terbinafine, Lamisil
Pulsed versus continuous terbinafine dosing in the treatment of dermatophyte onychomycosis.

Pavlotsky F, Armoni G, Shemer A, Trau H.

Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel. felixp post.tau.ac.il

BACKGROUND: The accepted regimen for terbinafine, one of the most effective treatments for dermatophyte onychomycosis, is continuous administration of 250 mg/day over 16 weeks. A few small studies, however, have raised the possibility of an alternative regimen: pulsed administration of 500 mg/day for 1 week, every 4 weeks (over 16 weeks), without decreasing treatment efficacy. OBJECTIVE: Our aim was to compare the efficacy and safety of both regimens in a large group of patients. METHODS: Retrospective analysis of 260 patients with culture proven dermatophyte onychomycosis treated in seven outpatient clinics run by two dermatologists using one of the terbinafine protocols on a chronological basis: 105 patients were treated using the continuous regimen during 1998/1999 and 155 patients were treated using the pulsed regimen during 1999/2002. Mycological and clinical cure were assessed 2 and 3 months, respectively, after completion of the last therapeutic course. Side effects were documented for the pulse regimen group only and compared with historical data previously published for the continuous protocol. RESULTS: The mycological, clinical and complete (mycological and clinical) cure rates of the toenails were 72.1%, 53.5% and 47.1% in the pulse regimen versus 82%, 35% and 34% in the continuous regimen, respectively (p=0.091, 0.0002 and 0.047, respectively). The mycological, clinical and complete cure rates of the fingernails were 91.7%, 83.3% and 79.2% respectively in the pulse group versus 100% (all parameters) in the continuous group (no significant difference). In general, both regimens were well tolerated and few side effects were reported. CONCLUSION: The pulsed regimen is at least as effective as continuous dosing and thus, at 50% less cost and more convenience, is preferable to a continuous regimen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15370400&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States.

Gupta AK.

Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook site), and the University of Toronto.

BACKGROUND: Recently a novel topical nail lacquer, ciclopirox solution 8%, has been approved for the treatment of onychomycosis. OBJECTIVE: This was undertaken to determine the most cost-effective treatment for the treatment of dermatophyte onychomycosis of the toes in the United States in 2000. METHODS: The nature of the problem was defined. The drug comparators were ciclopirox nail lacquer, terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A decision analytic model that reflected the manner in which pedal tinea unguium is managed was produced. Studies that have evaluated the efficacy of the nail lacquer and the oral antifungal agents for this indication were identified. Appropriate studies were used in a meta-analysis to determine the mycologic and clinical response rates when the drug comparators are used for the treatment for toe dermatophyte onychomycosis. For each drug comparator a cost of regimen analysis was carried out. This is the sum of the drug acquisition cost, the cost of medical management, and the cost of managing adverse effects. Next, the expected cost of management was calculated, disease free days were determined, and a sensitivity analysis was conducted. RESULTS: For each comparator the meta-analytic average mycologic cure (MC) rate and clinical response (CR) rates were: ciclopirox nail lacquer (MC: 52.6 +/- 4.2%, CR: 52.4 +/- 9.0%), griseofulvin (MC: 41.1 +/- 20.4%, CR: 33.7 +/- 14.1%), itraconazole (continuous) (MC: 66.3 +/- 4.2%, CR: 70.3 +/- 4.2%), itraconazole (pulse) (MC: 70.8 +/- 5.7%, CR: 73.6 +/- 4.6%), terbinafine (MC: 77.2 +/- 4.0%, CR: 75.3 +/- 2.9%), and fluconazole (MC: 65.6 +/- 7.1%, CR: 66.5 +/- 11.7%). The cost of regimen for the drug comparators was: ciclopirox nail lacquer $325.2, griseofulvin $1413.1, itraconazole (continuous) $1410.2, itraconazole (pulse) $811.7, terbinafine $890.1, and fluconazole $966.8. The cost/mycologic cure rate and expected cost/expected symptom free day were, ciclopirox nail lacquer ($618.2, 1.69), griseofulvin ($3438.2, 5.3), itraconazole (continuous) ($2126.9, 3.52), itraconazole (pulse) ($1146.4, 2.01), terbinafine ($1153.0, 2.14), and fluconazole ($1473.7, 2.10). The relative cost-effectiveness was ciclopirox nail lacquer 1.00, itraconazole (pulse) 1.19, fluconazole 1.24, terbinafine 1.27, itraconazole (continuous) 2.08, and griseofulvin 3.13. Sensitivity analysis indicated that ciclopirox nail lacquer was a cost effective alternative compared with the oral regimens of terbinafine, itraconazole (continuous), and griseofulvin when clinical response rate was used as the primary efficacy parameter. CONCLUSION: Ciclopirox nail lacquer solution 8% is a recent addition to the armamentarium of therapies available to the physician and patient for the treatment of onychomycosis. The nail lacquer is a cost effective agent compared with the oral antifungal therapies, terbinafine, itraconazole, fluconazole, and griseofulvin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11002199&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
[Cloning of the Aspergillus fumigatus squalene epoxidase gene.]

