application of the 5% gel.
• Systemic dapsone exposure is very minimal (<1% of the applied dose).
• Plasma concentrations do not accumulate over time with repeated applications over a 1-year period.4,5
• Even with continued topical administration of dapsone 5% gel, plasma dapsone concentrations remained >100-fold lower than the peak level obtained after a single 100-mg oral dose of dapsone.
Efficacy Data
In clinical trials evaluating the efficacy and safety of dapsone 5% gel, approximately 60% of subjects in both the active and vehicle treatment arms presented at baseline with facial acne vulgaris of at least moderate severity, characterized by an average of 30 inflammatory and 50 non-inflammatory lesions.2 Figure 2 depicts the pooled patient disposition data from two large, 12-week, Phase III trials, DAP 0203 and DAP 0204. Efficacy results, evaluated based on investigator static determination of “clear or almost clear” at study endpoint (week 12), and percent reduction of inflammatory, non-inflammatory and total lesion counts at week 12 as compared to baseline, are graphically demonstrated in Figures 3 and 4. Regardless of the efficacy parameter evaluated, dapsone 5% gel proved to be superior to vehicle, both clinically and statistically.
Dapsone 5% gel twice daily has been evaluated in a trial that assessed efficacy and safety results based on its use in combination with either benzoyl peroxide gel 4% once daily, adapalene gel 0.1% once daily, or placebo vehicle (active monotherapy arm) in patients with facial acne vulgaris.3 The study design of this trial is outlined in Figure 5.
Baseline lesion count characteristics were very similar to those described above for the pivotal Phase III studies, with the majority of patients graded as moderately severe. Data on efficacy are tabulated in Figure 6 based on total lesion count reductions, with similar trends observed with inflammatory and non-inflammatory lesion counts.
Interestingly, efficacy results achieved with dapsone 5% gel used in combination with a placebo vehicle (essentially reflecting monotherapy with topical dapsone) were consistent with those obtained in the pivotal Phase III studies. Study discontinuations were uncommon with only one patient stopping treatment due to lack of efficacy. As with the pivotal Phase III trials, no major safety concerns emerged during the study.
Safety Data
The gel formulation of topical dapsone is aqueous-based and is devoid of ethanol or other astringent-type alcohols. Clinical studies inclusive of >2,000 study participants with facial acne vulgaris treated with dapsone 5% gel revealed favorable skin tolerability, including use as monotherapy or in combination with either adapalene 0.1% gel or benzoyl peroxide 4% gel.2-5 The most commonly observed application-site reactions associated with use of dapsone 5% gel were erythema and dryness, with the majority rated as mild in severity. Based on long-term safety data, the rate of application-site reactions was <3.1%. Application-site symptoms such as burning and pruritus were reported by <2% of study subjects based on both spontaneous reporting and elicited responses.
Dermal safety studies of dapsone 5% gel completed in 385 subjects demonstrated no evidence of photoallergy, phototoxicity or contact hypersensitivity.6
Based on data available from multiple studies completed with dapsone 5% gel, no reports of major adverse events such as hemolytic anemia, methemoglobinemia, or agranulocytosis, were associated with dapsone, even among patients with G6PD deficiency.2-5 Short-term and long-term pharmacokinetic data coupled with clinical and laboratory evidence from large studies suggested that dapsone 5% gel was not associated with systemic toxicities that are sometimes observed with oral dapsone therapy.
Summary of Points
Dapsone exhibits anti-inflammatory properties, which support its use for treating acne vulgaris, primarily related to its suppressive effects on neutrophil recruitment, migration and enzymatic activity. Use of oral dapsone for acne vulgaris is limited by potential systemic toxicities, primarily hematologic abnormalities — especially in patients who have G6PD deficiency. Topical dapsone 5%, formulated as an aqueous gel, has been extensively studied, with >2,000 people treated in Phase III trials (N=1,506) and other studies, including long-term evaluations (N=486).
