Terbinafine Treatment Research Articles

Prolonged Drug-Drug Interaction between Terbinafine and Perphenazine

I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in particular, akathisia. Her symptoms did not disappear for 6 weeks, and so at 2 weeks prior to this most recent admission she had stopped taking terbinafine. However, these symptoms persisted for 3 weeks after discontinuing terbinafine. It is well known that terbinafine inhibits CYP2D6 and that perphenazine is metabolized mainly by CYP2D6. Thus, when terbinafine and perphenazine are coadministrated, the subsequent increase in the concentration of perphenazine may induce extrapyramidal symptoms. Thus, terbinafine therapy may be associated with the induction and persistence of extrapyramidal symptoms, including akathisia. This case report emphasizes the importance of monitoring drug-drug interactions in patients undergoing terbinafine and perphenazine therapy.

Treatment of refractory fingernail onychomycosis caused by nondermatophyte molds with methylaminolevulinate photodynamic therapy

Treatment of refractory fingernail onychomycosis caused by nondermatophyte molds with methylaminolevulinate photodynamic therapy

Onychomycosis Insensitive to Systemic Terbinafine and Azole Treatments Reveals Non-Dermatophyte Moulds as Infectious Agents

Onychomycosis Insensitive to Systemic Terbinafine and Azole Treatments Reveals Non-Dermatophyte Moulds as Infectious Agents

Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway

Aims Oral antifungal terbinafine has been reported to cause liver injury with inflammatory responses in a small percentage of patients. However the underlying mechanism remains unknown. To examine the inflammatory reactions, we investigated whether terbinafine and other antifungal drugs increase the release of pro-inflammatory cytokines using human monocytic cells. Main methods Dose- and time-dependent changes in the mRNA expression levels and the release of interleukin (IL)-8 and tumor necrosis factor (TNF)α from human monocytic THP-1 and HL-60 cells with antifungal drugs were measured. Effects of terbinafine on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK)1/2 were investigated. Key findings The release of IL-8 and TNFα from THP-1 and HL-60 cells was significantly increased by treatment with terbinafine but not by fluconazole, suggesting that terbinafine can stimulate monocytes and increase the pro-inflammatory cytokine release. Terbinafine also significantly increased the phosphorylation of ERK1/2 and p38 MAP kinase in THP-1 cells. Pretreatment with a MAP kinase/ERK kinase (MEK)1/2 inhibitor U0126 significantly suppressed the increase of IL-8 and TNFα levels by terbinafine treatment in THP-1 cells, but p38 MAPK inhibitor SB203580 did not. These results suggested that an ERK1/2 pathway plays an important role in the release of IL-8 and TNFα in THP-1 cells treated with terbinafine. Significance The release of inflammatory mediators by terbinafine might be one of the mechanisms underlying immune-mediated liver injury. This in vitro method may be useful to predict adverse inflammatory reactions that lead to drug-induced liver injury.

Successful Terbinafine Treatment for a Girl with Kerion Caused by a Microsporum Canis Infection

Oral griseofulvin is considered the 'gold standard' therapy for patients with kerion because it can interfere with the synthesis of proteins, cell walls and nucleic acids in growing dermatophytes including Trichophyton, Microsporum and Epidermophyton. Although cure rates of griseofulvin for Microsporum canis infections are significantly better than for terbinafine, the longer therapeutic course of griseofulvin causes poor compliance among infected children. We report a 2-yearold Chinese girl with kerion caused by M canis. She exhibited good clinical responses to 7 weeks of treatment with oral terbinafine (4 mg/kg per day) without any obvious adverse events. During 6 months of follow-up, her scalp lesion cleared completely with new hair regrowth and the laboratory evaluation of hematology and biochemistry study including liver transaminases was normal.

Involvement of the JNK activation in terbinafine‐induced p21 up‐regulation and DNA synthesis inhibition in human vascular endothelial cells

