Drugs

, Volume 68, Issue 13, pp 1787–1802 | Cite as

Local Treatment of Vulvovaginal Candidosis

General and Practical Considerations
  • José das Neves
  • Eugénia Pinto
  • Branca Teixeira
  • Gustavo Dias
  • Patrocínia Rocha
  • Teresa Cunha
  • Bárbara Santos
  • Maria H. Amaral
  • Maria F. Bahia
Therapy In Practice

Abstract

Vulvovaginal candidosis is a common worldwide female medical problem, occurring mostly in women of childbearing age. Currently available options for the treatment of this condition include local and oral (systemic) therapy. Both alternatives have been considered equally effective in the treatment of uncomplicated vulvovaginal candidosis, although oral regimens are often preferred by physicians and women. However, local treatment presents several advantageous and unique features that may favour this therapeutic approach. The availability of numerous antifungal drugs and products for topical administration makes the selection quite challenging as this task is mostly based on personal experience or anecdotal data. Also, recent advances have been made in topical antifungal formulations and there is an increasing availability of over-the-counter products. Therefore, a review of both general and practical considerations related to the local treatment of vulvovaginal candidosis is timely.

In summary, azoles and short-term regimens are usually recommended for the local treatment of vulvovaginal candidosis, with nystatin and boric acid considered as second-line alternatives. Unconventional approaches may also be regarded as suitable in patients refractory to usual treatments. In addition to the susceptibility of implicated Candida spp. to the antifungal agents, this choice should take into consideration other important issues such as particular situations (e.g. pregnancy, menopause, drug hypersensitivity), women’s preferences, and the availability, particularities and cost of antifungal formulations.

Keywords

Azole Bacterial Vaginosis Clotrimazole Mycological Cure Sertaconazole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Sobel JD. Vulvovaginal candidosis. Lancet 2007 Jun 9; 369(9577): 1961–71PubMedCrossRefGoogle Scholar
  2. 2.
    Watson MC, Grimshaw JM, Bond CM, et al. Oral versus intravaginal imidazole and triazole anti-fungal agents for the treatment of uncomplicated vulvovaginal candidiasis (thrush): a systematic review. BJOG 2002 Jan; 109(1): 85–95PubMedCrossRefGoogle Scholar
  3. 3.
    Nurbhai M, Grimshaw J, Watson M, et al. Oral versus intravaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Database Syst Rev 2007; (4): CD002845Google Scholar
  4. 4.
    McCaig LF, McNeill MM. Trends in prescribing for vulvovaginal candidiasis in the United States. Pharmacoepidemiol Drug Saf 2005 Feb; 14(2): 113–20PubMedCrossRefGoogle Scholar
  5. 5.
    Sobel JD. Vaginitis. N Engl J Med 1997 Dec 25; 337(26): 1896–903PubMedCrossRefGoogle Scholar
  6. 6.
    Ferrer J. Vaginal candidosis: epidemiological and etiological factors. Int J Gynaecol Obstet 2000 Dec; 71 Suppl. 1: 21–7CrossRefGoogle Scholar
  7. 7.
    Mitchell H. Vaginal discharge: causes, diagnosis, and treatment. BMJ 2004 May 29; 328(7451): 1306–8PubMedCrossRefGoogle Scholar
  8. 8.
    Sobel JD, Faro S, Force RW, et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998 Feb; 178(2): 203–11PubMedCrossRefGoogle Scholar
  9. 9.
    Richardson MD, Warnock DW. Fungal infection: diagnosis and management. 3rd ed. Maiden (MA): Blackwell Publishing, 2003CrossRefGoogle Scholar
  10. 10.
    Singh S, Sobel JD, Bhargava P, et al. Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy. Clin Infect Dis 2002 Nov 1; 35(9): 1066–70PubMedCrossRefGoogle Scholar
  11. 11.