Efficacy, favorable skin tolerability, and safety have been established based on data from available studies. No reports of significant systemic toxicity have emerged, including hematologic abnormalities, which is consistent with minimal systemic exposure after topical administration. Long-term pharmacokinetic analysis demonstrated no accumulation of dapsone based on plasma concentrations.
How Does Topical Dapsone Fit into Our Acne Treatment Armamentarium?
This certainly remains to be seen based on clinical experience and additional research, as the drug has not yet been released into the marketplace. The pivotal Phase III trials provide results achieved with monotherapy for facial acne vulgaris, mostly of moderate severity. However, acne vulgaris is usually treated with a combination therapy approach to optimize therapeutic benefits. The available combination therapy data suggest that dapsone 5% gel may be used concomitantly with other topical agents, such as benzoyl peroxide or a topical retinoid. Dapsone 5% gel appears to exhibit a favorable tolerability profile, both alone or in combination with benzoyl peroxide or adapalene, based on the available studies.
New options for treatment of common dermatoses, such as acne vulgaris, are always welcome. With further clinical research and experience, additional information may provide us with other applications for dapsone 5% gel for treatment of acne vulgaris, and possibly for other disease states such as rosacea.
Dapsone is a sulfone derivative that has long been established as an effective oral agent for the treatment of leprosy and neutrophilic dermatoses, most notably dermatitis herpetiformis. Pharmacologic properties of dapsone include anti-inflammatory activities, among which are suppression of neutrophil recruitment, migration and release of lysosomal enzymes.1
In the pre-isotretinoin era, oral dapsone was sometimes used to treat severe, refractory, inflammatory acne vulgaris, most frequently when conventional topical and systemic antibiotic therapies proved unsuccessful. Use of oral dapsone warrants pre-treatment evaluation of patients to screen for the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency, an uncommon genetic state that predisposes patients to hemolytic anemia.1
Recently, a topical formulation of dapsone as a 5% gel has been extensively evaluated regarding efficacy and safety in patients with facial acne vulgaris. In two pivotal multicenter, randomized, double-blind, placebo-controlled Phase III trials inclusive of 3,010 patients, 1,506 study participants were actively treated with topical dapsone 5% gel twice daily.2
Additional studies have examined the use of dapsone 5% gel in combination with other topical agents for treating acne vulgaris.3 Collectively, these trials have demonstrated consistent results in terms of efficacy, favorable tolerability, and safety, with no evidence of clinically relevant hematologic or systemic abnormalities, and no reported cases of hemolytic anemia. The following is a review of available data on dapsone 5% gel.
Pharmacokinetic Properties
Due to potential toxicity concerns related to oral administration of dapsone, systemic bioavailability after application of dapsone 5% gel has been evaluated in 15-day and 52-week pharmacokinetic studies.4,5 After a single oral dose of dapsone 100 mg, the mean peak plasma dapsone level was 1375 ng/ml. After topical application of dapsone 5% gel, the mean peak plasma dapsone level through day 14 was 19.7 ng/ml (see Figure 1).4 Further continued application of dapsone 5% gel over 52 weeks demonstrated no increase in plasma dapsone concentrations over time with levels ranging from 7.4 ng/ml to 11.3 ng/ml.5
These studies demonstrated the following:
• Dapsone was minimally absorbed after topical application of the 5% gel.
• Systemic dapsone exposure is very minimal (<1% of the applied dose).
• Plasma concentrations do not accumulate over time with repeated applications over a 1-year period.4,5
• Even with continued topical administration of dapsone 5% gel, plasma dapsone concentrations remained >100-fold lower than the peak level obtained after a single 100-mg oral dose of dapsone.
