Is terbinafine an effective treatment for feline sporotrichosis?

BACKGROUND: Terbinafine has been successfully used in the treatment of human sporotrichosis; however, its effectiveness in the treatment of feline sporotrichosis is unknown. Therefore, this study aimed to describe the use of terbinafine in the treatment of feline sporotrichosis. METHODS: A cohort study was conducted in cats with sporotrichosis to assess the effectiveness and safety of terbinafine (30‒60 mg/kg/day). Clinical examination and analysis of laboratory parameters were performed monthly until clinical signs resolved or terbinafine treatment was discontinued. RESULTS: Of the 54 cats with sporotrichosis included in the study, 19 were lost during follow-up and five were withdrawn from the study due to switching to treatment with another prescription drug. Of the remaining 30 cats, 10 achieved clinical cure, with a median treatment time of 18.5 weeks. Treatment failed in 18 cases, and two cats died. Twenty-two cats had adverse reactions to terbinafine treatment, and 10 cats showed elevation of serum transaminases. LIMITATION: Loss during follow-up was high, which makes it difficult to draw accurate conclusions regarding clinical outcomes. CONCLUSION: The low rate of clinical cure observed suggests that terbinafine does not represent an effective treatment option for cases of feline sporotrichosis.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

First case report of tinea corporis caused by Trichophyton indotineae in Latin America.

A case of tinea corporis by Trichophyton indotineae observed in Argentina is presented. The patient had a history of having spent 18 months in Tulum, Mexico. She was suffering from tinea corporis in the anterior region of both thighs and the gluteal area. A mycological study was performed and T. mentagrophytes complex was isolated. The fungus was later identified as T. indotineae by DNA sequencing and treatment with SUBA-itraconazole was initiated with good clinical response.

Sporotrichosis in Older Adults: A Cohort Study of 911 Patients from a Hyperendemic Area of Zoonotic Transmission in Rio de Janeiro, Brazil.

Generally, older people tend to suffer from more severe infections than younger adults. In addition, there are accumulations of comorbidities and immune senescence in some cases. This cohort study evaluated the clinical and epidemiological characteristics of older adults (≥60 years old) with sporotrichosis. The cohort consisted of 911 patients with a median age of 67 years, most of whom were female (72.6%), white (62.1%), and afflicted with comorbidities (64.5%). The lymphocutaneous form occurred in 62% of the patients, followed by the fixed form (25.7%), cutaneous disseminated form (8.9%), and extracutaneous/disseminated forms (3.3%). In this study, we draw attention to the frequency of osteoarticular involvement (2.1%) secondary to skin lesions such as osteomyelitis and/or tenosynovitis. A clinical cure was achieved in 87.3% of cases. Itraconazole was used in 81.1% of cases, while terbinafine was used in 22.7% of cases, usually in low doses. Survival analysis showed that the median treatment time was 119 days, and the multiple Cox model demonstrated that the presentation of a black coloration and diabetes was associated with a longer treatment time required to establish a cure. Therefore, these subgroups should be monitored more closely to reduce possible difficulties during treatment. It would be interesting to conduct more studies analyzing older adults with sporotrichosis from different geographic areas to better comprehend the disease in this group.

Terbinafine Nanohybrid: Proposing a Hydrogel Carrying Nanoparticles for Topical Release.

A poloxamer 407 (P407)-Casein hydrogel was chosen to carry polycaprolactone nanoparticles carrying terbinafine (PCL-TBH-NP). In this study, terbinafine hydrochloride (TBH) was encapsulated into polycaprolactone (PCL) nanoparticles, which were further incorporated into a poloxamer-casein hydrogel in a different addition order to evaluate the effect of gel formation. Nanoparticles were prepared by the nanoprecipitation technique and characterized by evaluating their physicochemical characteristics and morphology. The nanoparticles had a mean diameter of 196.7 ± 0.7 nm, PDI of 0.07, negative ζ potential (-0.713 mV), high encapsulation efficiency (>98%), and did not show cytotoxic effects in primary human keratinocytes. PCL-NP modulated terbinafine was released in artificial sweat. Rheological properties were analyzed by temperature sweep tests at different addition orders of nanoparticles into hydrogel formation. The rheological behavior of nanohybrid hydrogels showed the influence of TBH-PCL nanoparticles addition in the mechanical properties of the hydrogel and a long-term release of the nanoparticles from it.

α-Cyclodextrin-based poly(pseudo)rotaxane for antifungal drug delivery to the vaginal mucosa.