    Spinillo A, Capuzzo E, Egbe TO, et al. Torulopsis glabrata vaginitis. Obstet Gynecol 1995 Jun; 85(6): 993–8PubMedCrossRefGoogle Scholar
  12. 12.
    Martens MG, Hoffman P, El-Zaatari M. Fungal species changes in the female genital tract. J Low Genit Tract Dis 2004 Jan; 8(1): 21–4PubMedCrossRefGoogle Scholar
  13. 13.
    Ferris DG, Nyirjesy P, Sobel JD, et al. Over-the-counter anti-fungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002 Mar; 99(3): 419–25PubMedCrossRefGoogle Scholar
  14. 14.
    Walker PP, Reynolds MT, Ashbee HR, et al. Vaginal yeasts in the era of “over the counter” antifungals. Sex Transm Infect 2000 Dec; 76(6): 437–8PubMedCrossRefGoogle Scholar
  15. 15.
    Fidel Jr PL, Sobel JD. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin Microbiol Rev 1996 Jul; 9(3): 335–48PubMedGoogle Scholar
  16. 16.
    Giraldo P, Neuer A, Korneeva IL, et al. Vaginal heat shock protein expression in symptom-free women with a history of recurrent vulvovaginitis. Am J Obstet Gynecol 1999 Mar; 180 (3 Pt 1): 524–9PubMedCrossRefGoogle Scholar
  17. 17.
    Nyirjesy P. Chronic vulvovaginal candidiasis. Am Fam Physician 2001 Feb 15; 63(4): 697–702PubMedGoogle Scholar
  18. 18.
    Strus M, Kucharska A, Kukla G, et al. The in vitro activity of vaginal Lactobacillus with probiotic properties against Candida. Infect Dis Obstet Gynecol 2005 Jun; 13(2): 69–75PubMedCrossRefGoogle Scholar
  19. 19.
    Sobel JD, Chaim W. Vaginal microbiology of women with acute recurrent vulvovaginal candidiasis. J Clin Microbiol 1996 Oct; 34(10): 2497–9PubMedGoogle Scholar
  20. 20.
    Fidel Jr PL. Immunity in vaginal candidiasis. Curr Opin Infect Dis 2005 Apr; 18(2): 107–11PubMedCrossRefGoogle Scholar
  21. 21.
    Sundstrom P. Adhesion in Candida spp. Cell Microbiol 2002 Aug; 4(8): 461–9PubMedCrossRefGoogle Scholar
  22. 22.
    Schaller M, Bein M, Korting HC, et al. The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium. Infect Immun 2003 Jun; 71(6): 3227–34PubMedCrossRefGoogle Scholar
  23. 23.
    Watson MC, Bond CM. Evidence-based guidelines for non-prescription treatment of vulvovaginal candidiasis (VVC). Pharm World Sci 2003 Aug; 25(4): 129–34PubMedCrossRefGoogle Scholar
  24. 24.
    Eckert LO, Hawes SE, Stevens CE, et al. Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm. Obstet Gynecol 1998 Nov; 92(5): 757–65PubMedCrossRefGoogle Scholar
  25. 25.
    Ryan CA, Courtois BN, Hawes SE, et al. Risk assessment, symptoms, and signs as predictors of vulvovaginal and cervical infections in an urban US STD clinic: implications for use of STD algorithms. Sex Transm Infect 1998 Jun; 74 Suppl. 1: 59–76CrossRefGoogle Scholar
  26. 26.
    Sihvo S, Ahonen R, Mikander H, et al. Self-medication with vaginal antifungal drugs: physicians’ experiences and women’s utilization patterns. Fam Pract 2000 Apr; 17(2): 145–9PubMedCrossRefGoogle Scholar
  27. 27.
    Mardh PA, Wagstrom J, Landgren M, et al. Usage of antifungal drugs for therapy of genital Candida infections, purchased as over-the-counter products or by prescription: I. Analyses of a unique database. Infect Dis Obstet Gynecol 2004 Jun; 12(2): 91–7CrossRefGoogle Scholar
  28. 28.
