Skip to main content
SpringerLink
Log in

Pharmacoeconomic Analysis of Oral Antifungal Therapies Used to Treat Dermatophyte Onychomycosis of the Toenails

A US Analysis

  • Original Research Article
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Summary

Until a few years ago, griseofulvin and ketoconazole were the only 2 oral agents available for the treatment of dermatophyte onychomycosis of the toenails. With the availability of the newer antifungal agents, such as itraconazole, terbinafine and fluconazole, the armamentarium of drugs available to treat onychomycosis has expanded.

The objective of this study was to determine the relative cost effectiveness of the most commonly used oral antifungal agents in the US for the treatment of dermatophyte onychomycosis of the toenails from the perspective of a third-party payer. The time horizon was 3 years.

A 5-step approach was used in this pharmacoeconomic analysis. First, the purpose of the study, the comparator drugs and their dosage regimens were defined. In step II, the medical practice and resource-consumption patterns associated with the treatment of onychomycosis were identified. In step III, a metaanalysis was performed on all studies meeting prespecified criteria, and the mycological cure rates of the comparator drugs were determined. In step IV, the treatment algorithm for the management of onychomycosis was constructed for each drug. The cost-of-regimen analysis for each comparator incorporated the drug acquisition cost, medical-management cost and cost of managing adverse drug reactions. The expected cost per patient, number of symptom-free days (SFDs), cost per SFD and the relative cost effectiveness for the comparator drugs were calculated. In step V, a sensitivity analysis was performed.

The drug comparators for this study were griseofulvin, itraconazole (continuous and pulse), terbinafine and fluconazole. The mycological cure rates [mean ± standard error (SE)] from the meta-analysis were griseofulvin 24.5 ± 6.7%, itraconazole (continuous) 66.4 ± 6.1%, itraconazole (pulse) 76 ± 9.3%, terbinafine 74 ± 7% and fluconazole 59%. The cost per mycological cure was griseofulvin $US8089, itraconazole (continuous) $US1877, itraconazole (pulse) $US991, terbinafine $US1125 and fluconazole $US1506. The corresponding cost per SFD was griseofulvin $US7.05, itraconazole (continuous) $US2.18, itraconazole (pulse) $US1.26, terbinafine $US1.28 and fluconazole $US2.12. The resulting ratios of cost per SFD relative to itraconazole (pulse) [1.00] were terbinafine 1.02, itraconazole (continuous) 1.73, fluconazole 1.69 and griseofulvin 5.62.

In conclusion, in this analysis, itraconazole (pulse) and terbinafine were the most cost-effective therapies for dermatophyte onychomycosis of the toenails, both being substantially more cost effective than griseofulvin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gupta AK, Jain HC, Lynde CW, et al. Prevalence of unsuspected onychomycosis in patients visiting dermatologists’ offices in Ontario, Canada: a multicenter study of 2001 patients. Int J Dermatol 1997; 36: 783–7

    Article  PubMed  CAS  Google Scholar 

  2. Charif M, Elewski BE. The prevalence of onychomycosis in Northeastern Ohio. Arch Dermatol 1997; 133: 1172–3

    Article  PubMed  Google Scholar 

  3. Pardo-Costello V, Pardo OA. Diseases of the nails. Springfield (IL): Charles C Thomas, 1960

    Google Scholar 

  4. Achten G, Wanet-Rouard J. Onychomycoses in the laboratory. Mykosen 1978; 21: 125–7

    Google Scholar 

  5. Grigoriu D, Grigoriu A. Les onychomycoses. Rev Med Suisse Romande 1975; 95: 839–49

    PubMed  CAS  Google Scholar 

  6. Gupta AK, Sauder DN, Shear NH. Antifungal agents: an overview. Part II. J Am Acad Dermatol 1994; 30: 911–33

    Article  PubMed  CAS  Google Scholar 

  7. Gupta AK, Scher RK, De Doncker P. Current management of onychomycosis. Dermatol Clin 1997; 15 (1): 121–35

    Article  PubMed  CAS  Google Scholar 

  8. De Doncker P, Decroix J, Pierard GE, et al. Itraconazole pulse therapy is effective in the treatment of onychomycosis: a pharmacokinetic/pharmacodynamic and clinical evaluation. Arch Dermatol 1996; 132: 34–41

    Article  PubMed  CAS  Google Scholar 

  9. Marchetti A, Piech CT, Mc Ghan WF, et al. Pharmacoeconomic analysis of oral therapies for onychomycosis: a US model. Clin Ther 1996; 18 (4): 757–77

