1Division of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Science Center (Sunnybrook site) and the University of Toronto, Toronto, Canada.
2Mediprobe Laboratories Inc., Toronto, Ontario, Canada.
3University of Western Ontario, London, Ontario, Canada.
Vulvovaginal candidiasis is a common occurrence among women over 25 years of age. The likelihood of developing infection increases with pregnancy, the use of oral contraceptives or antibiotics, or immune disorders. However, in many cases, the etiology of the disorder is unknown. Sobel1 suggests that some cases of reinfection may actually be cases of relapse, due to either inadequate testing methods, which result in false-negative results after treatment, or to ineffective treatments. Misdiagnosis of the causative organism may also result in ineffective treatment. The most common causal Candida species is C. albicans. However, other, less easily eradicated species may also be involved.
itraconazole, vaginal candidiasis
Itraconazole (Sporanox®, Janssen Pharmaceuticals) is a triazole with fungistatic activity against Candida species, particularly C. albicans. Itraconazole reaches high concentrations in tissue due to a high affinity for proteins, particularly keratin.2 Active levels of the drug may persist in vaginal epithelium for four days after a one-day treatment.2 It has been suggested that a cause of relapse in women with vaginal candidiasis is the re-emergence of Candida organisms from deeper layers of vaginal tissue.3, 4 Oral therapy, unlike topical therapy, may be effective against these “hidden” organisms.
While the majority of cases of vulvovaginal candidiasis are caused by C. albicans, some infections are caused by other Candida species, including C. tropicalis and C. glabrata.5 An increasing number of infections appear to be caused by these other Candida species: 9.9% of cases in 1988 increased to 17.2% in 1995.6 Itraconazole may have a greater in vitro activity against non-albicans species than other azoles, like fluconazole.7 Therefore, itraconazole may be more effective against a broader range of causative organisms.
Itraconazole is effective and safe in the treatment of vulvovaginal candidiasis8-15 (see Table 1). Treatment regimens of itraconazole 200mg/day for 3 consecutive days8,9,11 or 200mg given twice in one day9,12,14 have resulted in a high mycological and clinical cure. Studies have also demonstrated mycological cure rates similar to standard treatments, like clotrimazole12,13 and fluconazole.14,15
Approximately 5% of women experience recurrent infection, which is defined as at least four episodes in one year, or three episodes known to be unrelated to the use of antibiotics.5 Itraconazole may be used prophylactically in order to reduce relapse rates16-18 (Table 2). Upon cessation of prophylactic treatment, recurrence rates tend to be high in women with a previous history of recurrent vulvovaginal candidiasis.
|Author||Study Design||Regimen (n)||Mycological Cure||Comments (Clinical and Safety Evaluations)|
|Sanz Sanz, Hernanz9||Randomized dose-finding|
|Bloch, et al10||Open, prospective, dose-finding|
|Silva-Cruz, et al11||Randomized, double-blind, placebo-controlled|
|Tobin, et al12||Multicentre, single-blind, randomized, parallel-group|
|Stein, Mummaw13||Randomized, controlled|
|Woolley, Higgins14||Randomized, controlled|
|Mikamo, et al15||Randomized, controlled|
Table 1: Studies evaluating the efficacy of itraconazole in the treatment of vulvovaginal candidiasis.
|Author||Study Design||Regimen (n)||Mycological Cure||Comments (Clinical Cure and Safety)|
|Creatas, et al16||Open|
|Spinillo, et al17||Randomized, controlled|
|Guaschino, et al18||Prospective, non-randomized|
Table 2: Studies evaluating the efficacy of itraconazole in the prophylactic treatment of vulvovaginal candidiasis.
Itraconazole appears to be an effective treatment for acute and chronic vulvovaginal candidiasis. Oral therapy tends to be shorter in duration than topical therapy. Moreover, patients often prefer oral treatment due to the shorter treatment period and to the ease of administration compared to topical treatments, resulting in increased patient compliance.3 As well, itraconazole used as a prophylactic treatment is a viable option in preventing future recurrence of infection.