    Cejtin HE, Mason ED. A guide to the diagnosis and treatment of vaginitis and cervicitis. Hosp Physician 2000; 36(10): 53–63Google Scholar
  29. 29.
    Wiesenfeld HC, Macio I. The infrequent use of office-based diagnostic tests for vaginitis. Am J Obstet Gynecol 1999 Jul; 181(1): 39–41PubMedCrossRefGoogle Scholar
  30. 30.
    Baeten JM, Nyange PM, Richardson BA, et al. Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study. Am J Obstet Gynecol 2001 Aug; 185(2): 380–5PubMedCrossRefGoogle Scholar
  31. 31.
    Fidel Jr PL. Cutright J, Steele C. Effects of reproductive hormones on experimental vaginal candidiasis. Infect Immun 2000 Feb; 68(2): 651–7Google Scholar
  32. 32.
    Cotch MF, Hillier SL, Gibbs RS, et al. Epidemiology and outcomes associated with moderate to heavy Candida colonization during pregnancy. Vaginal Infections and Prematurity Study Group. Am J Obstet Gynecol 1998 Feb; 178(2): 374–80Google Scholar
  33. 33.
    Fidel Jr PL. History and update on host defense against vaginal candidiasis. Am J Reprod Immunol 2007 Jan; 57(1): 2–12PubMedCrossRefGoogle Scholar
  34. 34.
    Neves NA, Carvalho LP, De Oliveira MA, et al. Association between atopy and recurrent vaginal candidiasis. Clin Exp Immunol 2005 Oct; 142(1): 167–71PubMedCrossRefGoogle Scholar
  35. 35.
    Helfgott A, Eriksen N, Bundrick CM, et al. Vaginal infections in human immunodeficiency virus-infected women. Am J Obstet Gynecol 2000 Aug; 183(2): 347–55PubMedCrossRefGoogle Scholar
  36. 36.
    Spinillo A, Capuzzo E, Acciano S, et al. Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis. Am J Obstet Gynecol 1999 Jan; 180 (1 Pt 1): 14–7PubMedCrossRefGoogle Scholar
  37. 37.
    de Leon EM, Jacober SJ, Sobel JD, et al. Prevalence and risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes. BMC Infect Dis 2002; 2: 1PubMedCrossRefGoogle Scholar
  38. 38.
    Patel DA, Gillespie B, Sobel JD, et al. Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study. Am J Obstet Gynecol 2004 Mar; 190(3): 644–53PubMedCrossRefGoogle Scholar
  39. 39.
    Banerjee K, Curtis E, de San Lazaro C, et al. Low prevalence of genital candidiasis in children. Eur J Clin Microbiol Infect Dis 2004 Sep; 23(9): 696–8PubMedCrossRefGoogle Scholar
  40. 40.
    Demirezen S, Dirlik OO, Beksac MS. The association of Candida infection with intrauterine contraceptive device. Cent Eur J Public Health 2005 Mar; 13(1): 32–4PubMedGoogle Scholar
  41. 41.
    Meyer H, Goettlicher S, Mendling W. Stress as a cause of chronic recurrent vulvovaginal candidosis and the effectiveness of the conventional antimycotic therapy. Mycoses 2006 May; 49(3): 202–9PubMedCrossRefGoogle Scholar
  42. 42.
    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR 2006; 55: 1–94Google Scholar
  43. 43.
    Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis 2004 Jan 15; 38(2): 161–89PubMedCrossRefGoogle Scholar
  44. 44.
    Mendling W, Seebacher C. Guideline vulvovaginal candidosis: guideline of the German Dermatological Society, the German Speaking Mycological Society and the Working Group for Infections and Infectimmunology of the German Society for Gynecology and Obstetrics. Mycoses 2003; 46 (9–10): 365–9PubMedCrossRefGoogle Scholar
  45. 45.
    British Association of Sexual Health and HIV (BASHH), Clinical Effectiveness Group. National guideline for the management of vulvovaginal candidiasis. London: BASHH, 2002Google Scholar
  46. 46.
