Otes Capsule

Otes is indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in females with a history of RVVC who are not of reproductive potential. If specimens for fungal culture are obtained prior to therapy, antifungal therapy may be instituted before the results of the cultures are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

Oteseconazole is an antifungal drug. Oteseconazole exposure-response relationships and the time course of pharmacodynamic response are unknown. Oteseconazole is an azole metalloenzyme inhibitor targeting the fungal sterol, 14α demethylase (CYP51), an enzyme that catalyzes an early step in the biosynthetic pathway of ergosterol, a sterol required for fungal cell membrane formation and integrity. Inhibition of CYP51 results in the accumulation of 14-methylated sterols, some of which are toxic to fungi. Through the inclusion of a tetrazole metal-binding group, oteseconazole has a lower affinity for human CYP enzymes.

There are two recommended Oteseconazole dosage regimens:

Oteseconazole-only dosage regimen-

• On Day 1: Administer Oteseconazole 600 mg (as a single dose), then
• On Day 2: Administer Oteseconazole 450 mg (as a single dose), then
• Beginning on Day 14: Administer Oteseconazole 150 mg once a week (every 7 days) for 11 weeks (Weeks 2 through 12).

Fluconazole/Oteseconazole dosage regimen-

• On Day 1, Day 4, and Day 7: Administer fluconazole 150 mg orally, then
• On Days 14 through 20: Administer Oteseconazole 150 mg once daily for 7 days, then
• Beginning on Day 28: Administer Oteseconazole 150 mg once a week (every 7 days) for 11 weeks (Weeks 4 through 14).

Administer Oteseconazole orally with food. Swallow the capsules whole. Do not chew, crush, dissolve, or open the capsules.

BCRP (Breast Cancer Resistance Protein) Substrates: Concomitant use of Otes 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.

Oteseconazole is contraindicated in:

• Females of reproductive potential
• Pregnant and lactating women
• Patients with known hypersensitivity to oteseconazole

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

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

Oteseconazole 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. There 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

Embryo-Fetal Toxicity: Otes is contraindicated in females of reproductive potential, and in pregnant and lactating women. Based on animal studies, Otes may cause fetal harm. The drug exposure window of approximately 690 days (based on 5 times the half-life of Otes) 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 Otes is contraindicated in females of reproductive potential, and in pregnant and lactating women because of potential risks to a fetus or breastfed infan.

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

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

Renal Impairment: No dosage adjustment of Otes is recommended in patients with mild to moderate renal impairment.

Hepatic Impairment: No dosage adjustment of Otes is recommended in patients with mild hepatic impairment (ChildPugh A).

Other Antifungal preparations

Store at 20°C to 25°C. Protect from light when removed from the outer carton. Keep the medicine out of the reach of children.