Oral Terbinafine Research Articles

Current Management of Onychomycosis and Dermatomycoses.

Three newer oral antifungal agents, itraconazole, terbinafine and fluconazole, have revolutionized treatment of superficial mycoses. The tissue pharmacokinetics of itraconazole and terbinafine allow much shorter courses of therapy- with higher efficacy-in the treatment of onychomycosis, compared to other oral agents. Itraconazole pulse dosing and terbinafine daily dosing have shown comparable efficacy against dermatophyte onychomycosis; similar itraconazole regimens have been effective against nondermatophyte infections. Refractory clinical patterns of nail disease appear to be more responsive to oral antifungal therapy when combined with adjunctive therapy, such as debridement. These agents are effective against cutaneous dermatophytosis, with shorter treatment regimens. Tinea versicolor may be treated with a single-dose, intermittent, or daily regimen of an oral azole agent, depending on the drug selected. These newer oral antifungal agents have been proven effective against tinea capitis; effective regimens are shorter than those for griseofulvin. The safety profile of these newer agents has been very favorable.

New antifungal agents and preparations

In neutropenic patients amphotericin B remains the drug of choice for the treatment of systemic fungal infections. On the basis of a superior efficacy in combination with a lower toxicity, the triazoles have superseded the older azoles. Regularly, amphotericin B and a triazole are used simultaneously without any evidence from clinical trials that such a strategy is safe and efficacious. Liposomal preparation, lipid complex or colloidal dispersion of amphotericin B have been produced successfully to reduce toxicity. However, there is only one small randomised study that hints at the superiority of liposomal amphotericin B over amphotericin B deoxycholate. Promising new agents like candins, sordarins, high dose oral terbinafine, the third generation azoles, and liposomal nystatin are under development. The first phase II study on voriconazole in the treatment of pulmonary aspergillosis has produced encouraging results. The major promise of the new candins lies in the activity against Candida species, including those resistant to the azoles and polyenes, and in a mechanism of action totally different from the established antifungals. Cytokines and colony stimulating factors are theoretically very promising but there are no clinical studies that warrant routine use.

Oral terbinafine treatment for toenail onychomycosis: follow-up after 5-6 years

Oral terbinafine treatment for toenail onychomycosis: follow-up after 5-6 years

Oral griseofulvin remains the treatment of choice for tinea capitis in children.

Tinea capitis is one of the most common infections of children. The standard treatment is griseofulvin. Itraconazole and terbinafine have in large part replaced griseofulvin in the treatment of onychomycosis and, in addition to fluconazole and ketoconazole, are evolving treatments for tinea capitis. The purpose of this review is to compare the efficacy, safety, and cost of oral antifungal agents for tinea capitis. Small, open-label studies of itraconazole, terbinafine, and fluconazole have reported encouraging results, suggesting that these drugs may be effective alternatives to griseofulvin; however, in large controlled studies griseofulvin continues to exhibit greater or equal efficacy. Ketoconazole appears to be the least efficacious. All five drugs appear relatively safe, however, only griseofulvin has a long track record of safety, is Food and Drug Administration (FDA) approved for the treatment of tinea capitis in children, and has the least known drug interactions. Fluconazole is FDA approved for use in children more than 6 months of age, yet not for the treatment of tinea capitis. Oral griseofulvin and terbinafine tablets are the least expensive of the antifungal agents; griseofulvin suspension is, however, more expensive than fluconazole suspension. For the combined reasons of efficacy, safety, and cost, and a long track record of use, we feel oral griseofulvin is still the present treatment of choice for tinea capitis. Newer antifungals are currently under investigation, and their role in treating tinea capitis in children is still being defined.

A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis.

