What’s new in treatment?
Until recently, the main standard of care for RVVC has been oral fluconazole-based therapy. For patients whose symptoms do not respond to oral fluconazole therapy, oteseconazole is now available as a noninferior treatment option to fluconazole for both induction and maintenance therapy. Like other azoles, oteseconazole works by inhibiting a fungal enzyme (CYP51) that is essential in fungal cell membrane integrity and fungal growth.20 Oteseconazole is a more selective inhibitor of the fungal CYP51 enzyme and has demonstrated excellent potency against Candida species in in vitro pharmacologic studies.21
In a phase 3 study that evaluated the safety and efficacy of oteseconazole in the treatment and prevention of RVVC, oteseconazole was found to be both safe and efficacious in both the induction and maintenance phases of treatment for RVVC.20 In this trial, induction and maintenance with oteseconazole was compared with induction with fluconazole and placebo maintenance. Among the 185 participants with culture-verified RVVC, the oteseconazole regimen (n = 123) was associated with fewer recurrences of culture-verified VVC infections than was the fluconazole induction/placebo maintenance regimen (n = 62) during the 48-week maintenance phase of therapy (5% vs 42%).20
Single- and dual-drug dosing regimens of oteseconazole are recommended based on previous trial data that compared safety and efficacy of oteseconazole versus fluconazole induction therapy and oteseconazole versus placebo maintenance therapy.22 However, widespread use of oteseconazole regimens are limited due to its higher costs and limited access to the drug outside of a research setting.20
Single-drug induction therapy with oteseconazole consists of a single 600-mg oral dose on day 1 followed by a second dose of 450 mg orally on day 2. Starting on day 14, maintenance therapy starts with a single oral dose of 150 mg and is continued weekly for 11 weeks.22
Dual-drug induction therapy consists of oral fluconazole 150 mg on days 1, 4, and 7 followed by daily dosing of oral oteseconazole 150 mg on days 14 through 20. Then, starting on day 28, weekly dosing of oral oteseconazole 150 mg is continued for 11 weeks.22
Effects on pregnancy and lactation. Concerns of oteseconazole’s fetal teratogenicity are based on animal reproduction studies that reported ocular abnormalities from in utero exposure. Human data are insufficient to determine if oteseconazole is excreted in breast milk or what its effects are on milk production. Among breastfed infants whose mothers were exposed to oteseconazole during lactation, no adverse outcomes were reported, but follow up of oteseconazole-exposed infants was limited. 22 Therefore, use of oteseconazole among pregnant and/or lactating persons with RVVC is contraindicated at this time. The long-half life (approximately 138 days) of oteseconazole may preclude use among persons attempting pregnancy. 22
Other therapies. The other common classes of antifungal therapy used in the treatment of RVVC include the polyenes (for example, amphotericin B) and echinocandins (such as caspofungin) drug classes. Emerging azole-resistance among Candida species has been recognized as a significant concern from the Centers for Disease Control and Prevention. 7 Echinocandins, which are generally better tolerated and have a lower adverse side effect profile than polyenes, are a promising therapeutic class, but currently they are limited to intravenous options. SCY-078, a novel oral echinocandin in development, has shown in vitro fungicidal activity against multiple albicans and non-albicans Candida species in pharmacokinetic/pharmacodynamic studies.23
Continued development of alternative, non-azole-based therapies for Candida species is needed.●