Clear choices in managing epidermal tinea infections

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Applied Evidence

Clear choices in managing epidermal tinea infections

J Fam Pract. 2003 November;52(11):850-862

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References

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8. Kates SG, Nordstrom KM, McGinley KJ, Leyden JJ. Microbial ecology of interdigital infections of toe web spaces. J Am Acad Dermatol 1990;22:578-582.

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10. Rosen T. Dermatophytosis: diagnostic pointers and therapeutic pitfalls. Consultant 1997;37:1545-1557.

11. Sinski JT, Swanson JR, Kelley LM. Dermatophyte test medium: clinical and quantitative appraisal. J Inves Dermatol 1972;58:405-411.

12. Saag MS, Dismukes WE. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother 1988;32:1-8.

13. Crawford F, Hart R, Bell-Syer S, Torgerson D, Young P, Russell I. Topical treatments for fungal infections of the skin and nails of the foot (Cochrane Review). In: The Cochrane Library, Issue 1, 2003. Oxford: Update Software.

14. Polak A. Antifungal activity of four antifungal drugs in the cutaneous retention time test. Sabouraudia 1984;22:501-503.

15. Gupta AK, Einarson TR, Summerbell RC, Shear NH. An overview of topical antifungal therapy in dermatomycosis.A North American perspective. Drugs 1998;55:645-674.

16. Drake LA, Dinehart SM, Farmer ER, et al. Guidelines of care for superficial mycotic infections of the skin: tinea corporis, tinea cruris, tinea faciei, tinea manuum, and tinea pedis. Guidelines/Outcomes Committee. American Academy of Dermatology. J Am Acad Dermatol 1996;34:282-286.

17. Jordon RE, Rapini RP, Rex IH, Jr, et al. Once-daily naftifine cream 1% in the treatment of tinea cruris and tinea corporis. Int J Dermatol 1990;29:441-442.

18. Budimulja U, Bramono K, Urip S, et al. Once daily treatment with terbinafine 1% cream (Lamisil) for one week is effective in the treatment of tinea corporis and tinea cruris. A placebo-controlled study. Mycoses 2001;44:300-306.

19. Schuster I, Schaude M, Schatz F, et al. Preclinical characteristics of allylamines. In: Berg D, Plempel M, eds. Sterol Biosynthesis Inhibitors. Chichester, England: Ellis Horwood; 1988;449-470.

20. Evans EG, Seaman RA, James IG. Short-duration therapy with terbinafine 1% cream in dermatophyte skin infections. Br J Dermatol 1994;130:83-87

21. Bonifaz A, Saul A. Comparative study between terbinafine 1% emulsion-gel versus ketoconazole 2% cream in tinea cruris and tinea corporis. Eur J Dermatol 2000;10:107-109.

22. Chren MM, Landefeld CS. A cost analysis of topical drug regimens for dermatophyte infections. JAMA 1994;272:1922-1925.

23. Davis R, Balfour JA. Terbinafine. A pharmacoeconomic evaluation of its use in superficial fungal infections. Pharmacoeconomics. 1995;8:253-269.

24. Rosen T, Schell BJ, Orengo I. Anti-inflammatory activity of antifungal preparations. Int J Dermatol 1997;36:788-792.

25. Savin R, De Villez RL, Elewski B, et al. One-week therapy with twice-daily Butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial. J Amer Acad Dermatol 1997;36:S15-S19.

26. Greer DL, Weiss J, Rodriguez DA, Hebert AA, Swinehart JM. A randomized trial to assess once-daily topical treatment of tinea corporis with butenafine, a new antifungal agent. J Amer Acad Dermatol 1997;37:231-235.

27. Lesher JL, Babel DE, Stewart DM, et al. Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehi-cle-controlled, double-blind trial. J Amer Acad Dermatol 1997;36:S20-S24.

28. Sehgal VN. Ciclopirox: a new topical pyrodonium antimy-cotic agent. A double-blind study in superficial dermato-mycoses. Br J Dermatol 1976;95:83-88.