    World Health Organization. Guidelines for the management of sexually transmitted infections. Geneva: World Health Organization, 2001Google Scholar
  47. 47.
    Ringdahl EN. Treatment of recurrent vulvovaginal candidiasis. Am Fam Physician 2000 Jun 1; 61(11): 3306–12, 17PubMedGoogle Scholar
  48. 48.
    Sobel JD. Management of patients with recurrent vulvovaginal candidiasis. Drugs 2003; 63(11): 1059–66PubMedCrossRefGoogle Scholar
  49. 49.
    Thirion DJ, Zanetti LA. Potentiation of warfarin’s hypoprothrombinemic effect with miconazole vaginal suppositories. Pharmacotherapy 2000 Jan; 20(1): 98–9PubMedCrossRefGoogle Scholar
  50. 50.
    Lansdorp D, Bressers HP, Dekens-Konter JA, et al. Potentiation of acenocoumarol during vaginal administration of miconazole [letter]. Br J Clin Pharmacol 1999 Feb; 47(2): 225–6PubMedGoogle Scholar
  51. 51.
    Sobel JD. Use of antifungal drugs in pregnancy: a focus on safety. Drug Saf 2000 Jul; 23(1): 77–85PubMedCrossRefGoogle Scholar
  52. 52.
    Young GL, Jewell D. Topical treatment for vaginal candidiasis (thrush) in pregnancy. Cochrane Database Syst Rev 2001; (4): CD000225Google Scholar
  53. 53.
    Merkus JM. Treatment of vaginal candidiasis: orally or vaginally? J Am Acad Dermatol 1990 Sep; 23 (3 Pt 2): 568–72PubMedCrossRefGoogle Scholar
  54. 54.
    Kiss H, Witt A, Petricevic L, et al. Die orale kurzzeit-therapie der vulvovaginalen pilzinfektion als ein patientenorientiertes therapiekonzept. Geburtsh Frauenheilk 2001 Mar; 61(3): 133–7CrossRefGoogle Scholar
  55. 55.
    Nappi RE, Liekens G, Brandenburg U. Attitudes, perceptions and knowledge about the vagina: the International Vagina Dialogue Survey. Contraception 2006 May; 73(5): 493–500PubMedCrossRefGoogle Scholar
  56. 56.
    Drugstore.com [online]. Available from URL: at http://www.drugstore.com [Accessed 2008 Apr 12]
  57. 57.
    Joint Formulary Committee. British National Formulary. 55th ed. London: British Medical Association & Royal Pharmaceutical Society of Great Britain, 2008Google Scholar
  58. 58.
    NHS clinical knowledge summaries [online]. Available from URL: http://cks.library.nhs.uk [Accessed 2008 Apr 12]
  59. 59.
    Mardh PA, Rodrigues AG, Genc M, et al. Facts and myths on recurrent vulvovaginal candidosis: a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy. Int J STD AIDS 2002 Aug; 13(8): 522–39PubMedCrossRefGoogle Scholar
  60. 60.
    Moudgal VV, Sobel JD. Antifungal drugs in pregnancy: a review. Expert Opin Drug Saf 2003 Sep; 2(5): 475–83PubMedCrossRefGoogle Scholar
  61. 61.
    Acs N, Banhidy F, Puho E, et al. Teratogenic effects of vaginal boric acid treatment during pregnancy. Int J Gynaecol Obstet 2006 Apr; 93(1): 55–6PubMedCrossRefGoogle Scholar
  62. 62.
    Nwokolo NC, Boag FC. Chronic vaginal candidiasis: management in the postmenopausal patient. Drugs Aging 2000 May; 16(5): 335–9PubMedCrossRefGoogle Scholar
  63. 63.
    Welsh BM, Berzins KN, Cook KA, et al. Management of common vulval conditions. Med J Aust 2003 Apr 21; 178(8): 391–5PubMedGoogle Scholar
  64. 64.