Previously, we demonstrated that the extracellular signal-regulated kinase (ERK)-mediated pathway contributes to the terbinafine (TB)-induced increases of p21 and p53 protein level as well as decrease of DNA synthesis in human umbilical venous endothelial cells (HUVEC). The aim of this study is to examine the involvement of c-Jun NH2-terminal kinase (JNK) in the TB-induced increase of p21 protein level and DNA synthesis inhibition. Western blot analysis and kinase assay demonstrated that TB treatment increased both the protein level and the kinase activity of JNK1/2 in HUVEC. Transfection of HUVEC with JNK1 dominant negative (DN-JNK1) prevented the TB-induced increases of p21 and p53 protein level and decrease of DNA synthesis, suggesting that JNK1/2 activation is involved in the TB-induced cell cycle arrest in HUVEC. Moreover, over-expression of mitogen-activated protein kinase (MEK)-1 prevented the TB-induced increase of JNK1/2 protein levels, suggesting that MEK-1 is an upstream inhibitor of JNK. Transfection of HUVEC with DN-JNK1 prevented the TB-induced inhibition of ERK phosphorylation, suggesting that JNK1/2 might serve as a negative regulator of ERK. Taken together, our results suggest that JNK activation is involved in the TB-induced inhibition of ERK phosphorylation, p53 and p21 up-regulation and DNA synthesis inhibition in HUVEC.

Successful resolution of dermatophyte mycetoma following terbinafine treatment in two cats

Microsporum canis sensitive to itraconazole and terbinafine was isolated from two cats presented with generalized dermatophytosis and dermatophyte mycetoma. Itraconazole therapy was withdrawn through lack of efficacy in one cat (a Persian) and unacceptable adverse effects in the other (a Maine Coon). Both cats achieved clinical and mycological cure after 12–14 weeks therapy with 26–31 mg kg−1 terbinafine every 24 h per os (PO). Clinical signs in the Maine Coon resolved completely after 7 weeks treatment. Four weeks of therapy with additional weekly washes with a 2% chlorhexidine/2% miconazole shampoo following clipping produced a 98% reduction in the Persian cat's mycetoma, which was then surgically excised. Recurrent generalized dermatophytosis in the Persian cat has been managed with pulse therapy with 26 mg kg−1 terbinafine every 24 h PO for 1 week in every month. No underlying conditions predisposing to dermatophytosis were found in either cat despite extensive investigation. Terbinafine administration was associated with mild to moderate lethargy in the Persian cat, but no other adverse effects or changes in blood parameters were seen. To the best of the authors’ knowledge this is the first report of a dermatophyte mycetoma in a Maine Coon and of successful resolution of this condition in cats following terbinafine therapy.

Hair loss after terbinafine treatment

British Journal of DermatologyVolume 145, Issue 5 p. 842-842 Hair loss after terbinafine treatment B. Richert, B. Richert Dermatology Department, University of Liège, CHU Centre Ville, Quai Kurth 45, B-4020 Liège, Belgium E-mail: Bertrand.Richert@skynet.beSearch for more papers by this authorI. Uhoda, I. Uhoda Dermatology Department, University of Liège, CHU Centre Ville, Quai Kurth 45, B-4020 Liège, Belgium E-mail: Bertrand.Richert@skynet.beSearch for more papers by this authorM. De La Brassinne, M. De La Brassinne Dermatology Department, University of Liège, CHU Centre Ville, Quai Kurth 45, B-4020 Liège, Belgium E-mail: Bertrand.Richert@skynet.beSearch for more papers by this author B. Richert, B. Richert Dermatology Department, University of Liège, CHU Centre Ville, Quai Kurth 45, B-4020 Liège, Belgium E-mail: Bertrand.Richert@skynet.beSearch for more papers by this authorI. Uhoda, I. Uhoda Dermatology Department, University of Liège, CHU Centre Ville, Quai Kurth 45, B-4020 Liège, Belgium E-mail: Bertrand.Richert@skynet.beSearch for more papers by this authorM. De La Brassinne, M. De La Brassinne Dermatology Department, University of Liège, CHU Centre Ville, Quai Kurth 45, B-4020 Liège, Belgium E-mail: Bertrand.Richert@skynet.beSearch for more papers by this author First published: 07 July 2008 https://doi.org/10.1111/j.1365-2133.2001.04423.xCitations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume145, Issue5November 2001Pages 842-842 RelatedInformation

Inhibition of the ERK phosphorylation plays a role in terbinafine-induced p21 up-regulation and DNA synthesis inhibition in human vascular endothelial cells

