terbinafine, Lamisil
[Facial pigmentation following oral therapy with terbinafine.]

[Article in German]

Breuer K, Volker B, Gutzmer R, Kapp A, Werfel T.

Klinik und Poliklinik fur Dermatologie und Venerologie, Medizinische Hochschule Hannover, .

A 65-year-old patient presented with grey-brownish maculae localized on the face. He had been treated with oral terbinafine due to onychomycosis, and the first spots manifested after 4 weeks of therapy. Other drugs were not taken by the patient, who was otherwise in a healthy condition. Histology showed melanin localized within macrophages in the upper and lower dermis. Cutaneous side effects are well described in patients treated with terbinafine and usually present as urticaria or eczema. Severe reactions may occur in rare cases. Hyperpigmentation has not yet been described as a consequence of oral terbinafine. Grey hyperpigmentation as it occurred in our patient has been described as a side effect of therapy with minocycline, amiodarone, tricyclic antidepressants, or heavy metals. This case report shows that drug-induced hyperpigmentation should also be considered if the patient takes drugs not known for this kind of side effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15657730&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
Pharmacoeconomic analysis of sequential treatment pathways in the treatment of onychomycosis.

Frankum LE, Nightengale B, Russo CL, Sarnes M.

Applied Health Outcomes, Palm Harbor, Florida, USA. lfrankum applied-outcomes.com

This study examines the budgetary effect of using ciclopirox, itraconazole (pulse treatment), terbinafine, or itraconazole (continuous treatment) as first-, second-, or third-line therapy in the treatment of toenail onychomycosis by determining which therapeutic sequence is most cost effective. Using a disease treatment pathway model, alternative agents were compared based on cost per clinical response. The results from this sequential treatment analysis demonstrated that ciclopirox followed by itraconazole pulse and then terbinafine provides the lowest-cost approach to the treatment of onychomycosis (dollar 757.89 per clinical response), followed by the sequence of ciclopirox, terbinafine, and itraconazole pulse (dollar 796.13 per clinical response). This study provides a framework for formulary decision makers to evaluate a sequential treatment pathway that resembles actual practice.

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terbinafine, Lamisil
Biochemical characterization of terbinafine-resistant Trichophyton rubrum isolates.

Favre B, Ghannoum MA, Ryder NS.

Novartis Research Institute, Vienna, Austria.

We investigated the biochemical basis for resistance in six sequential clinical isolates of Trichophyton rubrum, from the same patient, which exhibited high-level primary resistance to terbinafine. Cellular ergosterol biosynthesis was measured by incorporation of [14C]acetate, and microsomal squalene epoxidase was assayed by conversion of [3H]squalene to squalene epoxide and lanosterol. Direct comparison was made with a terbinafine-susceptible reference strain of T. rubrum in which squalene epoxidase was previously studied. Resistant isolates displayed normal cellular ergosterol biosynthesis, although slight accumulation of radiolabeled squalene suggested reduced squalene epoxidase activity. Ergosterol biosynthesis in the resistant isolates was only inhibited by terbinafine concentrations above 1 microg/ml (IC50 5 microg/ml). In the reference strain, ergosterol biosynthesis was eliminated by terbinafine at 0.03 microg/ml in accordance with historical data. There was no significant difference in sensitivity between the six resistant isolates. Squalene epoxidase from resistant strains was three orders of magnitude less sensitive than normal enzyme to terbinafine (IC50 of 30 micromol/l and 19 n mol/l respectively). The epoxidase in the resistant strains was also unresponsive to tolnaftate. Resistance to terbinafine in these T. rubrum isolates appears to be due to alterations in the squalene epoxidase gene or a factor essential for its activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15682641&dopt=Abstract terbinafine Lamisil



terbinafine, Lamisil
In vitro susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine.

Gupta AK, Kohli Y, Li A, Faergemann J, Summerbell RC.

Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook Site) and the University of Toronto, Canada. agupta execulink.com

Fifty-five strains, either authentic or ex-type, of seven Malassezia species were investigated for in vitro susceptibility to various concentrations (0.03-64.0 microg/mL) of three azole drugs, ketoconazole, voriconazole and itraconazole, as well as the allylamine terbinafine, using the agar dilution method. All strains of the seven Malassezia species were susceptible to the three azole drugs at low concentrations. M. furfur, M. sympodialis, M. slooffiae, M. pachydermatis, M. globosa, M. obtusa and M. restricta were most sensitive to ketoconazole and itraconazole, with minimum inhibitory concentrations (MICs) ranging from < or = 0.03 to 0.125 microg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values < or = 0.03 microg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from </= 0.03 to 64.0 microg/mL. There were variations in susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Strains of M. furfur, M. globosa and M. obtusa were more tolerant to terbinafine than the remaining Malassezia species; M. sympodialis was highly susceptible. M. furfur strains tested with terbinafine ranged from highly susceptible to relatively resistant. Correct identification of Malassezia species could facilitate selection of appropriate antifungal therapy.

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terbinafine, Lamisil
Stability of terbinafine hydrochloride in an extemporaneously prepared oral suspension at 25 and 4 degrees C.

Abdel-Rahman SM, Nahata MC.

