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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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.

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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.

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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.

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Griseofulvin. Griseofulvin is the oldest of the systemic antifungal agents used for tinea infections, available for more than 40 years. Griseofulvin acts on susceptible fungal cells by inhibiting microtubule function. Griseofulvin is taken by adults once daily at 500 mg, for 4 to 6 weeks, and has demonstrated efficacy in the treatment of tinea infections.³³

In a systematic review of comparative trials, oral griseofulvin was found to be significantly inferior to oral terbinafine in the treatment of tinea pedis (LOE=1a).³³ Likewise, terbinafine was found to be superior to griseofulvin in the treatment of tinea corporis and tinea cruris (LOE=1b).³⁴ In comparisons with ketoconazole, griseofulvin was equivalent in the treatment of dermatophytosis (LOE=2a).³⁵

Griseofulvin has also been compared with itraconazole in various treatment schedules for tinea corporis, tinea cruris, tinea pedis, and tinea manus; it was found to be inferior in all treatment durations to a maximum of 3 months (LOE=1b).³⁶ In head-to-head comparisons between griseofulvin and fluconazole in the treatment of tinea corporis and tinea cruris, outcomes were not statistically significantly different, although a trend toward better clinical cures in the fluconazole arm was identified (LOE=1b).³⁷

Azoles. Studies have made limited comparisons among the azoles (ketoconazole, itraconazole, and fluconazole) in the treatment of dermatophytosis. Small comparisons with limited power between itraconazole and fluconazole³⁸ and between ketoconazole and fluconazole³⁹ have demonstrated similar cure rates of about 90% for all 3 agents (LOE=1b). In a placebo-controlled comparison for treatment of tinea cruris and tinea corporis, 100 mg/d of itraconazole for 14 days was highly curative (LOE=1b).⁴⁰ In placebo-controlled trials of the treatment of tinea pedis, itraconazole was found to provide statistically significant cure rates in as little as 1 week (LOE=1b).⁴¹

Systematic review of trials between itraconazole (100 mg/d for 4 weeks) and terbinafine (250 mg/d for 2 weeks) for tinea pedis showed a non-statistically significant trend toward higher cure rate in those treated with terbinafine (LOE=1a).³³

There are limited placebo-controlled trials evaluating fluconazole in the treatment of superficial fungal infections of the skin. In an open, noncomparative trial employing once-weekly dosing of fluconazole 150 mg for 1 to 4 weeks for tinea corporis and tinea cruris, clinical cure rate was 92% with long-term clinical cure rate of 88% (LOE=2b).⁴² Another study randomized 240 adults with skin dermatophytosis or cutaneous candidiasis to either flucona-zole 150 mg/wk or fluconazole 50 mg/d for a maximum of 4 weeks (non-tinea pedis) to 6 weeks (tinea pedis) with positive clinical response of greater than 90% in both arms of treatment (LOE=2b).⁴³ Fluconazole has not been evaluated in direct comparison with terbinafine in the treatment of dermatophytic skin infections. Comparisons between azoles and griseofulvin have been discussed above.

Terbinafine. Oral terbinafine is effective in the treatment of skin dermatophytes. In a double-blind, placebo-controlled study of terbinafine 125 mg taken twice daily for 6 weeks, 65% of patients had mycologic cure at 2 weeks post-treatment (LOE=1b).⁴⁴ In an open, noncon-trolled study of terbinafine 125 mg daily for one week, 100% mycologic cure was achieved in the treatment of tinea corporis and tinea cruris (LOE=2b).⁴⁵

As noted above, terbinafine has shown efficacy superior to griseofulvin and itraconazole. No well-designed, comparative study was identified that showed any oral antifungal agent to be superior to terbinafine in the treatment of dermatophytic skin infections.

TABLE 4
Oral antifungal medications in the treatment of dermatomycosis

Comparison (with treatment costs)*	SOR	Outcomes	NNT or reduction in risk of failure to cure	Comments
ITRACONAZOLE ($112–$223.99) vs placebo	A ^{40, 41}	Itraconazole with much greater efficacy than placebo	NNT = 1.7 at 8 weeks after 1 week of treatment for tinea pedis; 1.8 at 4 weeks after 2 weeks of treatment for tinea corporis and tinea cruris	In multiple, well-designed RCT for tinea pedis, tinea corporis and tinea cruris
TERBINAFINE ($112.99–$329.9) vs placebo	A ^{33, 44, 45}	Terbinafine with much greater efficacy than with placebo	NNT = 1.5 at 8 weeks after 2 weeks of treatment for tinea pedis	Systematic review of RCT for tinea pedis and multiple, non-comparative trials for tinea corporis and tinea cruris
ITRACONAZOLE ($112–$223.99) vs Griseofulvin ($50.99–$71.40)	A ³⁶	Itraconazole with greater efficacy than Griseofulvin	Risk difference = 19% in treatment of tinea cruris/corporis and 37% in treatment of tinea pedis/manus	Systematic review of RCT for tinea corporis, tinea cruris, tinea manuus, and tinea pedis
TERBINAFINE ($112.99–$223.99)vs Griseofulvin ($50.99–$71.40)	A ³³	Terbinafine with greater efficacy than Griseofulvin	Risk difference = 50% at 8 weeks post-treatment	Systematic review of RCT for tinea pedis
KETOCONAZOLE ($30.99–$61.99) vs Griseofulvin ($50.99–71.40)	A ³³	Approximately equal efficacy between Ketoconazole and Griseofulvin	Risk difference = No consistent difference favoring either agent	Systematic review of RCT for tinea pedis
FLUCONAZOLE ($13.99–$50.96) vs Griseofulvin ($50.99–$71.40)	A ³⁷	Non-significant trend toward greater efficacy with Fluconazole	Risk difference = 12%	RCT for tinea corporis and tinea cruris
FLUCONAZOLE ($13.99–$50.96) vs Ketoconazole ($30.99–$61.99)	B ³⁹	Approximately equal efficacy between Fluconazole and Ketoconazole	Risk difference = 4% favoring fluconazole at 7 weeks post-treatment	Small RCT for all dermatomycosis
ITRACONAZOLE ($112–$223.99) vs Fluconazole ($13.99–$50.96)	B ³⁸	Approximately equal efficacy between Fluconazole and Itraconazole	Risk difference = 5% favoring itraconazole at 10 weeks post-treatment	Small RCT for tinea manuum and tinea pedis
TERBINAFINE ($112.99–223.99) vs Itraconazole ($112–$223.99)	A ³³	Approximately equal efficacy between Terbinafine and Itraconazole	Risk difference = No consistent difference favoring either agent	Systematic review of RCT for tinea pedis
SOR, strength of recommendation; NNT, number needed to treat; RCT, randomized controlled trial
SOR: A = Multiple RCT or a systematic review of RCT; B = Trials of moderate strength, as in open trials, noncomparative trials, or RCT with small size or poor follow-up. (See page 865 for full explanation of SOR ratings.)
* Lowest cost available (including for generic agents) based upon internet listings of national on-line pharmacies, Drugstore.com, Eckerd.com, and Walgreens.com as of May 2003.