Tinea Capitis: Terbinafine for 1, 2, or 4 Weeks?

Source: Friedlander SF, Aly R, Krafchik B, et al. Terbinafine in the treatment of Trichophyton tinea capitis: a randomized, double-blind, parallel-group, duration-finding study. Pediatrics. 2002;109:602–607.To assess the effect of the duration of oral terbinafine treatment on the outcome of tinea capitis, investigators at 11 US and 3 Canadian centers used a doubleblind, randomized design to study 159 patients >4 years of age with culture-confirmed tinea capitis due to Trichophyton species. Subjects received terbinafine for 1, 2 or 4 weeks (dose <20 kg=62.5 mg/d, 20–40 kg=125 mg/d, >40 kg=250 mg/d); those treated with terbinafine for <4 weeks received placebo tablets to complete a 4-week treatment period. At baseline and at weeks 2 and 4 of active treatment, and 8 and 12 of follow-up, patients were assessed clinically (using a total signs and symptoms score [TSSS] with a range of 0 [no signs or symptoms] to 15), and by microscopic examination of scalp samples and fungal culture. Safety and tolerability were evaluated with adverse event reports, patient/parent reports, physical examination (baseline and week 4), and monitoring of blood counts, blood chemistries and urinalyses (baseline and weeks 2, 4 and 12). The primary outcome variable was complete cure at week 12, defined as negative culture and TSSS of 0. Secondary outcomes included effective treatment (negative culture and TSSS ≤2), clinical cure (TSSS 0), and mycological cure (fungal culture negative), all assessed at 12 weeks.Subjects had a mean age of 7.4 years; 87% were black and 57% were males. Fifty subjects received 1 week of terbinafine, 55 received 2 weeks and 54 received 4 weeks. T tonsurans was responsible for all but 2 infections. There were non-significant trends favoring 2 or 4 weeks of therapy (versus 1 week) in the primary and secondary outcome variables (TableT1).Most patients received daily doses of terbinafine between 3 and 6 mg/kg. Complete cure rates tended to be higher in those who received >4.5 mg/kg/d (60.6%) than in those who received less than this amount (39.7%). Eight adverse effects occurring in 6 subjects were considered possibly related to the study medication (5 gastrointestinal, and 1 each of headache, hyperesthesia, and transient leukopenia). No other clinically significant changes in laboratory parameters were observed. The authors conclude that when efficacy, cost and compliance are considered, 2–4 weeks of terbinafine therapy is optimal for patients with tinea capitis caused by T tonsurans.The standard treatment for tinea capitis in children is griseofulvin, 15–20 mg/kg/d of the microsize preparation, for 6 to 8 weeks.1,2 However, the duration of treatment required may reduce adherence, and some patients do not respond and/or require higher doses or more prolonged therapy. Thus, there has been great interest in exploring alternative therapeutic agents. Previous studies have confirmed the comparable therapeutic efficacy of griseofulvin and terbinafine for tinea capitis caused by T tonsurans (see AAP Grand Rounds 2001;5:49–50). A potential advantage of terbinafine is that its long half-life in skin and hair permits a shorter treatment course.3 In the present study, 2 weeks of terbinafine treatment was equivalent in efficacy to 4 weeks, although insufficient statistical power may have compromised the ability to discern differences between the treatment groups. It is of concern that only 50% of subjects achieved a complete cure, defined as an absence of signs and symptoms and a negative fungal culture. The authors speculate that inadequate compliance, reinfection or increased terbinafine clearance may have been responsible for this observation. Supporting the latter hypothesis is the finding that children who received >4.5 mg/kg/d appeared to have a higher cure rate (60.6%) than those who received a lower dose (39.7%). Terbinafine is not approved by the Food and Drug Administration for the treatment of tinea capitis; the optimal dose remains to be established, as does its safety in children. It should also be noted that terbinafine may be less effective than griseofulvin in the minority of cases of tinea capitis caused by Microsporum canis.4This research was supported by an educational grant from Novartis Pharma AG, and included 3 Novartis authors. There is no clear mention of whether or not Novartis was directly involved in collecting or interpreting data. Despite the multicenter study design, there was still a small number of subjects in each study arm so the study was underpowered to detect clinically important differences between arms, and there was a trend towards a better cure rate in the 4-week group. The authors report that the small difference between the 2 arms was unanticipated when power was calculated. This paper is also troubling since a pharmaceutical company will be motivated to find results supporting the shortest treatment duration possible in order to make their product maximally competitive with current products (griseofulvin, in this case). It is also noteworthy that the authors chose not to include griseofulvin as a treatment arm, which would have allowed their product to be directly compared against the current standard of care.

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