Previously, we showed that terbinafine (TB) induces cell-cycle arrest in cultured human umbilical vein endothelial cells (HUVEC) through an up-regulation of the p21 protein. The aim of this study is to delineate the molecular mechanisms underlying TB-induced increase of p21 protein. RT-PCR analysis demonstrated that the mRNA levels of p21 and p53 were increased in the TB-treated HUVEC. The p21 promoter activity was also increased by TB treatment. Transfection of HUVEC with p53 dominant negative (DN) abolished the TB-induced increases of p21 promoter activity and protein level, suggesting that the TB-induced increase of p21 is p53-dependent. Western blot analysis demonstrated that TB decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK). Over-expression of mitogen-activated protein kinase (MEK)-1, the immediate upstream activator kinase of ERK, abolished the TB-induced increases of p21 and p53 protein and decrease of thymidine incorporation. The ERK inhibitor (PD98059) enhanced the TB-induced inhibition of thymidine incorporation into HUVEC. Taken together, these data suggest that the decrease of ERK activity plays a role in the TB-induced up-regulation of p21 in HUVEC. On the other hand, pretreatment of the cells with geranylgeraniol (GGOH), farnesol (FOH), or Ras inhibitor peptide did not affect the TB-induced decrease of thymidine incorporation. Taken together, our results suggest that TB might cause a decrease of MEK, which in turn up-regulates p53 through the inhibition of ERK phosphorylation, and finally causes an increase of p21 expression and cell-cycle arrest.

Onychomycosis: a new emerging infectious disease in childhood population and adolescents. Report on treatment experience with terbinafine and itraconazole in 36 patients

Onychomycosis is a rare disease in children with an estimated prevalence ranging from 0% to 2.6%. Thus far, only limited experience with itraconazole and terbinafine treatment in children with onychomycosis is available in the literature. Evaluation of treatment experience with itraconazole or terbinafine in childhood onychomycosis. Thirty-six children and adolescents (aged 4-17 years, 18 males and 18 females) with clinical and mycologically proven onychomycosis were enrolled in the present study. METHODS AND OUTCOME: In 27 of 36 patients, the causative agent (Trichophyton rubrum in 26 cases and Trichophyton interdigitale in one patient) could be identified by means of cultivation. Nineteen patients were treated with itraconazole 200 mg once daily for 12 weeks, and 17 patients were treated with terbinafine for 12 weeks in a dosage according to their body weight, respectively. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. Clinical cure was achieved within 1 to 5 months after discontinuation in all patients treated with itraconazole and in all but two patients after cessation of terbinafine treatment. Neither in the itraconazole nor in the terbinafine group were serious adverse events reported. To our experience, a mycological and clinical cure appears in children in a shorter time after treatment discontinuation (average 2-5 months) compared with adults. Itraconazole and terbinafine seem to be safe and effective in childhood onychomycosis; therefore, these antifungals seem to be potential alternatives to griseofulvin.

Evaluation of persistence of terbinafine in the hair of normal cats after 14 days of daily therapy

This study determined the residual concentration of terbinafine in cat hair after 14 days of oral treatment. Ten clinically normal cats were administered terbinafine orally at a daily dose of 34-45.7 mg kg(-1) for a total of 14 days. Areas of 15 cm(2) were shaved on the lateral thorax at day 0 and weekly for 8 weeks after the last dose of terbinafine. The hair samples were analysed by high-pressure liquid chromatography to determine the persistence of terbinafine over time. The mean terbinafine concentration in hair was 2.30 ng mg(-1) after 14 days of therapy. The half life was 1.84 weeks after the last dose of terbinafine. With a 99% confidence interval, the concentration of terbinafine remained in the cat hair at or above 0.03 ng mg(-1) (minimal inhibitory concentration (MIC)(90) = 0.03 microg mL(-1)) for 5.3 weeks. Slight deviations in the complete blood cell count and serum chemistry values were not attributed to terbinafine. Four cats experienced vomiting during the terbinafine treatment; two of these cats also experienced intense facial pruritus followed by a macular to papular skin reaction 7-14 days after the discontinuation of terbinafine. In summary, terbinafine persists in hair at concentrations above the MIC for several weeks after stopping medication, even after short-term therapy (14 days). These results suggest that pulse therapy of terbinafine should be further researched and potentially considered as a treatment modality for feline dermatophytosis, an approach that would decrease treatment duration while maintaining effectiveness.

Genome-wide expression profiling of the response to terbinafine in Candida albicans using a cDNA microarray analysis