    Bryskier A. Antimicrobial agents: antibacterials and antifungals. 1st ed. Washington, DC: ASM Press, 2005Google Scholar
  65. 65.
    Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole antifungal agents. Clin Microbiol Rev 1999 Jan; 12(1): 40–79PubMedGoogle Scholar
  66. 66.
    Dismukes WE. Introduction to antifungal drugs. Clin Infect Dis 2000 Apr; 30(4): 653–7PubMedCrossRefGoogle Scholar
  67. 67.
    Heikkila H, Stubb S, Reitamo S. A study of 72 patients with contact allergy to tioconazole. Br J Dermatol 1996 Apr; 134(4): 678–80PubMedCrossRefGoogle Scholar
  68. 68.
    Sanglard D, Odds FC. Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis 2002 Feb; 2(2): 73–85PubMedCrossRefGoogle Scholar
  69. 69.
    Phillips AJ. Treatment of non-albicans Candida vaginitis with amphotericin B vaginal suppositories. Am J Obstet Gynecol 2005 Jun; 192(6): 2009–12PubMedCrossRefGoogle Scholar
  70. 70.
    Dan M. Severe vulvovaginitis associated with intravaginal nystatin therapy. Am J Obstet Gynecol 2001 Jul; 185(1): 254–5PubMedCrossRefGoogle Scholar
  71. 71.
    Sobel JD, Chaim W, Nagappan V, et al. Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. Am J Obstet Gynecol 2003 Nov; 189(5): 1297–300PubMedCrossRefGoogle Scholar
  72. 72.
    Ray D, Goswami R, Banerjee U, et al. Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Diabetes Care 2007 Feb; 30(2): 312–7PubMedCrossRefGoogle Scholar
  73. 73.
    Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis 1997 Apr; 24(4): 649–52PubMedCrossRefGoogle Scholar
  74. 74.
    Horowitz BJ. Topical flucytosine therapy for chronic recurrent Candida tropicalis infections. J Reprod Med 1986 Sep; 31(9): 821–4PubMedGoogle Scholar
  75. 75.
    White DJ, Habib AR, Vanthuyne A, et al. Combined topical flucytosine and amphotericin B for refractory vaginal Candida glabrata infections. Sex Transm Infect 2001 Jun; 77(3): 212–3PubMedCrossRefGoogle Scholar
  76. 76.
    Garcia Figueroa RG, Sauceda L, Ramirez Palacios D, et al. Eficacia y seguridad de ciclopirox olamina en crema vaginal al 1% contra terconazol en crema vaginal al 0.8% en el tratamiento de candidiasis genital. Ginecol Obstet Mex 2000 Apr; 68: 154–9PubMedGoogle Scholar
  77. 77.
    Friese K, Neumann G, Siebert J. Topical antiseptics as an alternative in the treatment of acute vulvovaginal candidosis. Arch Gynecol Obstet 2003 Aug; 268(3): 194–7PubMedCrossRefGoogle Scholar
  78. 78.
    Molteni B, D’Antuono A, Bandini P, et al. Efficacy and tolerability of a new chlorhexidine-based vaginal gel in vaginal infections. Curr Med Res Opin 2004 Jun; 20(6): 849–53PubMedCrossRefGoogle Scholar
  79. 79.
    Petersen EE, Weissenbacher ER, Hengst P, et al. Local treatment of vaginal infections of varying etiology with dequalinium chloride or povidone iodine: a randomised, double-blind, active-controlled, multicentric clinical study. Arzneimittelforschung 2002; 52(9): 706–15PubMedGoogle Scholar
  80. 80.
    Stevens DA, Calderon L, Martinez M, et al. Zeamatin, clotrimazole and nikkomycin Z in therapy of a Candida vaginitis model. J Antimicrob Chemother 2002 Sep; 50(3): 361–4PubMedCrossRefGoogle Scholar
  81. 81.
