Pharmacotherapy of onychomycosis

[en] Fungal infections of the nails are frequent in some segments of the population. Dermatophytes, yeasts and moulds are potential pathogens. A series of antifungal treatments are available to the clinician, differing by both their mechanistic nature and mode of administration. The pharmacodynamic and pharmacokinetic properties of each antifungal agent are distinct. This review focuses on the characteristics of amorolfine, bifonazole, ciclopirox, fluconazole, griseofulvin, itraconazole, ketoconazole, ravuconazole, R126638 and terbinafine. Single drug treatments and combined therapies are presented. None of the current drug regimens have demonstrated reliable efficacy against all cases of onychomycosis. Treatment failures, relapses and reinfections remain stubborn problems in the management of onychomycosis.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Baran, R.

Gupta, A. K.

Pierard, Gérald ; Université de Liège - ULiège > Département des sciences cliniques > Dermatopathologie

Language :

English

Title :

Pharmacotherapy of onychomycosis

Publication date :

April 2005

Journal title :

Expert Opinion on Pharmacotherapy

ISSN :

1465-6566

eISSN :

1744-7666

Publisher :

Ashley Publications Ltd, London, United Kingdom

Volume :

Issue :

Pages :

609-624

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 14 February 2011

Statistics

Number of views

42 (0 by ULiège)

