IBREXAFUNGERP TAB

Clinical Criteria Summary

Signs and symptoms consistent with vulvovaginal candidiasis (VVC) which has not responded to trials of both a topical azole preparation AND fluconazole (unless contraindicated or not tolerated)
At least 3 episodes of recurrent symptomatic VVC in 12 months and has failed at least 6 months of maintenance fluconazole (unless contraindicated or not tolerated, or isolate is documented to be fluconazole-resistant)

For patients who can become pregnant: Pregnancy MUST be excluded prior to receiving ibrexafungerp
For patients who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 days after stopping treatment

Any other indication (e.g., off-label for invasive candidiasis, invasive aspergillosis) should be restricted to Infectious Diseases or other facility authorized provider

CDC STI guidelines recommend vaginal culture or PCR be obtained from women with complicated VVC to confirm clinical diagnosis and identify non–albicans Candida
Culture and susceptibility testing should be considered for patients who remain symptomatic due to increasing C. albicans azole resistance and frequent azole resistance in non–albicans Candida
Normal dose for treatment of VVC: 300mg twice daily for 1 day; decrease to 150mg twice daily for 1 day in those on strong CYP3A inhibitors
Normal dose for prevention of recurrent VVC: 300mg administered 12 hours apart for 1 day monthly for 6 months

Treatment of vulvovaginal candidiasis (VVC) in adult and post-menarchal pediatric females.

Risk of fetal toxicity: Associated with fetal malformations in pregnant rabbits during organogenesis.
Lactation: No data available regarding presence in human or animal milk, effects on breast-fed infants, or effects on milk production.
Verify pregnancy status in females of reproductive potential prior to initiating treatment.
Effective contraception must be used during treatment and for 4 days after completion.

Common: Diarrhea, nausea, abdominal pain, dizziness, vomiting.
Serious adverse reactions: None reported during clinical trials.
Other adverse reactions (<2% of patients): Dysmenorrhea, flatulence, back pain, elevated transaminases, vaginal bleeding, rash/hypersensitivity reactions.

CYP3A4 Substrate: Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) may significantly increase serum concentration; recommend dose reduction to 150 mg approximately 12 hours apart for one day.
CYP3A4 Inducers: Strong/moderate CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort, long-acting barbiturates, bosentan, efavirenz, etravirine) likely to significantly reduce serum concentration; avoid concomitant administration.
CYP3A4, P-gp, and OATP1B3 Inhibitor: Effect on pharmacokinetics of substrates not considered clinically significant due to short treatment duration.

Pregnancy: Contraindicated due to potential fetal harm.
Lactation: Insufficient data regarding presence in milk or effects on infants/milk production.
Females of Reproductive Potential: Verify pregnancy status prior to starting treatment.
Geriatric Use (≥65 years): Insufficient trial numbers to determine response differences; no clinically meaningful pharmacokinetic differences observed compared to younger patients.

Indicated for acute, moderate-severe VVC in non-pregnant adult females with azole-resistant organisms or contraindications to topical/oral azole antifungals.
Represents the only approved non-azole treatment regimen for VVC.
Clinical failure should be investigated fully; if azole resistance is suspected, culture and susceptibility testing are recommended.
Diarrhea and other gastrointestinal side effects are common and dose-dependent.