New antifungal agents for the treatment of onychomycosis - Tips from Other Journals

Author: Richard Sadovsky
Date: May 1, 1997

The management of onychomycosis has been frustrating for physicians and patients. Mainstays of therapy, griseofulvin and ketoconazole, have been disappointing with low cure and high relapse rates. Two new antifungal agents recently have been approved. Itraconazole was approved for the treatment of dermatophyte onychomycosis in 1995, and terbinafine was approved in 1996. Gupta and associates reviewed two cases of severe onychomycosis (one was treated with itraconazole and one was treated with terbinafine) and discuss current management now available for onychomycosis.

The two cases involved a husband and a wife. Both presented with onychomycosis of several years' duration that had not responded to griseofulvin therapy or several topical treatments. Patient 1 was given terbinafine, 250 mg per day continuously for 12 weeks. Patient 2 was started on itraconazole intermittent pulse therapy, 200 mg twice a day for one week each month for a total of three months. In this patient, ankle edema developed that may have been the result of an interaction between itraconazole and nifedipine. Complete cure was noted in both patients 12 months after discontinuing therapy.

Griseofulvin has a poor cure rate (zero percent to 17 percent) even after several months of therapy. Relapse rates are also relatively high (33 percent to 40 percent). Ketoconazole also appears to have poor cure rates and is associated with transient liver test elevations and with symptomatic hepatic reactions. Although liver inflammation is generally reversible, permanent liver damage can occur. This complication is idiosyncratic and does not appear to be dose related.

Terbinafine, given 250 mg daily for 12 weeks, has a cure rate of 41 percent to 71 percent in published studies. The currently advocated regimen for itraconazole is 200 mg twice daily for one week, repeated as pulse therapy monthly for three or four cycles. Complete cure of toenail onychomycosis occurred in 64 percent and 72 percent of patients receiving the three-pulse and four-pulse regimen, respectively, in published studies. Dosing in the United States is 200 mg per day given as continuous dosing for three months. A complete cure occurs with this regimen in 36 percent to 61 percent of patients.

Itraconazole and terbinafine are much more effective than griseofulvin. Longer courses of medication may be needed if more than 75 percent of the nail bed or the nail matrix is involved. Prevention of tinea pedis after cure is an important factor in deterring relapses. Topical therapy may be useful in mild onychomycosis. Fluconazole is currently being tested as another promising treatment.

The clinical diagnosis of onychomycosis should be confirmed with a positive potassium hydroxide test and culture. Concomitant drug therapy risks and monitoring considerations are still being developed. Adverse effects with itraconazole include gastrointestinal disturbances, liver enzyme elevations, headache, menstrual disorder, rash and dizziness. Itraconazole may interact with terfenadine, astemizole, cisapride, oral midazolam and oral triazolam. Adverse effects with terbinafine include headache, gastrointestinal disturbances, elevated liver enzymes, rash, and visual and taste disturbances. Terbinafine has fewer drug interactions than itraconazole; the most important interactions occur with cimetidine and rifampin.

The authors conclude that the new generation of antifungals, notably itraconazole and terbinafine, have shortened treatment courses for onychomycosis and improved cure rates.

RICHARD SADOVSKY, M.D. Gupta AX, et al. Onychomycosis. New therapies for an old disease. West J Med 1996;165:349-51.

COPYRIGHT 1997 American Academy of Family PhysiciansCOPYRIGHT 2004 Gale Group

 
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