DRUG INTERACTIONS( summary)

1. Effect of VIVJOA on Other Drugs BCRP (Breast Cancer Resistance Protein) Transporter Substrates Oteseconazole is a BCRP inhibitor. Concomitant use of VIVJOA with BCRP substrates (e.g., rosuvastatin) may increase the exposure of BCRP substrates (e.g., rosuvastatin), which may increase the risk of adverse reactions associated with these drugs.

Use the lowest possible starting dose of the BCRP substrate or consider reducing the dose of the substrate drug and monitor for adverse reactions.

DRUG INTERACTIONS-(details)

 BCRP (Breast Cancer Resistance Protein) Substrates: Concomitant use of VIVJOA with BCRP substrates may increase the exposure of drugs that are BCRP substrates, which may increase the risk of adverse reactions associated with these drugs.

Use the lowest possible starting dose of the BCRP substrate or consider reducing the dose of the substrate drugs and monitor for adverse reactions.

U.S. FDA APPROVED DRUGS SURING 2022                                        

Serial No 11

Name of the Drug-   VIVJOYA

Active Ingredient -   Ostesonazole

Pharmacological Classification- To  remove the incidence of recurrent                                                                             Candidiasis Vulvovaginal  candidiasis (RVVC) in                                                           females  with a history of  RVVC who are not of                                                             reproductive potential                                                                                                                                                                                             Date of Approval-         4/26/22                                                                   

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                                 VIVJOA™ safely and effectively.                                                                                          See full prescribing information for VIVJOA™. VIVJOA™ (oteseconazole) capsules, for oral use

Initial U.S. Approval: 2022

INDICATIONS AND USAGE

 VIVJOA™ is an azole antifungal indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in females with a history of RVVC who are NOT of reproductive potential.

ADVERSE REACTIONS-

 The most frequently reported adverse reactions (incidence > 2%) were headache and nausea.

CONTRAINDICATIONS

• Females of Reproductive Potential 

 • Pregnant and Lactating women 

 • Hypersensitivity to oteseconazole 

WARNINGS AND PRECAUTIONS-

 0: 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. 

DOSAGE AND ADMINISTRATION

 • There are two recommended VIVJOA dosage regimens: a VIVJOAonly regimen and a Fluconazole/VIVJOA regimen. Use one of these two dosage regimens.

 o Administer VIVJOA orally with food.

• For the VIVJOA-only

Dosage Regimen: 

o On Day 1: Administer VIVJOA 600 mg (as a single dose), then

o On Day 2: Administer VIVJOA 450 mg (as a single dose),

then o Beginning on Day 14: Administer VIVJOA 150 mg once a week (every 7 days) for 11 weeks (Weeks 2 through 12)

 • For the Fluconazole/VIVJOA Dosage Regimen, prescribe fluconazole

and: (2.3) o On Day 1, Day 4, and Day 7: Administer fluconazole 150 mg orally

, then o On Days 14 through 20: Administer VIVJOA 150 mg once daily for 7 days,

then o Beginning on Day 28: Administer VIVJOA 150 mg once a week (every 7 days) for 11 weeks (Weeks 4 through 14).

Storage and Handling-

Store at 20? C to 25? C (68? F to 77? F); excursions permitted between 15? C and 30? C (59? F to 86? F) [See USP Controlled Room Temperature]. Protect from light when removed from the outer carton.

 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Embryo-Fetal Toxicity -                                                                                                    Advise patients that VIVJOA is contraindicated in females of reproductive potential and in pregnant women because it may cause.fetal harm ]

 Lactation -                                                                                                                Advise patients that VIVJOA is contraindicated in lactating women because it may cause harm to the breastfed infant .

Important Administration Instructions-                                                                 Advise patients that VIVJOA must be taken with food, and that capsules must be swallowed whole and not chewed, crushed, dissolved, or opened 

Concomitant Administration with BCRP Transporter Substrates -                               Advise patients to inform their health care provider if they are taking a BCRP substrate (e.g., rosuvastatin). Concomitant use with VIVJOA may increase the exposure of drugs that are BCRP substrates, which may increase the risk of adverse reactions associated with these drugs 

Manufactured for and distributed by: Mycovia Pharmaceuticals, Inc. Durham, NC 27703 Patent numbers: 8,236,962, 8,754,227,10,173,998,10,464,921,10,836,740, 9,840,492,10,414,751

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Oteseconazole is an antifungal drug 

2. Pharmacodynamics Oteseconazole exposure-response relationships and the time course of pharmacodynamic response are unknown.

 Cardiac Electrophysiology -

At 5 times the maximum exposures for the recommended dose, VIVJOA does not prolong the QT interval to any clinically relevant extent.