Efficacy Data
In clinical trials evaluating the efficacy and safety of dapsone 5% gel, approximately 60% of subjects in both the active and vehicle treatment arms presented at baseline with facial acne vulgaris of at least moderate severity, characterized by an average of 30 inflammatory and 50 non-inflammatory lesions.2 Figure 2 depicts the pooled patient disposition data from two large, 12-week, Phase III trials, DAP 0203 and DAP 0204. Efficacy results, evaluated based on investigator static determination of “clear or almost clear” at study endpoint (week 12), and percent reduction of inflammatory, non-inflammatory and total lesion counts at week 12 as compared to baseline, are graphically demonstrated in Figures 3 and 4. Regardless of the efficacy parameter evaluated, dapsone 5% gel proved to be superior to vehicle, both clinically and statistically.
Dapsone 5% gel twice daily has been evaluated in a trial that assessed efficacy and safety results based on its use in combination with either benzoyl peroxide gel 4% once daily, adapalene gel 0.1% once daily, or placebo vehicle (active monotherapy arm) in patients with facial acne vulgaris.3 The study design of this trial is outlined in Figure 5.
Baseline lesion count characteristics were very similar to those described above for the pivotal Phase III studies, with the majority of patients graded as moderately severe. Data on efficacy are tabulated in Figure 6 based on total lesion count reductions, with similar trends observed with inflammatory and non-inflammatory lesion counts.
Interestingly, efficacy results achieved with dapsone 5% gel used in combination with a placebo vehicle (essentially reflecting monotherapy with topical dapsone) were consistent with those obtained in the pivotal Phase III studies. Study discontinuations were uncommon with only one patient stopping treatment due to lack of efficacy. As with the pivotal Phase III trials, no major safety concerns emerged during the study.
Safety Data
The gel formulation of topical dapsone is aqueous-based and is devoid of ethanol or other astringent-type alcohols. Clinical studies inclusive of >2,000 study participants with facial acne vulgaris treated with dapsone 5% gel revealed favorable skin tolerability, including use as monotherapy or in combination with either adapalene 0.1% gel or benzoyl peroxide 4% gel.2-5 The most commonly observed application-site reactions associated with use of dapsone 5% gel were erythema and dryness, with the majority rated as mild in severity. Based on long-term safety data, the rate of application-site reactions was <3.1%. Application-site symptoms such as burning and pruritus were reported by <2% of study subjects based on both spontaneous reporting and elicited responses.
Dermal safety studies of dapsone 5% gel completed in 385 subjects demonstrated no evidence of photoallergy, phototoxicity or contact hypersensitivity.6
Based on data available from multiple studies completed with dapsone 5% gel, no reports of major adverse events such as hemolytic anemia, methemoglobinemia, or agranulocytosis, were associated with dapsone, even among patients with G6PD deficiency.2-5 Short-term and long-term pharmacokinetic data coupled with clinical and laboratory evidence from large studies suggested that dapsone 5% gel was not associated with systemic toxicities that are sometimes observed with oral dapsone therapy.
Summary of Points
Dapsone exhibits anti-inflammatory properties, which support its use for treating acne vulgaris, primarily related to its suppressive effects on neutrophil recruitment, migration and enzymatic activity. Use of oral dapsone for acne vulgaris is limited by potential systemic toxicities, primarily hematologic abnormalities — especially in patients who have G6PD deficiency. Topical dapsone 5%, formulated as an aqueous gel, has been extensively studied, with >2,000 people treated in Phase III trials (N=1,506) and other studies, including long-term evaluations (N=486).
Efficacy, favorable skin tolerability, and safety have been established based on data from available studies. No reports of significant systemic toxicity have emerged, including hematologic abnormalities, which is consistent with minimal systemic exposure after topical administration. Long-term pharmacokinetic analysis demonstrated no accumulation of dapsone based on plasma concentrations.
How Does Topical Dapsone Fit into Our Acne Treatment Armamentarium?
