Terbinafine

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Abstract
Terbinafine is an allylamine antifungal agent which has fungicidal activity against a wide variety of dermatophytes, moulds and certain dimorphic fungi, and fungistatic activity against Candida albicans. Oral terbinafine 250 mg/day is effective in the treatment of superficial dermatophyte infections such as onychomycosis, tinea pedis and tinea corporis/cruris, generally achieving mycological cure in >80% of patients. The drug is also effective in children with tinea capitis when administered orally in the dosage range 62.5 to 250 mg/day for 4 weeks. Comparative data indicate that oral terbinafine is more effective than continuous or intermittent itraconazole in dermatophyte onychomycosis, and is as effective as itraconazole 400 mg/day in tinea pedis. The drug has shown greater efficacy than griseofulvin in dermatophyte onychomycosis, tinea pedis and tinea corporis/cruris, and comparable efficacy in children with tinea capitis. Additionally, oral terbinafine is more effective than ketoconazole 200 mg/day in tinea corporis/cruris. Topical terbinafine 1% formulations are effective when applied once or twice daily for up to 2 weeks, achieving mycological cure in >80% of patients with tinea pedis, tinea corporis/cruris, cutaneous candidiasis and pityriasis versicolor. Its formulations are at least as effective as miconazole 2% cream and naftifine 1% gel in tinea pedis, and more effective than clotrimazole 1% cream, bifonazole 1% cream and oxiconazole 1% lotion. Mycological cure rates achieved with terbinafine generally improve after treatment cessation, reflecting the drug’s fungicidal mechanism of action and its residual effect in tissue. Terbinafine is well tolerated after oral or topical administration and has a relatively low potential for drug interactions. Pharmacoeconomic data support the use of terbinafine in dermatophyte infections of the skin or nails. Conclusions: Evidence suggests that oral terbinafine is the treatment of choice for dermatophyte onychomycosis, as it achieves high rates of mycological and clinical cure, is generally well tolerated and has a relatively low potential for drug interactions. It must also be considered a first-line treatment option, along with itraconazole, in cutaneous mycoses which warrant systemic treatment; topical terbinafine is a treatment of choice in less extensive mycoses. The use of terbinafine in non-dermatophyte or mixed infections has not been fully defined. Terbinafine is an allylamine antifungal agent which suppresses biosynthesis of ergosterol, an essential component of fungal cell membranes, via inhibition of the fungal enzyme squalene epoxidase. In vitro susceptibility tests have shown terbinafine to have primarily fungicidal activity against dermatophytes, moulds and certain dimorphic fungi, but only fungistatic activity against Candida albicans. In general, terbinafine is more active than the azole antifungals (including itraconazole) against dermatophytes, but less active against yeasts. In volunteers, maximum plasma concentrations (Cmax) of 0.86 to 1.34 mg/L were achieved within 2 hours after administration of a 250mg oral dose of terbinafine. The oral bioavailability of the drug is at least 70%. Terbinafine is extensively distributed to body tissues after oral administration and has a large steady-state volume of distribution (947.5L). The drug is rapidly delivered to the stratum corneum, nails and hair after oral administration, primarily via sebum, but is not excreted in eccrine sweat. Diffusion into the nail plate occurs within 1 week of the start of oral treatment, and levels of the drug are detectable for up to 36 weeks after treatment cessation. Terbinafine undergoes extensive hepatic metabolism, but its biotransformation utilises Topical therapy. Topical terbinafine 1% formulations are effective in the treatment of cutaneous mycoses when applied once or twice daily for up to 2 weeks. In general, mycological cure is achieved in >80% of patients with tinea pedis or tinea corporis/cruris. As with oral therapy, mycological and clinical response generally improves after treatment cessation. Comparative studies in patients with tinea pedis have shown that 1 week’s treatment with terbinafine is as effective as 4 weeks’ treatment with miconazole 2% cream and more effective than 4 weeks’ treatment with clotrimazole 1% cream. In addition, topical formulations of terbinafine have efficacies similar to naftifine 1% gel and greater than bifonazole 1% cream or oxiconazole 1% lotion. To date, no studies have compared terbinafine with other topical agents in the treatment of patients with tinea corporis and/or tinea cruris, but mycological cure rates >84% were found in placebo-controlled studies. Topical terbinafine is highly effective in the treatment of cutaneous candidiasis and pityriasis versicolor, achieving mycological cure in 93 and 85% of patients, respectively. Furthermore, a preliminary study found that terbinafine cured scalp lesions in 61% of patients with seborrhoeic dermatitis caused by Malassezia furfur (the pathogen also responsible for pityriasis versicolor). Oral terbinafine 250 mg/day was well tolerated in >25 000 patients treated for a median duration of 12 weeks in a large postmarketing surveillance study. 10.5% of patients reported adverse events, with gastrointestinal disturbance (4.9%) and cutaneous reactions (2.3%) being the most frequently reported events. In comparative studies, the incidence of adverse events associated with oral terbinafine 250 mg/day tended to be lower than that reported with griseofulvin 500 mg/day (11 vs 29%) and similar to that reported with itraconazole 200 mg/day (6 vs 9%). Serious dermatological (<0.01%), haematological (<0.01%) and hepatobiliary (300 μmol/L), and may be needed in those taking rifampicin or cimetidine. For topical treatment of skin infections, the appropriate formulation of terbinafine 1% (cream, gel, solution or spray) should be applied once or twice daily for 1 week in patients with tinea pedis, tinea corporis/cruris or cutaneous candidiasis and 2 weeks in patients with pityriasis versicolor.

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