Topical metronidazole combination therapy in the clinical management of rosacea

Metronidazole was the first topical agent approved by the U.S. Food and Drug Administration for the treatment of rosacea. Several controlled studies have confirmed the efficacy and safety of topical metronidazole 0.75% gel, lotion and cream and 1% cream for rosacea. At present, little data exists regarding the use of combination topical therapy in rosacea management, although anecdotal evidence and preliminary studies suggest at least some additive benefit when topical metronidazole is used in combination with sulfacetamide 10% /sulfur 5%. In this paper, the results of observational experience evaluating topical metronidazole 0.75% gel used in combination with other topical rosacea therapies and/or subantimicrobial dose doxycycline are reported.     

Metronidazole in the treatment of rosacea: do formulation, dosing, and concentration matter?

BACKGROUND: Topical metronidazole is commonly used in the management of rosacea. No consensus on the optimal formulation, concentration, or dosing regimen exists. PURPOSE: To assess the relative efficacy of metronidazole cream, gel, and lotion at concentrations of 0.75% and 1%, in dosing regimens of once and twice daily. METHODS: A meta-analysis of published metronidazole efficacy rates was performed. RESULTS: In non-weighted analysis, the mean efficacy was 28.2% (95% confidence interval [CI], 22.0%-34.4%) for the cream, 38.4% (95% CI, 18.4%-58.4%) for the gel, and 35% for the lotion. Confidence intervals for QD versus BID dosing and 0.75% versus 1% concentrations also overlapped. In weighted analysis, the mean reduction was 31.3% for the cream, 22.1% for the gel, and 35% for the lotion. CONCLUSIONS: Metronidazole cream, gel, and lotion vehicles have similar efficacies. There were no substantial differences between concentrations of 0.75% and 1%, or between once daily and twice daily regimens.     

Optimal management of papulopustular rosacea: rationale for combination therapy

The pathophysiology of papulopustular rosacea (PPR) is primarily characterized by inflammation associated with several factors such as abnormal innate immune response, neurovascular dysregulation, stratum corneum barrier dysfunction, and depletion of antioxidant reserve, with no definitive evidence supporting an underlying microbial etiology. Several molecular inflammatory pathways have now been identified that enable the development of therapeutic agents that target the signs and symptoms of disease by modifying specific pathophysiological mechanisms. Available evidence demonstrates that topical and oral agents commonly used to treat PPR appear to modify some of these pathophysiological mechanisms and may prove to be complimentary when used in combination potentially leading to better therapeutic outcomes. During the past two decades, six clinical studies have been published on the benefits of combining oral and topical therapies for PPR. Four studies suggest that doxycycline, including anti-inflammatory dose doxycycline (doxycycline 40 mg modified-release capsule once daily) can be combined with topical metronidazole or azelaic acid in patients with PPR to achieve more rapid control of a flare. At present, subantimicrobial dosing of a tetracycline agent that also maintains anti-inflammatory activity has only been established with doxycycline. Although antibiotic doses of tetracycline agents (such as doxycycline, minocycline, and tetracycline) are known to be effective for PPR, the use of subantimicrobial dosing of doxycycline avoids the risk of antibiotic resistance.     

Combined effect of anti-inflammatory dose doxycycline (40-mg doxycycline, usp monohydrate controlled-release capsules) and metronidazole topical gel 1% in the treatment of rosacea

Research into the pathophysiology of rosacea suggests a central role for inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). Effective treatments for rosacea, including topical metronidazole and systemic antibiotics, have anti-inflammatory activity, which may be more important than their antimicrobial activity in this setting. Phase III studies have substantiated the efficacy of anti-inflammatory dose doxycycline (40-mg doxycycline monohydrate controlled-release capsules) administered once daily for the treatment of inflammatory lesions of rosacea. Results of a 16-week, randomized, double-blind, placebo-controlled study of anti-inflammatory dose doxycycline plus topical metronidazole gel 1% for mild to moderate rosacea are presented here. At week 12, metronidazole was discontinued and patients continued on either placebo or doxycycline. Combination therapy significantly reduced inflammatory lesion counts as early as week 4 and through week 12 compared to topical metronidazole 1% gel monotherapy. The combined therapy appeared effective and well-tolerated.     