Candida albicans is the most frequently seen opportunistic human fungal pathogen. Terbinafine is an allylamine antifungal agent that has been proven to have high clinical efficacy in the therapy of fungal infections, the mechanism of action of terbinafine involves the specific inhibition of fungal squalene epoxidase, resulting in ergosterol deficiency and accumulation of intracellular squalene. We used cDNA microarray analysis technology to monitor global expression profile changes of Candida albicans genes in response to terbinafine treatment, and we anticipated a panoramic view of the responses of Candida albicans cells to the representatives of allylamine antifungal agents at the molecular level in an effort to identify drug class-specific and mechanism-independent changes in gene expression. Candida albicans strain ATCC 90028 was exposed to either medium alone or terbinafine at a concentration equivalent to the 1/2 minimal inhibitory concentrations (MICs, 4 mg/L) for 90 minutes. RNA was isolated and gene expression profiles were compared to identify the changes in the gene expression profile using a cDNA microarray analysis. Differential expression of 10 select genes detected by cDNA microarray analysis was confirmed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). A total of 222 genes were found to be responsive to terbinafine, including 121 up-regulated genes and 101 down-regulated genes. These included genes encoding membrane transport proteins belonging to the members of the ATP-binding cassette (ABC) or major facilitator superfamily (MFS; CDR1, AGP2, GAP6, PHO84, HOL3, FCY23, VCX1), genes involved in stress response and detoxification (CDR1, AGP2, HOL3), and gene involved in the ergosterol biosynthesis pathway (ERG12). The results of semi-quantitative RT-PCR were consistent with that of the cDNA microarray analysis. The up-regulation of the gene encoding the multidrug resistance efflux pump CDR1 may contribute to the terbinafine resistance in Candida albicans. However, the precise roles of other affected genes remain unclear, further studies of these genes and their respective products that play roles in the context of antifungal resistance are warranted.

爪白癬に対するＴｅｒｂｉｎａｆｉｎｅの治療効果―２年間の経過観察―

Over the 2 year period from October, 1997 to September, 2005, the clinical efficacy of 125 mg/day of terbinafine was evaluated in 356 patients with onychomycosis. Of these, 253 patients were followed up for 6 months after oral treatment of terbinafine, 120 for 1 year, and 56 for 2 years. The improvement ratio increased depending on follow-up period: 30.4% in 6 months, 65.0% in 1 year, and 67.9% in 2 years. However, in 25 patients who showed regression from onychomycosis at the 1 year period, 8 patients (32.0%) relapsed. The muddy rate of the first toenail was decreased from pre-treatment with terbinafine in 92.1% at 6 months, 91.7% at 1 year and 87.5% at 2 years. It is considered that efficacy of this medication is maintained within 1 year after the treatment, but the number of patients who experience a relapse is likely to increase from 1 year to 2 years.

Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway

We showed previously that terbinafine, an allylamine with fungicidal activity, could inhibit angiogenesis by suppressing the endothelial cell proliferation. In the present study, we further showed that terbinafine (0-120 micromol/L) dose dependently inhibited the adhesion and migration of human umbilical vascular endothelial cells (HUVEC). Western blot analysis showed that terbinafine decreased the levels of Ras protein and membrane-bound RhoA protein. Moreover, the terbinafine-induced migration inhibition in HUVEC was prevented by pretreatment with farnesol or geranylgeraniol. Pretreatment of HUVEC with Ras inhibitor peptide or a ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor, Y27632, abolished the farnesol- or geranylgeraniol-induced prevention effect on the terbinafine-induced migration inhibition, respectively. These data suggest that the consuming or depletion of geranylgeranyl pyrophosphate and consequent suppression of protein geranylgeranylation and farnesylation, which is essential for activation of Rho GTPases and Ras, respectively, might account for the terbinafine-induced inhibition of HUVEC migration. The levels of phosphorylated focal adhesion kinase and paxillin protein and the mRNA levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were also decreased by terbinafine treatment. Taken together, these results indicate that suppression of Rho-mediated pathway might be involved in the signal transduction leading to the inhibition of cell migration caused by terbinafine in HUVEC.

Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects

Paroxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine. Two 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing. Compared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (C(max)) of paroxetine, by 1.9-fold (6.4 +/- 2.4 versus 12.1 +/- 2.9 ng/ml, p < 0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0-48)] of paroxetine by 2.5-fold (127 +/- 67 vs 318 +/- 102 ng/ml, p < 0.001). Elimination half-life differed significantly (15.3 +/- 2.4 vs 22.7 +/- 8.8 h, p < 0.05), although the magnitude of alteration (1.4-fold) was smaller than C(max )or AUC. The present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state.