    Article  PubMed  CAS  Google Scholar 

  10. Arikian SR, Einarson TR, Kobelt-Nguyen G, et al. A multinational pharmacoeconomic analysis of oral therapies for onychomycosis. Br J Dermatol 1994; 130 Suppl. 43: 35–44

    Article  PubMed  Google Scholar 

  11. Van Doorslaer EKA, Tormans G, Gupta AK, et al. Economic evaluation of antifungal agents in the treatment of toenail onychomycosis in Germany. Dermatology 1996; 193: 239–44

    Article  PubMed  Google Scholar 

  12. Der Simonian R, Laird NM. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–8

    Article  Google Scholar 

  13. Velanovich V. Meta-analysis for combining Bayesian probabilities. Med Hypotheses 1 1991; 35: 192–5

    Article  CAS  Google Scholar 

  14. Be Dell LS, editor. Mosby’s complete drug reference. Physicians Gen Rx. ed. St. Louis: Mosby-Year Book Inc., 1997

    Google Scholar 

  15. Health Care Finance Administration. 1995 Annual Medicare Physician Fee Schedule-Carrier File. Baltimore: Empire New York Carrier, 1995

    Google Scholar 

  16. Health Care Finance Administration. 1995 Clinical Diagnostic Lab Fee Schedule-Carrier File. Baltimore: Empire New York Carrier, 1995

    Google Scholar 

  17. Janssen Pharmaceutica Inc. Itraconazole product monograph. Titusville (NJ): Janssen Pharmaceutica Inc., 1996

    Google Scholar 

  18. Sandoz Pharmaceuticals Corporation Inc. Terbinafine product monograph. East Hanover (NJ): Sandoz Pharmaceuticals Corporation Inc., 1996

    Google Scholar 

  19. Faergemann J, Anderson C, Hersle K, et al. Double-blind, parallel-group comparison of terbinafine and griseofulvin in the treatment of toenail onychomycosis. J Am Acad Dermatol 1995; 32: 750–3

    Article  PubMed  CAS  Google Scholar 

  20. Montero-Gei M, Robles-Soto ME, Schlager H. Fluconazole in the treatment of severe onychomycosis. Int J Dermatol 1996; 35: 587–8

    Article  PubMed  CAS  Google Scholar 

  21. Villars VV, Jones TC. Special features of the clinical use of oral terbinafine in the treatment of fungal diseases. Br J Dermatol 1992; 126: 61–9

    Article  PubMed  Google Scholar 

  22. Gupta AK, De Doncker P, Scher RK, et al. Itraconazole for the treatment of onychomycosis: an overview. Int J Dermatol. In press

  23. Scher RK. A placebo-controlled, randomized, double-blind trial of once weekly fluconazole (150, 300 or 140mg) in the treatment of distal subungual onychomycosis of the toenail. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 1997 Sep 28-Oct 1; Toronto

  24. Einarson TR, Arikian SR, Doyle JJ. Rank-order stability analysis (ROSA): testing pharmacoeconomic data. Med Decis Making 1995; 15: 367–72

    Article  PubMed  CAS  Google Scholar 

  25. Davies RR, Everall JD, Hamilton E. Mycological and clinical evaluation of griseofulvin for chronic onychomycosis. BMJ 1967; 3: 464–9

    Article  PubMed  CAS  Google Scholar 

  26. Russell B, Frain-Bell W, Riddell RW, et al. Chronic ringworm infection of the skin and nails treated with griseofulvin. Lancet 1960; I: 1140–7

    Google Scholar 

  27. Svejgaard E. Oral ketoconazole as an alternative to griseofulvin in recalcitrant dermatophyte infections and onychomycosis. Acta Derm Venereol (Stockh) 1985; 65: 143–9

    CAS  Google Scholar 

  28. Korting HC, Schafer-Korting M, Zienicke H, et al. Treatment of tinea unguium with medium and high doses of ultramicrosize griseofulvin compared with that with itraconazole. Antimicrob Agents Chemother 1993; 37: 2064–8

    Article  PubMed  CAS  Google Scholar 

  29. WalsØe I, Stangerup M, Svejgaard E. Itraconazole in onychomycosis: Open and double-blind studies. Acta Derm Venereol (Stockh) 1990; 70: 137–40

    Google Scholar 

  30. Arenas R, Fernandez G, Dominguez L. Onychomycosis treated with itraconazole or griseofulvin alone with and without a topical antimycotic or keratolytic agent. Int J Dermatol 1991; 30: 586–9

    Article  PubMed  CAS  Google Scholar 

  31. Hofmann H, Bräutigam M, Weidinger G, et al. Treatment of toenail onychomycosis: A randomized, double-blind study with terbinafine and griseofulvin. Arch Dermatol 1995; 131: 919–22