This certainly remains to be seen based on clinical experience and additional research, as the drug has not yet been released into the marketplace. The pivotal Phase III trials provide results achieved with monotherapy for facial acne vulgaris, mostly of moderate severity. However, acne vulgaris is usually treated with a combination therapy approach to optimize therapeutic benefits. The available combination therapy data suggest that dapsone 5% gel may be used concomitantly with other topical agents, such as benzoyl peroxide or a topical retinoid. Dapsone 5% gel appears to exhibit a favorable tolerability profile, both alone or in combination with benzoyl peroxide or adapalene, based on the available studies.
New options for treatment of common dermatoses, such as acne vulgaris, are always welcome. With further clinical research and experience, additional information may provide us with other applications for dapsone 5% gel for treatment of acne vulgaris, and possibly for other disease states such as rosacea.
Dapsone is a sulfone derivative that has long been established as an effective oral agent for the treatment of leprosy and neutrophilic dermatoses, most notably dermatitis herpetiformis. Pharmacologic properties of dapsone include anti-inflammatory activities, among which are suppression of neutrophil recruitment, migration and release of lysosomal enzymes.1
In the pre-isotretinoin era, oral dapsone was sometimes used to treat severe, refractory, inflammatory acne vulgaris, most frequently when conventional topical and systemic antibiotic therapies proved unsuccessful. Use of oral dapsone warrants pre-treatment evaluation of patients to screen for the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency, an uncommon genetic state that predisposes patients to hemolytic anemia.1
Recently, a topical formulation of dapsone as a 5% gel has been extensively evaluated regarding efficacy and safety in patients with facial acne vulgaris. In two pivotal multicenter, randomized, double-blind, placebo-controlled Phase III trials inclusive of 3,010 patients, 1,506 study participants were actively treated with topical dapsone 5% gel twice daily.2
Additional studies have examined the use of dapsone 5% gel in combination with other topical agents for treating acne vulgaris.3 Collectively, these trials have demonstrated consistent results in terms of efficacy, favorable tolerability, and safety, with no evidence of clinically relevant hematologic or systemic abnormalities, and no reported cases of hemolytic anemia. The following is a review of available data on dapsone 5% gel.
Pharmacokinetic Properties
Due to potential toxicity concerns related to oral administration of dapsone, systemic bioavailability after application of dapsone 5% gel has been evaluated in 15-day and 52-week pharmacokinetic studies.4,5 After a single oral dose of dapsone 100 mg, the mean peak plasma dapsone level was 1375 ng/ml. After topical application of dapsone 5% gel, the mean peak plasma dapsone level through day 14 was 19.7 ng/ml (see Figure 1).4 Further continued application of dapsone 5% gel over 52 weeks demonstrated no increase in plasma dapsone concentrations over time with levels ranging from 7.4 ng/ml to 11.3 ng/ml.5
These studies demonstrated the following:
• Dapsone was minimally absorbed after topical application of the 5% gel.
• Systemic dapsone exposure is very minimal (<1% of the applied dose).
• Plasma concentrations do not accumulate over time with repeated applications over a 1-year period.4,5
• Even with continued topical administration of dapsone 5% gel, plasma dapsone concentrations remained >100-fold lower than the peak level obtained after a single 100-mg oral dose of dapsone.
Efficacy Data
In clinical trials evaluating the efficacy and safety of dapsone 5% gel, approximately 60% of subjects in both the active and vehicle treatment arms presented at baseline with facial acne vulgaris of at least moderate severity, characterized by an average of 30 inflammatory and 50 non-inflammatory lesions.2 Figure 2 depicts the pooled patient disposition data from two large, 12-week, Phase III trials, DAP 0203 and DAP 0204. Efficacy results, evaluated based on investigator static determination of “clear or almost clear” at study endpoint (week 12), and percent reduction of inflammatory, non-inflammatory and total lesion counts at week 12 as compared to baseline, are graphically demonstrated in Figures 3 and 4. Regardless of the efficacy parameter evaluated, dapsone 5% gel proved to be superior to vehicle, both clinically and statistically.
