Which Oral Antifungal Is Best for Toenail Onychomycosis?

From the Clinical Inquiries Family Physicians Inquiries Network

Jose R. Hinojosa, MD Which oral antifungal is best Corpus Christi Family Practice Residency Program, Corpus for toenail onychomycosis? Christi, Texas Kristin Hitchcock, MSI Department of Preventive Medicine, Northwestern Evidence-based answer University, Chicago, Ill Terbinafine, 250 mg taken daily for 12 mycologic cure rates, tolerability, and cost weeks, is the best regimen for toenail effectiveness (strength of recommendation onychomycosis due to better clinical and [SOR]: A, meta-analyses). Clinical commentary This expensive treatment someone is willing to pay out of pocket, is not always a high priority ® however, I will now use terbinafine, based In my practice of mostly uninsured Dowdenon this review. AtHealth one of my practices,Media patients, onychomycosis treatment is not itraconazole was available at a reduced a high priority. The recommendedCopyright drug,For personalprice, but that discountuse onlyis outweighed by terbinafine, is costly and not available the superior safety profile of terbinafine. as a generic. Since this is primarily a José E. Rodríguez, MD cosmetic problem, we usually don’t treat Florida State University College of Medicine, it in my population. In the rare case that Tallahassee fast track Terbinafine z Evidence summary Lower relapse rates has the best rates Fungal infections of the nail (onychomy- with terbinafine of long-term cure cosis) are often treated for relief of local Longer-term mycologic cure and clinical symptoms and cosmetic reasons. Gris- relapse rates have also been reported. A eofulvin, fluconazole, itraconazole, and 5-year blinded prospective study found terbinafine have all been used orally. long-term mycologic cures of 46% for A meta-analysis comparing the effi- terbinafine vs 13% for itraconazole cacy of terbinafine (Lamisil), pulse-dosed (number needed to treat [NNT]=4.3). and continuous-dosed itraconazole (Spo- This study also showed a lower clinical ranox), fluconazole (Diflucan), and gris- relapse for terbinafine (21% vs 48%; eofulvin showed mycological cure rates NNT=3.7).3 A cost-efficacy analysis of of varying degrees for each treatment terbinafine, itraconazole, and griseoful- (Table).1 Another meta-analysis of 6 vin found terbinafine to be the most cost- studies comparing terbinafine with itra- effective (Table).4 conazole reported odds ratios ranging A randomized, double-blind, con- from 1.8 (95% confidence interval [CI], trolled trial compared daily terbinafine 1.1–2.8) to 2.9 (95% CI, 1.9–4.1), indi- with pulse-dose terbinafine.5 Daily cating an 80% to 190% increased like- terbinafine (250 mg for 3 months) had a lihood of clinical cure with terbinafine 70.9% mycologic cure, while pulse-dose compared with itraconazole.2 terbinafine (500 mg daily for 1 week per

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n table I Efficacy and cost of treating toenail onychomycosis1,4 al

c Treatment Mycological Cost per cure* cure rates

Clini Terbinafine 76% (± 3%) $ 645 (continuous)

Itraconazole (pulse-dose) 63% (± 7%) $ 856

Itraconazole (continuous) 59% (± 5%) $ 1845

Griseofulvin 60% (± 6%) $ 2722

Fluconazole 48% (± 5%) Not reported

* Cost includes drug, monitoring, and office visits (in 1996 dollars).

month for 3 months) had only a 58.7% References mycologic cure (relative risk [RR]=1.21 1. Gupta AK, ryder je, johnson AM. Cumulative meta-analysis of systemic antifungal agents for [95% CI, 1.02–1.43]; NNT=8.2). There the treatment of onychomycosis. Br J Dermatology was no significant difference in tolerabil- 2004; 150:537–544. ity of the regimens. 2. Krob AH, Fleischer AB Jr, D’Agostino R Jr, Feldman SR. Terbinafine is more effective than itraconazole Terbinafine is well-tolerated by most in treating toenail onychomycosis: results from a patients. A telephone survey after treat- meta-analysis of randomized controlled trials. J ment with daily terbinafine or pulse-dose Cutan Med Surg 2003; 7:306–311. 3. Sigurgeirsson B, Olafsson JH, Steinsson JB, Paul itraconazole reported greater ease and C, Billstein S, Evans EG. Long-term effectiveness convenience, and higher overall satisfac- of treatment vs itraconazole in onychomycosis: a tion with continuous terbinafine vs pulse- 5-year blinded prospective follow-up study. Arch Dermatology 2002; 138:353–357. fast track 6 dose itraconazole. 4. Angello JT, Voytovich RM, Jan SA. A cost/efficacy Do not prescribe A multicenter trial of diabetic patients analysis of oral antifungals indicated for the treat- with onychomycosis (mean ± SD age, ment of onychomycosis: griseofulvin, itraconazole, terbinafine for and terbinafine. Am J Manag Care 1997; 3:442– 55.7 ± 11.7 years) revealed that terbin- 450. patients with afine had comparable efficacy and caused 5. Warshaw EM, Fett DD, Bloomfield HE, et al. Pulse no hypoglycemic reactions in this group, versus continuous terbinafine for onychomycosis: chronic or active a randomized, double blind, controlled trial. J Am who were being treated with insulin or Acad Dermatol 2005; 53:578–584 liver disease 7 oral hypoglycemics. The terbinafine pre- 6. Warshaw eM, Bowman T, Bodman MA, Kim jj, scribing information suggests not using Silva S, Mathias SD. Satisfaction with onychomycosis treatment. Pulse versus continuous dosing. J the drug for patients with chronic or ac- Am Podiatr Med Assoc 2003; 93:373–379. tive liver disease and recommends check- 7. Farkas B, Paul C, Dobozy A, Hunyadi J, Horvath A, ing a pretreatment AST and ALT.8 Fekete G. Terbinafine (Lamasil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a Recommendations from others multicentre trial. Br J Dermatology 2002; 146:254– 260 Guidelines from the British Associa- 8. Physicians’ Desk Reference. 61st ed. Montvale, tion of Dermatologists point out that NJ: Thomson PDR; 2007. terbinafine is superior to itraconazole, 9. Roberts DT, Taylor WD, Boyle J, for the British As- and consider it a first-line treatment be- sociation of Dermatologists. Guidelines for treatment of onychomycosis. Br J Dermatol 2003; cause it has a better cure rate and lower 148:402–410. 9 relapse rate. UpToDate suggests oral 10. Goldstein AO, Goldstein BG. Onychomycosis. Up- terbinafine as initial treatment for ToDate [database online]. updated April 3, 2006. Available at: www.uptodate.com. Accessed on Au- onychomycosis at a dose of 250 mg daily gust 4, 2006. for 12 weeks.10 n

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