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Aczone topical

Generic Name: Dapsone topical
Class: Skin and Mucous Membrane Agents, Miscellaneous
ATC Class: D10AX05
Chemical Name: Diaminodiphenylsulfone
Molecular Formula: C12H12N2O2S
CAS Number: 80-08-0

Introduction

Synthetic sulfone1 2 3 5 18 with anti-infective and anti-inflammatory effects.2 3 5 18

Uses for Aczone

Acne Vulgaris

Topical treatment of acne vulgaris.1 2 3 4 11

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Effective against inflammatory acne lesions and, to a lesser extent, noninflammatory acne lesions.2 3

Aczone Dosage and Administration

Administration

Topical Administration

Administer topically to the skin as a 5% gel.1

For external use only.1 Do not use orally or intravaginally; avoid contact with the mouth and eyes.1

Gently cleanse and dry the acne-affected area prior to application.1 Apply a pea-sized amount of dapsone 5% gel in a thin layer; rub in gently and completely.1

The gel is gritty with visible drug substance particles.1 Wash hands after applying the gel.1

Dosage

Pediatric Patients

Acne Vulgaris
Topical

Children ≥12 years of age: Apply a thin layer of dapsone 5% gel to cleansed affected area twice daily.1

Reassess use of the drug if improvement does not occur after 12 weeks of treatment.1

Has been used for up to 12 months in clinical studies.3

Adults

Acne Vulgaris
Topical

Apply a thin layer of dapsone 5% gel to the cleansed affected area twice daily.1

Reassess use of the drug if improvement does not occur after 12 weeks of treatment.1

Has been used for up to 12 months in clinical studies.3

Cautions for Aczone

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Sensitivity Reactions

Moderate erythema has been reported when topical dapsone 5% gel was evaluated in combined contact sensitization/irritation studies.1 Pruritus,2 3 6 rash,3 and contact dermatitis6 were reported in some patients receiving the topical gel for treatment of acne vulgaris.

Oral dapsone has been associated with hypersensitivity reactions that include severe dermatologic reactions.1 7 16 (See Dermatologic Reactions under Cautions.) Hypersensitivity reactions reported with oral dapsone have also included fever, malaise, hepatitis, and hemolysis.10

Topical dapsone did not induce phototoxicity or photoallergy in human dermal safety studies.1

Hematologic Effects

Oral dapsone has been associated with dose-related hemolysis and hemolytic anemia.1 14 Agranulocytosis also reported in patients receiving oral dapsone.1 9 Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are more prone to hemolysis when receiving certain drugs.1 G6PD deficiency is most prevalent in populations of African, South Asian, Middle Eastern, and Mediterranean ancestry.1

There were no reports of clinically relevant hemolysis or hemolytic anemia in clinical studies evaluating topical dapsone 5% gel in individuals with acne vulgaris, including individuals with G6PD deficiency.1 2 3 6 However, laboratory changes suggestive of hemolysis (slight decreases in hemoglobin) occurred in some individuals with G6PD deficiency using the topical gel.1 2 6

If signs and symptoms suggestive of hemolytic anemia occur, discontinue topical dapsone therapy.1

Because of the potential for hemolytic reactions, do not use topical dapsone 5% gel in individuals receiving oral dapsone or antimalarial agents.1 (See Specific Drugs under Interactions.)

Concomitant use of topical dapsone 5% gel and co-trimoxazole may increase the risk of hemolysis in patients with G6PD deficiency.1 (See Specific Drugs under Interactions.)