The newer antifungal agents itraconazole, terbinafine and fluconazole have become available to treat onychomycosis over the last 10 years. During this time period these agents have superseded griseofulvin as the agent of choice for onychomycosis. Unlike griseofulvin, the new agents have a broad spectrum of action that includes dermatophytes, Candida species and nondermatophyte moulds. Each of the 3 oral antifungal agents, terbinafine, itraconazole and fluconazole, is effective against dermatophytes with relatively fewer data being available for the treatment of Candida species and nondermatophyte moulds. Itraconazole is effective against Candida onychomycosis. Terbinafine may be more effective against C. parapsilosis compared with C. albicans; furthermore with Candida species a higher dose of terbinafine or a longer duration of therapy may be required compared with the regimen for dermatophytes. The least amount of experience in treating onychomycosis is with fluconazole. Griseofulvin is not effective against Candida species or the nondermatophyte moulds. The main use of griseo-fulvin currently is to treat tinea capitis. Ketoconazole may be used by some to treat tinea versicolor with the dosage regimens being short and requiring the use of only a few doses. The preferred regimens for the 3 oral antimycotic agents are as follows: itraconazole - pulse therapy with the drug being administered for 1 week with 3 weeks off treatment between successive pulses; terbinafine - continuous once daily therapy; and fluconazole - once weekly treatment. The regimen for the treatment of dermatophyte onychomycosis is: itraconazole - 200mg twice daily for I week per month x 3 pulses; terbinafine - 250 mg/day for 12 weeks; or, fluconazole - 150 mg/wk until the abnormal-appearing nail plate has grown out, typically over a period of 9 to 18 months. For the 3 oral antifungal agents the more common adverse reactions pertain to the following systems, gastrointestinal (for example, nausea, gastrointestinal distress, diarrhoea, abdominal pain), cutaneous eruption, and CNS (for example, headache and malaise). Each of the new antifungal agents is more cost-effective than griseofulvin for the treatment of onychomycosis and is associated with high compliance, in part because of the shorter duration of therapy. The newer antifungal agents are generally well tolerated with drug interactions that are usually predictable.

Dermatophytosis of the external auditory meatus

Dermatophytosis of the external auditory meatus is believed to be a fairly rare disease. In the past three and a half years we have had seven cases of dermatophytosis in the external auditory meatus. All cases except one were associated with tinea of other lesions. Case 1: A 44-year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 2: A 14-year-old boy, the son of case 1 had no tinea elsewhere on his body, including the auricle. He scratched the auditory meatus with an earpick which his father had used. Case 3: A 62-year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 4: A 50-year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 5: A 36-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea cruris. Case 6: A 30-year-old woman had tinea of the auricle. Case 7: A 68-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea manuum. Endoscopic examination (except for cases 4 and 7) revealed dry cerumen from cartilaginous to bony region of the external auditory meatus. Direct examination using KOH method of the cerumen in all cases demonstrated numerous fungal elements. Fungal cultures identified Trichophyton rubrum except for cases 3 and 6. All cases were successfully treated with oral itraconazole or terbinafine. We suggest that tinea of the external auditory meatus is frequently associated with that of the auricle.

Combined treatment with surgery and short duration oral antifungal therapy in patients with limited dermatophyte toenail infection

BACKGROUND: Localized nail infection with dermatophyte fungi occurs both as a primary presentation of fungal disease and as a pattern of failure of previous treatment, even with modern antifungal agents. METHODS: Twelve patients (six treatment failures and six previously untreated) were confirmed to have dermatophyte infection of their toenails, and were then treated with surgical removal of the affected area of nail, followed by 28 days of oral terbinafine (250 mg/day). RESULTS: Repeat mycology 12 months after the oral treatment confirmed mycological cure in all patients, and all treated nails were clinically normal. Histology of excised nail showed appearances compatible with a dermatophytoma. CONCLUSIONS: Combined modality treatment is successful and well tolerated for localized nail disease, and provides a useful means of dealing with treatment failure after conventional oral treatment as well as primary therapy of limited nail disease. (J Dermatol Treat (2000) 11: 259-262)

A Caes of Tinea Capitis in an Adult Due to Trichophyton Rubrum

Tinea capitis in adults, especially healthy, is known to be rare but a signi6cant increase in case has recently been observed. Trichophyton rubrum is an anthropophilic, the commonest dermatophyte affecting man but rarely involves the scalp and hair. We describe a 63-year-old healthy woman with tinea capitis due to T. rubrum who has clinical improvement after oral terbinafine therapy. (Ann Dermatol 12(3) 189~192, 2000).

