American Family Physician
`
`February 15, 2010 Table of Contents
`
`STEPS
`
`New Drug Reviews
`
`Dapsone (Aczone) 5% Gel for the Treatment of Acne
`
`BARRY COUTINHO, MBBS, University of Pittsburgh Medical Center, Shadyside Family Medicine
`Residency Program, Pittsburgh, Pennsylvania
`
`Dapsone is an antibiotic that has been used since the 1940s for the treatment of leprosy and skin
`disorders such as dermatitis herpetiformis and nodulocystic acne. Dapsone (Aczone) 5% gel is approved
`by the U.S. Food and Drug Administration (FDA) for the treatment of acne vulgaris in adults and children
`older than 12 years. Although dapsone has antibacterial and anti-inflan~natory activity, the mechanism of
`action in the treatment of acne is unknown,
`
`Drug
`
`Dosage
`
`Dose form Cost*
`
`Dapsone (Aczone) 5% gel Apply twice daily 30-g tube $146
`*~Estimated retail price (rounded to the nearest dollar) of one month’s treatment based on information
`obtained at http://www.druClstore.com (accessed January 14, 2010).
`
`SAFETY
`Orally administered dapsone is known to cause hematologic reactions, including met-hemoglobinemia;
`hemolysis, especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; and
`agranulocytosis. These reactions are less likely with topical treatment. Hemolytic anemia has been shown
`not to occur in patients with G6PD deficiency with acne who were treated with topical therapy,za
`
`However, the manut’acturer warns of an increased risk of hemolysis in patients who use a combination of
`topical dapsone and oral trimethoprim/sult’amethoxazole (Bactrim, Septra).3 Dapsone gel should not be
`used in patients who are taking oral dapsone or antimalarial medications because of the potential for
`hemolytic reactions. Dapsone gel is FDA pregnancy category C; safety has not been established in
`breastfeeding mothers.3
`
`TOLERABILITY
`Adverse effects of dapsone gel therapy occur mainly at the site of applicatinn~ The most conmlon are
`&Tness (16 percent), elTthema (13 percent), and oiliness/peeling (13 percent)] These reactions are most
`likely caused by the gel vehicle. Application of dapsone gel followed by benzoyl peroxide causes a
`temporary local yellow or orange discoloration of the skin and t’acial hair; this reaction typically resolves
`in one to eight weeks.~
`
`EFFECTIVENESS
`Studies show that dapsone gel has modest effectiveness in the treatment of moderately severe
`inflammatory and noninflanmlatory acne. Two studies show a clinical success rate of 40.5 versus 32.8
`
`percent with placebo over a 12-week period (number needed to treat 13), as defined by global
`assessment and a statistically significant reduction in the percentage of lesinnsf- Dapsone gel is more
`
`effective in reducing inflammatory lesions (i.e., papules, pustules, and nodules) than noninflammatory
`lesions (i.e., open and closed comedones), with up to 50 percent reduction by 12 weeks of use, compared
`with a 42 percent response with placebo J- For comparison, large studies of patients with moderately
`severe acne show up to 90 percent clearing of lesinns atter six to eight weeks ofretinoid plus benzoyl
`peroxide therapy.6- Although there may be a response to initial treatment with dapsone gel within one to
`two weeks, this rate is not t’aster than the response to a combination of a retinoid and benzoyl peroxide.
`
`Dapsone gel has not been directly compared with more established therapies (e.g., topical retinoid
`monotherapy) or combination topical therapies (e.g., benzoyl peroxide plus either a topical antibiotic or a
`retinoid).
`
`PRICE
`A 30-g tube of dapsone 5% gel costs approximately $146. This is higher than the cost ofa 20-g tube of
`tretinoin (RetinA) 0.025% gel ($40 [brand: $81]) or a 30-g tube of clindamycin (Cleocin) 1% gel ($18
`
`[brand: $63]).
`
`SIMPLICITY
`A pea-sized amotmt of dapsone gel should be applied in a thin layer to the ache-affected areas twice
`daily and rubbed in gently and completely] Although elTthema and th’yness are common adverse effects,
`
`they are generally mild and rarely require discontinuation of treatment. For more severe reactions,
`dapsone gel therapy should be discontinued and alternate topical medications substituted.
`
`1 of 2
`
`Almirall EXHIBIT 2017
`Amneal v. Almirall
`IPR2018-00608
`
`

`

`Bottom Line
`
`Topical dapsone gel will decrease the percentage of lesions in patients with miM to moderate acne,
`
`especially inflarranatory lesions. Although not directly compared, dapsone gel has lower response rates
`
`than currently available topical treatments that are less expensive. It may have a role in those few
`
`patients who are allergic to or cannot tolerate other treatments, but should not be used as first-line
`
`therapy.
`
`Address correspondence to Barry Coutinho, MBBS, at coutinhobv@upmc.edu. Reprints are not available from the
`author.
`
`Author disclosure: Nothing to disclose.
`
`REFERENCES
`
`1. Piette WW, Taylor S, Pariser D, Jarratt M, Sheth P, Wilson D. Hematologic safety of dapsone gel, 5%, for
`topical treatment ofacne vulgaris. Arch Dermatol. 2008;144(12):1564-1570.
`
`2. Lucky AW, Maloney JM, Roberts J, et al., for the Dapsone Gel Long-Term Safety Study Group. Dapsone gel
`
`5% for the treatment of acne vulgaris: safety and efficacy of long-term (1 year) treatment. J Drugs Dermatol.
`
`2007;6(10):981-987.
`
`3. ACZONE (dapsone) gel 5% [prescribing information]. Irvine, Calif.: Allergan, Inc; Revised March 2009.
`
`http://www.allerqan.com/assets/pdf/aczone pi.pdf. Accessed June 1, 2009.
`
`4. Draelos ZD, Carter E, Maloney JM, et al., for the United States/Canada Dapsone Gel Study Group. Two
`randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris. J
`
`AmAcadDermatel. 2007;56(3):439.e 1-439.e 10.
`
`5. Stotland M, Shalita AR, Kissling RF. Dapsone 5% gel: a review of its efficacy and safety in the treatment of
`
`acne vulgaris. Am J Clin Dermatol. 2009;10(4):221-227.
`
`6. Leyden JJ. A review of the use of combination therapies for the treatment of acne vulgaris. J Am Acad
`
`Dermatol. 2003;49(3 suppl):S200-S210.
`
`STEPS new drug reviews cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each independent review is
`provided by authors who have no financial association with the drug manufacturer.
`
`The series coordinator for AFP is Allen F. Shaughnessy, PharmD, Tufts University Family Medicine Residency
`Program at Cambridge Health Alliance, Malden, Mass.
`
`A collection of STEPS published in AFP is available at http://www.aafp.orq/afp/steps.
`
`2 of 2
`
`