terbinafine, Lamisil
Antimycotic susceptibility testing of mould-fungi with allylamines by disk diffusion.

Venugopal PV, Venugopal TV.

Institute of Microbiology, Madurai Medical College.

Susceptibility testing of 17 clinical isolates of mould-fungi, which included Aspergillus spp., (8) Penicillium spp., (2) Paecilomyces spp., (1) Cladosporium spp., (1) Pyrenochaeta romeroi (1) Rhizopus spp., 2. Syncephalastrum spp., (1) and Mortierella spp., (1) were carried out against allylamines-naftifine and terbinafine-(Sandoz Forchungsinstitut) by agar dilution and disk diffusion techniques. Terbinafine was more active than naftifine inhibiting 50 and 90% of the fungi other than zygomycetes at a concentration of 0.5 and 1 microgram/ml whereas the values for naftifine were 2.5 and 10 micrograms/ml. The MIC range for zygomycetes for terbinafine and naftifine were 1-->100 and 100-->100 respectively. The MICs and the sizes of zones of inhibition around the disks correlated well and the degree of correlation was measured by regression analysis. The correlation coefficients for naftifine and terbinafine were-0.9597 and -0.9174 (P < 0.007) respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8772831&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents.

Favre B, Ryder NS.

Department of General Dermatology, SANDOZ Research Institute, Vienna, Austria.

Squalene epoxidase (SE) is the primary target of the allylamine antimycotic agents terbinafine and naftifine and also of the thiocarbamates. Although all of these drugs are employed primarily in dermatological therapy, SE from dermatophyte fungi has not been previously investigated. We report here the biochemical characterization of SE activity from Trichophyton rubrum and the effects of terbinafine and other inhibitors. Microsomal SE activity from T. rubrum was not dependent on soluble cytoplasmic factors but had an absolute requirement for NADPH or NADH and was stimulated by flavin adenine dinucleotide. Kinetic analyses revealed that under optimal conditions the Km for squalene was 13 microM and its Vmax was 0.71 nmol/h/mg of protein. Terbinafine was the most potent inhibitor tested, with a 50% inhibitory concentration (IC50) of 15.8 nM. This inhibition was noncompetitive with regard to the substrate squalene. A structure-activity relationship study with some analogs of terbinafine indicated that the tertiary amino structure of terbinafine was crucial for its high potency, as well as the tert-alkyl side chain. Naftifine had a lower potency (IC50, 114.6 nM) than terbinafine. Inhibition was also demonstrated by the thiocarbamates tolciclate (IC50, 28.0 nM) and tolnaftate (IC50, 51.5 nM). Interestingly, the morpholine amorolfine also displayed a weak but significant effect (IC50, 30 microM). T. rubrum SE was only slightly more sensitive (approximately twofold) to terbinafine inhibition than was the Candida albicans enzyme. Therefore, this difference cannot fully explain the much higher susceptibility (> or = 100-fold) of dermatophytes than of yeasts to this drug. The sensitivity to terbinafine of ergosterol biosynthesis in whole cells of T. rubrum (IC50, 1.5 nM) is 10-fold higher than that of SE activity, suggesting that the drug accumulates in the fungus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8834895&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Effect of oral terbinafine treatment on cyclosporin pharmacokinetics in organ transplant recipients with dermatophyte nail infection.

Jensen P, Lehne G, Fauchald P, Simonsen S.

Department of Dermatology, Rikshospitalet, University of Oslo, Norway.

Eleven patients with either kidney, heart or lung transplants, immunosuppressed with cyclosporin A, and with culture-proven dermatophyte toe nail infection, were given 250 mg terbinafine orally daily for 12 weeks. No changes in cyclosporin A dosage were made. A statistically significant decrease in mean specific cyclosporin A blood trough levels was found at 4, 8 and 12 weeks. No other statistically significant changes in the pharmacokinetic profile of cyclosporin A were seen. Terbinafine possibly induces a cyclosporin A metabolic degradation, which, however, is of little clinical significance. Terbinafine treatment is a safe therapeutical option in cyclosporin A-treated patients with dermatophyte nail infection. Cyclosporin A levels should be controlled during treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8869684&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Taste loss to terbinafine: a case-control study of potential risk factors.

Stricker BH, Van Riemsdijk MM, Sturkenboom MC, Ottervanger JP.

Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.

1. To identify risk factors associated with taste loss to terbinafine, we performed a case-control study of 87 reports of probably terbinafine-induced taste loss and 362 controls on terbinafine without taste loss, who had filled prescriptions from the same pharmacy and GP. Data on general health, diet, alcohol, smoking, drug use and medical history were collected by means of a self-administered questionnaire. 2. The mean latent period between first intake of terbinafine and taste loss was 35 days. Most patients recovered within 4 months after discontinuation. Cases were significantly older than controls. The odds ratio of taste loss in patients of 65 years and older was 4.4 in comparison with persons younger than 35 years of age (95% CI: 1.4-16.1). The risk in persons with a body mass index (BMI) below 21 kg m-2 was 4.4 times higher than in those with a BMI of more than 27 kg m-2 (95% CI: 1.6-14.2). The risk of taste loss in patients of 55 years and older with a BMI below 21 kg m-2 was 12.8 times higher than that in patients below 35 years of age (95% CI: 1.9-88.6). 3. A low BMI, a history of taste loss, and ageing are risk factors for developing taste loss to terbinafine. Prescription of this drug to elderly patients with low BMI and low daily intake of nutrients requires careful follow-up.