A cohort study on the risk of acute liver injury among users of ketoconazole and other antifungal drugs.

The aim of this cohort study was to estimate the risk of clinical acute liver injury among users of oral antifungals identified in the general population of the General Practice Research Database in UK. The cohort included 69 830 patients, 20-79 years old, free of liver and systemic disease, who had received at least one prescription for either oral fluconazole, griseofulvin, itraconazole, ketoconazole, or terbinafine between 1991 and 1996. Sixteen cases of acute liver injury were identified and validated. Ten cases occurred during nonuse of oral antifungals with a background rate of 0.6 per 100,000 person-months (95% confidence interval 0.3,1.1). Five cases occurred during current use of oral antifungals. Two were using ketoconazole, another two itraconazole, and one terbinafine. Incidence rates of acute liver injury were 134.1 per 100 000 person-months (36.8,488.0) for ketoconazole, 10.4 (2.9-38.1) for itraconazole, and 2.5 (0.4,13. 9) for terbinafine. The remaining case was associated with past use of fluconazole. Ketoconazole was the antifungal associated with the highest relative risk, 228.0 (95% confidence interval 33.9,933.0), when compared with the risk among nonusers, followed by itraconazole and terbinafine with relative risks of 17.7 (2.6,72.6) and 4.2 (0.2, 24.9), respectively. Ketoconazole and itraconazole were the two oral antifungal associated with a marked increase of clinical acute liver injury. The risk associated with ketoconazole should be taken into account when prescribing it as initial treatment for uncomplicated fungal infections.

Oral terbinafine (Lamisil) in the short-term treatment of fungal infections of the skin: results of a post-marketing surveillance study.

Oral terbinafine (Lamisil, Novartis Pharma AG, Basel, Switzerland) is an effective therapy for fungal infections of the skin and nails. A post-marketing surveillance study was undertaken to evaluate the clinical efficacy and safety of oral terbinafine. A total of 454 patients with clinically and mycologically confirmed superficial fungal infections of the skin were enrolled from 79 dermatology clinics. Patients received oral terbinafine (250 mg day-1) for 2 weeks. Specific signs and symptoms were assessed by standard questionnaire before, immediately after, and 4 weeks after treatment. Observed improvements in patients after 2 weeks treatment were: erythema 81%, blistering 33%, exudation 50%, scaling 89%, pruritus 83%. After 4 weeks treatment, erythema was absent in 85% of patients, blistering and exudation in 99.7%, scaling in 82%, and pruritus in 94%. Overall clinical efficacy was assessed as good to excellent in 97% of patients. Adverse effects--mainly gastrointestinal and minor skin rashes--were reported in 5.3% of patients. The results of this study confirm that oral terbinafine is safe and highly effective for the short-term treatment of fungal skin infections.

Generalized pustular eruptions associated with oral terbinafine.

