Dapsone
Dapsone Prescribing Information
Dapsone gel, 7.5%, is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older.
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.
Dapsone Gel, 7.5% contains 75 mg of dapsone, USP per gram. The gel is off-white to yellow, smooth, homogenous and essentially free of foreign matter.
There are no available data on dapsone gel, 7.5%, use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. The systemic absorption of dapsone in humans following topical application is low relative to oral dapsone administration
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 (Cmax) and area under the concentration-time curve from 0 to 24 hours post dose (AUC0-24h) 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 12-15 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 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.
The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
None.
• Methemoglobinemia: Cases of methemoglobinemia have been reported. Discontinue dapsonegel if signs of methemoglobinemia occur ().5.1 Hematological EffectsMethemoglobinemiaCases 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)].HemolysisOral 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)].• Hemolysis: Some patients with Glucose-6-phosphate Dehydrogenase (G6PD) deficiency using topical dapsone developed laboratory changes suggestive of hemolysis () (5.1 Hematological EffectsMethemoglobinemiaCases 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)].HemolysisOral 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)].).8.6 Glucose-6-phosphate Dehydrogenase (G6PD) DeficiencyIndividuals 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)].