3.Pharmacokinetics-

The AUC of oteseconazole increased approximately dose proportionally while the Cmax increased less than dose proportionally over a dose range of 20 mg (0.13 times thelowest recommended dose) to 320 mg (0.53 times the highest recommended dose).

The pharmacokinetic parameters of oteseconazole associated with the administration of the recommended dosing regimen of VIVJOA are presented in Table 1.

 Pharmacokinetic (PK) Parameters of Oteseconazole PK Parametera Mean (± SD) Cmax (µg/mL) 2.8 (1.25) AUC24h (h·µg/mL) 64.2 (29.4) Cmin (µg/mL) 2.5 (1.19) a Following repeat dose administration of VIVJOA at the approved recommended dosage for RVVC at the end of treatment.

Absorption-

The time to peak plasma concentrations of oteseconazole was approximately 5 to 10 hours.

Effect of Food -                                                                                                          Administration of VIVJOA with a high-fat, high-calorie meal (800-1000 Calories; 50% fat) increased Cmax and AUC0-72h by 45% and 36%, but no significant differences were observed with a low-fat, lowcalorie meal.

Distribution -                                                                                                                      The central volume of distribution of oteseconazole is approximately 423 L. Oteseconazole is 99.5- 99.7% bound to plasma proteins. Animal studies indicated that oteseconazole exposures in vaginal tissue are comparable to plasma exposures.

Elimination-                                                                                                                    The median terminal half-life of oteseconazole is approximately 138 days.

Metabolism-                                                                                                             Oteseconazole does not undergo significant metabolism.

Excretion-                                                                                                                        Following oral administration of radiolabeled oteseconazole, approximately 56% of the radiolabeled dose was recovered in feces primarily through biliary excretion and 26% was recovered in urine.

Specific Populations -                                                                                               There were no clinically significant differences in the pharmacokinetics of oteseconazole based on sex, race/ethnicity or mild to moderate renal impairment.

Drug Interaction Studies-                                                                                          BCRP substrates: Oteseconazole increased the Cmax and AUC0-24h of rosuvastatin, a BCRP substrate, by 118% and 114%, respectively

 Other Drugs:                                                                                                                     No clinically significant differences in the pharmacokinetics of the following drugs were observed when co-administered with oteseconazole: Midazolam (sensitive CYP3A4 substrate), ethinyl estradiol (CYP3A4 substrate), norethindrone (CYP3A4 substrate), or digoxin (P-gp substrate).

 USE IN SPECIFIC POPULATION

1. Pregnancy Risk Summary-

VIVJOA is contraindicated in females of reproductive potential and in pregnant women. Based on animal studies, VIVJOA may cause fetal harm when administered to pregnant women.

There are limited human data in pregnant women who were exposed to VIVJOA during the clinical trials; these data are insufficient to exclude a potential risk of cataracts or other eye abnormalities in human infants.

2. Lactation Risk Summary-

VIVJOA is contraindicated in lactating women and females of reproductive potential. There are no data on the presence of oteseconazole in human or animal milk or data on the effects of oteseconazole on milk production.

here were no reported adverse effects in breastfed infants following maternal exposure to oteseconazole during lactation; however, given the limited duration of follow-up of the oteseconazole-exposed infants during the post-natal period, no conclusions can be drawn from these data

3. Females of Reproductive Potential-

VIVJOA is contraindicated in females of reproductive potential based on animal findings. 

4. Pediatric Use -

VIVJOA is contraindicated in females of reproductive potential. Based on animal studies, VIVJOA may cause fetal harm when administered to a pregnant woman or potential harm to the breastfed infant.

5. Geriatric Use-

Clinical studies of VIVJOA did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

6. Renal Impairment-                                   

 No dosage adjustment of VIVJOA is recommended in patients with mild to moderate renal impairment (i.e., estimated glomerular filtration rate (eGFR) by the modification of diet in renal disease (MDRD) equation 30-89 mL/min)

 Clinical studies of VIVJOA did not include sufficient numbers of patients with severe renal impairment (eGFR 15-29 mL/min) or end-stage renal disease (ESRD), defined as eGFR <15 mL/min, to determine the safety of VIVJOA in this population. Therefore, VIVJOA is not recommended for use in patients with severe renal impairment or ESRD (with or without dialysis).

7. Hepatic Impairment-

No dosage adjustment of VIVJOA is recommended in patients with mild hepatic impairment (ChildPugh A). There is insufficient information to determine the safety of VIVJOA in patients with moderate or severe hepatic impairment (Child-Pugh B-C). Therefore, VIVJOA is not recommended for use in patients with moderate or severe hepatic impairment