A clinical trial of topical terbinafine (a new allylamine antifungal) in the treatment of tinea pedis Edgar B. Smith, MD, Nopadon Noppakun, MD, and Richard C. Newton, MD Galveston and McAllen, Texas, and Bangkok, Thailand Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% creamcompared with placebo vehicle inthetreatment oftinea pedis. Of the20patients who were evaluated for efficacy, 10received terbinafine and 10received placebo. Except for the terbinafine-treated patients being an average of 11years older thanthepatients receiving placebo andthemedian duration ofdisease being 6 weeks longer inthe placebo group, the two groups were demographically and clinically similar. Results of mycologic tests and clinical findings showed terbinafine to besignificantly more effective than placebo in the treatment of tinea pedis. Significantly more terbinafine-treated patients than placebo-treated patients showed conversion tonegative culture andmicroscopy at endoftherapy anda significant reduction inscored signs andsymptoms. Overall efficacy at follow-up (combined mycologic and clinical findings) was also significantly greater intheterbinafine group (78%) thanin theplacebo group (zero) (p < 0.001). Unexplained elevation ofliver function testresults was noted in threeplacebo-treated patients and in one terbinafine-treated patient, but these changes were notconsidered clinically relevant or drug related. (J AM ACAD DERMATOL 1990;23: 790-4.) Despite the excellent progress made in the development of antifungal drugs during the past two decades, more effective agents are still needed to treat superficialfungal infections. This is partly because of the increasing number of more immunocompromised patients who are difficult to treat and partly because of the emergence of dermatophyte strains relatively resistant to grisefulvin. Among the most recent antimycotic agents developed is terbinafine (Lamisil). Terbinafine is related to the topical antimycotic naftifine and both are members of a newclass of antifungaldrugs, the allylamines. Unlike azole antimycotics, allylamines specifically inhibit squalene epoxidase and thereby interfere withergosterol biosynthesis in a dose-dependent wayinvariouspathogenic fungi. I The primaryeffect From the Department of Dermatology, University of Texas Medical Branch. Sponsored in part by an educational grant fromSandoz Pharmaceuticals Corp. East Hanover, N.J., and by Pharmaquest Corp., Corte Madera, Calif. Reprint requests: EdgarB.Smith,MD,Chairman Department ofDermatology, University of Texas Medical Branch, Route G-83, Galveston, TX 77550.

16/0/23517

790

is a fungicidal action believed to result from heavy accumulation of squalene in treated fungi.2 The antimycoticabilities of the allylaminesare of great interest from a therapeutic standpoint because of their broad spectrum of activity, their primary fungicidal rather than fungistatic activity, and their favorable toxicological profile. I, 3 In particular, the primary fungicidal quality of the allylaminesmake them distinctfrom the highlyprescribed azole-based antifungals, which are primarily fungistatic. To date, just a few clinical trials of terbinafine havebeen published. These indicate that terbinafine is both topically and orally effective against most dermatophytes as well as some common yeast infections.v" However, none of these comparative studieswasplacebocontrolled. We report the results of a randomized, placebo-controlled trial of topical terbinafine in the treatment of tinea pedis. PATIENTS AND METHODS

Twenty-three patients were enrolled in the study. Patients had to be at least 18years of agewith tinea pedis documented clinically and by positive KOH microscopy andfungal culture. Exclusion criteria included receipt of systemic antifungal drugs in the preceding 4 weeks of topical antifungal therapy during the preceding 2 weeks.

Volume 23 Number 4, Part 2 October 1990

Treatment of tinea pedis with topical terbinafine 791 100

90 >.

8'

80

E

70

'8>.

•

TERBINAFINE

~

Placebo

Ql

~

60

~

50

.-=~

40

Ql

30

til

c:: s:

E

~

ll.

?fl.

20 10

0

a

2

3

4

6 (follow-up)

Treatment week

Fig. 1. Percentage ofpatients withnormal microscopy findings andnegative culture during and after topical terbinafine treatment fortineapedis. (Noplacebo-treated patients returned for the 2-week posttreatment follow-up to enable meaningful comparison at that interval.)

Concomitant medication for chronic diseases suchas diabetes mellitus or hypertension was continued. In a double-blind manner,the patients were randomly assigned to apply either terbinafine 1% cream or itsvehicle (placebo) twice daily for 4 weeks. The selection of a 4-week treatment period was basedon standardtherapy for tineapedis withmost currently available antifungals. Therapy was started on the basis of clinical findings and positive KOH preparations. However, if the culture failed to confirm the diagnosis, the patientwas removed from the study. Patientswereremoved from the study if they did not attend weekly follow-up visits or did not comply in any way with the study protocol. Finally, patientscould be discontinued from the studyif theyexperienced severe adverse events or inefficacy. At eachweekly visit, the following signs andsymptoms were scored on a scale of 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe): erythema, pustules, desquamation, incrustation, vesiculation, and pruritus. In addition,skinscrapings weretakenfor KOH microscopy and culture, andadverseevents weredocumented. Laboratory testsofhematologic, liver, and kidney function weredone beforeand at the end of therapy. At the end of therapy and again at the 2-week posttreatment follow-up, a combined mycologic andclinical evaluation was made of each patient's response. Effective treatment was defined as either (1) complete cure-s-normal microscopy findings and negative culture with no residual signs or symptoms or (2) mycologic

cure-s-normal microscopy findings and negative culture with mildresidual erythema and/or desquamation and/ or pruritus (total score