Dapsone 5% gel twice daily has been evaluated in a trial that assessed efficacy and safety results based on its use in combination with either benzoyl peroxide gel 4% once daily, adapalene gel 0.1% once daily, or placebo vehicle (active monotherapy arm) in patients with facial acne vulgaris.3 The study design of this trial is outlined in Figure 5.
Baseline lesion count characteristics were very similar to those described above for the pivotal Phase III studies, with the majority of patients graded as moderately severe. Data on efficacy are tabulated in Figure 6 based on total lesion count reductions, with similar trends observed with inflammatory and non-inflammatory lesion counts.
Interestingly, efficacy results achieved with dapsone 5% gel used in combination with a placebo vehicle (essentially reflecting monotherapy with topical dapsone) were consistent with those obtained in the pivotal Phase III studies. Study discontinuations were uncommon with only one patient stopping treatment due to lack of efficacy. As with the pivotal Phase III trials, no major safety concerns emerged during the study.
Safety Data
The gel formulation of topical dapsone is aqueous-based and is devoid of ethanol or other astringent-type alcohols. Clinical studies inclusive of >2,000 study participants with facial acne vulgaris treated with dapsone 5% gel revealed favorable skin tolerability, including use as monotherapy or in combination with either adapalene 0.1% gel or benzoyl peroxide 4% gel.2-5 The most commonly observed application-site reactions associated with use of dapsone 5% gel were erythema and dryness, with the majority rated as mild in severity. Based on long-term safety data, the rate of application-site reactions was <3.1%. Application-site symptoms such as burning and pruritus were reported by <2% of study subjects based on both spontaneous reporting and elicited responses.
Dermal safety studies of dapsone 5% gel completed in 385 subjects demonstrated no evidence of photoallergy, phototoxicity or contact hypersensitivity.6
Based on data available from multiple studies completed with dapsone 5% gel, no reports of major adverse events such as hemolytic anemia, methemoglobinemia, or agranulocytosis, were associated with dapsone, even among patients with G6PD deficiency.2-5 Short-term and long-term pharmacokinetic data coupled with clinical and laboratory evidence from large studies suggested that dapsone 5% gel was not associated with systemic toxicities that are sometimes observed with oral dapsone therapy.
Summary of Points
Dapsone exhibits anti-inflammatory properties, which support its use for treating acne vulgaris, primarily related to its suppressive effects on neutrophil recruitment, migration and enzymatic activity. Use of oral dapsone for acne vulgaris is limited by potential systemic toxicities, primarily hematologic abnormalities — especially in patients who have G6PD deficiency. Topical dapsone 5%, formulated as an aqueous gel, has been extensively studied, with >2,000 people treated in Phase III trials (N=1,506) and other studies, including long-term evaluations (N=486).
Efficacy, favorable skin tolerability, and safety have been established based on data from available studies. No reports of significant systemic toxicity have emerged, including hematologic abnormalities, which is consistent with minimal systemic exposure after topical administration. Long-term pharmacokinetic analysis demonstrated no accumulation of dapsone based on plasma concentrations.
How Does Topical Dapsone Fit into Our Acne Treatment Armamentarium?
This certainly remains to be seen based on clinical experience and additional research, as the drug has not yet been released into the marketplace. The pivotal Phase III trials provide results achieved with monotherapy for facial acne vulgaris, mostly of moderate severity. However, acne vulgaris is usually treated with a combination therapy approach to optimize therapeutic benefits. The available combination therapy data suggest that dapsone 5% gel may be used concomitantly with other topical agents, such as benzoyl peroxide or a topical retinoid. Dapsone 5% gel appears to exhibit a favorable tolerability profile, both alone or in combination with benzoyl peroxide or adapalene, based on the available studies.
New options for treatment of common dermatoses, such as acne vulgaris, are always welcome. With further clinical research and experience, additional information may provide us with other applications for dapsone 5% gel for treatment of acne vulgaris, and possibly for other disease states such as rosacea.