This work aimed to evaluate poly(pseudo)rotaxanes (PPRs) potential for vaginal antifungal delivery. For this, PPRs containing terbinafine (TB) 2 % were obtained using two small surfactants, Kolliphor® RH40 and Gelucire® 48/16, and different α-cyclodextrin (α-CD) concentrations (5 and 10 %). PPRs were characterized by their physicochemical characteristics, irritation, and mucoadhesion capabilities. Formulations' performance was assessed in a vertical penetration model, which uses ex vivo entire porcine vagina. Conventional penetration experiments with excised vaginal tissue were performed as a control. Results showed all formulations were non-irritant according to the HET-CAM test. Furthermore, PPRs with 10 % αCD showed superior mucoadhesion (p < 0.05). Conventional horizontal penetration studies could not differentiate formulations (p > 0.05). However, PPRs with 10 % αCD presented a better performance in vertical ex vivo studies, achieving higher drug penetration into the vaginal mucosa (p < 0.05), which is probably related to the formulation's prolonged residence time. In addition, the antifungal activity of the formulations was maintained against Candida albicans and C. glabrata cultures. More importantly, the formulation's viscosity and drug delivery control had no negative impact on the antifungal activity. In conclusion, the best performance in a more realistic model evidenced the remarkable potential of PPRs for vaginal drug delivery.

What to expect when AGEP is induced by terbinafine? Case report and critical review of the literature.

BACKGROUND: Acute Generalised Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or subcorneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury, and allergens. OBJECTIVES AND METHODS: We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and SARS-CoV vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A PubMed search helped retrieve all terbinafine-induced AGEP case reports. AGEP-specific Sideroff criteria were analysed in terbinafine-induced cases and compared to other trigger causes. CONCLUSIONS: When the AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin for several weeks after exposure, even after discontinuation, and the disease severity may be potentialised by additional factors such as concomitant viral infections or vaccination.

Poly(pseudo)rotaxanes formed by mixed micelles and α-cyclodextrin enhance terbinafine nail permeation to deeper layers.

This work aimed to develop water-based formulations for onychomycosis topical treatment using micelles of small pegylated surfactants associated with α-cyclodextrin (αCD) to deliver terbinafine to the nail. Kolliphor® RH40 (RH40) and Gelucire® 48/16 (GEL) single and mixed micelles (RH40:GEL 1:1) were prepared. αCD was added to the surfactants dispersions to form poly(pseudo)rotaxanes (PPR). Formulations were characterized in terms of drug solubilization (3 to 34-fold increase), particle size (9-11 nm) and Z-potential (+0.3 - +1.96 mV), blood compatibility (non-hemolytic), rheological behavior (solid-like viscoelastic properties after 5-10% αCD addition), drug release and interaction with the nail plate. GEL micelles and surfactant-10% αCD PPRs notably hydrated the nail plate. The high viscosity of PPR led to a slower drug release, except for RH40:GEL +10% αCD that surprisingly released terbinafine faster. The RH40:GEL +10% αCD formulation delivered twice more amount of terbinafine to deeper regions of nail plate compared to other formulations. The results evidenced the potential of PPR formed by small pegylated surfactants as a water-based formulation for nail drug delivery.

Association between terbinafine hydrochloride and sperm DNA fragmentation - case report.

OBJECTIVE: To present the case of a man with normozoospermia and a high level of fragmented spermatozoa, which origin seems to be associated with long-term treatment with terbinafine hydrochloride. CASE DESCRIPTION: A 20-year-old male healthy patient, with no history of disease and addictions, used an antifungal (terbinafine hydrochloride) for one year to treat a toenail. During this treatment, he participated in a study to evaluate a method of sperm DNA fragmentation analysis. He had 99% fragmented sperm, primarily attributed to prolonged abstinence. The samples that were analyzed later indicated that the high fragmentation could be associated with the antifungal treatment and that with a 2-day abstinence and absence of treatment the fragmentation rate was again comparable with that of fertile men (15%). CONCLUSION: Terbinafine hydrochloride is likely to cause problems in male fertility, mainly affecting DNA sperm integrity. Further studies are needed to confirm this observation and to determine at what level of the genitourinary tract the alteration of DNA occurs.

Importance of Mevalonate Pathway Lipids on the Growth and Survival of Primary and Metastatic Gastric Carcinoma Cells.