Peripheral Neuropathy

Oral dapsone has been associated with peripheral neuropathy (motor loss and muscle weakness).1

Peripheral neuropathy was not reported in clinical studies evaluating topical dapsone 5% gel for the treatment of acne vulgaris.1

Dermatologic Reactions

Oral dapsone has been associated with serious skin reactions, including toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria.1 7

Although erythema,1 pruritus,2 3 and rash3 were reported in clinical studies evaluating topical dapsone 5% gel for the treatment of acne vulgaris, more severe dermatologic reactions were not reported.1

Specific Populations

Pregnancy

Category C.1

Oral dapsone has been associated with embryocidal effects in rats and rabbits when used in dosages approximately 800 and 500 times, respectively, the systemic exposure (based on AUC) observed in human females receiving the maximum recommended dosage of topical dapsone 5% gel.1 These effects were probably secondary to maternal toxicity.1

Use during pregnancy only if potential benefits outweigh potential risks to the fetus.1

Lactation

Distributed into milk following oral administration.1 Systemic absorption is low following topical application of dapsone 5% gel; however, because of the potential to cause adverse reactions in nursing infants, discontinue nursing or discontinue topical dapsone therapy.1

Pediatric Use

Safety and efficacy not established in children <12 years of age.1

Geriatric Use

Insufficient experience with topical dapsone 5% gel in geriatric patients ≥65 years of age to determine whether such individuals respond differently than younger individuals.1

Common Adverse Effects

Local reactions at the application site (oiliness/peeling, dryness, erythema).1 2

Interactions for Aczone

Although only small amounts of dapsone are absorbed systemically following topical application to skin, the possibility that drug interactions could occur should be considered.1 Concomitant use of oral dapsone and certain drugs (e.g., rifampin, anticonvulsants, St. John’s wort) may increase the formation of dapsone hydroxylamine, a dapsone metabolite associated with hemolysis.1 In addition, concomitant use of oral dapsone and folic acid antagonists (e.g., pyrimethamine) may increase the likelihood of adverse hematologic effects.1

Specific Drugs

Drug

Interaction

Comments

Antimalarial agents

Increased risk of hemolytic reactions if topical dapsone used concomitantly with antimalarial agents1

Do not use topical dapsone in patients receiving antimalarial agents1

Benzoyl peroxide

In vitro, combinations of topical dapsone 5% gel and topical benzoyl peroxide resulted in an orange discoloration17

Concomitant use of topical dapsone 5% gel and topical benzoyl peroxide in individuals with acne vulgaris may result in temporary local yellow or orange discoloration of the skin and facial hair;1 usually resolves in 4–57 days1

Co-trimoxazole

Concomitant use of topical dapsone 5% gel and oral co-trimoxazole results in increased systemic exposure to dapsone and dapsone metabolites; pharmacokinetics of co-trimoxazole not affected1 5

Possible increased risk of hemolysis in patients with G6PD deficiency1

Dapsone, oral

Increased risk of hemolytic reactions if oral and topical dapsone used concomitantly1

Do not use topical dapsone in patients receiving oral dapsone1

Aczone Pharmacokinetics

Absorption

Bioavailability

Absorbed systemically following topical application to skin.1 5

In patients with acne vulgaris skin lesions, plasma concentrations of dapsone are detectable within 2 hours after the first dose of topical dapsone 5% gel.5

After topical application of dapsone 5% gel to acne vulgaris skin lesions on the face, upper back, shoulders, and/or upper chest (up to approximately 22.5% of total body surface area) twice daily for 14 days, mean peak plasma concentrations of the drug were 19.4 ng/mL and the median time to peak concentrations after a dose was 9 hours.5

In a long-term safety study of dapsone 5% gel, there was no evidence that systemic exposure increases over time.1

Systemic exposure (AUC) following a 14-day regimen of dapsone 5% gel is 126 times lower than systemic exposure (AUC) following a single 100-mg dose of oral dapsone.5

Special Populations

Systemic dapsone exposure following topical application of dapsone 5% gel in children 12–15 years of age is similar to that reported in those ≥16 years of age.1

Stability

Storage

Topical

Gel

20–25°C (may be exposed to 15–30°C).1 Do not freeze.1

Actions

  • Synthetic sulfone1 2 3 5 18 with anti-infective and anti-inflammatory effects.3 5 18

  • For dermatologic use, dapsone is commercially available in an aqueous gel base.1