Number of downloads

1 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

BARAN R, HAY RJ, TOSTI A, HANEKE E: A new classification of onychomycosis. Br. J. Dermatol. (1998) 119:567-571.
BARAN R: Diagnostic clinique des onychomycoses. In: Onychomycoses. Baran R, Piérard GE (Eds). Abrégés Masson, Paris (2004), pp 37-90.
ARRESE JE, PIERARD-FRANCHIMONT C, GREIMERS R, PIERARD GE: Fungi in onychomycosis. A study by immunohistochemistry and dual flow cytometry. J. Eur. Acad. Dermatol. Venereol. (1995) 4:123-130.
PIERARD GE, ARRESE JE, DE DONCKER P, PIERARD-FRANCHIMONT C: Present and potential diagnostic techniques in onychomycosis. J. Am. Acad. Dermatol. (1996) 34:273-277.
PIERARD GE, ARRESE JE, QUATRESOOZ P: Histomycologie de la biodiversité des onychomycoses. In: Onychomycoses. Baran R, Piéard GE (Eds). Abrégés Masson, Paris (2004), pp 91-104.
EVANS EGV: Causative pathogens in onychomycosis and the possibility of treatment resistance. A review. J. Am. Acad. Dermatol. (1998) 38:S32-S36.
ARRESE JE, PIERARD-FRANCHMONT C, PIERARD GE: Facing up to the diagnostic uncertainty and management of onychomycosis. Int. J. Dermatol. (1999) 38:S1-S6.
CHABASSE D, BARAN R, FEUILHADE DE CHAUVIN MJ: Les onychomycoses. I-Epidémiologie, étiologie. J. Mycol. Med. (2000) 10:177-190.
CHABASSE D: Epidémiologie et étiologie des onychomycoses. In: Onychomycoses. Baran R, Piérard GE (Eds). Abrégés Masson, Paris (2004), pp 1-35.
ARRESE JE, PIERARD-FRANCHIMONT C, PIERARD GE: A plea to bridge the gap between antifungals and onychomycosis management. Am. J. Clin. Dermatol. (2001) 2:281-284.
ARRESE JE, PIERARD GE: Treatment failures and relapses in onychomycosis: a stubborn clinical problem. Dermatology (2003) 207:255-260.
ARRESE JE, DE DONCKER P, ODDS F, PIERARD GE: Reduction in the growth of non dermatophyte moulds by itraconazole: evaluation by corneofungimetry bioassay. Mycoses (1998) 41:461-465.
OSBORNE CS, LEITNER I, FAVRE B, RYDER NS: Antifungal drug response in an in vitro model of dermatophyte nail infection. Med. Mycol. (2004) 42:159-163.
FLAGOTHIER C, PIERARD-FRANCHIMONT C, PIERARD GE: New insights in the effect of amorolfine nail lacquer. Mycoses (2005) 48(2):91-94.
DE DONCKER P: Pharmacokinetics of orally administered antifungals in onychomycosis. Int. J. Dermatol. (1999) 38:S10-S27.
POLAK AM, DIXON DM: Antifungal activity of amorolfine in vitro and in vivo. In: Recent trends in the discovery, development and evaluation of antifungal agents. Fromtling R (Ed.) JR Prous Science Publications, Barcelona, Spain (1987) 555-573.
POLAK AM: Preclinical date and mode of action of amorolfine. Clin. Exp. Dermatol. (1992) 1:8-12.
MENSING H, POLAK-WYSS A, SPLANEMANN V: Determination of the subungual antifungal activity of amorolfine after 1 month's treatment in patients with onychoycosis: comparison of two nail lacquer formulations. Clin. Exp. Dermatol. (1992) 17:S29-S32.
POLAK A: Kinetics of amorolfine in human nails. Mycoses (1993) 36:101-103.
LAUHARANTA J: Comparative efficacy and safety of amorolfine nail lacquer 2% versus 5% once weekly. Clin. Exp. Dermatol. (1992) 1:41-43.
REINEL D, CLARKE C: Comparative efficacy and safety of amorolfine nail lacquer 5% in onychomycosis, once weekly versus twice-weekly. Clin. Exp. Dermatol. (1992) 1:44-49.
ZAUG M, BERGSTRASSER M: Amorolfine in the treatment of onychomycoses and dermatomycoses (an overview). Clin. Exp. Dermatol. (1992) 18:61-70.
MALESZKA R, RATAJCZAK V, TUREK-KRASINSKA K et al.: The use of amorolfine in the treatment of dermatophyte onychomycosis. Prz. Dermatol. (2002) 89:493.