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terbinafine, Lamisil
Economic evaluation of antifungal agents in the treatment of toenail onychomycosis in Germany.

Van Doorslaer EK, Tormans G, Gupta AK, Van Rossem K, Eggleston A, Dubois DJ, De Doncker P, Haneke E.

Institute for Medical Technology Assessment, Erasmus University, Rotterdam, The Netherlands.

BACKGROUND: The strategies for the management of onychomycosis have changed since the availability of the newer generation of antifungal agents, particularly, itraconazole and terbinafine. Itraconazole (1-week pulse) therapy may have higher efficacy and an improved adverse-effects profile compared to the continuous therapy regimen. OBJECTIVE: We performed a pharmacoeconomic evaluation of the most commonly used treatments in Germany for toenail onychomycosis from a health care payer perspective. METHODS: A 5-step approach was used. Firstly, the purpose of the study, the comparator drugs, their dosage regimens and the time frame of the analysis were defined. Next, the medical practice and resource consumption patterns associated with the treatment of onychomycosis were identified. In step III, a meta-analysis was used to determine the relative efficacy of the comparator drugs. In step IV, a decision tree of the treatment algorithms was constructed for each comparator. The expected cost analysis and cost-effectiveness analysis were also performed. Finally, a sensitivity analysis was carried out. RESULTS: For the four main comparator drugs used to treat toenail onychomycosis in Germany, the clinical response rates (clinical cure plus marked improvement) at the end of the follow-up period (month 12 after starting therapy) were, for itraconazole (1-week pulse dosing): 89.8 +/- 3% (mean +/- SE), terbinafine: 79.4 +/- 10%, itraconazole (continuous dosing): 77.5 +/- 9%, and ciclopirox nail varnish: 55 +/- 5%. Itraconazole (1-week pulse dosing) was most cost-effective at DM 1,107 per successful treatment, followed by oral terbinafine at DM 1,224, ciclopirox nail varnish and itraconazole (continuous dosing). Sensitivity analyses indicated that itraconazole (1-week pulse dosing) and terbinafine had similar cost-effectiveness ratios. CONCLUSION: Itraconazole is an effective, broad-spectrum triazole used as continuous or pulse therapy in the treatment of onychomycosis. Itraconazole (1-week pulse) and terbinafine are the most cost-effective therapies for toenail onychomycosis.

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terbinafine, Lamisil
Postmarketing surveillance of oral terbinafine in the UK: report of a large cohort study.

O'Sullivan DP, Needham CA, Bangs A, Atkin K, Kendall FD.

Sandoz Pharmaceuticals UK Ltd, Frimley, Camberley, UK.

1. The safety profile of terbinafine, the first orally active allylamine, was monitored in the UK in a post-marketing setting. The study recruited 10,361 patients, a number which is approximately 5% of the population who received oral terbinafine in the UK during the period of the study. 2. Follow-up data were available on 9,879 patients. During the course of the study 14.5% patients reported medical events. 49% were thought to be possibly or probably related to terbinafine treatment. Seventy-four of the events (< 1%) were classified as 'serious' and of these only five were assessed as possibly or probably related to treatment. 3. Taste disturbance occurred in 0.6% of the patients and emerged as the only new adverse reaction probably attributable to terbinafine: this was significantly commoner in females and reversible on stopping treatment, with a median time to recovery of 42 days. 4. The study approach successfully combined hospital based dermatology outpatient and general practice centres. Source data verification was conducted on 13% of the cohort selected randomly. 5. Overall, the denominator-based description of the safety profile in actual practice shows terbinafine to be well-tolerated against a wide background of age and coexisting illness.

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terbinafine, Lamisil
Open label trial of the efficacy and tolerability of Lamisil (Terbinafine) 500 mg once daily in the treatment of onychomycosis due to candida.

Zaidi Z, Jafri N, Khan K, Hasan P, Kapadia N.

Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi.

An open label trial of Lamisil (Terbinafine) 500 mg daily for 16 weeks was conducted on 20 patients with Onychomycosis due to candida. Of these, 15 patients could complete the trial. Total number of target nails infected was 21. The follow-up period was from 16 to 52 weeks. At 16 weeks, 71% cases showed clinical improvement and 67% had mycological cure. Thirty-three percent had complete cure at 52 weeks. The results show that Terbinafine is effective against candida but requires a longer duration of treatment. The drug was well tolerated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9000820&dopt=Abstract terbinafine Lamisil