PURPOSE: This preclinical study aims to determine the effect of drugs that alter isoprenoids and cholesterol metabolism in the homeostasis of gastric carcinoma cell lines in the search for new therapeutic targets for stomach cancer. MATERIALS AND METHODS: Primary (AGS) and metastatic (NCI-N87) gastric cancer cell lines were treated with simvastatin and terbinafine, two inhibitors of the mevalonate pathway, and avasimibe, an inhibitor of cholesterol esterification. Cell viability and growth were measured as well as cholesterol levels and the expression of the hydroxy methyl-glutaryl CoA reductase (HMGCR) and the LDL receptor (LDLR). RESULTS: Primary and metastatic gastric carcinoma cells show different sensitivity to drugs that affect isoprenoid synthesis and the metabolism and uptake of cholesterol. Isoprenoids are involved in the growth and viability of both types of cells, but the role of free and esterified cholesterol for metastatic gastric cell survival is not as evident as for primary gastric cancer cells. Differential expression of LDLR due to mevalonate pathway inhibition suggests variations in the regulation of cholesterol uptake between primary and metastatic cancer cells. CONCLUSION: These results indicate that at least for primary gastric cancer, statins and avasimibe are promising candidates as potential novel antitumor drugs that target the metabolism of isoprenoids and cholesterol of gastric tumors.

A Retrospective Study of Tinea Capitis Management in General Pediatric Clinics and Pediatric Emergency Departments at 2 US Centers.

We examine management practices of tinea capitis at 2 US academic centers. The majority of providers treated tinea capitis with the oral antifungal agent griseofulvin and did not obtain a fungal culture. We recommend newer antifungal treatments such as terbinafine and fluconazole and obtaining a fungal culture for effective treatment.

Toxicidad hepática inducida por terbinafina en el contexto de una pandemia por SARS-CoV-2: reporte de un caso

La terbinafina es un fármaco que puede inducir daño hepático agudo. Presentamos el caso de un paciente varón de 40 años que desarrolló disfunción hepática después de 35 días de tratamiento con terbinafina por onicomicosis. El estudio anátomo patológico demostró: hepatitis aguda en resolución, además de ductopenia y colestasis. Estos hallazgos, sin el antecedente de hepatitis viral o autoinmune, son consistentes con el diagnóstico de daño hepático inducido por drogas (DILI). En este reporte presentamos el primer caso en nuestro país de un paciente que es afectado por una enfermedad hepática aguda: injuria hepática inducida por terbinafina, al cual se le asoció posteriormente infección por SARS-CoV-2 en el contexto de una pandemia.

Terbinafine is a drug that can induce acute liver damage. We present the case of a 40-year-old male patient who developed liver dysfunction after 35 days of terbinafine treatment for onychomycosis. The anatomopathological study showed: acute hepatitis in resolution, in addition to ductopenia and cholestasis. These findings, without a history of viral or autoimmune hepatitis, are consistent with the diagnosis of drug-induced liver damage (DILI). In this report we present the first case in our country of a patient who is affected by an acute liver disease: terbinafine-induced liver injury, to which SARS-CoV-2 infection was later associated in the context of a pandemic.

Evaluation of activity and toxicity of combining clioquinol with ciclopirox and terbinafine in alternative models of dermatophytosis.

Dermatophytosis is a superficial fungal infection that affects humans and is very common in small animals. The treatment using the most commonly used antifungals is failing, and new therapeutic alternatives are required to combat the resistance of these fungal infections. Previous studies by the group have shown that clioquinol is an important therapeutic alternative in the treatment of dermatophytosis. The object was to conduct studies of antidermatophytic activity and the irritant potential from the double and triple combinations of clioquinol, terbinafine and ciclopirox in ex vivo and in vivo alternative models. To evaluate the irritant potential of antifungal combinations, the alternative HET-CAM method (chicken egg test chorioallantoic membrane) was used. Ex vivo models were used to assess the effectiveness of antifungal combinations, using pig hooves and veterinary fur. Any possible tissue damage was to assess through in histopathology of swine ears. HET-CAM results showed that all combinations can be classified as non-irritating, corroborated by the results of the histopathological evaluation of the pig's ear skin. Only the double combinations managed to remove 100% of the colony-forming units (CFU) formed on the pig's hooves. The clioquinol + terbinafine combination and the triple combination were more effective than clioquinol + ciclopirox in eradicating the preformed biofilm in fur of veterinary origin. These results show the potential of formulations of clioquinol in combination with antifungals for use in humans and in the veterinary field to combat dermatophytosis, as an important alternative therapy, for use in the near future.