GUPTA AK: Ciclopirox: an overview. Int. J. Dermatol. (2001) 40:305-310.
BOHN M, KRAEMER K: The dermatopharmacologic profile of ciclopirox 8% nail lacquer. J. Am. Pediatr. Med. Assoc. (2000) 90:491-494.
BOHN M, KRAEMER K: Dermatopharmacology of ciclopirox nail lacquer topical solution 8% in the treatment of onychomycosis. J. Am. Acad. Dermatol. (2000) 43: S57-S69.
MARKUS A: Hydroxy-pyridones: outstanding biological properties. In: Hydroxy-pyridones as antifungal agents with special emphasis on onychomycosis. Shuster (ed.) Springer, Berlin, Germany (1999).
CESCHIN-ROQUES C, HANEL H, PRUJA-BOUGARET S, LUC J, VANDERMANDER J, MICHEL G: Ciclopirox nail lacquer 8%: in vivo penetration into and through nails and in vitro effect. Skin Pharmacol. (1991) 4:89-94.
BARAN R, HAY RJ, ECKART H, TOSTI A, PIRACCINI BM: Onychomycosis: The current approach to diagnosis and therapy. Martin Dunitz Ltd., London, UK (1999) p 44.
SEEBACHER C: Action mechanisms of modern antifungal agents and resulting problems in the management of onychomycosis. Mycoses (2003) 46:506-510.
JOMARD P, LUC J, ROQUES C: Activité fongicide in vitro du ciclopirox. J. Mycol. Med. (2004) 14:78-82.
GUPTA AK, JOSEPH WS: Ciclopirox 8% nail lacquer in the treatment of onychomycosis of the toenails in the United States. J. Am. Podriat. Med. Assoc. (2000) 90:495-501.
SEEBACHER C, NIETSCH KH, ULBRICHT HM: A multicenter, open-label study of the efficacy and safety of ciclopirox nail lacquer solution 8% for the treatment of onychomycosis in patients with diabetes. Cutis (2001) 68:17-22.
NOLTING S: Open studies of ciclopirox nail lacquer in onychomycosis. A review. In: Hydroxy-Pyridones as antifungal agents with special emphasis on onychomycosis. Shuster S, Springer-Verlag, Berlin, Germany (1999) pp 75-80.
GUPTA AK, FLECKMAN P, BARAN R: Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J. Am. Acad. Dermatol. (2000) 43:S70-S80.
PIERARD GE, RURANGIRWA A, PIERARD-FRANCHIMONT C: Bioavailability of fluconazole and ketoconazole in human stratum corneum and oral mucosa. Clin. Exp. Dermatol. (1991) 16:168-171.
HUMPHREY MJ, JEVONS S, TARBIT MH: Pharmacokinetic evaluation of UK-49, 858, a metabolically stable triazole antifungal drug, in animals and man. Antimicrob. Agents Chemother. (1985) 28:648-653.
DEBRUYNE D, RYCKELYNCK JP: Clinical pharmacokientics of fluconazole. Clin. Pharmacokinet. (1993) 24:10-27.
FAERGEMANN J, LAUFEN H: Levels of fluconazole in normal and diseased nails during and after treatment of oychomycosis in toenails with fluconazole 150 mg once weekly. Acta Derm. Venereol. (1996) 76:219-221.
HAY RJ: Pharmacodynamic and pharmacokinetic evaluation of fluconazole in skin and nails. Int. J. Dermatol. (1992) 31:S6-S7.
WILDFEUER A, FAERGEMANN J, LAUFEN H et al.: Bioavailability of fluconazole in the skin after oral medication. Mycoses (1994) 37:127-130.
FRAKI J, HEIKKILA H, KERO M et al.: An open-label, non-comparative study of the efficacy and safety of fluconazole in the treatment of onychomycosis. Current Ther. Res. (1997) 58:481-491.
RICH P, SCHER RK, BRENEMAN D et al.: Pharmacokinetics of three doses (150, 300 and 450 mg) in distal subungual onychomycosis of the toenail. J. Am. Acad. Dermatol. (1998) 38: S103-S109.
SAVIN RC, DRAKE L, BABLE D et al.: Pharmacokinetics of three once weekly doses (150, 300 and 450 mg) in distal subungual onychomycosis of the fingernail. J. Am. Acad. Dermatol. (1998) 38: S110-S116.
