Ibrexafungerp (Monograph)

Brand name: Brexafemme
Drug class:

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

Introduction

Ibrexafungerp citrate is a triterpenoid antifungal agent.

Uses for Ibrexafungerp

Ibrexafungerp citrate has the following uses:

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

Reduction in the incidence of recurrent vulvovaginal candidiasis (RVVC) in adult and post-menarchal pediatric females.

Ibrexafungerp Dosage and Administration

General

Ibrexafungerp citrate is available in the following dosage form(s) and strength(s):

Tablets: 150 mg of ibrexafungerp

Administration

Ibrexafungerp citrate may be taken with or without food.

Prior to initiating treatment, verify pregnancy status in females of reproductive potential. Reassess pregnancy status prior to each dose when ibrexafungerp is used monthly for 6 months for reduction in the incidence of RVVC.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Treatment of Vulvovaginal Candidiasis

• The recommended dosage of ibrexafungerp in post-menarchal pediatric females is 300 mg (two tablets of 150 mg) administered approximately 12 hours apart (e.g., in the morning and in the evening) for one day, for a total daily dosage of 600 mg (four 150-mg tablets).

• With concomitant use of a strong CYP3A inhibitor, administer ibrexafungerp 150 mg approximately 12 hours apart (e.g., in the morning and in the evening) for one day. No dosage adjustment is warranted in patients with concomitant use of a weak or moderate CYP3A inhibitor.

Reduction in the Incidence of Recurrent Vulvovaginal Candidiasis

• The recommended dosage of ibrexafungerp in post-menarchal pediatric females is 300 mg (two tablets of 150 mg) administered approximately 12 hours apart (e.g., in the morning and in the evening) for one day, for a total daily dosage of 600 mg (four 150-mg tablets) monthly for 6 months.

• With concomitant use of a strong CYP3A inhibitor, administer ibrexafungerp 150 mg approximately 12 hours apart (e.g., in the morning and in the evening) for one day. No dosage adjustment is warranted in patients with concomitant use of a weak or moderate CYP3A inhibitor.

Adults

Treatment of Vulvovaginal Candidiasis

• The recommended dosage of ibrexafungerp in adult females is 300 mg (two tablets of 150 mg) administered approximately 12 hours apart (e.g., in the morning and in the evening) for one day, for a total daily dosage of 600 mg (four 150-mg tablets).

• With concomitant use of a strong CYP3A inhibitor, administer ibrexafungerp 150 mg approximately 12 hours apart (e.g., in the morning and in the evening) for one day. No dosage adjustment is warranted in patients with concomitant use of a weak or moderate CYP3A inhibitor.

Reduction in the Incidence of Recurrent Vulvovaginal Candidiasis

• The recommended dosage of ibrexafungerp in adult females is 300 mg (two tablets of 150 mg) administered approximately 12 hours apart (e.g., in the morning and in the evening) for one day, for a total daily dosage of 600 mg (four 150-mg tablets) monthly for 6 months.

• With concomitant use of a strong CYP3A inhibitor, administer ibrexafungerp 150 mg approximately 12 hours apart (e.g., in the morning and in the evening) for one day. No dosage adjustment is warranted in patients with concomitant use of a weak or moderate CYP3A inhibitor.

Related/similar drugs

fluconazole, nystatin topical, clotrimazole topical, Diflucan, itraconazole, miconazole topical

Cautions for Ibrexafungerp

Contraindications

• Pregnancy.

• Hypersensitivity to ibrexafungerp.

Warnings/Precautions

Risk of Embryo-Fetal Toxicity

Based on findings from animal studies, ibrexafungerp citrate is contraindicated during pregnancy because it may cause fetal harm. In animal reproduction studies, ibrexafungerp administered orally to pregnant rabbits during organogenesis was associated with fetal malformations including absent forelimb(s), absent hindpaw, absent ear pinna, and thoracogastroschisis at dose exposures greater or equal to approximately 5 times the human exposure at the recommended human dose (RHD).

For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with ibrexafungerp. Reassessment of pregnancy status prior to each dose is recommended when ibrexafungerp is used monthly for 6 months for reduction in the incidence of RVVC. Advise females of reproductive potential to use effective contraception during treatment of VVC and throughout the 6-month treatment period for reduction in the incidence of RVVC with ibrexafungerp and, for 4 days after the last dose.

