VIVJOA

5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity : Based on animal studies, VIVJOA may cause fetal harm. The drug exposure window of approximately 690 days (based on 5 times the half-life of oteseconazole) precludes adequate mitigation of the embryo-fetal toxicity risks. Advise patients that VIVJOA is contraindicated in females of reproductive potential, and in pregnant and lactating women because of potential risks to a fetus or breastfed infant. ( 5.1 , 8.1 , 8.2 , 8.3 ) 5.1 Embryo-Fetal Toxicity VIVJOA is contraindicated in females of reproductive potential, and in pregnant and lactating women. Based on animal studies, VIVJOA may cause fetal harm. The drug exposure window of approximately 690 days (based on 5 times the half-life of oteseconazole) precludes adequate mitigation of the embryo-fetal toxicity risks. Ocular abnormalities were observed in the offspring of pregnant rats dosed at 7.5-mg/kg/day during organogenesis through lactation in pre and postnatal developmental studies. The observed ocular abnormalities included cataracts, opacities, exophthalmos/buphthalmos, optic nerve/retinal atrophy, lens degeneration and hemorrhage. Ocular abnormalities occurred at doses about 3.5 times the steady state clinical exposure seen with patients being treated for RVVC. Advise patients that VIVJOA is contraindicated in females of reproductive potential, and in pregnant and lactating women because of potential risks to a fetus or breastfed infant [see Use in Specific Populations (8.1 , 8.2 , 8.3) ].

6 ADVERSE REACTIONS The most frequently reported adverse reactions (incidence > 2%) were headache and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mycovia Pharmaceuticals, Inc. at 1-855-299-0637 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 580 patients were treated with VIVJOA in three clinical trials (Trial 1, Trial 2, and Trial 3) [see Clinical Studies (14) ] . Patients in the clinical trials were women with RVVC who received VIVJOA treatment for 12 weeks. The mean age of the patient population was 34 years (range:16-78 years), with 84% of patients aged 18-44 years and 16% of patients aged 45 years and older. Although females of reproductive potential were included in the clinical safety data, VIVJOA is contraindicated in females of reproductive potential due to the risk of embryo-fetal toxicity [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , 8.3 , 8.4) ] . The clinical trials population was 75% (435/580) White, 17% (96/580) Black or African American, 6% (36/580) Asian, and 2% (13/580) Other women. Fifteen percent (86/580) of all women were Hispanic/Latino. Patients enrolled in the induction and maintenance phases of the clinical trials were treated with different VIVJOA dosage regimens versus comparators [see Clinical Studies (14) ] . The adverse reaction that led to discontinuation in 1 of 580 (0.2 %) VIVJOA-treated patients was allergic dermatitis. Overall, similar percentages of serious adverse reactions and adverse reactions leading to drug discontinuation were reported across the VIVJOA and comparator patient dosing groups. The most frequently reported adverse reactions (incidence >2%) among VIVJOA-treated patients in Trial 1, Trial 2 and Trial 3 were headache (includes headache, migraines, sinus headaches) (7.4%) and nausea (3.6%). Other Adverse Reactions The following selected adverse reactions occurred in <2% of patients receiving VIVJOA in Trial 1, Trial 2 and Trial 3: Laboratory investigations: Increased blood creatine phosphokinase Gastrointestinal disorders: Dyspepsia Vascular disorders: Hot flush Renal and urinary disorders: Dysuria Reproductive system and breast disorders: Menorrhagia (includes genital hemorrhage, menorrhagia; menometrorrhagia; uterine hemorrhage, vaginal hemorrhage) metrorrhagia; vulvovaginal irritation (includes vulvovaginal burning sensation, vulvovaginal discomfort, and vulvovaginal pain) Laboratory Findings Elevations in Creatine Phosphokinase Serum creatine phosphokinase (CPK) (an indirect marker of muscle injury/necrosis) elevations greater than or equal to 10 times the upper limit of normal were observed in 11 (1.9%) patients treated with VIVJOA versus 2 (0.7%) patients in the comparator groups during the VIVJOA clinical trials. The elevations were transient.