Evaluation of mechanical and rheological properties of metronidazole gel as local delivery system

Rosacea is a chronic multifactorial vascular skin disorder that affects about 10 percent of the general population. Metronidazole is an effective antibiotic in the treatment of moderate-tosevere rosacea. Metronidazole is a suitable drug in cases of resistance to tetracycline or erythromycin, but it has also been shown that oral metronidazole may increase the side effects (e.g., peripheral neuropathy). Oral metronidazole should not be used for more than three months, and hence topical metronidazole gel is the best therapeutic choice in rosacea (especially during pregnancy). This study examined the mechanical (adhesiveness, cohesiveness, extrudability, spreadability, homogeneity) and rheological (viscosity), skin irritant and drug release properties of different metronidazole gel formulations that contain anionic emulsifying wax, glycerin and lactic acid in different proportions. The release studies were conducted using Franz diffusion cells and Silastic membrane as a barrier. The results indicated that gel compressibility, hardness, and adhesiveness, are the factors that influence the ease of gel removal from the container, ease of gel application onto the mucosal membrane, and gel bioadhesion. The findings showed that there exists a strong negative correlation between the spreadability of a formulation and its cohesiveness, the spreadability of a formulation is inversely proportional to its cohesiveness. However, sorbitol solution (70%) concentration was not significantly correlated with drug release. In addition, drug release was significantly reduced as the concentration of anionic emulsifying wax increased and the concentration of lactic acid decreased. The maximum metronidazole release was achieved at a pH of 4–6. Data obtained from in vitro release studies were fitted to various kinetic models and high correlation was obtained in the Higuchi and first order models. The results showed that all the gel formulations showed good extrudability, viscosity, cohesiveness, homogeneity and spreadability.     

Topical metronidazole: a new therapy for rosacea

The chemistry, mechanism of action, pharmacokinetics, and adverse effects of topically applied metronidazole are reviewed, and the drug's use and efficacy in the treatment of rosacea and other conditions are discussed. Metronidazole is a synthetic, nitroimidazole-derivative antibacterial and antiprotozoal agent. For topical use, metronidazole is available in the United States as an aqueous gel. Polar reduction products of the drug appear to be responsible for its antimicrobial effects, which include disruption of DNA. The mechanism by which metronidazole ameliorates the lesions and erythema of rosacea may be related to anti-inflammatory or immunosuppressive actions of the drug rather than to suppression of skin bacteria. Metronidazole does not seem to be appreciably absorbed after topical application to the skin. Little is known about the distribution and elimination of topically applied metronidazole. Topical metronidazole has been designated an orphan drug by the FDA for the treatment of rosacea. In clinical studies metronidazole 0.75% topical gel or 1% cream resulted in improvement in inflammatory lesions in 68-96% of patients. Like other currently available therapies, metronidazole is only palliative; when the drug is withdrawn, symptoms commonly recur. Topical metronidazole has been used with some success in the treatment of decubitus and other ulcers and in certain dental conditions. The drug seems to have low toxicity and generally is well tolerated when applied topically. The principal adverse effects are local reactions, such as burning and stinging. Topical metronidazole provides another option for the treatment of rosacea.     

Medical treatment of rosacea with emphasis on topical therapies

Due to the development and release of newer topical formulations, the diagnosis and treatment of rosacea has received renewed attention over the past 3-5 years both in the literature and at medical symposia. Rosacea is a very common facial dermatosis. In the US, rosacea is estimated to affect > 14 million people, predominantly adults with approximately 60% of cases diagnosed before the age of 50. A frustrating aspect of the disease is its inherent chronicity punctuated with periods of exacerbation and relative remission. A variety of subtypes have been identified which correlate with clinical presentation. Although the pathogenesis of rosacea is poorly understood, multiple topical agents are available. The efficacy of topical therapy for rosacea relates primarily to reduction in inflammatory lesions (papules, pustules), decreased intensity of erythema, a reduction in the number and intensity of flares and amelioration of symptoms, which may include stinging, pruritus and burning. The list of main topical agents utilised for the treatment of rosacea include metronidazole, sulfacetamide-sulfur, azelaic acid and topical antibiotics (clindamycin, erythromycin). Depending on the severity at initial presentation, topical therapy may be combined with systemic antibiotic therapy (e.g., oral tetracycline derivative). Newer therapeutic choices primarily involve improved vehicle formulations, which demonstrate favourable skin tolerability and cosmetic elegance.     