Specific Populations

Pregnancy

Based on findings from animal studies, ibrexafungerp use is contraindicated in pregnancy because it may cause fetal harm. In pregnant rabbits, oral ibrexafungerp administered during organogenesis was associated with fetal malformations including absent forelimb(s), absent hindpaw, absent ear pinna, and thoracogastroschisis at dose exposures greater or equal to approximately 5 times the human exposure at the RHD. Oral ibrexafungerp administered to pregnant rats during organogenesis was not associated with fetal toxicity or increased fetal malformations at a dose exposure approximately 5 times the human exposure at the RHD. Available data on ibrexafungerp use in pregnant women are insufficient to draw conclusions about any drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

There is a pregnancy safety study for ibrexafungerp citrate. If ibrexafungerp citrate is inadvertently administered during pregnancy or if pregnancy is detected within 4 days after a patient receives the drug, pregnant women exposed to ibrexafungerp citrate and healthcare providers should report pregnancies to the manufacturer (SCYNEXIS) at 1-888-982-7299.

Animal Data: In a rat embryo-fetal study, ibrexafungerp was administered to pregnant rats by oral gavage from gestation days (GDs) 6 through 17 at doses of 10, 20, 35, and 50 mg/kg/day. No fetal malformations or changes in embryo-fetal survival or fetal body weights occurred with any of the doses of ibrexafungerp up to the high dose of 50 mg/kg/day (approximately 5 times the RHD based on plasma AUC comparison).

In an embryo-fetal study in rabbits, ibrexafungerp was administered by oral gavage at doses of 10, 25, and 50 mg/kg/day from GD 7 through GD 19. In the mid-dose group administered 25 mg/kg/day (approximately 5 times the RHD based on AUC comparison), fetal malformations, including absent ear pinna, craniorachischisis, thoracogastroschisis, trunk kyphosis, absent forelimbs, absent forepaws, and absent hindpaw occurred in a single fetus. Malformations including absent hindpaw and anencephaly occurred with an increased litter incidence in the high-dose group of 50 mg/kg/day (approximately 13 times the RHD based on AUC comparison), and other malformations occurred in single fetuses and litters including absent ear pinna, thoracogastroschisis, absent forelimb, and absent thyroid gland. No changes in embryo-fetal survival or fetal body weights were observed with any of the ibrexafungerp doses, and fetal malformations were not observed with the 10 mg/kg/day dose of ibrexafungerp (approximately 2 times the RHD based on AUC comparison).

In a pre-postnatal study in rats, ibrexafungerp was administered by oral gavage from GD 6 through the lactation period until lactation day 20 in maternal doses of 10, 20, 35, and 50 mg/kg/day. No maternal toxicity or adverse effects on the survival, growth, behavior, or reproduction of first-generation offspring occurred with any of the ibrexafungerp doses up to the high dose of 50 mg/kg/day (approximately 5 times the RHD based on AUC comparison).

Lactation

There are no data on the presence of ibrexafungerp in either human or animal milk, the effects on the breast-fed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ibrexafungerp citrate and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition.

Females and Males of Reproductive Potential

Based on animal data, ibrexafungerp citrate may cause fetal harm when administered to a pregnant female.

For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with ibrexafungerp. Reassessment of pregnancy status prior to each dose is recommended when ibrexafungerp is used monthly for 6 months for reduction in the incidence of RVVC.

For treatment of VVC, advise females of reproductive potential to use effective contraception during treatment with ibrexafungerp and for 4 days after the last dose.

For reduction in the incidence of RVVC, advise females of reproductive potential to use effective contraception throughout the 6-month treatment period with ibrexafungerp and, for 4 days after the last dose.

Pediatric Use

The safety and effectiveness of ibrexafungerp citrate for treatment of VVC have been established in post-menarchal pediatric females. Ibrexafungerp is also indicated for the reduction in the incidence of RVVC. Use of ibrexafungerp citrate in post-menarchal pediatric patients is supported by evidence from adequate and well-controlled studies of the drug in adult non-pregnant women with additional pharmacokinetic and safety data from post-menarchal pediatric females.