[Article in Chinese]

Liu W, May GS, Kontoyiannis DP, Li RY.

Department of Dermatology, Peking University First Hospital, Beijing 100034, China.

OBJECTIVE: To clone Aspergillus fumigatus squalene epoxidase gene and to further investigate its role in terbinafine resistance. METHODS: The A.fumigatus genomic DNA library was transformed into pyrG-A. fumigatus strain protoplasts with polyethylene glycol-mediated transformation protocol. TRB-resistant pyrG+ transformants were then isolated by being plated on MM-U with TRB (0.625 mg/L) plates. After confirmation of terbinafine-resistance by using both disk diffusion and NCCLS M38-A microdilution antifungal susceptibility testing, the gene conferring terbinafine-resistance was identified. Finally, the gene was cloned and retransformed into pyrG-A. fumigatus strain. RESULTS: From a total of 5x10(4) transformants, one TRB-resistant pyrG+ transformant was isolated, which showed the terbinafine-specific resistance without cross-resistance to any other antifungals. A. fumigatus squalene epoxidase gene was further identified to confer this terbinafine-resistance. As a result, the complete A. fumigatus squalene epoxidase gene was firstly cloned. Finally, the transformants with extra copies of A. fumigatus squalene epoxidase gene, again, showed the specific resistance to terbinafine. CONCLUSION: Extra copies of A. fumigatus squalene epoxidase gene, which was cloned for the first time in this study, could result in A. fumigatus resistance to terbinafine. This is a novel mechanism of terbinafine-resistance that needs further investigation for its clinical significance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15489926&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Griseofulvin versus terbinafine in the treatment of tinea capitis: a meta-analysis of randomized, clinical trials.

Fleece D, Gaughan JP, Aronoff SC.

Department of Pediatrics, Temple University Children's Medical Center, 5th Floor, 3509 N Broad St, Philadelphia, PA 19140, USA. fleeced tuhs.temple.edu

OBJECTIVE: Tinea capitis, a common pediatric infection in the United States, is caused mainly by Trichophyton species and affects many urban children. Although the current treatment of choice is oral griseofulvin, terbinafine has been shown to be variably effective in several comparative, randomized trials. The purpose of this study was to perform a meta-analysis of randomized, clinical trials comparing the efficacies of oral terbinafine and oral griseofulvin for the treatment of childhood tinea capitis. METHODS:The Medline database was searched for randomized, clinical studies comparing griseofulvin and terbinafine for the treatment of tinea capitis. Acceptance criteria included oral administration of griseofulvin for at least 6 weeks and the identification of a pathogenic dermatophyte from the scalp at the time of enrollment in the study. Scalp culture status at least 8 weeks after enrollment was used as the outcome. The common odds ratio (OR) with 95% confidence intervals (CIs), the Cochran-Mantel-Haenszel test for significance, and the Breslow-Day test for homogeneity were calculated. RESULTS:Six articles that satisfied all inclusion criteria were identified. These studies were combined by using outcomes at 12 to 16 weeks after enrollment. The common OR was 0.86 (95% CI: 0.57-1.27). When the 5 studies that identified Trichophyton species as the predominant pathogen were combined, using outcomes 12 weeks after enrollment, the results nearly favored terbinafine (OR: 0.65 [95% CI: 0.42-1.01]). For outcomes at 8 weeks after enrollment, no difference was found between the agents (OR: 0.84 [95% CI: 0.54-1.32]). Consclusions.A 2- to 4-week course of terbinafine is at least as effective as a 6- to 8-week course of griseofulvin for the treatment of Trichophyton infections of the scalp. Griseofulvin is likely to be superior to terbinafine for the rare cases caused by Microsporum species.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15520113&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
The development of the method for the determination of terbinafine in cat's plasma and hair.

