Lamisil (Terbinafine)
Lamisil® | Desenex Max® | Lamisil® AT | Lamisil® AT Athletes Foot | Lamisil® AT Jock Itch
Classification:
Antiinfective Agents
Dermatological Agents
Description: Terbinafine is an antifungal agent that is administered either orally or topically. It is pharmacologically similar to naftifine. Oral terbinafine is highly effective for treating onychomycosis due to its fungicidal activity and ability to concentrate within the nail and has been found to be superior to griseofulvin and to itraconazole for the treatment of onychomycosis. The rate of relapse was also worse with griseofulvin than terbinafine. Clinical cure rates for the treatment of onchomycosis with terbinafine are approximately 50-70%. Current studies are evaluating the use of terbinafine in other mycotic infections. Oral terbinafine has been utilized in small open-label studies as an alternative treatment for bronchopulmonary aspergillosis refractory to to other treatments; in some cases terbinafine has suppressed or erradicated the disease. Topical terbinafine was approved by the FDA in 1993. Terbinafine oral tablets were approved May 13, 1996. Terbinafine cream received approval for over-the-counter use for the treatment of tinea pedis in March 1999.
Mechanism of Action: The allylamine antifungals probably exert their antifungal effect through interfering with fungal sterol biosynthesis by inhibiting the enzyme squalene monooxygenase, a key enzyme in sterol biosynthesis in fungi. The accumulation of squalene weakens the cell membrane in sensitive fungi. The inhibition of squalene monooxygenase creates a deficiency in ergosterol, a component of fungal membranes necessary for normal growth. Terbinafine has fungicidal activity against dermatophytes. It is less active, however, against Candida spp.
Pharmacokinetics: Terbinafine is administered orally and topically. Systemic absorption from the topical formulation was highly variable in a study of 16 patients, 8 of whose sites of application were compromised by stripping the stratum corneum. In many patients, there were no measurable amounts of the metabolite or the parent drug. Systemic absorption of topically administered terbinafine is 37 times lower than that which occurs with oral administration. Oral terbinafine is well absorbed from the gut, reaching peak plasma concentrations within 2 hours; bioavailabillity is roughly 40% due to first-pass metabolism. Administration with food increases the serum AUC of terbinafine by 20%. Although terbinafine is 99% protein-bound, it is widely distributed, including the CNS, hair, and nail beds. Terbinafine is detectable within the stratum corneum in as little as 24 hours after the initiation of therapy. Following 2 weeks of therapy at the recommended doses, terbinafine remains in the skin for up to 3 months. The elimination half-life of terbinafine is about 36 hours. The terminal half-life is about 200-400 hours, representing the slow redistribution from skin and adipose tissue. Drug may be detected in the nail for up to 90 days after treatment has stopped. Most of the oral dose is metabolized through oxidation and hydrolysis to 5 known metabolites that are inactive. The primary metabolite is N-desmethylterbinafine (10-15%). Roughly 70% of an oral terbinafine dose is excreted in the urine as these conjugated and unconjugated metabolites.
Dosage adjustment of oral terbinafine is not needed in elderly patients since the pharmacokinetics in elderly patients were shown to be comparable to healthy volunteers. Pediatric patients appear to metabolize terbinafine via the same pathways as adults. Terbinafine clearance is reduced by approximately 50% in patients with hepatic cirrhosis and renal impairment (CrCl <= 50 ml/min) compared to normal adult volunteers.
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References
. Hofmann H, Brautigam M, Weidinger G, et al. Treatment of toenail onychomycosis: a randomized, double-blind study with terbinafine and griseofulvin. Arch Dermatol 1995;131:919-22.
. Hankeke E, Tausch I, Vrautigam M, et al. Short-duration treatment of fingernail dermatophytosis: a randomized, double-blind study with terbinafine and griseofulvin. J Am Acad Dermatol 1995;32:72-7.
. Brautigam M, Nolting S, Schopf RE et al. Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Br Med J 1995;311:919-22.
[ Revised 8/31/2005 3:00:00 PM ]
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