Pharmacokinetic studies indicate that 1–2% of the dose is absorbed when applied as a solution on the back under an occlusive dressing. Ciclopirox olamine is available as a 1% cream and lotion (Loprox) for the topical treatment of dermatomycosis, candidiasis, and tinea versicolor. The incidence of adverse reactions has been low. Pruritus and worsening of clinical disease have been reported. The potential for allergic contact dermatitis is small.
Topical 8% ciclopirox olamine (Penlac nail lacquer) is approved for the treatment of mild to moderate onychomycosis of fingernails and toenails. Although well tolerated with minimal side effects, the complete cure rates in clinical trials are between 5.5% and 8.5%.
Tavaborole is the first oxaborole antifungal drug approved for the treatment of toenail onychomycosis. Tavaborole blocks fungal protein synthesis by inhibiting aminoacyl-transfer ribonucleic acid synthetase. Tavaborole is available as a 5% solution (Kerydin) that should be applied to the affected toenails once daily for 48 weeks. Complete cure rates in clinical trials are between 6.5% and 9.1%.
ALLYLAMINES: NAFTIFINE & TERBINAFINE
Naftifine hydrochloride and terbinafine (Lamisil) are allylamines that are highly active against dermatophytes but less active against yeasts. The antifungal activity derives from selective inhibition of squalene epoxidase, a key enzyme for the synthesis of ergosterol (see Figure 48–1).
They are available as 1% creams and other forms for the topical treatment of dermatophytosis, to be applied on a twice-daily dosing schedule for 1–2 weeks. Adverse reactions include local irritation, burning sensation, and erythema. Contact with mucous membranes should be avoided.
Butenafine hydrochloride (Mentax) is a benzylamine that is structurally related to the allylamines. As with the allylamines, butenafine inhibits the epoxidation of squalene, thus blocking the synthesis of ergosterol, an essential component of fungal cell membranes. Butenafine is available as a 1% cream to be applied once daily for the treatment of superficial dermatophytosis.
Tolnaftate is a synthetic antifungal compound effective topically against dermatophyte infections caused by Epidermophyton, Microsporum, and Trichophyton. It is also active against P orbiculare but not against Candida.
Tolnaftate (Aftate, Tinactin) is available as a cream, solution, powder, or powder aerosol for application twice daily to infected areas. Recurrences following cessation of therapy are common, and infections of the palms, soles, and nails are usually unresponsive to tolnaftate alone. The powder or powder aerosol may be used chronically following initial treatment in patients susceptible to tinea infections. Tolnaftate is generally well tolerated and rarely causes irritation or allergic contact dermatitis.
Nystatin and amphotericin B are useful in the topical therapy of C albicans infections but ineffective against dermatophytes. Nystatin is limited to topical treatment of cutaneous and mucosal candida infections because of its narrow spectrum and negligible absorption from the gastrointestinal tract following oral administration. Amphotericin B has a broader antifungal spectrum and is used intravenously in the treatment of many systemic mycoses (see Chapter 48) and to a lesser extent in the treatment of cutaneous Candida infections.