The safety and effectiveness of ibrexafungerp citrate have not been established in pre-menarchal pediatric females.

Geriatric Use

Clinical studies with ibrexafungerp citrate did not include sufficient numbers of individuals 65 years of age and older to determine whether they respond differently from younger individuals. No clinically meaningful differences in the pharmacokinetics of ibrexafungerp were observed in geriatric patients compared to younger adults.

Common Adverse Effects

The most frequent adverse reactions (≥2%) reported with ibrexafungerp in clinical trials of VVC were diarrhea, nausea, abdominal pain, dizziness, and vomiting.

The most frequent adverse reactions (≥2%) reported with ibrexafungerp in clinical trials of RVVC were headache, abdominal pain, diarrhea, nausea, urinary tract infection, and fatigue.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Concomitant use of strong CYP3A inhibitors increases ibrexafungerp exposure. Reduce ibrexafungerp dose with concomitant use of a strong CYP3A inhibitor to 150 mg twice daily for one day.

• Concomitant use of strong and moderate CYP3A inducers may significantly reduce ibrexafungerp exposure. Avoid concomitant administration of ibrexafungerp with strong or moderate CYP3A inducers.

Actions and Spectrum

Mechanism of Action

Ibrexafungerp, a triterpenoid antifungal agent, inhibits glucan synthase, an enzyme involved in the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall.

Ibrexafungerp has concentration-dependent fungicidal activity against Candidaspecies as measured by time kill studies. Ibrexafungerp retains in vitro antifungal activity when tested at pH 4.5 (the normal vaginal pH).

Spectrum

Ibrexafungerp has been shown to be active against most isolates of Candida albicans both in vitro and in clinical infections.

The following in vitro data are available, but their clinical significance is unknown. Ibrexafungerp has in vitro activity against most isolates of the following microorganisms: Candida auris, Candida dubliniensis, Candida glabrata, Candida guilliermondii, Candida keyfr, Candida krusei, Candida lusitaniae, Candida parapsilosis, and Candida tropicalis.

In vitro studies have not demonstrated antagonism between ibrexafungerp and azole or echinocandin antifungals.

Resistance

The potential for resistance to ibrexafungerp has been evaluated in vitro and is associated with mutations of the fks-2 gene; the clinical relevance of these findings is unknown. Ibrexafungerp retains activity against most fluconazole-resistant Candida species. No resistance development was observed after monthly ibrexafungerp dosing in patients with RVVC.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling.

• Advise patients that ibrexafungerp is contraindicated in pregnancy since it may cause fetal harm.

• Inform females of reproductive potential that their healthcare provider will verify that they are not pregnant prior to initiating ibrexafungerp treatment.

• Advise females of reproductive potential that reassessing pregnancy status prior to each dose is recommended when ibrexafungerp is used monthly for 6 months for reduction in the incidence of RVVC.

• For treatment of VVC, advise females of reproductive potential to use effective contraception while taking ibrexafungerp and for 4 days after the last dose.

• For reduction in the incidence of RVVC, advise females of reproductive potential to use effective contraception throughout the 6-month treatment period with ibrexafungerp and for 4 days after the last dose.

• Advise females to inform their healthcare provider of a known or suspected pregnancy.

• Advise patients who have inadvertently taken ibrexafungerp during pregnancy that there is a pregnancy safety study that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to the manufacturer (SCYNEXIS) at 1-888-982-7299.

• For treatment of VVC, inform the patient that each ibrexafungerp dose consists of two tablets. A total treatment course for VVC is two doses taken approximately 12 hours apart and consists of a total of four tablets.

• For reduction in the incidence of RVVC, inform the patients that the total treatment course is for six months. Each dose consists of two tablets taken approximately 12 hours apart for a total daily dosage of four tablets, taken monthly for six months.

• If the first two tablets are taken in the morning, the second two tablets should be taken that same day in the evening. If the first two tablets are taken in the afternoon or evening, the second two tablets should be taken the following morning.

• Inform the patient that ibrexafungerp can be taken with or without food.

• Advise the patient to inform their health care provider if they are taking any other medications as certain medications can increase or decrease blood concentrations of ibrexafungerp or ibrexafungerp may increase or decrease blood concentrations of certain medications.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

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