    Article  PubMed  CAS  Google Scholar 

  32. Goldfarb NJ, Sulzberger MB. Experiences in one hundred thirty-seven patients with oral griseofulvin. Arch Dermatol 1960; 81: 859–62

    Article  PubMed  CAS  Google Scholar 

  33. Kaminsky A. Comparative effects of griseofulvin on onychomycosis and on psoriasis. Arch Dermatol 1960; 60 (5): 838–40

    Article  Google Scholar 

  34. Williams DI. Griseofulvin and Trichophyton rubrum infections. Arch Dermatol 1960; 81: 769–71

    Article  PubMed  CAS  Google Scholar 

  35. Hay RJ, Clayton YM, Griffiths WAD, et al. A comparative double-blind study of ketoconazole and griseofulvin in dermatophytosis. Br J Dermatol 1985; 112: 691–6

    Article  PubMed  CAS  Google Scholar 

  36. Piepponen T, Blomqvist K, Brandt H, et al. Efficacy and safety of itraconazole in the long-term treatment of onychomycosis. J Antimicrob Chemother 1992; 29: 195–205

    Article  PubMed  CAS  Google Scholar 

  37. Stevenson CJ, Djavahiszwili N. Chronic ringworm of the nails. Lancet 1961; I: 373–4

    Article  Google Scholar 

  38. Levin H, Alden HS, Ajello L. Use of griseofulvin in office practice. Arch Dermatol 1960; 81 (5): 827–32

    Article  PubMed  CAS  Google Scholar 

  39. Quintaville P. Onychomycosis treated with ultrafine griseofulvin. J Am Podiat Assoc 1966; 56: 119–20

    Google Scholar 

  40. Dillaha CJ, Jansen GT. Dosage requirements of griseofulvin in onychomycosis due to Trichophyton rubrum. Arch Dermatol 1960; 81: 192–198

    Article  Google Scholar 

  41. Blank H, Smith GJ, Roth FJ, et al. Griseofulvin for the systemic treatment of dermatomycoses. JAMA 1959; 171: 2168–74

    Article  CAS  Google Scholar 

  42. Maibach HI, Kligman AM. Short-term treatment of onychomycosis with griseofulvin. Arch Dermatol 1960; 18: 733–4

    Article  Google Scholar 

  43. González-Ochoa A, Ahumada-Padilla M. New schemes in the treatment of dermatophytoses with griseofulvin. Arch Dermatol 1960; 81 (5): 833–7

    Article  PubMed  Google Scholar 

  44. Haneke E, Tausch I, Bräutigam M, et al. Short-duration treatment of fingernail dermatophytosis: a randomized, doubleblind study with terbinafine and griseofulvin. J Am Acad Dermatol 1995; 32: 72–7

    Article  PubMed  CAS  Google Scholar 

  45. Willemsen M, De Doncker P, Willems J, et al. Posttreatment itraconazole levels in the nail. J Am Acad Dermatol 1992; 26: 731–5

    Article  PubMed  CAS  Google Scholar 

  46. Haneke E, Delescluse J, Plinck EPB, et al. The use of itraconazole in onychomycosis. Eur J Dermatol 1996; 6: 7–10

    CAS  Google Scholar 

  47. De Backer M, De Keyser P, De Vroey C, et al. A 12−week treatment for dermatophyte toe onychomycosis: terbinafine 250mg/day vs. itraconazole 200mg/day-a double-blind comparative trial. Br J Dermatol 1996; 134 Suppl. 46: 16–7

    Article  PubMed  Google Scholar 

  48. Bräutigam M, Nolting S, Schopf RE, et al. Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. BMJ 1995; 311: 919–22

    Article  PubMed  Google Scholar 

  49. Arenas R, Dominguez-Cherit J, Fernández LM. Open randomized comparison of itraconazole versus terbinafine in onychomycosis. Int J Dermatol 1993; 34: 138–43

    Article  Google Scholar 

  50. Odom R, Daniel R, Aly R. A double-blind, randomized comparison of itraconazole capsules and placebo in the treatment of onychomycosis of the toenail. J Am Acad Dermatol 1996; 35 (1): 110–1

    Article  PubMed  CAS  Google Scholar 

  51. Jones HE, Zaias N. Double-blind, randomized comparison of itraconazole capsules and placebo in onychomycosis of toenail. Int J Dermatol 1996; 35 (8): 589–90

    Article  PubMed  CAS  Google Scholar 

  52. Havu V, Brandt H, Heikkilä H, et al. A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis. Br J Dermatol 1997; 136: 230–4

