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We have treated 48 cases of onychomycosis (of which 37 were caused by dermatophytes, 10 by yeasts and one by Scopulariopsis brevicaulis) with 200 mg ketoconazole daily. We obtained recovery in 65 p. 100 of the cases of onyxis caused by dermatophytes and in 80 p. 100 of the cases of onychomycosis due to Candida. The one patient presenting an infection with Scopulariopsis brevicaulis recovered in 13 months. The average duration necessary to obtain complete recovery was 6 1/2 months for onychomycosis of the hands due to dermatophytes and 12 1/2 months for those of the feet. Perionyxis due to Candida needed 2 months of treatment with this drug, however 6 months of treatment were necessary to obtain recovery for onycholysis due to Candida. Biological tests remained normal and the side-effects were minimal and essentially gastrointestinal in our study. Ketoconazole is an effective treatment for onychomycosis: it is active against the different mycotic agents infecting nails and well tolerated by the patient. Several minor effects such as itching, nausea, headache and more serious reactions such as erythrodermia and hepatitis have been reported. Regular control and biological tests are therefore necessary. Patients with other diseases should avoid the use of ketoconazole for treatment of onychomycosis.
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PMID:[Ketoconazole and onychomycosis]. 608 41

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 During this time period these agents have superseded griseofulvin as the agent of choice for onychomycosis.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.
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PMID:A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis. 1064 75

Fifty-four patients received an intermittent regimen of itraconazole (26 of them were finger onychomycosis and 28 toe onychomycosis) and were followed-up for nine months. The result showed that the clinical cure rate of fingernails was 88.5% and the mycologic cure rate was 96.4%, while the clinical cure rate of toes was 82.1% and the mycologic cure rate was 96.4%. Few adverse events were observed by 7.4%, just like nausea, gastric discomfort etc. It suggests that the pulse administration system is highly effective and has a few side-effects.
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PMID:[Intermittent-pulse treatment of onychomycosis with orally administered itraconazole]. 1193 47

We present a case of histologic changes resembling acute cellular rejection in a liver transplant patient treated with terbinafine. Approximately 5 years after orthotopic liver transplantation, a 51-year-old Hispanic man developed elevated liver enzyme levels. A biopsy sample was interpreted as acute cellular rejection, and the patient was treated with increased immunosuppression. Review of medications showed that the patient had been started on terbinafine approximately 4 weeks earlier for onychomycosis, and it was discontinued. A follow-up visit 2 weeks later revealed progressive jaundice, malaise, and nausea, and evaluation of a second liver biopsy sample revealed marked centrilobular cholestasis and severe bile duct damage, consistent with terbinafine hepatotoxicity. Although these histologic changes have been described in treated patients with both normal and abnormal livers, the potential for confusion with acute rejection in patients with hepatic transplantation has not previously been reported.
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PMID:Histologic changes resembling acute rejection in a liver transplant patient treated with terbinafine. 1261 88

We describe a previously healthy woman who developed liver cirrhosis as a sequela of acute hepatic injury that was induced by ketoconazole administration to treat onychomycosis. The initial presentation of the disease was of a typical acute hepatitis, characterized by nausea, anorexia, fatigue, and jaundice that developed during the administration of ketoconazole. Many other causes of hepatitis were absent in the patient. Even though the hepatic injury was gradually resolved for several months after cessation of the drug, the liver function was not completely restored. Six months after the onset of illness, a follow-up abdominal computed tomography and peritoneoscopic liver biopsy were performed. They revealed a marked reduction in the liver volume and a definite cirrhotic change, which persisted for more than 5 years. The case suggests that the administration of ketoconazole can cause liver cirrhosis through acute hepatic injury within a short time under certain circumstances.
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PMID:Liver cirrhosis developed after ketoconazole-induced acute hepatic injury. 1467 75

In this open, randomized and comparative study, the safety and efficacy of systemic intermittent itraconazole and terbinafine was examined in 30 patients with onychomycosis. The patient with positive mycological culture and also the patients with positive microscopy and negative culture were investigated. Patients were randomly assigned: 15 patients in each group received either 200mg itraconazole or 250 mg terbinafine twice daily during the first week of a 4 weeks cycle. The treatment duration was 16 weeks and was followed-up for 36 weeks. Both the treatment regimen showed significant reduction in onychomycosis affected areas after 8 weeks and maximum reduction was observed at the end of 36 weeks. At the end point of the follow-up period, the clinical cure rates (no residual deformity or with some deformity) were 86.7% in the itraconazole group and 100% in the terbinafine group. The mycological cure rates were 86.7% and 100% respectively. However, no statistically significant differences between the treatment groups were seen in clinical, mycological (P= 0.864) and severity assessment (P= 0.220). Nausea, abdominal cramp, headache, back pain and flu like syndrome are the adverse effects more frequently reported. At least one adverse effect was reported by 17 patients, of them 12 belonged to itraconazole group and 5 to terbinafine group and the difference was statistically significant (P= 0.027). The overall therapeutic effectiveness, safety and cost affectivity were in favor of Terbinafine pulse therapy.
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PMID:Study of oral itraconazole and terbinafine pulse therapy in onychomycosis. 1646 68

The prevalence of onychomycosis is nearly 20% in patients aged >60 years. In North America, 90% of toenail onychomycosis is caused by dermatophytes (Trichophyton species). Distal-lateral subungual onychomycosis is the most common clinical presentation. The potassium hydroxide test is the most cost-effective diagnostic method. Although nail clipping for histology using periodic acid-Schiff stain is more sensitive, it is much more expensive. Elderly patients have specific risk factors for poor response to therapy for onychomycosis, including frequent nail dystrophy, slow growth of nails and increased prevalence of peripheral vascular disease and diabetes mellitus. Elderly people with diabetes should be treated for onychomycosis to prevent secondary bacterial infections and subsequent complications. Terbinafine is the drug of choice for dermatophyte onychomycosis, with greater mycological cure rates, less serious and fewer drug interactions, and a lower cost than continuous itraconazole therapy. Adjunct debridement may improve the clinical and complete cure rates compared with terbinafine alone. Common adverse effects of terbinafine in the elderly include nausea, sinusitis, arthralgia and hypercholesterolaemia. For onychomycosis caused by Candida or nondermatophyte moulds, there is no superior systemic therapy. In general, topical nail lacquers, amorolfine and ciclopirox are not practical for elderly patients because of the recommended frequency of application, periodic routine debridement of affected nails and long duration of therapy. However, nail lacquers may be a good option as monotherapy for patients with superficial white onychomycosis or in combination with systemic antifungal therapy for patients with predisposing factors for poor response or recurrence.
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PMID:Onychomycosis in the elderly : drug treatment options. 1743 24

Terbinafine is a commonly prescribed antifungal agent used in the treatment of trichophytic onychomycosis and chronic cutaneous mycosis that are resistant to other treatments. This case report highlights a rarely documented but important adverse hepatic reaction that was caused by the use of oral terbinafine. A woman in her thirties presented with a 3-week history of jaundice, malaise, itching, nausea, decreased appetite, weight loss, dark orange urine and intermittent non-radiating epigastric pain. She had recently finished a 3-week course of oral terbinafine for a fungal nail infection. Liver biopsy findings were consistent with chronic active hepatitis secondary to a drug reaction. A few days after initial presentation, the patient developed erythema nodosum. Delayed development of erythema nodosum secondary to terbinafine could not be excluded.
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PMID:A curious case of cholestasis: oral terbinafine associated with cholestatic jaundice and subsequent erythema nodosum. 2548 Jan 38