29. Bogaert H, Cordero C, Ollague W, Savin RC, Shalita AR, Zaias N. Multicentre double-blind clinical trials of ciclopirox olamine cream 1% in the treatment of tinea corporis and tinea cruris. J Int Med Res 1986;14:210-216.

30. Beyer M. Selected double-blind comparative studies on the efficacy and tolerance of ciclopiroxolamine solution and cream [in German]. Arzneimittelforschung 1981;31:1378-1381.

31. Rosen T, Schell BJ, Orengo I. Anti-inflammatory activity of antifungal preparations. Int J Dermatol 1997;36:788-792.

32. Woscoff A, Carageli S. Treatment of tinea pedis with sulconazole nitrate 1% cream or miconazole nitrate 2% cream. Curr Ther Res 1986;39:753-757.

33. Bell-Syer SEM, Hart R, Crawford F, Torgerson DJ, Tyrell W, Russell I. Oral treatments for fungal infections of the skin of the foot (Cochrane Review). In: The Cochrane Library, Issue 1, 2003. Oxford: Update Software.

34. Voravutinon V. Oral treatment of tinea corporis and tinea cruris with terbinafine and griseofulvin: a randomized double-blind comparative study. J Med Assoc Thai. 1993;76:388-393.

35. Hay RJ, Clayton YM, Griffiths WA, Dowd PM. A comparative double-blind study of ketoconazole and griseofulvin in dermatophytosis. Br J Dermatol 1985;112:691-696.

36. Lachapelle JM, De Doncker P, Tennstedt D, Cauwenbergh G, Janssen PA. Itraconazole compared with griseo-fulvin in the treatment of tinea corporis/cruris and tinea pedis/mannus: An interpretation of the clinical results of all completed double-blind studies with respect to the pharmacokinetic profile. Dermatology 1992;184:45-50.

37. Faergemann J, Mork NJ, Haglund A, Odegard T. A multi-centre (double-blind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol 1997;136:575-577.

38. Difonzo EM, Papini M, Cilli P, et al. A double blind study comparison of itraconazole and fluconazole in tinea pedis and tinea manuum. J Eur Acad Dermatol Venereol 1995;4:148-152.

39. Fischbein A, Haneke E, Lacner K. Comparative evaluation of oral fluconazole and oral ketoconazole in the treatment of fungal infections of the skin. Intl J Dermatol 1992;31:12-16.

40. Pariser DM, Pariser RJ, Ruoff G, Ray TL. Double-blind comparison of itraconazole and placebo in the treatment of tinea corporis and tinea cruris. J Amer Acad Dermatol 1994;31:232-234.

41. Svejgaard E, Avnstorp C, Wanscher B, Nilsson J, Heremans A. Efficacy and safety of short-term itracona-zole in tinea pedis: a double-blind, randomized, placebo-controlled trial. Dermatology 1998;197:368-372.

42. Suchil P, Gei FM, Robles M, Perera-Ramirez A, Welsh O, Male O. Once-weekly oral doses of fluconazole 150 mg in the treatment of tinea corporis/cruris and cutaneous candidiasis. Clin Exp Dermatol 1992;17:397-401.

43. Nozickova M, Koudelkova V, Kulikova Z, Malina L, Urbanowski S, Silny W. A comparison of the efficacy of oral fluconazole, 150 mg/week versus 50 mg/day, in the treatment of tinea corporis, tinea cruris, tinea pedis, and cutaneous candidiasis. Intl J Dermatol 1998;37:703-705.

44. Savin RC, Zaias N. Treatment of chronic moccasin-type tinea pedis with terbinafine: a double-blind, placebo-controlled trial. J Am Acad Dermatol 1990;23:804-807.

45. Farag A, Taha M, Halim S. One-week therapy with oral terbinafine in cases of tinea cruris/corporis. Br J Dermatol 1994;131:684-686.

