Oteseconazole (Monograph)

Drug class: Azoles

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Azole antifungal; selective inhibitor of fungal lanosterol demethylase.

Uses for Oteseconazole

Vulvovaginal Candidiasis

Used to reduce incidence of recurrent vulvovaginal candidiasis in females with history of recurrent vulvovaginal candidiasis who are not of reproductive potential.

Recurrent vulvovaginal candidiasis as usually defined as 3 or more episodes of symptomatic vulvovaginal candidiasis in <1 year. Treatment guidelines from the CDC and Infectious Diseases Society of America (IDSA) recommend prolonged treatment courses for recurrent vulvovaginal candidiasis, typically with 7—14 days days of topical azole antifungal therapy or oral fluconazole administered every 3 days for a total of 3 doses, followed by a maintenance antifungal regimen. Oteseconazole is not addressed in these guidelines because the drug was approved after guideline publication.

Oteseconazole Dosage and Administration

Administration

Administer orally with food.

Swallow capsule whole; do not chew, crush, dissolve, or open capsules.

Dosage

Adults

Recurrent Vulvovaginal Candidiasis

Oral

Day 1: 600 mg as single dose

Day 2: 450 mg as single dose

Day 14: Start maintenance dosing of 150 mg once weekly (every 7 days) for 11 weeks (weeks 2 through 12)

Recurrent Vulvovaginal Candidiasis in Combination with Fluconazole

Oral

Fluconazole must be prescribed separately.

Days 1, 4, 7: fluconazole 150 mg once daily

Days 14–20: oteseconazole 150 mg once daily for 7 days

Day 28: start maintenance dosing of oteseconazole 150 mg once weekly (every 7 days) for 11 weeks (weeks 4 through 14).

Special Populations

Hepatic Impairment

No dosage adjustment recommended in mild or moderate hepatic impairment (Child-Pugh class A or B).

Not studied in patients with severe (Child-Pugh class C) hepatic impairment.

Renal Impairment

No dosage adjustment in mild to severe renal impairment (eGFR 15—89 mL/minute).

The effect of end-stage renal disease (eGFR <15 mL/minute) on pharmacokinetics of oteseconazole not known.

Geriatric Patients

No specific population dosage recommendations at this time.

Cautions for Oteseconazole

Contraindications

• Females of reproductive potential.

• Pregnant and lactating women.

• Known hypersensitivity to oteseconazole.

Warnings/Precautions

Warnings

Embryo-fetal Toxicity

Contraindicated in females of reproductive potential and in pregnant and lactating women. Based on animal studies, may cause fetal harm. Drug exposure window of approximately 690 days (based on 5 times the half-life) precludes adequate mitigation of embryo-fetal toxicity risks.

Advise patients that oteseconazole is contraindicated in females of reproductive potential, and in pregnant and lactating women because of potential risks to fetus or breast-fed infant.

Specific Populations

Pregnancy

Contraindicated in females of reproductive potential and pregnant women. Limited human data in pregnant women exposed to oteseconazole during clinical trials; data are insufficient to exclude potential risk of cataracts or other eye abnormalities in human infants.

Lactation

Contraindicated in lactating women and females of reproductive potential. No data on presence of oteseconazole in human or animal milk or the effects on milk production.

Females and Males of Reproductive Potential

Contraindicated in females of reproductive potential based on animal findings. Drug exposure window of approximately 690 days (based on 5 times the half-life) precludes adequate mitigation of the embryo-fetal toxicity risks.

Females who are not of reproductive potential defined as: persons who are biological females who are postmenopausal or have other reason for permanent infertility (e.g., tubal ligation, hysterectomy, salpingo-oophorectomy).

Pediatric Use

Safety and effectiveness in premenarchal pediatric female patients not established.

Geriatric Use

Clinical studies did not include sufficient numbers of subjects ≥65 years of age to determine whether they respond differently than younger subjects.

Hepatic Impairment

Not studied in patients with severe (Child-Pugh class C) hepatic impairment.

Renal Impairment

The effect of end-stage renal disease (eGFR <15 mL/minute) on pharmacokinetics of oteseconazole not known.

Dialysis not expected to alter drug exposure.

Common Adverse Effects

Most common adverse effects (≥2%): headache, nausea.

Drug Interactions

Not a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)2, organic anion transporter (OAT)1, and OAT3.

BCRP inhibitor.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Unlikely to impact concomitant medications that are substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, and 2D6.

Drugs Affecting or Affected by Transport Systems

Concomitant use with BCRP substrates may increase exposure of BCRP substrate, which may increase risk of adverse reactions associated with these drugs.

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

Specific Drugs

Oteseconazole Pharmacokinetics

Absorption

Bioavailability

AUC increases approximately dose proportionally, while C_max increases less than dose proportionally over dosage range of 20-320 mg.

Onset

Time to peak plasma concentrations (T_max): approximately 5 to 10 hours.

Effect of Food

Administration with high-fat, high-calorie meal (800—1000 calories, 50% fat) increases C_max and AUC_0-72h by 45% and 36% respectively; no significant differences observed with low-fat, low-calorie meal.

Distribution

Extent

Exposure in vaginal tissue comparable to plasma exposure in animal studies.

Elimination

Plasma Protein Binding

99.5—99.7%.

Metabolism

Does not undergo significant metabolism.

Elimination Route

56% in feces primarily through biliary excretion; 26% in urine.

Half-life

Median terminal half-life: approximately 138 days.

Special Populations

No clinically significant differences in pharmacokinetics based on sex or race/ethnicity.

Stability

Storage

Oral

Capsules

Store at 20-25°C; excursions permitted between 15—30°C. Protect from light when removed from outer carton.

Actions and Spectrum

• Azole metalloenzyme inhibitor targeting fungal sterol 14-alpha-demethylase (CYP51), an enzyme that catalyzes an early step in biosynthetic pathway of ergosterol, a sterol required for fungal cell member formation and integrity.

• Inhibition of CYP51 results in accumulation of 14-methylated sterols, some of which are toxic to fungi.

• Through inclusion of a tetrazole metal-binding group, has a lower affinity for human CYP enzymes.

• Has been shown active against most isolates of microorganisms associated with recurrent vulvovaginal candidiasis, including Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. lusitaniae,and C. dubliniensis. While in vitro data available, clinical significance is unknown.

• Potential for increases in minimum inhibitory concentrations (MICs) evaluated in vitro, including specific mechanisms of resistance.

• Increases in MIC associated with upregulation of efflux pumps CDR1, MDR1, and azole target, lanosterol 14-alpha-demethylase (CYP51).

• Against certain Candida species, maintained meaningful in vitro activity against clinical isolates resistant to fluconazole.

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information).

• Advise patients that oteseconazole must be taken with food and that capsules must be swallowed whole and not chewed, crushed, dissolved, or opened.

• Advise patients that oteseconazole is contraindicated in females of reproductive potential and in pregnant women because it may cause fetal harm.

• Advise patients that oteseconazole is contraindicated in lactating women because it may cause harm to the breast-fed infant.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Oteseconazole is obtained through designated specialty pharmacies. Contact manufacturer or consult the oteseconazole website ([Web]) for specific availability information.

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