KATZ HI: Drug interactions of the newer oral antifungal agents. Br. J. Dermatol. (1999) 141:S26-S32.
GUPTA AK, KATZ HI, SHEAR NH: Drug interactions with itraconazole, fluconazole and terbinafine and their management. J. Am. Acad. Dermatol. (1999) 41:237-249.
SHEAR N, DRAKE L, GUPTA A et al.: The implications and management of drug interactions with itraconazole, fluconazole and terbinafine. Dermatology (2000) 201:196-203.
SHAPIRO LE, SHEAR NH: Drug interactions: proteins, pumps, and P450s. J. Am. Acad. Dermatol. (2002) 47:467-484.
KONNIKOV N, RAYNHAM H: Oral antifungal agents. In: Fitzpatrick's Dermatology in general medicine. 6th edn. Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA. Katz SI (Eds) Mc Graw-Hill, New York, USA (2003) 2443-2448.
PIERARD GE, ARRESE ESTRADA J, PIERARD-FRANCHIMONT C: Treatment of onychomycosis. Traditional approaches. J. Am. Acad. Dermatol. (1993) 29:S41-S45.
GUPTA AK, SCHER RK, DE DONCKER P: Current management of onychomycosis. Dermatol. Clin. (1997) 15:121-135.
SCHÄFER-KORTING M, KORTING HC, MUTSCHLER E: Human plasma and skin blister fluid levels of griseofulvin following a single oral dose. Eur. J. Clin. Pharmacol. (1985) 29:109-113.
KORTING HC, SCHÄFER-KORTING M, ZIENICKE H et al.: Treatment of tinea unguium with medium and high doses of ultramicrosize griseofulvin compared with itraconazole. Antimicrob. Ag. Chemoth. (1993) 37:2064-2068.
KABASAKALIAN P: Parameters affecting absorption of griseofulvin in a human subject using urinary metabolite excretion data. J. Pharm. Sci. (1970) 59:595.
BATES TR, SEQUEIRA JAL: Use of 24 hr urinary excretion to assess the bioavailability of grisefulvin in humans. J. Pharm. Sci. (1975) 64:709.
VAN CUTSEM J: Oral, topical and parenteral antifungal treatment with itraconazole in normal and in immunocompromised animals. Mycoses (1989) 32:14-34.
CAUWENBERGH G, DEGREEF H, HEYKANTS J, WOESTENBORGHS R, VAN ROOY P, HAVERANS K: Pharmacokinetic profile of orally administered itraconazole in human skin. J. Am. Acad. Dermatol. (1988) 18:263-268.
GUPTA AK, SHEAR NH: The new oral antifungal agents for onychomycosis of the toenails. J. Eur. Acad. Dermatol. Vener. (1999) 13:1-13.
PIERARD GE, ARRESE JE, PIERARD-FRANCHIMONT C: Itraconazole. Expert Opin. Pharmacother. (2000) 1:287-304.
PIERARD GE, ARRESE JE, PIERARD-FRANCHIMONT C: Itraconazole corneofungimetry bioassay on Malassezia species. Mycoses (2004) 47:418-421.
PIERARD GE, KHARFI M, SALOMON-NEIRA MD, KAMOUN MR, PIERARD-FRANCHIMONT C: Itraconazole in human aspergillosis revisited. J. Mycol. Med. (2004) 14:192-200.
GROLL AH, PISCITELLI SC, WALSH TJ: Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv. Pharmacol. (1998) 44:343-500.
VAN CUTSEM J, VAN GERVEN F, JANSSEN PAJ: Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. Rev. Infect Dis. (1987) 9:S15-S32.
PIERARD GE, ARRESE JE, DE DONCKER P: Antifungal activity of itraconazole and terbinafine in human stratum corneum: a comparative study. J. Am. Acad. Dermatol. (1995) 32:429-435.
GUPTA AK, DE DONCKER P, SCHER RK et al.: Itraconazole for the treatment of onychomycosis. Int. J. Dermatol. (1998) 37(4):303-308.
LEYDEN J: Pharmacokinetics and pharmacology of terbinafine and itraconazole. J. Am. Acad. Dermatol. (1998) 38: S42-S47.
BARAN R, DE DONCKER P: Lateral edge nail involvement indicates poor prognosis for treating onychomycosis with the new systemic antifungals. Acta Derm. Venereol. (1996) 76:82-83.
HAVU V, BRANDT H, HEIKKILA H et al.: Continuous and intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison. Br. J. Dermatol. (1999) 140:96-101.
