Dapsone Gel

Dapsone Gel, 5%, is indicated for the topical treatment of acne vulgaris.

None.

Trimethoprim-Sulfamethoxazole

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. Systemic exposure (AUC0-12) of dapsone and N-acetyl-dapsone (NAD) were increased by about 40% and 20% respectively in the presence of TMP/SMX. Notably, systemic exposure (AUC0-12) of dapsone hydroxylamine (DHA) was more than doubled in the presence of TMP/SMX. Exposure from the proposed topical dose is about 1% of that from the 100 mg oral dose, even when co-administered with TMP/SMX.

Topical Benzoyl Peroxide

Topical application of Dapsone Gel followed by benzoyl peroxide in subjects with acne vulgaris resulted in a temporary local yellow or orange discoloration of the skin and facial hair (reported by 7 out of 95 subjects in a clinical study) with resolution in 4 to 57 days.

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.

Concomitant Use with Drugs that Induce Methemoglobinemia

Concomitant use of Dapsone Gel 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)].

Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Dapsone has been shown to have an embryocidal effect in rats and rabbits when administered orally in doses of 75 mg/kg/day and 150 mg/kg/day (approximately 800 and 500 times the systemic exposure observed in human females as a result of use of the maximum recommended topical dose, based on AUC comparisons), respectively. These effects were probably secondary to maternal toxicity. Dapsone Gel, 5%, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Although systemic absorption of dapsone following topical application of Dapsone Gel, 5%, is minimal relative to oral dapsone administration, it is known that dapsone is excreted in human milk. Because of the potential for oral dapsone to cause adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Dapsone Gel, 5%, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy was evaluated in 1169 children aged 12-17 years old treated with Dapsone Gel, 5%, in the clinical studies. The adverse event rate for Dapsone Gel, 5%, was similar to the vehicle control group. Safety and efficacy was not studied in pediatric patients less than 12 years of age, therefore Dapsone Gel, 5%, is not recommended for use in this age group.

Geriatric Use

Clinical studies of Dapsone Gel, 5%, did not include sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients.

G6PD Deficiency

Dapsone Gel, 5% and vehicle were evaluated in a randomized, double-blind, cross-over design clinical study of 64 patients 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. There were 56 out of 64 subjects who had a Week 2 blood draw and applied at least 50% of treatment applications. Table 3 contains results from testing of relevant hematology parameters for these two treatment periods. Dapsone Gel was associated with a 0.32 g/dL drop in hemoglobin after two weeks of treatment, but hemoglobin levels generally returned to baseline levels at Week 12.

There were no changes from baseline in haptoglobin or lactate dehydrogenase during dapsone or vehicle treatment at either the 2-week or 12-week time point.

The proportion of subjects who experienced decreases in hemoglobin ≥1 g/dL was similar between Dapsone Gel, 5% and vehicle treatment (8 of 58 subjects had such decreases during dapsone treatment compared to 7 of 56 subjects during vehicle treatment among subjects with at least one on-treatment hemoglobin assessment). Subgroups based on gender, race, or G6PD enzyme activity did not display any differences in laboratory results from the overall study group. There was no evidence of clinically significant hemolytic anemia in this study. Some of these subjects developed laboratory changes suggestive of hemolysis.

Mechanism of Action

The mechanism of action of Dapsone Gel in treating acne vulgaris is not known.

Pharmacokinetics

An open-label study compared the pharmacokinetics of dapsone after Dapsone Gel, 5%, (110 ± 60 mg/day) was applied twice daily (~BSA 22.5%) for 14 days (n=18) with a single 100 mg dose of oral dapsone administered to a subgroup of patients (n=10) in a crossover design. On Day 14 the mean dapsone AUC0-24h was 415 ± 224 ng•h/mL for Dapsone Gel, 5%, whereas following a single 100 mg dose of oral dapsone the AUC0-infinity was 52,641 ± 36,223 ng•h/mL. Exposure after the oral dose of 100 mg dapsone was approximately 100 times greater than after the topical Dapsone Gel, 5% dose, twice a day.

In a long-term safety study of Dapsone Gel, 5% treatment, periodic blood samples were collected up to 12 months to determine systemic exposure of dapsone and its metabolites in approximately 500 patients. Based on the measurable dapsone concentrations from 408 patients (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 patients.

Microbiology

In Vivo Activity: No microbiology or immunology studies were conducted during Dapsone Gel clinical trials.

Drug Resistance: No dapsone resistance studies were conducted during Dapsone Gel clinical trials. Because no microbiology studies were done, there are no data available as to whether dapsone treatment may have resulted in decreased susceptibility of Propionibacterium acnes, an organism associated with acne, 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.

See FDA-approved patient labeling (Patient Information)

• Advise patient to seek immediate medical attention for cyanosis [see Warnings and Precautions (5.1)].
• Advise patient to use Dapsone Gel, 5%, as directed by the physician. Dapsone Gel, 5%, is for external topical use only. Dapsone Gel, 5%, is not for oral, ophthalmic or intravaginal use.
• Advise patients to report any signs of adverse reactions to their physician.
• Protect Dapsone Gel, 5%, from freezing.
• See Patient Information for additional information on safety, efficacy, general use, and storage of Dapsone Gel, 5%.

Distributed for Allergan
Irvine, CA 92612, U.S.A.
© 2017 Allergan. All rights reserved.
All trademarks are the property of their respective owners.
Made in the U.S.A.

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Principal Display Panel - Dapsone 5% Carton Label

PACIFIC

PHARMA®

NDC 60758-670-30

DAPSONE
gel, 5%

FOR TOPICAL USE ONLY

Rx only 30 g