46. Smith EB, Dickson JE, Knox JM. Tolnaftate powder in prophylaxis of tinea pedis. South Med J 1974;67:776-778.

47. Lewis JH, Zimmerman HJ, Benson GD, Ishak KG. Hepatic injury associated with ketoconazole therapy: analysis of 33 cases. Gastroenterology 1984;86:503-513.

48. Garcia Rodriguez LA, Duque A, Castellsague J, Perea-Gutthann S, Stricker BH. A cohort study on the risk of acute liver injury among users of ketoconazole and other antifungal drugs. Br J Clin Pharmacol 1999;48:847-852.

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50. Haldane DJ, Robart E. A comparison of calcofluor white, potassium hydroxide, and culture for the laboratory diagnosis of superficial fungal infection. Diagn Microbiol Infect Dis 1990;13:337-339.

51. Miller MA, Hodgson Y. Sensitivity and specificity of potassium hydroxide smears of skin scrapings for the diagnosis of tinea pedis. Arch Dermatol 1993;129:510-511.

In a systematic review of available randomized controlled trials, allylamines were found to be more efficacious than imidazoles in treating tinea pedis (LOE=1a).¹³ Terbinafine has also been compared with imidazoles for treatment of tinea cruris and tinea corporis and found to be significantly more effective (LOE=1b).²¹

Previous pharmacoeconomic analyses of imidazole versus allylamine topical therapy for dermatophyte infection have presented conflicting conclusions, with some reporting that the greater cost of allylamine agents outweighs their slightly greater efficacy,²² while others concluded that the more efficacious medication initially is more cost effective.²³ In the United States, terbinafine was approved for over-the-counter sale in 1999. Since then, the cost of terbinafine to consumers has declined significantly, to the point where it is now comparable to over-the-counter imidazoles (see Table 3 ). Allylamines have demonstrated some degree of intrinsic anti-inflammatory activity.²⁴

Butenafine. Butenafine is a topical benzylamine antifungal structurally related to the allylamines. Butenafine is fungicidal and has efficacy similar to the allylamines. In a 1-week trial of therapy for tinea pedis with twice-daily butenafine, mycological cure rates in excess of 75% were observed (LOE=1b).²⁵ In a trial of short-term therapy of tinea corporis, butenafine applied once-daily for 14 days led to high cure rates, symptom improvement, and increasing effectiveness 4 weeks after therapy was concluded (LOE=1b).²⁶ In treatment of tinea cruris, butenafine was highly effective in achieving mycologic cure after 2 weeks of once-daily treatment (LOE=1b).²⁷

Few trials directly compare butenafine and other topical agents, but in stand-alone or placebo-controlled trials, butenafine has demonstrated efficacy similar to the allylamines terbinafine and naftifine. Butenafine was approved for over-the-counter sale in the United States in 2000.

Ciclopirox. Ciclopirox is a substituted pyridone unrelated to the imidazole or allylamine agents. In double-blind, placebo-controlled trials, ciclopirox demonstrated significant efficacy in treating dermatophyte infections (LOE=1b).²⁸ In head-to-head trials with the imidazole agent clotrimazole, ciclopirox demonstrated equivalent or slightly greater efficacy (LOE=1b).^29,30

Ciclopirox applied twice daily is usually effective within 4 weeks of treatment. Ciclopirox is available only by prescription in the United States and is more expensive than most other topical antifungal agents. Ciclopirox has demonstrated intrinsic antiinflammatory activity equivalent to the allylamines (LOE=1b).³¹ Due to the availability of agents with comparable or superior efficacy at much lower costs, ciclopirox should not be considered a first- or second-line agent in treating epidermal tinea infections.

Tolnaftate. Tolnaftate is an over-the-counter antifungal agent that has been available in the US since 1965. Tolnaftate is inexpensive and has often been used in powder formulation as prophylaxis against tinea, especially tinea pedis.

