Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

6.1.   Pharmacodynamics
Pharmacotherapeutic group: Antifungal for topical use (ATC code D01A E15).
Terbinafine is an allylamine with antifungal activity mainly against dermatophytes.
Terbinafine interferes specifically with fungal sterol biosynthesis at an early step. This leads to a deficiency in ergosterol and to an intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine acts by inhibition of squalene epoxidase in the fungal cell membrane. The enzyme squalene epoxidase is not linked to the cytochrome P450 system. Terbinafine does not influence the metabolism of hormones or other drugs.
A phase III, randomized, double-blind, placebo-controlled clinical trial has been conducted to investigate the efficacy and safety of Lamisil Once in patients aged 12 years and over with tinea pedis. In this study, 273 patients which were treated with a single application of Lamisil Once (190 patients) or vehicle (83 patients) according to the directions for use were analysed for the efficacy.
The primary efficacy variable was the number of patients ‘effectively treated’ (negative microscopy, negative culture, total clinical signs and symptoms score 2 using a scoring scale of 0-3 for each individual sign/symptom, with no individual sign/symptom for pustules, incrustation, vesiculation and an individual score ≤1 for erythema, desquamation, pruritus,) 6 weeks after treatment. Secondary efficacy parameters included negative culture, negative microscopy, negative mycology (both negative microscopy and negative culture), clinical cure (total signs/symptoms score = 0), complete cure (negative mycology and clinical cure) and reinfection/relapse rate 12 weeks after treatment in patients effectively treated at week 6. Lamisil Once was significantly superior to placebo in effective treatment at week 6, with 63.2% of patients effectively treated compared to 16.9% in the placebo group. Lamisil Once was also significantly superior to placebo for all secondary measures of efficacy.
Twelve weeks after the single application the reinfection/relapse rate was low (12.5% of effectively treated patients in the terbinafine group had a positive culture at Week 12).
A total of five patients experienced adverse events thought to be treatment related. One patient in each of the placebo and Lamisil Once groups experienced a mild burning sensation, one patient in the placebo group experienced a moderate peripheral oedema, and one patient each in the Lamisil Once group experienced a mild pain and a moderate aggravation of pruritus.

Pharmacokinetic Properties