    Pirotta M, Gunn J, Chondros P, et al. Effect of Lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. BMJ 2004 Sep 4; 329(7465): 548PubMedCrossRefGoogle Scholar
  82. 82.
    Falagas ME, Betsi GI, Athanasiou S. Probiotics for prevention of recurrent vulvovaginal candidiasis: a review. J Antimicrob Chemother 2006 Aug; 58(2): 266–72PubMedCrossRefGoogle Scholar
  83. 83.
    Wozniak KL, Palmer G, Kutner R, et al. Immunotherapeutic approaches to enhance protective immunity against Candida vaginitis. Med Mycol 2005 Nov; 43(7): 589–601PubMedCrossRefGoogle Scholar
  84. 84.
    Magliani W, Conti S, Cassone A, et al. New immunotherapeutic strategies to control vaginal candidiasis. Trends Mol Med 2002 Mar; 8(3): 121–6PubMedCrossRefGoogle Scholar
  85. 85.
    Cassone A, De Bernardis F, Santoni G. Anticandidal immunity and vaginitis: novel opportunities for immune intervention. Infect Immun 2007 Oct; 75(10): 4675–86PubMedCrossRefGoogle Scholar
  86. 86.
    Hammer KA, Carson CF, Riley TV. Antimicrobial activity of essential oils and other plant extracts. J Appl Microbiol 1999 Jun; 86(6): 985–90PubMedCrossRefGoogle Scholar
  87. 87.
    Pina-Vaz C, Gonçalves Rodrigues A, Pinto E, et al. Antifungal activity of Thymus oils and their major compounds. J Eur Acad Dermatol Venereol 2004 Jan; 18(1): 73–8PubMedCrossRefGoogle Scholar
  88. 88.
    Hammer KA, Carson CF, Riley TV. Antifungal activity of the components of Melaleuca altemifolia (tea tree) oil. J Appl Microbiol 2003; 95(4): 853–60PubMedCrossRefGoogle Scholar
  89. 89.
    das Neves J, Amaral MH, Bahia MF. Vaginal drug delivery. In: Gad SC, editor. Pharmaceutical manufacturing handbook: production and processes. 1st ed. Hoboken (NJ): Wiley, 2008: 809–78CrossRefGoogle Scholar
  90. 90.
    das Neves J, Santos B, Teixeira B, et al. Vaginal drug administration in the hospital setting. Am J Health Syst Pharm 2008; 65(3): 254–9PubMedCrossRefGoogle Scholar
  91. 91.
    Merabet J, Thompson D, Saul Levinson R. Advancing vaginal drug delivery. Expert Opin Drug Deliv 2005 Jul; 2(4): 769–77PubMedCrossRefGoogle Scholar
  92. 92.
    Henzl MR. Properties of sustained-release single-dose formulations for vulvovaginal candidiasis: the example of butoconazole vaginal emulsion as a drug-sparing formulation. Am J Drug Deliv 2005; 3(4): 227–37CrossRefGoogle Scholar
  93. 93.
    Brown D, Henzl MR, Kaufman RH. Butoconazole nitrate 2% for vulvovaginal candidiasis: new, single-dose vaginal cream formulation vs. seven-day treatment with miconazole nitrate. Gynazole 1 Study Group. J Reprod Med 1999 Nov; 44(11): 933–8Google Scholar
  94. 94.
    Seidman LS, Skokos CK. An evaluation of butoconazole nitrate 2% site release vaginal cream (Gynazole-1) compared to fluconazole 150 mg tablets (Diflucan) in the time to relief of symptoms in patients with vulvovaginal candidiasis. Infect Dis Obstet Gynecol 2005 Dec; 13(4): 197–206PubMedCrossRefGoogle Scholar
  95. 95.
    del Palacio A, Sanz F, Sanchez-Alor G, et al. Double-blind randomized dose-finding study in acute vulvovaginal candidosis: comparison of flutrimazole site-release cream (1,2 and 4%) with placebo site-release vaginal cream. Mycoses 2000 Oct; 43(9–10): 355–65PubMedCrossRefGoogle Scholar
  96. 96.