DE DONCKER PD, DECROIX J, PIERARD GE et al.: Antifungal pulse therapy for onychomycosis. A pharmacokinetic and pharmacodynamic investigation of monthly cycles of 1-week pulse therapy with itraconazole. Arch. Dermatol. (1996) 132:34-41.
HAVU V, BRANDT H, HEIKKILA H et al.: A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toenail onychomycosis. Br. J. Dermatol. (1997) 136:230-234.
INGBER A: Intermittent low dose itraconazole treatment for onychomycosis-long term follow-up. Med. Mycol. (2001) 39:471-473.
BARONE JA, MOSKOVITCH BL, GUARNIERI J et al.: Enhanced bioavailabitity of itraconazole in hydroxypropyl-β-cyclodextrin solution versus capsules in healthy volunteers. Antimicrob. Agents. Chemother. (1998) 42:1862-1865.
VAN DE VELDE VJ, VAN PEER AP, HEYKANTS JJ et al.: Effects of food on the pharmacokinetics of a new hydroxypropyl-beta-cyclodextrin formlation of itraconazole. Pharmacother. (1996) 16:424-428.
MENICHETTI F, DEL FAVERO A, MARTINO P et al.: Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. Clin. Infect. Dis. (1998) 28:250-255.
GLASMACHER A, HALN C, MOLITOR E, MARKLEIN G, SAUERBRUCH T, SCHMIDT-WOLF IG: Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regiments using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules. Mycoses (1999) 42:591-600.
STEVENS DA: Itraconazole in cyclodextrin solution. Pharmacother. (1999) 19:603-611.
WARNOCK DW, TURNER A, BURKE J: Comparison of high performance liquid chromatographic and microbiological methods for determination of itraconazole. J. Antimicrob. Chemother. (1988) 21:93-100.
GUPTA AK, DE DONCKER P, HANEKE E: Itraconazole pulse therapy for the treatment of Candida onychomycosis. J. Eur. Acad. Dermatol. Venereol. (2000) 15(2):112-115.
DE DONCKER P, SCHER R, BARAN R et al.: Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients. J. Am. Acad. Dermatol. (1997) 36:173-177.
ODOM RB, ALI R, SCHER RK et al.: A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychopycosis of the fingernail. J. Am. Dermatol. (1997) 36:231-235.
HANEKE E, ABECK D, RING J: Safety and efficacy of intermittent therapy with itraconazole in finger- and toenail-onychomycosis: a multicentre trial. Mycoses (1998) 41:521-527.
DE DONCKER P, GUPTA AK, MARYNISSEN G et al.: Itraconazole pulse therapy for onychomycosis and dermatomycoses: an overview. J. Am. Acad. Dermatol. (1998) 37:969-974.
WANG DL, WANG AP, LI RY, WANG R: Therapeutic efficacy and safety of one-week intermittent therapy with itraconazole for onychomycosis in a Chinese patient population. Dermatology (1999) 199:47-49.
GUPTA AK, MADDIN S, ARLETTE J et al.: Itraconazole pulse therapy is effective in dermatophyte onychomycosis of the toenail: a double-blind placebo-controlled study. J. Dermatol. Treat. (2000) 11:33-37.
PIERARD-FRANCHIMONT C, DE DONCKER P, VAN DE VELDE V, JACQUMIN P, ARRESE JE, PIERARD GE: Paradoxical response to itraconazole treatment in a patient with onychomycosis caused by Microsporum gypseum. Ann. Soc. Belge Med. Trop. (1995) 75:211-217.
GROLL AH, PISCITELLI SC, WALSH TJ: Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv. Pharmacol. (1998) 44:343-500.
VENKATAKRISHNAN K, VON MOLTKE LL, GREENBLATT DJ: Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin. Pharmacokinet. (2000) 38:111-180.
GUPTA AK, CHWETZOFF E, DEL ROSSO J, BARAN R: Hepatic safety of itraconazole. J. Cutan. Med. Surg. (2002) 6:210-213.
