Dapsone 5% Gel: A New Option in Topical Therapy for Acne

Jerry Tan, MD, FRCPC


Skin Therapy Letter. 2012;17(8):1-3. 

In This Article

Evidence for Safety

In the phase 3 studies, few patients withdrew due to side effects (6 dapsone gel, 9 vehicle). The overall incidence of adverse events was similar in both groups. The most common local intolerance events were dryness (20%), erythema (16%), and other reactions (including facial stinging, peeling, sensitivity, flaking, greasiness, photosensitivity, acne breakouts, tingling, and skin tightness). Serious adverse events were observed in 9 subjects, but they were not considered to be related to the treatment (4 dapsone gel, 5 vehicle). No significant changes in hemoglobin or other laboratory values were noted, despite 44 subjects recruited with glucose-6-phosphate dehydrogenase (G6PD) deficiency (19 dapsone gel, 25 vehicle). For all patients, the most frequently reported laboratory abnormality was elevated creatine kinase (12 dapsone gel, 11 vehicle), the majority of which were attributed to physical activity.[2]

A long-term safety study was performed with 486 acne patients applying dapsone gel twice daily for 12 months. Application site reactions were reported in 8.2% and were mostly mild to moderate in severity - the most common being dryness in 3%, rash 3%, sunburn 2%, burning 2%, erythema 2%, pruritus 1%, aggravation of acne 1%, and peeling 1%.[4]

The pharmacokinetic profile of topical dapsone gel was evaluated by reviewing data from three prospective open label studies, two phase 1 pharmacokinetic studies, and a phase 3 long-term safety study. Blood samples were drawn at various times in each trial for assessment of drug and metabolite concentrations. In various settings ranging from 2 weeks to 12 months application of dapsone gel, systemic levels (area under the curve) of dapsone and metabolites were approximately 100-fold less than those after a single dose of oral dapsone. Furthermore, the concentrations of dapsone and its metabolites achieved steady state and did not increase with prolonged treatment with dapsone gel.[5]

Further evaluation of hemolysis risk in subjects during dapsone gel use was performed in 64 patients with G6PD deficiency. Subjects were randomized to 12 week treatment periods of either vehicle followed by dapsone gel or dapsone gel followed by vehicle. Chemical and hematological analyses were performed, as well as levels of dapsone and metabolites, along with spontaneous reports of adverse events. Reduction in mean hemoglobin concentration of 0.32 g/dL was observed from baseline to 2 weeks during dapsone gel treatment, unaccompanied by laboratory features of hemolysis. This change was no longer apparent at 12 weeks of treatment. Proportion of subjects with 1 g/dL reduction in hemoglobin was similar between treatment groups at both week 2 and week 12 and no clinical signs or symptoms of hemolytic anemia were observed. Thus, no clinical or laboratory evidence of drug-induced hemolytic anemia in patients with G6PD deficiency was observed during treatment with dapsone 5% gel.[6] The results of this study led to Health Canada and the US FDA removing the G6PD screening and monitoring requirements from the official label for this product.

Although sulfones, such as dapsone, have structural similarities to sulfonamides, the two compounds have distinct chemical properties, e.g., sulfones have both anti-inflammatory and antibacterial properties, whereas sulfonamides are antimicrobial agents. Additionally, sulphonamides have been implicated in sulfa sensitivites, but dapsone may be used in sulfonamide-allergic patients.[5,7]