In systematic reviews of available placebo-controlled trials, 1% tolnaftate was shown to be less effective against tinea pedis than the azoles and allylamines, with a number needed to treat of 3.6 for tinea pedis (LOE=1a).¹³ A comparative study has shown tolnaftate to be inferior to clotrimazole in the treatment of tinea pedis.³² With its demonstrated inferiority to the azoles and allylamines, tolnaftate should not be considered a first- or second-line treatment for tinea infections.

TABLE 3
Topical antifungal medications

Agent	Formulation	Frequency*	Duration*	NNT ^†	Cost ^‡
IMIDAZOLES
Clotrimazole	1% cream	Twice daily	2–4 weeks	2.9	$ 7.99 (15 g)
	1% solution				$ 6.99 (10 mL)
	1% swabs				$ 6.99 (36 ea.)
Econazole	1% cream	Twice daily	2–4 weeks	2.6	$16.85 (15 g)
Ketoconazole	2% cream	Once daily	2–4 weeks	No data available	$25.39 (15 g)
Miconazole	2% cream	Twice daily	2–4 weeks	2.8 (at 8 weeks)	$ 6.99 (15 g)
	2% spray				$ 5.99 (3.5 oz)
	2% powder				$ 5.99 (3.5 oz)
Oxiconazole	1% cream	Once to twice daily	2–4 weeks	2.9	$20.27 (15 g)
Oxiconazole	1% lotion	Once to twice daily	2–4 weeks	2.9	$34.19 (30 mL)
Sulconazole	1% cream	Once to twice daily	2–4 weeks	2.5	$13.75 (15 g)
Sulconazole	1% solution	Once to twice daily	2–4 weeks	2.5	$26.57 (30 mL)
ALLYLAMINES
Naftifine	1% cream	Once to twice daily	1–4 weeks	1.9	$27.69 (15 g)
Naftifine	1% gel	Once to twice daily	1–4 weeks	1.9	$51.39 (40 g)
Terbinafine	1% cream	Once to twice daily	1–4 weeks	1.6 (1.7 for tinea cruris/tinea corporis at 8 weeks)¹⁸	$ 8.99 (12 g)
Terbinafine	1% solution	Once to twice daily	1–4 weeks	1.6 (1.7 for tinea cruris/tinea corporis at 8 weeks)¹⁸	$ 9.99 (30 mL)
BENZYLAMINE
Butenafine	1% cream	Once to twice daily	1–4 weeks	1.9 (1.4 for tinea corporis and 1.5 for tinea cruris)^26,27	$ 9.99 (12 g)
OTHER
Ciclopirox	0.77% cream	Twice daily	2–4 weeks	2.1	$21.89 (15 g)
Ciclopirox	0.77% lotion	Twice daily	2–4 weeks	2.1	$37.99 (30 mL)
Tolnaftate	1% powder	Twice daily	4 weeks	3.6 (at 8 weeks)	$ 3.99 (4 oz)
	1% spray				$ 5.49 (4 oz)
	1% swabs				$ 6.99 (36 ea.)
*Manufacturer guidelines.
†NNT, number needed to treat. NNT is calculated from systematic review of all randomized controlled trials for tinea pedis at 6 weeks after the initiation of treatment³³ except where otherwise noted. (See “Number needed to treat,” page 866.)
‡Lowest cost available (including generic agents) based upon internet listings of national on-line pharmacies: www.drugstore.com, www.eckerd.com, and www.walgreens.com as of May 2003.

Oral antifungal agents

Oral antifungal agents are used for dermatophyte infections that are widespread, chronic, or markedly inflammatory, or that affect hyperkeratotic areas as in palmar or plantar tinea. They are also use for those with immuno-suppression,¹⁶ and for those in whom treatment with topical drugs has been unsatisfactory. Agents include griseofulvin, the azoles (ketoconazole, itraconazole, and fluconazole), and the allylamine terbinafine. Table 4 summarizes pertinent comparative data regarding these agents.