AHMAD SR, SINGER SJ, LEISSA BG: Congestive heart failure associated with itraconazole. Lancet (2001) 357:1716-1717.
ARRESE JE, FOGOUANG L, PIERARD-FRANCHIMONT C, PIERARD GE: Euclidean and fractal computer-assisted corneofungimetry. A comparison of 2% ketoconazole and 1% terbinafine topical formulations. Dermatology (2002) 204:222-227.
GUPTA AK, RYDER JE: The use of oral antifungal agents to treat onychomycosis. Dermatol. Clin. (2003) 21:469-479.
GUPTA AK, KOHLI Y, BATRA R: In vitro activities of posaconazole, ravuconazole, terbinafine, itraconazole and fluconazole against dermatophyte, yeast and non-dermatophyte species. Med. Mycol. (2005) 43:179-187.
GUPTA AK, LEONARDI C, STOLTZ RR et al.: A Phase I/II randomized, placebo-controlled, dose-ranging study evaluating the efficacy, safety and pharmacokinetics of ravuconazole in the treatment of onychomycosis. J. Eur. Acad. Dermatol. In press.
ODDS F, VAN GERVEN F, WOESTENBORGHS F et al.: Activity in vitro and in vivo of a novel azole antifungal agent: R126638. Antimicrob. Agents Chemother. (2004) 48:388-391.
VANDEN BOSSCHE H, AUSMA J, BOHETS H et al.: The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp and Microsporum canis. Antimicrob. Agents Chemother. (2004) 48:3272-3278.
PIERARD-FRANCHIMONT C, AUSMA J, WOUTERS L et al.: Activity of the triazole antifungal R126638 as assessed by corneofungimetry. Skin Pharmacol. Physiol. In press.
PIERARD GE, HENRY F, AUSMA J et al.: A proof-to-concept study on seborrheic dermatitis using R126638 as a potent oral anti- Malassezia agent. Skin Pharmacol. Physiol. In press.
JENSSEN JC: Pharmacokinetics of terbinafine in humans. J. Dermatol. Treat. (1990) 1:S15-S18.
KOVARIK JM, KIRKESSELI S, HUMBERT H, GRASS P, KUTZ K: Dose-proportional pharmacokinetics of terbinafine and its N-demethylated metabolite in healthy volunteers. Br. J. Dermatol. (1992) 126:S8-S13.
FAERGEMANN J, ZEHENDER H, MILLERIOUX L: Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), hair and nails during and after 250 mg terbinafine orally once per day for 7 and 14 days. Clin. Exp. Dermatol. (1994) 19:121-126.
SCHATZ F, BRAUTIGAM M, BOBROWOLSKI E et al.: Nail incorporation kinetics of terbinafine in onychomycosis patients. Clin. Exp. Dermatol. (1995) 20:377-383.
FINLAY AY, LEVER LR, THOMAS R, DYKES PJ: Nail matrix kinetics of oral terbinafine in onychoycosis and normal nails. J. Dermatol. Treat. (1990) 1:S51-S54.
FINLAY AY: Pharmacokinetics of terbinafine in the nail. Br. J. Dermatol. (1992) 126:S28-S32.
EVANS G, SIGURGEIRSSON B: Double blind, randomized study of continous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis. Br. Med. J. (1999) 318:1031-1035.
CRIBIER BJ, PAUL C: Long-term efficacy of antifungals in toenail onychomycosis: a critical review. Br. J. Dermatol. (2001) 145:446-452.
CRAWFORD F, YOUNG P, GODFREY C et al.: Oral treatments for toenail onychomycosis: a systematic review. Arch. Dermatol. (2002) 138:811-816.
HAUGH M, HELOU S, BOISSEL JP, CRIBIER BJ: Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials. Br. J. Dermatol. (2002) 147:118-21.
SIGURGEIRSSON B, OLAFSSON JH, STEINSSON JB et al.: Long-term effectiveness of treatment with terbinafine versus itraconazole in onychomycosis: a 5-year blinded prospective follow-up study. Arch. Dermatol. (2002) 138:353-357.
TOSTI A, PIRACCINI BM, STING HI et al.: Treatment of dermatophyte nail infections: an open randomized study comparing intermittent terbinafine therapy with continuous terbinafine treatment and intermittent itraconazole therapy. J. Am. Acad. Dermatol. (1996) 34(4):595-600.
