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Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial

      Abstract

      Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. Objective: Our purpose was to determine whether docosanol 10% cream (docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. Methods: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. Results: The median time to healing in the 370 docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients (P = .008; 95% confidence interval [CI]: 2, 22). The docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P = .002; 95% CI: 3, 16.5); (2) complete healing of classic lesions (P = .023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions (P < .001; 95% CI: 8, 25). Aborted episodes were experienced by 40% of the docosanol recipients versus 34% of placebo recipients (P = .109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with docosanol were mild and similar to those with placebo. Conclusion: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration. (J Am Acad Dermatol 2001;45:222-30.)
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      References

        • Higgins CR
        • Schofield JK
        • Tatnall FM
        • Leigh IM.
        Natural history, management and complications of herpes labialis.
        J Med Virol Suppl. 1993; 1: 22-26
        • Spruance SL.
        Herpes simplex labialis.
        in: Clinical management of herpes viruses. IOS Press, Amsterdam1995: 3-42
        • Spruance SL
        • Overall JC
        • Kern E
        • Krueger GG
        • Pliam V
        • Miller W.
        The natural history of recurrent herpes simplex labialis.
        N Engl J Med. 1997; 297: 69-75
        • Spruance SL.
        The natural history of recurrent oral-facial herpes simplex virus infection.
        Semin Dermatol. 1992; 11: 200-206
        • Shafran SD
        • Sacks SL
        • Aoki FY
        • Tyrrell DL
        • Schlech III, WF
        • Mendelson J
        • et al.
        Topical undecylenic acid for herpes simplex labialis: a multicenter, placebo-controlled trial.
        J Infect Dis. 1997; 176: 78-83
        • Spruance SL
        • Wenerstrom G.
        Pathogenesis of herpes simplex labialis. IV. Maturation of lesions within 8 hours after onset and implications for antiviral treatment.
        Oral Surg. 1984; 58: 667-671
        • Spruance SL
        • Rea TL
        • Thoming C
        • Tucker R
        • Saltzman R
        • Boon R.
        Penciclovir cream for the treatment of herpes simplex labialis: a randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group.
        JAMA. 1997; 277: 1374-1379
        • Raborn GW
        • for the Penciclovir Topical Collaborative Study Group
        Thirty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, LaSept 15-18, 1996
        • Katz DH
        • Marcelletti JF
        • Khalil MH
        • Pope LE
        • Katz LR.
        Antiviral activity of 1-docosanol, an inhibitor of lipid-enveloped viruses including herpes simplex.
        Proc Natl Acad Sci U S A. 1991; 88: 10825-10829
        • Katz DH
        • Marcelletti JF
        • Pope LE
        • Khalil MH
        • Katz LR
        • McFadden R.
        n-Docosanol: broad spectrum anti-viral activity against lipid-enveloped viruses.
        Ann N Y Acad Sci. 1994; 724: 472-488
        • Marcelletti JF
        • Pope LE
        • Khalil MH
        • McFadden RR
        • Katz LR
        • Katz DH.
        n-Docosanol®.
        Drugs of the Future. 1992; 17: 879-882
        • Pope LE
        • Marcelletti JF
        • Katz LR
        • Katz DH.
        Anti-herpes simplex virus activity of n-docosanol correlates with intracellular metabolic conversion of the drug.
        J Lipid Res. 1996; 37: 2167-2178
        • Pope LE
        • Marcelletti JF
        • Katz LR
        • Lin JY
        • Katz DH
        • Parish ML
        • et al.
        The anti-herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process.
        Antivir Res. 1998; 40: 85-94
        • Spruance SL
        • Schnipper LE
        • Overall Jr, J
        • Kern ER
        • Wester B
        • Modlin J
        • et al.
        Treatment of herpes simplex labialis with topical acyclovir in polyethylene glycol.
        J Infect Dis. 1982; 146: 85-90
        • Fiddian AP
        • Ivanyi L.
        Topical acyclovir in the management of recurrent herpes labialis.
        Br J Dermatol. 1983; 109: 321-326
        • Agresti A.
        An introduction to categorical data analysis.
        in: Wiley, New York1996: 60-64
        • Kaplan EL
        • Meier P.
        Nonparametric estimation from incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Gehan EA.
        A generalized Wilcoxon test for comparing arbitrarily singly-censored samples.
        Biometrika. 1965; 52: 203-223
        • Diaz-Mitoma F
        • Ruben M
        • Sacks SL
        • MacPherson P
        • Caissie G.
        Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes.
        J Clin Microbiol. 1996; 34: 657-663
        • Sacks SL
        • Aoki FY
        • Diaz-Mitoma F
        • Sellors J
        • Shafran SD
        • Canadian Cooperative Study Group
        Patient-initiated, twice daily oral famciclovir for early recurrent genital herpes reduces the onset and duration of viral shedding, the duration of lesions and their components and symptoms: a Canadian, multicenter, randomized, placebo-controlled, dose-ranging trial.
        JAMA. 1996; 276: 44-49
        • Sacks SL
        • Tyrrell DL
        • Lawee D
        • Schlech W
        • Gill MJ
        • Aoki FY
        • et al.
        for the Canadian Cooperative Study Group. Randomized, double-blind, placebo-controlled, clinic-initiated, Canadian multicenter trial of topical 3% edoxudine cream in the treatment of recurrent genital herpes.
        J Infect Dis. 1991; 164: 665-672
        • Guinan ME
        • MacCalman J
        • Kern ER
        • Overall Jr, JC
        • Spruance SL.
        Topical ether and herpes simplex labialis.
        JAMA. 1980; 243: 1059-1061
        • Chaput de Saintonge DM
        • Herxheimer A.
        Harnessing placebo effects in health care.
        Lancet. 1994; 344: 995-998