Collis Williams

 

Loceryl Nail Lacquer + terbinafine combination
The combination of Loceryl Nail Lacquer with terbinafine tablets was evaluated in a randomised, multicentre study based on amorolfine combined with terbinafine in two different courses compared with terbinafine alone in the treatment of dermatophytic toenail onychomycosis (identified by positive culture and direct examination) with matrix involvement.
Major end-point
Mycological responses: cure rate (negative direct examination and culture) at 3 months.
Secondary end-points
Global response rate (clinical and mycological cure) at 18 months. Mycological and clinical evaluations were performed regularly every three months for 18 months.
Comments
Why was the cure rate with terbinafine alone lower than in other publications
(37.5%)?
Several aspects of the methodology, assessment criteria, and results may account for why the results in the control group (which received oral terbinafine daily for twelve weeks) were poorer than those obtained in most previously published trials.
One reason for the difference ? and a major strength of the study ? is that patients with matrix involvement were selected. These infections are generally considered to be the most difficult to cure, since involvement of the most proximal part of the nail may affect the physiological aspects of nail metabolism, growth, and healing.
Recently, Epstein studied all clinical trials (series conducted with fewer than 15 patients) concerning the treatment of toenail onychomycosis. This author showed that standard courses of terbinafine achieved disease-free nails in approximately 35 to 50% of patients. The results of this study fall within this interval.

Results
147 patients were included in this trial.
– At 18 months:
? significantly better cure rate in the Loceryl Nail Lacquer + terbinafine
combination therapy group (12 weeks): cure rate = 72.3%, versus 44%
in group 1 and 37.5% in group 3.

Pharmacoeconomic aspects
The cost per cure of combined systemic and topical treatment was also evaluated in this study. The best ratio was in the AT12 ? Loceryl + terbinafine for 12 months – group in which the highest cure rate was obtained.
In fact, most of the adverse events occurred in the first six weeks of the study when each patient was being administered terbinafine. In addition, the failure rate was highest in the terbinafine alone group.

Rationale for combination therapy
Several of amorolfine?s properties suggest that it could be an ideal adjunct for terbinafine in the treatment of dermatophytic toenail infections with matrix involvement:
? The mechanisms of action of both drugs are complementary (both inhibit ergosterol biosynthesis).
? The two drugs reach the nail by different routes:
– amorolfine applied on the nail plate goes into the nail keratin and then through the nail bed,
– terbinafine reaches the nail both via the nail bed and matrix by diffusion from dermal vessels, and via the matrix by uptake into growing onychocytes

Amorolfine can thus reach the lateral edges of the nail where systemic drugs such as terbinafine penetrate least. Moreover, the nail lacquer formulation of amorolfine is far superior to conventional
vehicles and improves the performance and longevity of the active substance All of these reasons may explain the synergistic effect observed in this study.

In conclusion, this study indicates that substantial synergy may be generated by the combination of terbinafine and amorolfine in the treatment of severe toenail onychomycosis with matrix involvement.
Conclusion
CURE RATE (clinical and mycological)
Loceryl Nail Lacquer + Terbinafine for 12 weeks = 72.3%
Terbinafine alone for 12 weeks = 37.5%
The combination of once-weekly application of Loceryl Nail Lacquer plus terbinafine tablets for 12 weeks appeared to be more effective than terbinafine alone in curing patients with onychomycosis and matrix involvement.

Further Loceryl Nail Lacquer information, a Galderma product, is available from Collis Williams Ltd. Tel: 21 24 48 47, 21 22 41 04.
Fax: 21 22 41 71