Kozuh Erzen N, Kuzner J, Drobnic-Kossorok M.

Institute of Physiology, Pharmacology and Toxicology, Veterinary Faculty, University of Ljubljana, Slovenia.

Clinical investigations of terbinafine indicate its high treatment activity against infections by several dermatophytes. Its efficiency was tested also in the treatment of microsporosis in cats. The distribution of terbinafine in cat's plasma and hair is important for the identification of the drug efficiency. A fast and reliable reversed-phase high performance liquid chromatographic method with appropriate sample preparation has been developed. Reliability, good reproducibility and low detection limit (LOD 0.25 ng/ml) of the method enable determination of terbinafine in hair and also in plasma of cats infected with Microsporum canis treated by Lamisil tablets.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11005657&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro antifungal activity of sertaconazole compared with nine other drugs against 250 clinical isolates of dermatophytes and Scopulariopsis brevicaulis.

Carrillo-Munoz AJ, Guglietta A, Palacin C, Casals J, del Valle O, Guardia C, Rodriguez V, Quindos G.

Departamento de Microbiologia, Asesoria, Cientifica y de la Investigacion Aplicada, Hospital Vall d'Hebron, Barcelona, Espana. acarrillo ya.com

We have tested 250 strains belonging to 15 species of clinically important dermatophytes and Scopulariopsis against ten antifungal drugs using an agar diffusion method (NeoSensitabstrade mark, Rosco, Taastrup, Denmark). Some of the experimental factors were adapted to dermatophyte development, such as temperature (28 vs. 35 degrees C) and time of incubation (2-5 days vs. 21-74 h). The antifungals used are itraconazole, ketoconazole, miconazole, clotrimazole, sertaconazole, terbinafine, tioconazole, fluconazole, isoconazole and econazole. Except for fluconazole, all the drugs tested have shown to be highly effective, especially sertaconazole and terbinafine. Percentages of susceptibility ranged between 94% for terbinafine, 87.6% for sertaconazole and 86.4% clotrimazole; 81.6% econazole; 42.8% fluconazole; 57.2% isoconazole; 78.4% itraconazole; 74.4% ketoconazole; 73.3% miconazole, and 85.2% for tioconazole. Percentages of resistance were similar between sertaconazole and terbinafine (4%) but in contrast to the 48% obtained for fluconazole. 2004 S. Karger AG, Basel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15608448&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
[Is amphotericin B active against dermatophytes and Scopulariopsis brevicaulis?]

[Article in Spanish]

Carrillo-Munoz AJ, Santos P, del Valle O, Casals JB, Quindos G.

Departamento de Microbiologia, ACIA, Barcelona, Spain.

The in vitro antifungal activity of amphotericin B was compared with that of griseofulvin, ketoconazole, clotrimazole and terbinafine in 193 clinical isolates of dermatophytes and Scopulariopsis brevicaulis. An agar diffusion method was used (NeoSensitabs) to categorize the susceptibility of the isolates as susceptible, intermediate or resistant to the antifungal agents. Using this method and following a standardized protocol adapted to the growth conditions of the dermatophytes and the opportunistic mold S. brevicaulis (inoculum size, temperature and time period of incubation), it was found that the in vitro susceptibility rates were 72%, 94.3%, 81.9%, 72% and 86% for amphotericin B, terbinafine, griseofulvin, ketoconazole and clotrimazole, respectively. Resistance percentages were 12.4%, 3.6%, 18.1%, 10.4% and 4.1% for the same antifungal agents. Amphotericin B showed no antifungal activity against S. brevicaulis; its activity against dermatophytes was similar to that of ketoconazole, and lower than that for clotrimazole and terbinafine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15619653&dopt=Abstract terbinafine Lamisil