Continuous terbinafine treatment is more effective than intermittent treatment in toenail onychomycosis,

Continuous terbinafine treatment is more effective than intermittent treatment in toenail onychomycosis,

Evaluating Costs for Onychomycosis Treatments

Onychomycosis is a common problem. The desired outcome of treatment for patients and clinicians is complete cure (negative culture and negative potassium hydroxide examination results plus a completely normal nail). This cost analysis sought to determine the cost-effectiveness of treatments for onychomycosis using complete cure as a unit of effectiveness. A simplified cost-effectiveness analysis was conducted using complete cure rates from randomized, blinded clinical trials involving at least 50 participants. Trials were identified by searching the literature, manually searching for review articles, and reviewing medication package inserts. For each trial that met the entry criteria, three levels of cost were used to calculate medication cost per complete cure: commercial price, average wholesale price, and Veterans Affairs pharmacy price. In addition, a computerized economic model was used to determine total cost per complete cure, including all medical costs. The most cost-effective treatments were those that involved terbinafine: pulse, continuous, or in combination with other agents. Itraconazole, griseofulvin, and fluconazole were less cost-effective. Ciclopirox nail lacquer was at least three times more expensive than all other agents when evaluating total costs per complete cure. Overall, the lowest cost per complete cure resulted from terbinafine treatment, with most evidence supporting 3 months of continuous therapy.

Clinical and Histopathological Evaluation of Terbinafine Treatment in Cats Experimentally Infected with Microsporum canis

The efficacy of terbinafine hydrochloride (Lamisil©, Novartis) in the treatment of 27 M. canis infected cats was followed. Treatment was started on the 17th day post inoculation (p.i.), when successful experimental infection was proved. Nine cats were treated with low-dose terbinafine 10-20 mg/kg QD (LD group), nine cats were treated with high-dose terbinafine 30-40 mg/kg QD (HD group) and nine were left untreated as a control group (C group). The efficacy of the treatment was evaluated using Wood's lamp examination, fungal culture and histopathology. All cats were positive 14 days p.i. Sixty days p.i. 8 cats from the LD group, 9 from the C group and 2 cats from the HD group had fungi in the tissue. Ninety days p.i. the HD group was free of fungi in the skin and other tests became negative on the 120th day p.i. Statistically significant differences were found between the HD group and both of the other groups (p &lt; 0.005) on 60th and the 90th day p.i. Experimental infection with M. canis yielded an inflammatory reaction of a mononuclear and neutrophil type in the cat skin. Hyperplastic interstitial dermatitis was a predominant tissue reaction although other types were also present during the study.

Objective Assessment of Terbinafine‐Induced Taste Loss

Terbinafine (Lamisil), a widely prescribed oral antifungal agent, reportedly induces taste loss in 0.6% to 2.8% of those taking the drug. However, many so-called taste problems reflect olfactory problems, and the sole empirical study published on this topic, based on whole-mouth testing of a single subject, found no terbinafine-related deficit. In this study, we quantitatively assessed, using well-validated taste and smell tests, chemosensory function in six patients complaining of taste disturbance after terbinafine treatment and compared their test scores to those of six age-, race-, and sex-matched normal controls. Taste function was measured using a 96-trial regional test that assesses sweet, sour, bitter, and salty taste perception within the anterior (cranial nerve [CN] VII) and posterior (CN IX) lingual taste bud fields. Smell function was bilaterally evaluated using the 40-item University of Pennsylvania Smell Identification Test. Taste function for sweet-, sour-, and bitter-tasting stimuli was significantly depressed in both the anterior and posterior lingual regions. For sodium chloride, the decrements were confined to the posterior region. Olfactory function was within normal limits. These findings 1) support anecdotal case reports of taste loss after terbinafine use, 2) demonstrate that all four major taste qualities are affected, and 3) suggest that olfactory dysfunction is not involved. Because self-report markedly underestimates chemosensory deficits, more extensive quantitative testing of patients receiving terbinafine will likely reveal a much higher prevalence of terbinafine-induced taste loss than currently reported. Since being older than 65 years of age and having a low body mass index are reportedly risk factors for terbinafine-induced taste loss, physicians should be particularly on the alert for elderly persons taking this medication who may become depressed or alter their food intake in response to decreased taste sensation.

Tinea capitis caused by Microsporum canis treated with terbinafine

Tinea capitis is a disease found throughout the world. It frequently affects children and only rarely adults, usually post-menopausal women. Numerous dermatophytes of the genus Microsporum and Tricophyton can cause tinea capitis and griseofulvin is still today the treatment of choice. To study the effectiveness and tolerability of terbinafine treatment in tinea capitis caused by Microsporum canis we treated 26 patients - 22 children and four women - for a period of 12 weeks. Dosage adopted was 62.5 mg day(-1) in patients weighing less than 20 kg, 125 mg day(-1) in those weighing between 20 and 40 kg, and 250 mg day(-1) in patients weighing more than 40 kg. Clinical and mycological healing was achieved in 22 patients (84.6%), tolerability was excellent and in no cases were side effects or abnormal results in blood chemistry tests observed.