    Article  PubMed  CAS  Google Scholar 

  53. André J, De Doncker P, Laporte M, et al. Onychomycosis caused by Microsporum canis: treatment with itraconazole. J Am Acad Dermatol 1995; 32: 1052–3

    Article  PubMed  Google Scholar 

  54. Hanifin JM, Tofte SJ. Itraconazole therapy for recalcitrant dermatophyte infections. J Am Acad Dermatol 1988; 18: 1077–80

    Article  PubMed  CAS  Google Scholar 

  55. Rongioletti F, Robert E, Tripodi S, et al. Treatment of onychomycosis with itraconazole. J Dermatol Treat 1992; 2: 145–6

    Article  Google Scholar 

  56. Stary A, Storch M, Hörting-Müller I. Systemic treatment of onychomycosis with itraconazole: clinical and mycological results [abstract]. 3rd Congress of the European Academy of Dermatology and Venereology; 1993 Sep 26-30; Copenhagen, 348

    Google Scholar 

  57. Hay RJ, Clayton YM, Moore MK, et al. An evaluation of itraconazole in the management of onychomycosis. Br J Dermatol 1988; 119: 359–66

    Article  PubMed  CAS  Google Scholar 

  58. De Padova-Elder SM, Ditre CM, Kantor GR, et al. Candidiasis endocrinopathy syndrome. Arch Dermatol 1994; 130: 19–22

    Article  Google Scholar 

  59. Kim JA, Ahn KJ, Kim JM, et al. Efficacy and tolerability of itraconazole in patients with fingernail onychomycosis: a 6−week pilot study. Curr Ther Res 1995; 56: 1066–75

    Article  CAS  Google Scholar 

  60. De Doncker PRG, Scher RK, Baran RL, 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: 173–7

    Article  PubMed  Google Scholar 

  61. Hay RJ, Baran R, Moore MK, et al. Candida onychomycosis: an evaluation of the role of Candida species in nail disease. Br J Dermatol 1988; 118: 47–58

    Article  PubMed  CAS  Google Scholar 

  62. De-Doncker P, Van Lint J, Dockx P, et al. Pulse therapy with one-week itraconazole monthly for three or four months in the treatment of onychomycosis. Cutis 1995; 56: 180–3

    PubMed  CAS  Google Scholar 

  63. Itraconazole product monograph. Ontario: Jannsen-Ortho, 1997

    Google Scholar 

  64. Bonifaz A, Carrasco-Gerard E, Saúl A. Itraconazole in onychomycosis: Intermittent dose schedule. Int J Dermatol 1997; 36: 70–2

    Article  PubMed  CAS  Google Scholar 

  65. Haneke E, Ring J, Tajerbashi D, et al. Efficacy and safety of itraconazole 1 − week pulse therapy in the treatment of onychomycosis: an open German multicenter trial [poster presentation]. 54th Annual Meeting of the American Academy of Dermatology; 1996 Feb 10-15; Washington, DC

    Google Scholar 

  66. Tosti A, Piraccini BM, Stinchi C, 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: 595–600

    Article  PubMed  CAS  Google Scholar 

  67. Goodfield MJD, Andrew L, Evans EGV. Short term treatment of dermatophyte onychomycosis with terbinafine. BMJ 1992; 304: 1151–4

    Article  PubMed  CAS  Google Scholar 

  68. Van Der Schroeff JG, Cirkel PKS, Crijns MB, et al. A randomized treatment duration-finding study of terbinafine in onychomycosis. Br J Dermatol 1992; 126: 36–9

    Article  PubMed  Google Scholar 

  69. Galimberti R, Kowalczuk A, Flores V, et al. Onychomycosis treated with a short course of oral terbinafine. Int J Dermatol 1996; 35 (5): 374–5

    Article  PubMed  CAS  Google Scholar 

  70. Watson A, Marley J, Ellis D, et al. Terbinafine in onychomycosis of the toenail: a novel treatment protocol. J Am Acad Dermatol 1995; 33 (5 Pt 1): 775–9

    Article  PubMed  CAS  Google Scholar 

  71. Svejgaard EL, Brandrup F, Dragballe K, et al. Oral terbinafine in toenail dermatophytosis. Acta Derm Venereol (Stockh) 1997; 77: 66–9

    CAS  Google Scholar 

  72. Rakosi T. Terbinafine and onychomycosis [abstract]. Dermatologica 1990; 181: 174

    Google Scholar 

  73. Shuster S, Munro C. Single dose treatment of fungal nail disease [letter]. Lancet 1992; 339: 1066

    Article  PubMed  CAS  Google Scholar 

  74. Zaias N. Management of onychomycosis with oral terbinafine. J Am Acad Dermatol 1990; 23: 810–2

    Article  PubMed  CAS  Google Scholar 

  75. Baudraz-Rosselet F, Rakosi T, Wili PB, et al. Treatment of onychomycosis with terbinafine. Br J Dermatol 1992; 126: 40–6

