OTESECONAZOLE CAP,ORAL

Clinical Criteria Summary

Pregnancy or lactation
Person of child-bearing potential (defined as biological female who has no condition that constitutes permanent infertility (e.g. age greater than or equal to 47 years, tubal ligation, hysterectomy, salpingo-oophorectomy)

Acute signs and symptoms consistent with vulvovaginal candidiasis
At least 3 symptomatic episodes of vulvovaginal candidiasis in 12 months
Failure of at least 6 months of maintenance fluconazole (unless contraindicated, not tolerated or due to a fluconazole-resistant isolate expected to be susceptible to oteseconazole)

Induction with fluconazole 150mg on days 1,4 and 7, followed by 150mg oteseconazole daily for 7 days, then weekly for 11 weeks
Induction with oteseconazole 600mg on day 1, 450 mg on day 2, then 150mg weekly for 11 weeks (beginning day 14)

Indicated in females who are not of reproductive potential to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC)
Defined as biological females who DO NOT have a reason for permanent infertility (e.g., age ≥ 47 years, tubal ligation, hysterectomy, salpingo-oophorectomy)
Ideal population: post-menopausal women with RVVC (at least 3 symptomatic episodes in 12 months)

Monotherapy: OTE 600 mg on day 1, 450 mg on day 2, then 150 mg weekly for 11 weeks starting day 14
Sequential therapy with fluconazole: Fluconazole 150 mg as a single dose on days 1, 4, and 7 during induction; OTE 150 mg once daily days 14-20, then 150 mg once weekly for 11 weeks starting day 28
Long half-life (~690 days) allows for weekly dosing after initial treatment

Pregnancy or lactation
Persons of reproductive potential (due to embryo-fetal toxicity/ocular abnormalities in animal studies and very long half-life)
Previous hypersensitivity to OTE
Embryo and fetal toxicity: Animal studies show ocular abnormalities including cataracts, opacities, exophthalmos/buphthalmos, optic nerve/retinal atrophy, lens degeneration, and hemorrhage

Renal impairment: No dosage adjustment necessary for mild-moderate renal impairment (eGFR 30-89 mL/min); not recommended in severe renal impairment (eGFR <30 mL/min) or end-stage renal disease
Hepatic impairment: No dosage adjustment necessary for mild hepatic impairment (Child-Pugh A); use not recommended for moderate-severe hepatic impairment (Child-Pugh B-C) due to insufficient safety information
Geriatric: Very limited data in patients 65 years of age and older; unable to determine if they respond differently from younger patients

Indicated for prevention of RVVC either as monotherapy or in conjunction with fluconazole in women with multiple symptomatic episodes (≥3 over a 12-month period)
Ideal use is in post-menopausal women with RVVC for whom ibrexafungerp is not clinically appropriate or available
Potential use likely to be low due to contraindication in women of childbearing potential, as RVVC is most common in young women
Sustained remission may not always be successful; 50% of patients had a recurrent episode within 6 months of treatment completion
May maintain activity against some fluconazole-resistant Candida spp., though elevated MICs suggest at least partial cross-resistance with other azoles. Clinical significance of higher MICs is unknown.