We wish to thank J.E. Swan for her contribution to this manuscript.
- Sobel JD. Candidal vulvovaginitis. Clin Obstet Gynecol 36(1):153-65 (1993 Mar).
- Heykants J, Van Peer A, Van de Velde V, et al. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 32(Suppl 1):67-87 (1989).
- Rees T, Philips R. Multicenter comparison of one-day oral therapy with fluconazole or itraconazole in vaginal candidiasis. Int J Gynecol Obstet 37(Suppl):33-8 (1992).
- Fong IW. The value of chronic suppressive therapy with itraconazole versus clotrimazole in women with recurrent vaginal candidiasis. Genitourin Med 68(6):374-7 (1992 Dec).
- Ringdahl EN. Treatment of recurrent vulvovaginal candidiasis. Am Fam Physician 61(11):3306-12 (2000 Jun).
- Spinillo A, Capuzzo E, Gulminetti R, Marone P, Colonna L, Piazza G. Prevalence of and risk factors for fungal vaginitis caused by non-albicans species. Am J Obstet Gynecol 176(1 pt 1):138-41 (1997 Jan).
- Lynch ME, Sobel JD. Comparative in vitro activity of antimycotic agents against pathogenic vaginal yeast isolates. J Med Vet Mycol 32(4):267-74 (1994).
- Hay RJ, Dupont B, Graybill JR. First International Symposium on Itraconazole: a summary. Rev Infect Dis 9(Suppl 1):S1-3 (1987).
- Sanz Sanz F, del Palacio Hernanz A. Randomized comparative trial of three regimens of itraconazole for treatment of vaginal mycoses. Rev Infect Dis 9(Suppl 1):S139-42 (1987 Jan-Feb).
- Bloch B, Barnard PG, Burger GD, Meyer JS, Parkes JR, Smythe E. Itraconazole in the treatment of acute vaginal candidiasis. S Afr Med J 73(3):172-3 (1988 Feb).
- Silva-Cruz A, Andrade L, Sobral L, Francisca A. Itraconazole versus placebo in the management of vaginal candidiasis. Int J Gynecol Obstet 36(3):229-32 (1991 Nov).
- Tobin JM, Loo P, Granger SE. Treatment of vaginal candidosis: a comparative study of the efficacy and acceptability of itraconazole and clotrimazole. Genitourin Med 68(1):36-8 (1992 Feb).
- Stein GE, Mummaw N. Placebo-controlled trial of itraconazole for treatment of acute vaginal candidiasis. Antimicrob Agents Chemother 37(1):89-92 (1993 Jan).
- Woolley PD, Higgins SP. Comparison of clotrimazole, fluconazole and itraconazole in vaginal candidiasis. Br J Clin Pract 49(2):65-6 (1995 Mar-Apr).
- Mikamo H, Kawazoe K, Sato Y, Hayasaki Y, Tamaya T. Comparative study on the effectiveness of antifungal agents in different regimens against vaginal candidiasis. Chemotherapy 44(5):364-8 (1998 Sep-Oct).
- Creatsas GC, Charalambidis VM, Zagotzidou EH, Anthopoulou HN, Michailidis DC, Aravantinos DI. Chronic or recurrent vaginal candidosis: short-term treatment and prophylaxis with itraconazole. Clin Ther 15(4):662-71 (1993 Jul-Aug).
- Spinillo A, Colonna L, Piazzi G, Baltaro F, Monaco A, Ferrari A. Managing recurrent vulvovaginal candidiasis. Intermittent prevention with itraconazole. J Reprod Med 42(2):83-7 (1997 Feb).
- Guaschino S, De Seta F, Sartore A, et al. Efficacy of maintenance therapy with topical boric acid in comparison with oral itraconazole in the treatment of recurrent vulvovaginal candidiasis. Am J Obstet Gynecol 184(4):598-602 (2001 Mar).