An active 62-year-old man with noninsulin-dependent diabetes and chronic tinea pedis and tinea unguium developed a painless neurotrophic foot ulcer. His medical history was significant for mild hypercholesterolemia, chronic obstructive pulmonary disease, and long-term tobacco and alcohol use. Oral medications were Glyburide, Glucophage, Zestoretic, gemfibrozil, and aspirin, all of which had been administered daily for at least 8 months. There was no personal or family history of skin disease. After the ulcer failed to respond to conventional therapy, including wound care, debridement, and oral antibiotics, oral terbinafine was prescribed, 250 mg/day, for dermatophytosis-impaired wound healing. After 44 days of terbinafine therapy, the patient developed a generalized, erythematous, maculopapular, pruritic eruption accompanied by fatigue and chills. He denied cough, arthralgias, dizziness, hematuria, or exposure to anyone ill. Despite instructions to stop taking the medication, the patient erroneously continued to take terbinafine. One week later, he was referred to our institution. Physical examination revealed a nontoxic appearing middle-aged man with diffuse, confluent, erythematous plaques studded with pustules, lakes of pus, and crusted erosions and a fever of 38.9 °C ( 1, 2). Palms, soles, and mucous membranes were unaffected, and the groin was relatively spared. Toenails exhibited yellow–white discoloration, subungual debris, and onychauxis. Fingernails were normal. Lymphadenopathy was absent. A 1.3 cm by 1.7 cm superficial, painless ulcer without significant undermining was present on the left sole over the first metatarsophalangeal joint. There was decreased sensation from the toes to the midleg. Pedal pulses were palpable. Figure 1Open in figure viewerPowerPoint Extensive pustular eruption of acute onset involving the trunk and extremities Figure 2Open in figure viewerPowerPoint Erythematous plaques, pustules, lakes of pus, and crusted erosions Laboratory analyses revealed elevated white blood cell count (10.7 × 103 μL) with 11% eosinophils. Electrolytes, renal, thyroid, and liver function tests, urinalysis, and sedimentation rate were normal. A skin biopsy specimen showed an intraepidermal, spongiotic, vesiculopustular dermatitis with a superficial, perivascular, mixed inflammatory cell infiltrate of lymphocytes, neutrophils, and scattered eosinophils ( 3, 4). A periodic acid–Schiff stain was negative for fungi. Figure 3Open in figure viewerPowerPoint Vesiculopustular dermatitis with diffuse superficial perivascular infiltrate (original magnification, ×10) Figure 4Open in figure viewerPowerPoint Subcorneal neutrophilic pustule, perivascular infiltrate of mononuclear cells, neutrophils, and occasional eosinophils (original magnification, ×40) Terbinafine was stopped, but all other medications were continued. Hydrotherapy, twice-daily triamcinolone ointment, and a prednisone taper from 60 mg to 0 mg over 3 weeks were initiated. In 4 days, there was complete resolution of the fever and pustulosis and a significant reduction of the erythema. At 40 days, mildly pruritic, erythematous plaques persisted on the trunk and extremities. The temporal relationship strongly suggested terbinafine as the inciting agent in this patient. Oral provocation test was not performed due to unacceptable patient risk.

The new oral antifungal agents for onychomycosis of the toenails

To review the use of the new oral antifungal agents, itraconazole, terbinafine and fluconazole for the treatment of onychomycosis of the toenails. Until about 10 years ago the two oral agents available to treat onychomycosis were griseofulvin and ketoconazole. Since then the new oral antifungal agents have superseded the traditional oral agents for the management of toenail onychomycosis. Literature review. Itraconazole, terbinafine and fluconazole have been used approximately 100 million times to treat superficial mycoses. These agents are more effective than the traditional antimycotics for the treatment of pedal onychomycosis; furthermore, the new agents have a broader spectrum of action than griseofulvin. In general, itraconazole, terbinafine and fluconazole have a favorable adverse-effects profile with drug interactions that are usually predictable and manageable. The new oral antifungal agents have a high benefit-to-risk ratio when used to treat toenail onychomycosis.

An open study of tinea capitis in 50 children treated with a 2-week course of oral terbinafine

Background: Terbinafine is used in the treatment of dermatophyte infections. There have been several studies suggesting a good response to terbinafine in treating tinea capitis, specifically with dermatophytes of the Trichophyton species. Methods: We enrolled 50 consecutive children with a clinical diagnosis of tinea capitis into an open study using terbinafine for 2 weeks. Results: Clinical and mycologic cure occurred in more than 86% of patients with no side effects and good compliance. Conclusion: In this study terbinafine was a safe and effective treatment of tinea capitis in children, particularly when caused by the Trichophyton species. (J Am Acad Dermatol 1999;41:60-3.)