    Upmalis DH, Cone FL, Lamia CA, et al. Single-dose miconazole nitrate vaginal ovule in the treatment of vulvovaginal candidiasis: two single-blind, controlled studies versus miconazole nitrate 100 mg cream for 7 days. J Womens Health Gend Based Med 2000 May; 9(4): 421–9PubMedCrossRefGoogle Scholar
  97. 97.
    Barnhart K. Safety and efficacy of bedtime versus daytime administration of the miconazole nitrate 1200 mg vaginal ovule insert to treat vulvovaginal candidiasis. Curr Med Res Opin 2005 Jan; 21(1): 127–34PubMedCrossRefGoogle Scholar
  98. 98.
    Dellenbach P, Thomas JL, Guerin V, et al. Topical treatment of vaginal candidosis with sertaconazole and econazole sustained-release suppositories. Int J Gynaecol Obstet 2000 Dec; 71 Suppl. 1: 47–52CrossRefGoogle Scholar
  99. 99.
    Chang JY, Oh YK, Kong HS, et al. Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis. J Control Release 2002 Jul 18; 82(1): 39–50PubMedCrossRefGoogle Scholar
  100. 100.
    Bilensoy E, Rouf MA, Vural I, et al. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:beta-cyclodextrin complex. AAPS PharmSciTech 2006; 7(2): E38PubMedCrossRefGoogle Scholar
  101. 101.
    Pavelic Z, Skalko-Basnet N, Jalsenjak I. Characterisation and in vitro evaluation of bioadhesive liposome gels for local therapy of vaginitis. Int J Pharm 2005 Sep 14; 301(1–2): 140–8PubMedCrossRefGoogle Scholar
  102. 102.
    Ning MY, Guo YZ, Pan HZ, et al. Preparation and evaluation of proliposomes containing clotrimazole. Chem Pharm Bull 2005 Jun; 53(6): 620–4PubMedCrossRefGoogle Scholar
  103. 103.
    Ning M, Guo Y, Pan H, et al. Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole. Drug Dev Ind Pharm 2005 May; 31(4–5): 375–83PubMedGoogle Scholar
  104. 104.
    Motoyoshi K, Nozawa S, Yoshimura M, et al. The safety of propylene glycol and other humectants. Cosmet Toilet 1984; 99(10): 83–91Google Scholar
  105. 105.
    Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity [letter]. Lancet 1995 May 20; 345(8960): 1312–3PubMedCrossRefGoogle Scholar
  106. 106.
    Sestini S, Mori M, Francalanci S. Allergic contact dermatitis from benzyl alcohol in multiple medicaments. Contact Dermatitis 2004 May; 50(5): 316–7PubMedCrossRefGoogle Scholar
  107. 107.
    das Neves J, Bahia MF. Gels as vaginal drug delivery systems. Int J Pharm 2006 Aug 2; 318(1–2): 1–14PubMedCrossRefGoogle Scholar
  108. 108.
    Caswell M, Kane M. Comparison of the moisturization efficacy of two vaginal moisturizers: pectin versus polycarbophil technologies. J Cosmet Sci 2002 Mar–Apr; 53(2): 81–7PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • José das Neves
    • 1
    • 2
    • 3
  • Eugénia Pinto
    • 1
  • Branca Teixeira
    • 3
  • Gustavo Dias
    • 3
  • Patrocínia Rocha
    • 3
  • Teresa Cunha
    • 3
  • Bárbara Santos
    • 3
  • Maria H. Amaral
    • 2
  • Maria F. Bahia
    • 2
  1. 1.Department of Microbiology, CEQUIMED, Faculty of PharmacyUniversity of PortoPortoPortugal
  2. 2.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of PortoPortoPortugal
  3. 3.Department of PharmacyHospital Geral de Santo AntónioPortoPortugal

Personalised recommendations