GOODFIELD MJD, ANDREW L, EVANS EGV: Short term treatment of dermatophyte onychomycosis with terbinafine. Br. Med. J. (1992) 304:1151-1154.
LEBWOHL MG, DANIEL CR, LEYDEN J et al.: Efficacy and safety of terbinafine for nondermatophyte and mixed nondermatophyte toenail onychomycosis. Int. J. Dermatol. (2001) 40:358-360.
SVEJGAARD EL, BRANDRUP F, KRAGBALLE K et al.: Oral terbinafine in toenail dermatophytosis. Acta Derm. Venereol. (1997) 77:66-69.
HEIKKILÄ H, STUBB S: Long-term results in patients with onychomycosis treated with terbinafine or itraconazole. Br. J. Dermatol. (2002) 146:250-253.
BAUDRAZ-ROSSELET F, RAKOSI T, WILI PB, KENZELMAN R: Treatment of onychomycosis with terbinafine. Br. J. Dermatol. (1992) 126:S40-S46.
FINLAY AY, THOMAS R, DYKES PJ et al.: Descriptive correlations between various doses of oral terbinafine and concentrations in nail. J. Dermatol. Treat. (1994) 5:193-197.
ALPSOY E, YILMAZ E, BASALAN E: Intermittent therapy with terbinafine for dermatophyte toe onychomycosis: a new approach. J. Dermatol. (1996) 23:259-262.
ZAIAS N, REBELL G. The successful treatment of Trichophyton rubrum nail bed (distal subungal) onychomycosis with intermittent pulse-dosed terbinafine. Arch. Dermatol. (2004):140:691-695.
FAERGEMANN J, ZEHENDER H, BOUKHABZA A et al.: A double-blind comparison of levels of terbinafine and itraconazole in plasma, skin, sebum, hair and nails during and after oral medication. Acta Derm. Venereol. (1997) 77(1):74-76.
GUPTA AK, DEL ROSSO JQ: An evaluation of intermittent therapies used to treat onychomycosis and other dermatomycoses with the oral antifungal agents. Int. J. Dermatol. (2000) 39:401-411.
WATSON A, MARLEY J, ELLIS D, WILLIAMS T: Terbinafine in onychomycosis of the toenail: a novel treatment protocol. J. Am. Acad. Dermatol. (1995) 33:775-779.
GUPTA AK, BARAN R, SUMMERBELL R: Onychomycosis: strategies to improve efficacy and reduce recurrence. J. Eur. Acad. Dermatol. Venereol. (2002) 16:579-586.
MEDOFF G, KOBAYASHI GS, KWANG CN et al.: Potentialisation of rifampicin and flucocytosine as antifungal antibiotics by amphotericin B. Proc. Soc. Exp. Biol. Med. (1971) 138:571-574.
POLACK A: The past, present and future of antimycotic combination therapy. Mycoses (1999) 42:355-370.
RUBIN MA, CARROLL KC, CAHILL BC: Caspofungin in combination with itraconazole for the treatment of invasive aspergillosis in humans. Clin. Infect Dis. (2002) 34:1160-1161.
STEINBACH WJ, STEVENS DA, DENNING DW: Combination and sequential antifungal therapy for invasive aspergillosis: review of published in vitro and in vivo interactions and 6281 clinical cases from 1966 to 2001. Clin. Infect. Dis. (2003) 37:S188-S224.
KONTOYIANNIS DP, HACHEM R, LEWIS RE et al.: Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer (2003) 98:292-299.
SUGAR AM: Use of amphotericin B with azole antifungal drugs: what are we doing? Antimicrob. Agents Chemother. (1995) 39:1907-1912.
BOHME A, JUST-NUBLING G, BERGMANN L, SHAH PM, STILLE W, HOELZER D: Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies. J. Antimicrob. Chemother. (1999) 42:443-451.
GLASMACHER A, HAHN C, LEUTNER C et al.: Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole. Mycoses (1999) 42:443-451.
REPKA MA, MIDIDODDI PK, STODGHILL ST: Influence of human nail etching for the assessment of topical onychomycosis therapies. Int. J. Pharmacol. (2004) 282:95-106.
REPKA MA, MIDIDODDI PK, STODGHILL SP: Influence of human nail etching for the assessment of topical onychomycosis therapies. Int. J. Pharm. (2004) 282:95-106.