First report of cutaneous mycetoma by Paecilomyces variotii and the successful treatment with combined itraconazole and terbinafine along with resection surgeries.

Mycetoma is a progressively mutilating infectious disease of the subcutaneous tissue that affects the skin and deep structures, which is poorly responsive to chemotherapy. Here, we report a skin mycetoma caused by Paecilomyces variotii, an uncommon fungus of human infections, and the therapeutic approach that resulted in a complete cure of the patient.

Chromoblastomycosis caused by Fonsecaea monophora in Mexico.

Chromoblastomycosis is a chronic subcutaneous fungal infection caused by melanized fungi. It is usually an occupational mycosis affecting people in rural areas in tropical and subtropical regions. We present two cases of chromoblastomycosis in Mexican farmers, characterized by skin verrucous plaques. Direct examination with KOH 10% showed the presence of muriform cells. The fungal isolation was carried out in Sabouraud dextrose agar and molecular identification was achieved by 18S-ITS1-5.8S-ITS2-28S rRNA gene amplification and sequencing. Fonsecaeamonophora was identified in both cases. A therapy with itraconazole and terbinafine was used with a partial favorable response. However, patients did not return for medical examination after 4 months. The current status of the patients is unknown. We reported the first two cases of chromoblastomycosis caused by F. monophora in Mexico.

Actividad combinada de itraconazol y terbinafina sobre aislamientos clínicos de Neoscytalidium dimidiatum / Combined activity of Itraconazole and Terbinafine over clinical isolates of Neoscytalidium dimidiatum

Resumen Objetivo: Analizar la susceptibilidad de N. dimidiatum ante el efecto combinado de itraconazol y terbinafina. Métodos: Se determinó la concentración mínima inhibitoria y la concentración inhibitoria fraccionada in vitro, mediante el método del tablero de ajedrez, a 15 aislamientos clínicos provenientes de onicomicosis de diferentes pacientes, todos positivos por N. dimidiatum. Se prepararon ensayos por duplicado con diluciones combinadas de los antifúngicos y se evaluó el efecto de ambos fármacos. Resultados: La concentración mínima inhibitoria promedio de solo itraconazol aplicado a los aislamientos fue de 30,83 μg/mL y de 4,49 μg/mL combinado con terbinafina. La concentración mínima inhibitoria promedio de solo terbinafina fue de 0,33 μg/mL y de 0,07 μg/mL combinada con itraconazol. Hay diferencias estadísticamente significativas entre las concentraciones mínimas inhibitorias promedio de los antifúngicos analizados en solitario respecto de las concentraciones mínimas inhibitorias combinadas; para itraconazol (t = 2,958; gl = 14; p = 0,01) y (t = 4,721; gl = 14; p < 0,001) para terbinafina. El uso combinado evidenció 40 % de sinergismo. Conclusiones: La combinación itraconazol-terbinafina presentó un efecto sinérgico total para inhibir el crecimiento de N. dimidiatum; esto ofrece una alternativa terapéutica en el tratamiento de las onicomicosis.

Abstract Aim: Study the combined susceptibility patterns of Neoscytalidium dimidiatum to the effect of Itraconazole and Terbinafine. Background: The Minimum Inhibitory Concentration and Fractional Inhibitory Concentration were determined in vitro by the chessboard method for 15 clinical isolates of onychomycosis, from different patients, all positives for N. dimidiatum. Duplicated trials were prepared with combined dilutions of antifungals and the effect of both drugs was evaluated. Results: The average Minimum Inhibitory Concentration of Itraconazole when applied alone for the isolates was 30.83 μg/mL and 4.49 μg/mL when combined with Terbinafine. The average Minimum Inhibitory Concentration of Terbinafine alone was 0.33 μg/mL and 0.07 μg/mL when combined with Itraconazole. Statistically significant differences were found between the average Minimum Inhibitory Concentrations of the antifungals analyzed alone versus the Minimum Inhibitory Concentrations obtained by mixing both compounds. That is for Itraconazole (t = 2,958; gl = 14; p = 0,01) and (t = 4,721; gl = 14; p <0,001) for Terbinafine. Combined use showed 40 % synergism. Conclusions: The Itraconazole-Terbinafine combination had synergistic effect to inhibit the growth of N. dimidiatum, which offers a therapeutic alternative in the treatment of onychomycoses caused by this fungus.

[Tinea capitis: clinical features and therapeutic alternatives]. / Tinea capitis: aspectos clínicos y alternativas terapéuticas.