    Article  PubMed  Google Scholar 

  76. Goodfield MJD, Rowell NR, Forster RA, et al. Treatment of dermatophyte infection of the finger- and toe-nails with terbinafine (SF 86-327, Lamisil), an orally active fungicidal agent. Br J Dermatol 1989; 121: 753–7

    Article  PubMed  CAS  Google Scholar 

  77. Goodfield MJD. Short-duration therapy with terbinafine for dermatophyte onychomycosis: a multicentre trial. Br J Dermatol 1992; 126: 33–5

    Article  PubMed  Google Scholar 

  78. Goodfield MJD. Clinical results with terbinafine in onychomycosis. J Dermatol Treat 1990; 1: 55–7

    Article  Google Scholar 

  79. Zaias N, Serrano L. The successful treatment of finger Trichophyton rubrum onychomycosis with oral terbinafine. Clin Exp Dermatol 1989; 14: 120–3

    Article  PubMed  CAS  Google Scholar 

  80. Savin RC, Atton AV. Terbinafine in onychomycosis: a mini study. Int J Dermatol 1993; 32: 918–9

    Article  PubMed  CAS  Google Scholar 

  81. Eastcott DF. Terbinafine and onychomycosis [letter]. N Z Med J 1991; 104: 17

    PubMed  CAS  Google Scholar 

  82. Wong CK, Cho YL. Very short duration therapy with oral terbinafine for fingernail onychomycosis. Br J Dermatol 1995; 133: 329–47

    Article  PubMed  CAS  Google Scholar 

  83. Nolting S, Bräutigam M, Weidinger G. Terbinafine in onychomycosis with involvement by non-dermatophytic fungi. Br J Dermatol 1994; 130: 16–21

    Article  PubMed  Google Scholar 

  84. Segal R, Kritzman A, Cividalli L, et al. Treatment of Candida nail infection with terbinafine. J Am Acad Dermatol 1996; 35 (6): 958–61

    Article  PubMed  CAS  Google Scholar 

  85. Roberts DT, Richardson MD, Dwyer PK, et al. Terbinafine in chronic paronychia and Candida onychomycosis. J Dermatol Treat 1992; 3: 39–42

    Article  Google Scholar 

  86. Tosti A, Piraccini BM, Stinchi C, et al. Onychomycosis due to Scopulariopsis brevicaulis: clinical features and response to systemic antifungals. Br J Dermatol 1996; 135: 799–802

    Article  PubMed  CAS  Google Scholar 

  87. Lee KH, Kim YS, Kim MS, et al. Study of the efficacy and tolerability of oral terbinafine in the treatment of onychomycosis in renal transplant patients. Transplant Proc 1996; 28: 1488–9

    PubMed  CAS  Google Scholar 

  88. Einarson TR, Arikian SR, Shear NH. Cost-effectiveness analysis for onychomycosis therapy in Canada from a government perspective. Br J Dermatol 1994; 130: 32–4

    Article  PubMed  Google Scholar 

  89. Halpern MT, Palmer C. Modeling the cost-effectiveness of oral therapy for nail fungus. Am J Man Care 1996; 2: 59–66

    Google Scholar 

  90. Summerbell RC, Kane J, Krajden S. Onychomycosis, tinea pedis and tinea manuum caused by non-dermatophytic filamentous fungi. Mycoses 1989; 32: 609–19

    Article  PubMed  CAS  Google Scholar 

  91. Cauwenbergh G, Degreef H, Heykants J, et al. Pharmacokinetic profile of orally administered itraconazole in human skin. J Am Dermatol 1986; 18: 263–8

    Article  Google Scholar 

  92. Griseofulvin® Product Information, Physician’s Desk Reference. Montvale (NJ): Medical Economics Company, Inc., 1997: 2499–501

Download references

Author information

Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, Sunnybrook Health Science Center, and the University of Toronto, Toronto, Ontario, Canada

    Aditya K. Gupta

Authors
  1. Aditya K. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aditya K. Gupta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gupta, A.K. Pharmacoeconomic Analysis of Oral Antifungal Therapies Used to Treat Dermatophyte Onychomycosis of the Toenails. Pharmacoeconomics 13, 243–256 (1998). https://doi.org/10.2165/00019053-199813020-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-199813020-00007

Keywords

Search

Navigation