GUPTA AK, KONNIKOV N, LYNDE CW: Sequential pulse therapy with itraconazole and terbinafine to treat onychomycosis of the fingernails. J. Dermatol. Treat. (2000) 11:151-154.
GUPTA A, LYNDE CW, KONNIKOV N: Single-blind, randomized, prospective study of sequential itraconazole and terbinafine pulse compared with terbinafine pulse for the treatment of toenail onychomycosis. J. Am. Acad. Dermatol. (2001) 44:485-491.
PIERARD GE, PIERARD-FRANCHIMONT C, ARRESE JE: The boosted oral antifungal treatment for onychomycosis beyond the regular itraconazole pulse dosing regimen. Dermatology (2000) 200:185-187.
GOFFIN V, ARRESE J, PIERARD GE: Onychomycoses récalcitrantes et le 'low-cost BOAT' au fluconazole. Skin (2002) 5:145-147.
PIERARD GE, PIERARD-FRANCHIMONT C, ARRESE JE: The boosted antifungal topical treatment (BATT) for onychomycosis. Med. Mycol. (2000) 38:391-392.
HAY RJ: A comparison of tioconazole 28% nail solution versus base as an adjunct to oral griseofulvin in patients with onychomycosis. Clin. Exp. Dermatol. (1987) 12:175.
GUPTA AK and the ONYCHOMYCOSIS COMBINATION THERAPY STUDY GROUP: Randomized evaluation, blind, multicentre, Phase IV study of the efficacy and safety of ciclopirox nail laquer topical solution 8% in combination with oral terbinafine in the treatment of moderate to severe toenail onychomycosis. An analysis of dermatophyte positive patients. J. Drugs Dermatol. In press.
KIM HC, JUNG KB, SHIN DH, KIM KH: Comparison of compliance and cure rate of systemic antifungal therapy versus combination therapy with systemic and topical agent in toenail onychomycosis. Kor. J. Med. Mycol. (2002) 7:35-41.
LAUHARANTA J, ZAUG M, POLAK A et al.: Combination of amorolfine with griseofulvin: in vitro activity and clinical results in onychomycosis. J. Am. Med. Assoc. SEA (1993) 9(Suppl. 4):23.
ZAUG M: Amorolfine nail lacquer: clinical experience in onychomycosis. J. Eur. Acad. Dermatol. Venereol. (1995) 4:S23-S30.
BARAN R, FEUILHADE M, DATRY A et al.: A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycosis affecting the nail region. Br. J. Dermatol. (2000) 142:1177.
BARAN E, BOCHENSKI J, DUCZKOWSKI M, BARAN W: Combination therapy for onychomycosis with amorolfine nail lacquer and oral antifungal agents. Mikol. Lek. (2003) 10:79-83.
LECHA M, ALSINA M, TORRES M et al.: Amorolfine and itraconazole combination for severe toenail onychomycosis: results of an open randomised trial in Spain. Br. J. Dermatol. (2001) 145(Suppl. 60):21.
RIGOPOULOS D, KATOULIS A, IOANNIDES D et al.: A randomised trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis. Br. J. Dermatol. (2003) 149:151.
SERGEEV Y, SERGEEV A: Pulsed combination therapy: the new option for onychomycosis. Mycoses (2001) 44(Suppl. 1):68.
HARMAN S, ASHBEE HR, EVANS EG: Testing of antifungal combinations against yeasts and dermatophytes. J. Dermatol. Treat. (2004) 15:104-107.
EPSTEIN E: How often does oral treatment of toenail onychomycosis produce a disease-free nail? An analysis of published data. Arch. Dermatol. (1998) 134:1551-1554.
GOODFIELD MJD, EVANS EGV: Combined treatment with surgery and short duration oral antifungal therapy in patients with limited dermatophyte toenail infection. J. Dermatol. Treat. (2000) 11:259-262.
BARAN R, HAY RJ: Partial surgical avulsion of the nail in onychomycosis. Clin. Exp. Dermatol. (1985) 23:305-313.
BARAN R: Nail fungal infection and treatment. Hand Clin. (2002) 18:625-628.