Helping patients with recurrent vulvovaginal candidiasis

A patient walks up to the pharmacy counter with a box containing a fluconazole 150 mg capsule and asks “What else can be used to treat my yeast infection? I have taken five of these capsules in the last year and the infection keeps returning.” A patient is refilling her prescription for doxycycline for acne. You notice that she also has multiple vaginal antifungal products in her shopping basket. Pharmacists should be alert for scenarios such as these, as they could indicate a patient with recurrent vulvovaginal candidiasis (RVVC). Given the prevalence of RVVC, the significant impact it has on quality of life, and the availability of nonprescription treatments, pharmacists should familiarize themselves with the condition and treatment strategies so that they are optimally equipped to assist patients. Background and prevalence Vulvovaginal candidiasis (VVC), commonly known as a yeast infection, affects up to 75% of women of childbearing age at least once in their lifetime.1 Approximately 10% experience RVVC, which is defined as four or more symptomatic infections in the past year, with asymptomatic periods between infections.1-4 The prevalence of RVVC is likely underestimated due to women not seeking health professional care and instead utilizing over-the-counter therapies.5 The prevalence is estimated to increase substantially by 2030 due to increased antibiotic misuse, an aging but sexually active population using hormone replacement therapy, and an increased prevalence of predisposing conditions such as diabetes.6 Causes RVVC is primarily caused by azole-sensitive Candida albicans (85%–95% of cases); however, nonalbicans Candida species including C. glabrata, C. krusei, C. parapsilosis, C. africana and C. tropicalis have also been implicated.1,2,4,7 RVVC is not considered a sexually transmitted infection; it occurs for several reasons, with many cases being idiopathic.1,8 Risk factors Alterations in the normal vaginal microbiome, such as changes in the Lactobacillus community, can lead to Candida overgrowth.1,4 Antibiotic exposure can contribute to this change.9 Physical health conditions (e.g., obesity, diabetes, immunosuppression), as well as psychosocial stress and genetic polymorphisms, have all been linked to RVVC.1,4,7,10,11 Estrogen-containing hormonal contraceptives and replacement therapies may increase the risk of RVVC, although data are contradictory.4,7,12 Additional risk factors include use of intrauterine devices, condom/spermicide use, poor personal hygiene, wearing tight- fitting clothes, humid weather and vaginal douching.7,8 Signs and symptoms Physical symptoms include vaginal pruritus, irritation, external dysuria and dyspareunia.2 Signs include vulvar edema, erythema, excoriation and fissures.2 Vaginal discharge is often thick and white, and may appear like “cottage cheese.”2 RVVC can impact a woman’s self-confidence and lead to substantial self-stigma, shame, depression and anxiety.3,4 Approach to treatment All patients presenting with possible RVVC should be screened for causative risk factors, receive education about preventive strategies (e.g., personal hygiene, clothing choices, avoidance of douching), and be referred to a physician for a complete workup.4 As the signs and symptoms of RVVC are nonspecific, prior to proceeding with empiric antifungal therapy, a diagnosis should be confirmed via a wet mount preparation test and, if negative, a confirmatory vaginal culture.2 The need for a diagnostic workup for all cases is supported by a study which found that only 30% of women were able to correctly self-diagnose VVC and a past confirmed diagnosis did not change their ability to self-diagnose.5 First- and second-line treatments Currently available treatments offer symptomatic control of RVVC, but do not guarantee cure given that many women have risk factors, including genetic factors, which may be nonmodifiable.4 The most recent guidelines for RVVC treatment were published in 2016 (Table 1). Most Candida species, except for C. krusei and C. glabrata, respond well to oral fluconazole, making it the treatment of choice given its convenience and tolerability especially when compared to topical products, which may be inconvenient.2 RVVC treatment with fluconazole includes induction with 150 mg daily for 10–14 days, followed by six months of weekly oral fluconazole 150 mg as maintenance therapy.2 During weekly maintenance treatment for RVVC, about 5% of patients will have a breakthrough episode; however, following cessation of weekly treatments close to 50% of patients will experience a recurrent infection.4 If an acute infection reoccurs, patients should be referred for confirmatory diagnosis and will require another course of induction therapy before resuming maintenance treatment.2 There are anecdotal reports of women successfully maintained on weekly fluconazole for years.2 Patients may inquire about alternate therapies for maintenance; however, there are no randomized controlled trials on boric acid prophylaxis and studies of probiotics are of poor quality, with mixed results.13 A new oral antifungal (oteseconazole) specifically indicated for the treatment of RVVC was approved in the United States in April 2022 and is currently on fast-track, priority review by Health Canada.14 It has fewer drug interactions than fluconazole and covers additional Candida species.15 Practical tips The single 150 mg fluconazole capsule is not covered by most drug plans, even when prescribed by a physician. Consider a prescription for fluconazole tablets, which are covered under most public and private drug plans, especially if ongoing weekly maintenance treatments are planned, to avoid excess financial burden for the patient. Educate pharmacy technicians to be alert for signs of possible RVVC (see scenarios at the beginning of this column) and to refer these patients to you for consultation. Katelyn Halpape, BSP, ACPR, PharmD, BCPP, is a clinical pharmacist at the Dube Centre for Mental Health in Saskatoon, SK and an Assistant Professor in the College of Pharmacy and Nutrition at the University of Saskatchewan. References: Scurka E, Henault B, Ostroff ML, et al. Addressing recurrent vulvovaginal candidiasis. US Pharm 2022;47(9):22-6. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62(4):e1-50. Bradfield Strydom M, Walpola RL, McMillan S, et al. Lived experience of medical management in recurrent vulvovaginal candidiasis: a qualitative study of an uncertain journey. BMC Womens Health 2022;22:384. Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol 2016;214(1):15-21. Ferris DG, Nyirjesy P, Sobel JD, et al. Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002;99(3):419-25. Denning DW, Kneale M, Sobel JD, et al. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect Dis 2018;18(11):e339-47. Gonçalves B, Ferreira C, Tiago Alves C, et al. Vulvovaginal candidiasis: epidemiology, microbiology and risk factors. (accessed February 22, 2023). Yano J, Sobel JD, Nyirjesy P, et al. Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes. BMC Womens Health 2019;19(1):48. Xu J, Schwartz K, Bartoces M, et al. Effect of antibiotics on vulvovaginal candidiasis: a MetroNet study. J Am Board Fam Med 2008;21(4):261-8. Smeekens SP, van de Veerdonk FL, Kullberg BJ, et al. Genetic susceptibility to Candida infections. EMBO Mol Med 2013;5(6):805-13. 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;49(3):202-9. Dennerstein GJ, Ellis DH. Oestrogen, glycogen and vaginal candidiasis. Aust N Z J Obstet Gynaecol 2001;41(3):326-8. Belayneh M, Sehn E, Korownyk C. Recurrent vulvovaginal candidiasis. Can Fam Physician 2017;63(6):455. Mycovia Pharmaceuticals Inc. Mycovia Pharmaceuticals announces U.S. FDA acceptance and priority review of new drug application for oteseconazole for the treatment of recurrent vulvovaginal candidiasis. (accessed February 15, 2023). Sobel JD, Nyirjesy P. Oteseconazole: an advance in treatment of recurrent vulvovaginal candidiasis. Future Microbiol 2021;16(18):1453-61.

Helping patients with recurrent vulvovaginal candidiasis

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