Oxymetazoline hydrochloride cream for facial erythema associated with rosacea

Introduction: Rosacea is a chronic skin condition characterized by transient and persistent erythema of the central face. The symptom of persistent erythema can be particularly frustrating for both patients and physicians as it is difficult to treat.

Areas covered: Current treatment options for the treatment of rosacea include metronidazole, azelaic acid, sodium sulfacetamide-sulfur, and brimonidine. Until recently, brimonidine gel was the only option approved specifically for the treatment of facial erythema. However, oxymetazoline hydrochloride 1% cream is a newly FDA approved topical medication for adult rosacea patients. A primarily alpha-1a agonist, oxymetazoline hydrochloride (HCl) is thought to diminish erythema through vasoconstriction. Our paper seeks to evaluate evidence for topical oxymetazoline HCl with respect to its efficacy and safety for its approved indication of treating the persistent erythema associated with rosacea.

Expert commentary: While assessment of available clinical trial data indicates that the medication is as effective as other available treatment for controlling rosacea-associated erythema with minimal risk of adverse effects, studies of long-term duration and direct comparison will be necessary to establish its place in treatment guidelines and clinical practice. As further evidence becomes available, the real-world clinical potential of topical oxymetazoline cream will become clearer.     

Rosacea: where are we now?

Advances continue to be made in the classification and treatment of rosacea, a chronic dermatologic syndrome. A new empiric classification system identifies 4 rosacea subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) that may aid in more precise diagnosis. Several new therapies have recently been approved for treatment of rosacea. Azelaic acid 15% gel is a new first-tier topical agent proven effective in reducing inflammatory lesions and erythema. New formulations of metronidazole and sulfacetamide 10%/sulfur 5% that offer cosmetic or tolerability advantages are now available. Intense pulsed light therapy has demonstrated effectiveness in reducing flushing, erythema, and telangiectases, with greater tolerability than existing laser systems. Other treatments under investigation include low-dose doxycycline hyclate (which may provide greater safety than existing oral antibiotics), benzoyl peroxide/clindamycin gel, and tacrolimus ointment (for steroid-induced rosacea). With this expanded armamentarium of medical and light-based therapies, clinicians can now implement a multifaceted approach to treatment, crafting new treatment combinations to address the unique and evolving features of rosacea in each individual patient.     

Gel vehicles are not inherently more irritating than creams

BACKGROUND: It has been thought that topical gels are inherently more irritating than topical creams. Nevertheless, the irritancies of topical products are potentially quite variable, and a priori assumptions about relative irritancy of gels versus creams may not be accurate. PURPOSE: To determine whether a metronidazole gel formulation is more or less irritating to the skin compared to metronidazole creams. METHODS: A total of 32 normal, healthy volunteers were tested using irritancy patches with 0.75% metronidazole gel and cream, 1% metronidazole cream, and petrolatum (used as the "negative control"). Blinded observers evaluated the application sites for signs of irritancy. A numerical score was assigned to these irritancy patch sites each day for 21 days, or until significant irritation developed, and cumulative irritancy scores were calculated for the study period. A mixed model of variance analysis was performed. RESULTS: After 21 days of evaluation, analysis of the mean cumulative irritancy scores for each of the agents used showed there to be no statistical difference in irritancy potential between the metronidazole gel and the metronidazole creams. However, the 1% metronidazole cream was significantly more irritating than petrolatum. CONCLUSION: There was no significant difference in the cumulative irritancy potential of cream and gel preparations of metronidazole. The irritancy of topical formulations for treating rosacea should be considered on a case by case basis.     

Diagnosis and treatment of rosacea: state of the art

Rosacea is a common disorder that is both under recognized and undertreated. Prevalence figures indicate that it may be present in 1 of every 10 adults in a primary care waiting room. Untreated, patients with rosacea can suffer significant emotional, workplace, and social impairments. While rosacea has been recognized since ancient times, only recently have investigators begun to identify the pathophysiologic elements responsible for the characteristic erythema, flushing, dysesthesias, and papulopustular manifestations of the disease. Although the etiology of rosacea is unclear, inflammation appears to be a central element. Experimental evidence suggests that abnormalities of the skin's innate and adaptive immune responses may play pivotal roles. Once recognized, effective topical and systemic therapies can be prescribed to lessen the impact of the disease on the patient's life. Although initially administered in an empiric fashion, it now seems clear that the role of antibiotics in patients with rosacea depends upon their anti-inflammatory rather than their antimicrobial properties. Consequently, practitioners have the opportunity to practice good antibiotic stewardship when treating the disease, particularly with systemic therapies. Therapy with subantimicrobial dosing and with topical treatments can modulate the inflammation of rosacea without exerting antibiotic pressure responsible for the emergence of antibiotic resistance.     