Oral therapy of common superficial fungal infections of the skin

Although superficial fungal infections of the skin often respond to topical agents, systemic therapy is sometimes necessary. This article gives a review of the effectiveness of the oral antifungal agents fluconazole, itraconazole, and terbinafine in the treatment of pityriasis versicolor, tinea corporis/cruris, and tinea pedis. Four hundred milligrams fluconazole as a single dose and 200 mg itraconazole daily for 5 to 7 days were effective in the treatment of pityriasis versicolor; terbinafine taken orally appears to be ineffective in pityriasis versicolor. Tinea corporis and tinea cruris were effectively treated by 50 to 100 mg fluconazole daily or 150 mg once weekly for 2 to 3 weeks, by 100 mg itraconazole daily for 2 weeks or 200 mg daily for 7 days, and by 250 mg terbinafine daily for 1 to 2 weeks. Tinea pedis has been effectively treated with pulse doses of 150 mg fluconazole once weekly, with 100 mg itraconazole daily for 2 weeks or 400 mg daily for 1 week, and with 250 mg terbinafine daily for 2 weeks. (J Am Acad Dermatol 1999;40:S31-4.)

Efficacy of oral terbinafine in feline dermatophytosis due to Microsporum canis

Microsporum canis is the dermatophyte most commonly responsible for ringworm in cats. The purpose of this paper was to evaluate the in vivo efficacy of oral terbinafine (Larnisil; Sandoz) in the treatment of feline ringworm caused by M canis, and to consider this drug as an alternative to griseofulvin or imidazoles. Fifteen cats infected with M canis were treated orally once daily with 30 mg/kg of terbinafine over a 2-week period. All treated animals were checked for dermatophytes on the last day of treatment, a month later and 3 months after the last administration of the drug. Only 12 cats could be used in the whole trial and 11 of these (92%) showed a complete cure. Terbinafine could be an effective alternative to griseofulvin when fungal resistance or idiosyncrasic intolerance are shown and, compared with griseofulvin, could give a faster rate of cure and less relapses.

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. 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.

Onychomycosis: recognition, diagnosis, and management.

About 20% of the US population between the ages of 40 and 60 years have fungal nail disease, or onychomycosis. The incidence of this infection is increasing worldwide. Most cases of onychomycosis in the United States are caused by dermatophytes, but nondermatophyte fungi (molds or yeasts) may also be causative agents. To confirm the diagnosis of onychomycosis, a potassium hydroxide examination should be performed. A culture is necessary to determine the fungal pathogen and to aid in selecting appropriate therapy. Worldwide, fluconazole (not yet approved in the United States for onychomycosis), itraconazole, and oral terbinafine have superseded griseofulvin and ketoconazole as the agents of choice in treating onychomycosis. These newer systemic compounds have higher cure rates and cause fewer side effects than traditional agents. Intermittent dosing with itraconazole (3 or 4 one-week pulses of 200 or 400 mg daily) is the latest advance in the treatment of onychomycosis. This regimen has been found to be at least as safe and effective as short-term continuous therapy, yet more flexible, convenient, and economical.

Tineas—Superficial Dermatophyte Infections

Tineas—Superficial Dermatophyte Infections

Onychomycosis in children: prevalence and management.

Onychomycosis in children is often accompanied by tinea pedis and a family history of onychomycosis. The prevalence of onychomycosis in children is substantially lower than that of adults; therefore it is important to confirm the clinical diagnosis. The most common presentation of onychomycosis is the distal and lateral subungual type. The organism most commonly isolated in North America is Trichophyton rubrum. Oral antifungal therapy is required, especially when the onychomycosis is of moderate to severe intensity, with nail matrix involvement. The new oral antifungal agents itraconazole, terbinafine, and fluconazole are being increasingly used for the treatment of onychomycosis. Review of the literature suggests that these agents are effective and safe in managing onychomycosis in children. The short duration of therapy required with these drugs should help improve compliance. The data suggest that the new oral antifungal agents have a role in the treatment of onychomycosis in children. Further experience will help us better position these drugs when evaluating the management of onychomycosis in children.

Onychomycosis in a 2-year-old child successfully treated with oral terbinafine

Several factors may predispose persons to onychomycosis, such as preexisting tinea pedis, humidity, hyperhidrosis, trauma, and immunosuppression. Onychomycosis is common in the elderly perhaps because of slow nail growth. A hereditary factor has been proposed with a possible genetic link in distal subungual onychomycosis by Trichophyton rubrum infection in a dominant autosomal pattern.1 There have been scattered reports of onychomycosis in children, the youngest of whom was 10 weeks old.2