A descriptive observational and cross-sectional study was carried out. The clinical characteristics, etiologic agents, treatments and outcome of 33 cases of tinea capitis in the Mycology Unit at Francisco J. Muñiz Hospital of Buenos Aires City between January 2015 and December 2019 were analyzed. The median age of the patients was 7 years, 21 of whom were male, 3 were HIV-positive and 22 had pets. The isolated etiologic agents were the following: Microsporum canis in 22 cases, Trichophyton tonsurans in 8, Nannizzia gypsea in 2 and Trichophyton mentagrophytes in one patient. Suppurative tinea capitis (krion Celsi) was detected in 10 cases and the same number of patients presented other skin locations of their dermatophytosis in addition to those in the scalp. Twenty-one cases were orally treated with griseofulvin and 12 with terbinafine. Those patients with suppurative tinea capitis received drops of betamethasone by mouth besides the antifungal drugs. All patients had good clinical and mycological response to the treatments, all lesions disappeared, and mycological studies turned negative by the end of the treatments. We conclude that both drugs were effective for the treatment of tinea capitis; however, lesions in those cases receiving terbinafine involuted more slowly.

Atypical chlamydoconidium-producing Trichophyton tonsurans strains from Ceará State, Northeast Brazil: investigation of taxonomy by phylogenetic analysis and biofilm susceptibility.

Chlamydoconidium-producing Trichophyton tonsurans strains isolated in Northeastern Brazil have morphological features different from the classic description of this dermatophyte species. This study investigated the phylogenetic relationship of chlamydoconidium-producing T. tonsurans strains isolated in Northeastern Brazil. Also, the effect of terbinafine and farnesol on mature biofilms of T. tonsurans strains was evaluated. The mass spectra of T. tonsurans strains were investigated by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The ITS and LSU loci regions of rDNA and the partial ß-tubulin gene were sequenced and the phylogenetic tree was analysed. The effects of terbinafine and farnesol on mature T. tonsurans biofilms were evaluated through the analysis of metabolic activity, quantification of biomass and observation by scanning electron microscopy. MALDI-TOF MS spectra of the chlamydoconidium-producing T. tonsurans strains differed from the spectrum of the control strain (ATCC 28942), presenting an intense ion peak at m/z 4155 Da. Phylogenetic tree analysis showed that the chlamydoconidium-producing strains isolated in Northeastern Brazil are allocated to a single cluster, differing from strains isolated from other countries. As for mature T. tonsurans biofilms, farnesol reduced biomass and metabolic activity by 64.4 and 65.9 %, respectively, while terbinafine reduced the biomass by 66.5 % and the metabolic activity by 69 %. Atypical morphological characteristics presented by chlamydoconidium-producing T. tonsurans strains result from phenotypic plasticity, possibly for adaptation to environmental stressors. Also, farnesol had inhibitory activity against T. tonsurans biofilms, demonstrating this substance can be explored for development of promising anti-biofilm drugs against dermatophytes.

Potentiation of antifungal activity of terbinafine by dihydrojasmone and terpinolene against dermatophytes.

Dermatophytoses are infections that affect keratinized tissues. Their main etiologic agents are fungi of the genera Microsporum and Trichophyton. The emergence of resistant fungi and the clinical relevance of dermatophytosis have encouraged studies that aim to increase the arsenal of drugs or act on mechanisms that confer multiple drug resistance. This study investigated the modulating activity of terbinafine promoted by dihydrojasmone and terpinolene against Microsporum canis LM 216, Trichophyton interdigitale H6 and T. interdigitale Δmdr2. The minimum inhibitory concentration (MIC) of test drugs was determined by broth microdilution. The effect of the drugs tested on plasma membrane functionality was analysed. Terbinafine MIC was determined in sub-inhibitory concentrations of monoterpenes. Finally, it was performed an association study with terbinafine and monoterpenes. Dihydrojasmone presented lower MIC values than terpinolene. All fungi were sensitive to terbinafine, starting at 1 µg ml-1 . All tested drugs increased K+ release (P < 0·05), affecting the functionality of the plasma membrane. Dihydrojasmone modulated the sensitivity of all strains against terbinafine, and terpinolene modulated the sensitivity of M. canis LM 216 and T. interdigitale Δmdr2. The monoterpenes and terbinafine drug associations presented synergism. In conclusion, the results suggest that the dihydrojasmone and terpinolene are promising antifungal agents that potentiate the antifungal activity of terbinafine against dermatophytes.