Azelaic acid 15% gel in the treatment of rosacea

Rosacea represents a chronic inflammatory dermatosis of uncertain pathophysiology. There are several associated risk factors and the need for long-term treatment is well recognized. This diverse disease is frequently difficult to manage and has a significant impact on quality of life. There are several topical and oral treatments available, of which azelaic acid 15% gel (Finacea) is the first new treatment for rosacea in more than a decade. Azelaic acid per se has multiple modes of action in rosacea, but an anti-inflammatory effect achieved by reducing reactive oxygen species appears to be the main pharmacological action. Clinical studies have shown that azelaic acid 15% gel is an effective and safe first-line topical therapeutic option in patients with mild-to-moderate papulopustular rosacea. Significant continuous improvement in the number of inflammatory lesions and in erythema has been shown over a period of 15 weeks. Adverse effects associated with azelaic acid 15% gel are mostly mild or transient and do not usually necessitate discontinuation of therapy.     

Cumulative irritation potential of metronidazole gel compared to azelaic acid gel after repeated applications to healthy skin

BACKGROUND: Metronidazole 0.75% gel and azelaic acid 15% gel are commonly used to treat rosacea. Irritation is a common side effect. OBJECTIVE: To assess the cumulative irritation potential of metronidazole 0.75% gel and azelaic acid 15% gel. METHODS: Metronidazole 0.75% gel, azelaic acid 15% gel, and a white petrolatum negative control were applied under occlusive conditions to the upper back of a total of 33 healthy subjects. There were twelve 24-hour applications (4 times a week) and three 72-hour applications on weekends during a 3-week period. Skin reactions (erythema score +/- other local reaction) were assessed within 15 to 30 minutes of removal of the products. RESULTS: The mean cumulative irritancy index of metronidazole 0.75% gel was significantly lower than that of azelaic acid 15% gel and not significantly higher than the negative control product. There was increasing cumulative irritancy with azelaic acid; no cumulative irritancy was seen for either metronidazole or white petrolatum. CONCLUSION: Metronidazole 0.75% gel is less irritating in sustained use than azelaic acid 15% gel.     

Pharmacokinetics and therapeutic efficacy of metronidazole at different dosages.

Metronidazole, a drug effective against certain protozoal and anaerobic infections, was given female patients with Trichomoniasis urogenitalis. Group I received twice daily 250 mg of metronidazole (supplied as 250 mg tablets Vagimid). Group II received in a single dose 1.0 g (4 tablets); and group III, 2.0 g (8 tablets). Serum and urine metronidazole levels were measured polarographically. Kinetic parameters were determined from the measured values of the concentration time curve by a computing program. An exact control of the therapeutic result was carried out. In all patients peak serum levels occurred within 1-3 hr and averaged 5.1 +/- 1.7 microgram/ml after 250 mg doses, 19.6 +/- 3.8 microgram/ml after 1.0 g doses and 40.6 +/- 9.3 microgram/ml after 2.0 g doses. About 35% of the administered dose was recovered in the urine in 12 hr and about 50% in 24 hr. Metronidazole shows protein binding of 10-20% equally in vivo and in vitro. Minimum trichomonacidic concentrations of nearly 1 microgram/ml were still present 12 hr after oral application of 250 mg metronidazole, and 24 hr to 36 hr, respectively after 1.0 g and 2.0 g daily doses. The cure rate was 100%. No serious side effects ocurred in any of the patients.     

