Oteseconazole

Approved Indication:

• Prevention of recurrent vulvovaginal candidiasis (RVVC):
  Indicated in postmenopausal women or women who are permanently infertile to reduce the incidence of recurrent vulvovaginal candidiasis, defined as having at least three episodes within 12 months.

Off-label Uses (Clinically Accepted):

• Investigated for acute treatment of vulvovaginal candidiasis.
• Potential use in resistant Candida species infections under clinical trials.

Route of Administration: Oral
Dosage Form: Capsule (150 mg)
Administration: Take with food; swallow whole—do not crush, chew, or split.

Adult Dose (Women not of reproductive potential):

• Day 1: 600 mg (four 150 mg capsules) as a single dose.
• Day 2: 450 mg (three 150 mg capsules) as a single dose.
• Days 14 to 90: 150 mg once weekly for 11 weeks.

Alternate Regimen (With Fluconazole):

• Days 1, 4, and 7: Fluconazole 150 mg orally.
• Days 14 to 20: Oteseconazole 150 mg once daily for 7 days.
• Days 28 to 98: Oteseconazole 150 mg once weekly for 11 weeks.

Special Populations:

• Elderly: No dosage adjustment required.
• Renal Impairment: Not recommended in severe renal dysfunction (eGFR <15 mL/min); no adjustment for mild to moderate impairment.
• Hepatic Impairment: Avoid use in severe impairment; no adjustment needed for mild to moderate impairment.
• Pediatrics: Not indicated.

Oteseconazole is a selective tetrazole antifungal that inhibits fungal lanosterol 14α-demethylase (CYP51), a key enzyme in the biosynthesis of ergosterol, an essential component of the fungal cell membrane. By blocking ergosterol synthesis, it disrupts fungal membrane integrity, leading to inhibition of fungal cell growth and death. It has a high specificity for fungal CYP51, with minimal interaction with human CYP enzymes, resulting in lower toxicity and fewer systemic side effects.

• Absorption: Well absorbed orally; food enhances absorption.
• Time to Peak Concentration: Approximately 5 to 10 hours.
• Bioavailability: High oral bioavailability when taken with food.
• Distribution: Extensive distribution with a large volume of distribution; highly protein-bound (~99.5%).
• Metabolism: Minimally metabolized; does not undergo significant hepatic metabolism.
• Elimination Half-life: Approximately 138 days, allowing for extended once-weekly maintenance dosing.
• Excretion: Primarily eliminated in feces; a small fraction in urine.

• Pregnancy: Contraindicated. Animal studies have shown embryo-fetal toxicity, including developmental abnormalities. Should not be used in women of reproductive potential.
• Lactation: Not recommended during breastfeeding. Unknown if excreted into human milk; potential risk to nursing infants.

• Primary Class: Antifungal Agent
• Subclass: Oral Tetrazole, Selective Lanosterol 14α-demethylase (CYP51) Inhibitor

• Women of reproductive potential, including pregnant or breastfeeding women.
• Known hypersensitivity to oteseconazole or any excipients in the formulation.
• Severe hepatic or renal impairment (use not established).

• Embryo-Fetal Toxicity: Strictly contraindicated in women of childbearing potential due to fetal risk.
• Long Half-life: The extended half-life may prolong systemic exposure and potential adverse effects.
• Use in Organ Dysfunction: Avoid in severe hepatic or renal dysfunction.
• Monitoring: Consider liver function tests in prolonged use; monitor for signs of hypersensitivity or unusual reactions.

Common Side Effects:

• Headache
• Nausea
• Diarrhea
• Nasopharyngitis
• Urinary tract infections

Less Common/Serious Side Effects:

• Elevated creatine phosphokinase (CPK)
• Dizziness
• Vaginal burning or itching
• Hypersensitivity reactions (rare)

Timing:
Mild side effects generally appear within the first week; serious effects are rare but require medical attention if observed.

• BCRP Substrates (e.g., rosuvastatin): May increase serum levels; consider dose adjustment.
• CYP3A4 Substrates (e.g., midazolam): Minimal interaction; clinically insignificant.
• Hormonal Contraceptives: Not recommended in reproductive-age women, so interaction data is limited.
• Other Antifungals: Concurrent use with other azoles is not recommended.

• Oteseconazole is the first FDA-approved drug specifically for prevention of recurrent vulvovaginal candidiasis in non-reproductive women.
• Included in updated clinical guidelines for fungal infections as a next-generation agent with high specificity and low resistance potential.
• No updates regarding pediatric or reproductive-age populations; usage remains restricted to postmenopausal or infertile women.

• Storage Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Humidity Protection: Protect from moisture.
• Light Sensitivity: Store in original container; avoid direct light.
• Handling Precautions: Do not crush, split, or chew capsules. Swallow whole with food.
• Do Not Freeze.