College of Pharmacy, The Ohio State University, Wexner Institute for Pediatric Research, Children's Hospital, Columbus 43210, USA.

The stability of terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension at 25 and 4 degrees C was studied. Twenty 250-mg terbinafine tablets were crushed to a fine powder and diluted to a concentration of 25 mg/mL with sweetened vehicle. The suspension was stored in amber polyethylene prescription bottles at 25 or 4 degrees C. Samples were taken on days 0, 7, 14, 28, 42, 56, 70, and 91 for duplicate analysis of terbinafine content by high-performance liquid chromatography and to observe any changes in color and odor; pH was measured as well. Through the initial 42 days, the mean concentration of terbinafine in the samples stored at both temperatures was >93% of the initial concentration; by day 56, the mean concentration was <88%. No appreciable changes in color or odor were observed during the study period. The apparent pH of the suspension decreased slightly over the 91 days, from an initial 5.6 to 5.5. Terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension was stable for up to 42 days in polyethylene prescription bottles at 25 and 4 degrees C.

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terbinafine, Lamisil
A cost/efficacy analysis of oral antifungals indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine.

Angello JT, Voytovich RM, Jan SA.

HIP Health Plan of New Jersey, North Brunswick, USA.

This analysis was conducted at HIP Health plan of New Jersey (a Northeastern group model health maintenance organization) to determine the most cost-effective therapy among the three currently available oral antifungal drugs that are indicated for the treatment of onychomycosis: griseofulvin, itraconazole, and terbinafine. Costs of an appropriate and complete treatment regimen were calculated for each of the three drugs based on average wholesale price. Efficacy was determined by meta-analysis of the published literature for those studies where appropriate treatment regimens for onychomycosis were put to use. Efficacy outcome measures were limited to mycologic cure rates in the more recalcitrant cases of toenail onychomycosis. From these measures of cost and efficacy, a cost/efficacy ratio was calculated for each drug by dividing the cost per treatment by the weighted average mycological cure rate. This ratio represents the cost per mycologically cured infection. The final outcome measure (the cost per mycologically cured infection) was $2,721.28, $1,845.05, and $648.96, for griseofulvin, itraconazole, and terbinafine continuous therapies, respectively. For itraconazole and terbinafine pulse therapy, the costs were $855.88 and $388.50, respectively. For both continuous and pulse therapy, terbinafine is apparently the most cost-effective drug, followed by itraconazole and then by griseofulvin. Terbinafine has the fewest drug interactions and the highest treatment success rate.

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terbinafine, Lamisil
Pharmacoeconomic analysis of oral antifungal therapies used to treat dermatophyte onychomycosis of the toenails. A US analysis.

Gupta AK.

Department of Medicine, Sunnybrook Health Science Center, Toronto, Ontario, Canada. agupta execulink.com

Until a few years ago, griseofulvin and ketoconazole were the only 2 oral agents available for the treatment of dermatophyte onychomycosis of the toenails. With the availability of the newer antifungal agents, such as itraconazole, terbinafine and fluconazole, the armamentarium of drugs available to treat onychomycosis has expanded. The objective of this study was to determine the relative cost effectiveness of the most commonly used oral antifungal agents in the US for the treatment of dermatophyte onychomycosis of the toenails from the perspective of a third-party payer. The time horizon was 3 years. A 5-step approach was used in this pharmacoeconomic analysis. First, the purpose of the study, the comparator drugs and their dosage regimens were defined. In step II, the medical practice and resource-consumption patterns associated with the treatment of onychomycosis were identified. In step III, a meta-analysis was performed on all studies meeting prespecified criteria, and the mycological cure rates of the comparator drugs were determined. In step IV, the treatment algorithm for the management of onychomycosis was constructed for each drug. The cost-of-regimen analysis for each comparator incorporated the drug acquisition cost, medical-management cost and cost of managing adverse drug reactions. The expected cost per patient, number of symptom-free days (SFDs), cost per SFD and the relative cost effectiveness for the comparator drugs were calculated. In step V, a sensitivity analysis was performed. The drug comparators for this study were griseofulvin, itraconazole (continuous and pulse), terbinafine and fluconazole. The mycological cure rates [mean +/- standard error (SE)] from the meta-analysis were griseofulvin 24.5 +/- 6.7%, itraconazole (continuous) 66.4 +/- 6.1%, itraconazole (pulse) 76 +/- 9.3%, terbinafine 74 +/- 7% and fluconazole 59%. The cost per mycological cure was griseofulvin $US8089, itraconazole (continuous) $US1877, itraconazole (pulse) $US991, terbinafine $US1125 and fluconazole $US1506. The corresponding cost per SFD was griseofulvin $US7.05, itraconazole (continuous) $US2.18, itraconazole (pulse) $US1.26, terbinafine $US1.28 and fluconazole $US2.12. The resulting ratios of cost per SFD relative to itraconazole (pulse) [1.00] were terbinafine 1.02, itraconazole (continuous) 1:73, fluconazole 1.69 and griseofulvin 5.62. In conclusion, in this analysis, itraconazole (pulse) and terbinafine were the most cost-effective therapies for dermatophyte onychomycosis of the toenails, both being substantially more cost effective than griseofulvin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10178650&dopt=Abstract terbinafine Lamisil