  • Mechanism of action in the treatment of acne vulgaris not known, but may result from a combination of both anti-inflammatory and anti-infective effects.1 2 3 18

  • Dapsone exerts a variety of anti-inflammatory effects.2 3 18 The drug may inhibit myeloperoxidase- and hydrogen peroxide-based cytotoxic systems in neutrophils or may act as a scavenger of reactive oxygen species, thereby minimizing inflammation associated with generation of these reactive species.18

  • The anti-infective effects of dapsone involve inhibition of folic acid synthesis in susceptible organisms.18

  • In vitro, dapsone has some antibacterial activity against Propionibacterium acnes.18 It is not known whether topical dapsone therapy results in decreased susceptibility of P. acnes to other drugs used to treat acne.1

Advice to Patients

  • Importance of using as directed by the clinician and only for condition prescribed.1

  • Advise patient that topical dapsone is for external use only and should not be used orally or intravaginally; importance of avoiding contact with the mouth and eyes.1

  • Importance of storing at room temperature and protecting the drug from freezing.1

  • Importance of informing clinician of glucose-6-phosphate dehydrogenase (G6PD) deficiency.1

  • Importance of reporting any signs of adverse reactions to a clinician.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, especially topical agents applied to the skin (e.g., preparations containing benzoyl peroxide).1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Dapsone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Gel

5%

Aczone

Allergan

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Allergan. Aczone (dapsone) gel 5% prescribing information. Irvine, CA. 2009 Mar.

2. Draelos ZD, Carter E, Maloney JM et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J Am Acad Dermatol. 2007; 56:439.e1-10.

3. Lucky AW, Maloney JM, Roberts J et al. Dapsone gel 5% for the treatment of acne vulgaris: safety and efficacy of long-term (1 year) treatment. J Drugs Dermatol. 2007; 6:981-7. [PubMed 17966175]

4. Raimer S, Maloney JM, Bourcier M et al. Efficacy and safety of dapsone gel 5% for the treatment of acne vulgaris in adolescents. Cutis. 2008; 81:171-8. [PubMed 18441772]

5. Thiboutot DM, Willmer J, Sharata H et al. Pharmacokinetics of dapsone gel, 5% for the treatment of acne vulgaris. Clin Pharmacokinet. 2007; 46:697-712. [PubMed 17655376]

6. Piette WW, Taylor S, Pariser D et al. Hematologic safety of dapsone gel, 5%, for topical treatment of acne vulgaris. Arch Dermatol. 2008; 144:1564-70. [PubMed 19075138]

7. Agrawal S, Agarwalla A. Dapsone hypersensitivity syndrome: a clinico-epidemiological review. J Dermatol. 2005; 32:883-9. [PubMed 16361748]

9. Coleman MD. Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention. Toxicology. 2001; 162:53-60. [PubMed 11311458]

10. Corp CC, Ghishan FK. The sulfone syndrome complicated by pancreatitis and pleural effusion in an adolescent receiving dapsone for treatment of acne vulgaris. J Pediatr Gastroenterol Nutr. 1998; 26:103-5. [PubMed 9443128]

11. Del Rosso JQ. Newer topical therapies for the treatment of acne vulgaris. Cutis. 2007; 80:400-10. [PubMed 18189027]

14. Ismail R. Acne fulminans with dapsone induced haemolysis: a case report. Med J Malaysia. 1987; 42:124-6. [PubMed 2971861]

16. Tomecki KJ, Catalano CJ. Dapsone hypersensitivity. The sulfone syndrome revisited. Arch Dermatol. 1981; 117:38-9. [PubMed 6450569]

17. Dubina MI, Fleischer AB. Interaction of topical sulfacetamide and topical dapsone with benzoyl peroxide. Arch Dermatol. 2009; 145:1027-9. [PubMed 19770443]

18. Center for Drug Evaluation and Research. Microbiology review of NDA application 21-794. 2005 Jun 20.

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