Update on rosacea and anti-inflammatory-dose doxycycline

Approximately 13 million individuals in the United Sates suffer from rosacea, a recurrent disease that may require long-term therapy. Topical and oral antibiotics have been used to treat rosacea; however, high-dose antibiotics or long-term, low-dose antibiotics commonly used for the treatment of rosacea flares or for rosacea maintenance therapy, respectively, can lead to the development of antibiotic-resistant organisms. The first oral medication approved by the U.S. Food and Drug Administration for the treatment of rosacea in the United States is Oracea (CollaGenex Pharmaceuticals Inc., Newtown, PA, USA). Oracea is a 40 mg capsule of doxycycline monohydrate, containing 30 mg immediate-release and 10 mg delayed-release doxycycline beads ("anti-inflammatory-dose doxycycline"). Anti-inflammatory-dose doxycycline is not an antibiotic and does not lead to the development of antibiotic-resistant organisms. Each capsule of anti-inflammatory-dose doxycycline contains a total of 40 mg of anhydrous doxycycline as 30 mg of immediate-release and 10 mg of delayed-release beads. In contrast to other oral therapies, anti-inflammatory-dose doxycycline is taken once daily, which may increase treatment compliance. The results of two phase III trials have been encouraging, leading to the recent release (summer 2006) of Oracea for the treatment of rosacea in the United States. Anti-inflammatory-dose doxycycline should not be used by individuals with known hypersensitivity to tetracyclines or increased photosensitivity, or by pregnant or nursing women (anti-inflammatory-dose doxycycline is a pregnancy category-D medication). The risk of permanent teeth discoloration and decreased bone growth rate make anti-inflammatory-dose doxycycline contraindicated in infants and children. However, when used appropriately in patients with rosacea, anti-inflammatory-dose doxycycline may help prolong the effectiveness and life span of our most precious antibiotics.     

甲硝唑凝胶治疗中、重度酒渣鼻随机双盲、安慰剂对照临床试验

目的 :评价 0 .75 %甲硝唑凝胶治疗中、重度酒渣鼻的临床疗效和安全性。方法 :采用随机、双盲、安慰剂对照方法 ;病人在皮损区域局部外用0 .75 %甲硝唑凝胶或安慰剂 ,每日 2次 ,疗程 12wk。结果 :可分析病例 6 2例 ,其中甲硝唑组 31例 ,安慰剂组 31例。治疗后炎性损害百分数 ,甲硝唑组与安慰剂组在wk 4时分别为 (2 9± 38) %vs (1±83) % (P >0 .0 5 ) ,wk 8时为 (49± 5 1) %vs (3±83) % (P <0 .0 5 ) ,wk 12时为 (5 6± 4 2 ) %vs (2 1± 4 8) % (P <0 .0 1)。wk 12时红斑消失甲硝唑组和安慰剂组分别为 8%和 4 % ,2组比较差异无显著意义 (P >0 .0 5 )。用药后局部刺激反应 ,甲硝唑组为 2 9% ,安慰剂组为 2 3% ,均为轻、中度 ,2组比较差异无显著意义 (P >0 .0 5 )。结论 :0 .75 %甲硝唑凝胶治疗中、重度酒渣鼻的疗效肯定 ,安全性高     

Assessment of skin barrier function in rosacea patients with a novel 1% metronidazole gel

The skin of patients with rosacea is extremely sensitive and hyper-reactive to dietary, environmental, and topical factors. Accordingly, the management of rosacea involves not only choosing appropriate medication and treatment for daily skin care, but also avoiding known trigger factors. Recently, 1% metronidazole, a mainstay of topical rosacea therapy, was reformulated in a gel vehicle that contains hydrosolubilizing agents (HSA) niacinamide, beta cyclodextrin, and a low concentration of propylene glycol. It is designed to solubilize greater concentrations of metronidazole than is possible in water alone while reducing the potential for irritation and barrier disruption. A 2-week study was undertaken by the author to evaluate the effect of the new 1% metronidazole gel on the skin barrier in 25 women with mild to moderate rosacea. Statistically significant improvement in disease severity, erythema, desquamation, and skin irritation was noted by the investigator by the end of week 1, which continued throughout the study. After 2 weeks, subjects noted improvements in skin condition and rosacea. Results of noninvasive assessments showed no disruption of the skin barrier. Furthermore, there was an increasing trend in skin hydration that approached statistical significance.     

Ivermectin 1% (CD5024) for the treatment of rosacea

Introduction: Rosacea is a chronic and recurrent disease with a variety of cutaneous manifestations. The disorder is a centrofacial inflammatory dermatosis with significant financial, physical and psychological impacts. There are a number of topical, oral and systemic treatments available. Yet, treatment for rosacea remains difficult. The multifactorial nature of the disease combined with an incomplete understanding of the pathophysiology is challenging for providers and patients.

Areas covered: This article provides an in-depth review of rosacea treatment and emerging use of ivermectin 1% cream for papulopustular rosacea based on multiple clinical trials. The PubMed database was searched using the combination of keywords "ivermectin, rosacea, and papulopustular."

Expert opinion: Topical ivermectin 1% cream has emerged as a novel agent for treatment of papulopustular rosacea. The drug targets the Demodex mite which is increased in patients with rosacea. Though ivermectin 1% is a clinically efficacious medication, poor adherence continues to remain an issue due to topical application. Ultimately, the agent has the potential to be an effective drug when used as a single or combination agent. With the move to limit chronic antibiotic use, topical agents such as ivermectin 1% will continue to thrive as a specialized niche in the rosacea market.     

Common and alternate oral antibiotic therapies for acne vulgaris: a review

Acne vulgaris is an extremely common disorder affecting many adolescents and adults throughout their lifetimes. The pathogenesis of acne is multifactorial and is thought to involve excess sebum, follicular hyperkeratinization, bacterial colonization, and inflammation. Many therapeutic options exist for treating acne, including topical benzoyl peroxide, topical and oral antibiotics, topical and oral retinoids, and oral contraceptives. Oral antibiotics have been a mainstay in the treatment of acne for decades and function by exerting an antibacterial effect by reducing the follicular colonization of Propionibacterium acnes. Systemic antibiotics also have anti-inflammatory and immunomodulatory properties. This article reviews the English language literature on the efficacy of various systemic antibiotics for treating acne vulgaris, including second-line and less historically used medications. We discuss the tetracyclines, including subantimicrobial dose doxycycline, macrolides (notably azithromycin), trimethoprim-sulfamethoxazole, cephalosporins, and fluoroquinolones as treatment options for acne vulgaris.     

Terbinafine. An update of its use in superficial mycoses.

Terbinafine is an allylamine antifungal agent which has fungicidal activity against a wide variety of dermatophytes, moulds and certain dimorphic fungi, and fungistatic activity against Candida albicans. Oral terbinafine 250 mg/day is effective in the treatment of superficial dermatophyte infections such as onychomycosis, tinea pedis and tinea corporis/cruris, generally achieving mycological cure in > 80% of patients. The drug is also effective in children with tinea capitis when administered orally in the dosage range 62.5 to 250 mg/day for 4 weeks. Comparative data indicate that oral terbinafine is more effective than continuous or intermittent intraconazole in dermatophyte onychomycosis, and is as effective as itraconazole 400 mg/day in tinea pedis. The drug has shown greater efficacy than griseofulvin in dermatophyte onychomycosis, tinea pedis and tinea corporis/cruris, and comparable efficacy in children with tinea capitis. Additionally, oral terbinafine is more effective than ketoconazole 200 mg/day in tinea corporis/cruris. Topical terbinafine 1% formulations are effective when applied once or twice daily for up to 2 weeks, achieving mycological cure in > 80% of patients with tinea pedis, tinea corporis/cruris, cutaneous candidiasis and pityriasis versicolor. Its formulations are at least as effective as miconazole 2% cream and naftifine 1% gel in tinea pedis, and more effective than clotrimazole 1% cream, bifonazole 1% cream and oxiconazole 1% lotion. Mycological cure rates achieved with terbinafine generally improve after treatment cessation, reflecting the drug's fungicidal mechanism of action and its residual effect in tissue. Terbinafine is well tolerated after oral or topical administration and has a relatively low potential for drug interactions. Pharmacoeconomic data support the use of terbinafine in dermatophyte infections of the skin or nails. CONCLUSIONS: Evidence suggests that oral terbinafine is the treatment of choice for dermatophyte onychomycosis, as it achieves high rates of mycological and clinical cure, is generally well tolerated and has a relatively low potential for drug interactions. It must also be considered a first-line treatment option, along with itraconazole, in cutaneous mycoses which warrant systemic treatment; topical terbinafine is a treatment of choice in less extensive mycoses. The use of terbinafine in non-dermatophyte or mixed infections has not been fully defined.