Ibrexafungerp is an oral triterpenoid antifungal agent indicated for the treatment of vulvovaginal candidiasis (VVC) and to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in post-menarchal persons. Based on animal studies, ibrexafungerp may cause fetal harm; therefore, ibrexafungerp use is contraindicated during pregnancy. The most frequent adverse reactions reported with ibrexafungerp in clinical trials were abdominal pain, diarrhea, dizziness, fatigue, headache, nausea, urinary tract infection, and vomiting.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-May be administered with or without food.
Gastrointestinal adverse reactions reported in ibrexafungerp-treated patients during clinical trials include diarrhea (7.7% to 16.7%), nausea (5.4% to 11.9%), abdominal pain (10% to 11.4%), and vomiting (2%).
Neurologic adverse reactions reported in ibrexafungerp-treated patients during clinical trials include headache (17.6%), dizziness (including postural dizziness, 3.3%), and fatigue (3.1%).
Dysmenorrhea, flatulence, back pain, elevated hepatic enzymes, vaginal bleeding, and rash/hypersensitivity reactions were reported in less than 2% of ibrexafungerp-treated patients during clinical trials.
Urinary tract infection was reported in 3.8% of ibrexafungerp-treated patients during clinical trials.
Ibrexafungerp is contraindicated in patients with ibrexafungerp hypersensitivity.
Ibrexafungerp use is contraindicated during pregnancy due to the potential for fetal harm. Available data on ibrexafungerp use in pregnant women are insufficient to determine any drug-associated risks of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. In pregnant rabbits, oral ibrexafungerp administered at exposures approximately 5-times or more the recommended human exposure during organogenesis was associated with fetal malformations, including absent forelimb(s), absent hindpaw, absent ear pinna, and thoracogastroschisis. However, no changes in embryo-fetal survival or fetal body weights were observed at any dose, and fetal malformations were not observed when ibrexafungerp was dosed at approximately 2-times the recommended human exposure based on AUC comparison. Oral ibrexafungerp administered at exposures approximately 5-times the recommended human exposure to pregnant rats during organogenesis was not associated with fetal toxicity or increased fetal malformations. There is a pregnancy safety study for ibrexafungerp. If a pregnant woman is inadvertently exposed to ibrexafungerp or if pregnancy is detected within 4 days after a patient receives ibrexafungerp, report the exposure to the manufacturer at 1-888-982-7299.
There are no data on the presence of ibrexafungerp in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ibrexafungerp and any potential adverse effects on the breast-fed child from ibrexafungerp or the underlying maternal condition.
Ibrexafungerp is associated with reproductive risk. Verify pregnancy status in persons of reproductive potential with pregnancy testing before initiating treatment and prior to each monthly dose when ibrexafungerp is used for recurrent vulvovaginal candidiasis. Discuss contraception requirements with the patient. Advise persons of reproductive potential to use effective contraception during treatment and for 4 days after the final dose.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Candida albicans, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida sp., Candida tropicalis
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of vulvovaginal candidiasis (VVC):
Oral dosage:
Adults: 300 mg PO every 12 hours for 1 day. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents (post-menarchal): 300 mg PO every 12 hours for 1 day. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For reduction in the incidence of recurrent vulvovaginal candidiasis (RVVC) (vulvovaginal candidiasis prophylaxis):
Oral dosage:
Adults: 300 mg PO every 12 hours for 1 day of every month for 6 months. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents (post-menarchal): 300 mg PO every 12 hours for 1 day of every month for 6 months. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Maximum Dosage Limits:
-Adults
600 mg/day PO.
-Geriatric
600 mg/day PO.
-Adolescents
Post-menarchal: 600 mg/day PO.
Pre-menarchal: Safety and efficacy have not been established.
-Children
Post-menarchal: 600 mg/day PO.
Pre-menarchal: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed for patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). Administration in patients with severe hepatic impairment (Child-Pugh Class C) has not been studied.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Adagrasib: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with adagrasib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of ibrexafungerp by 5.8-fold.
Amobarbital: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with clarithromycin. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Apalutamide: (Major) Avoid concurrent administration of ibrexafungerp with apalutamide. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and apalutamide is a strong CYP3A inducer.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Atazanavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with atazanavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Atazanavir; Cobicistat: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with atazanavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively. (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with cobicistat. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Barbiturates: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Bexarotene: (Major) Avoid concurrent administration of ibrexafungerp with bexarotene. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Bosentan: (Major) Avoid concurrent administration of ibrexafungerp with bosentan. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and bosentan is a moderate CYP3A inducer.
Butalbital; Acetaminophen: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Carbamazepine: (Major) Avoid concurrent administration of ibrexafungerp with carbamazepine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
Cenobamate: (Major) Avoid concurrent administration of ibrexafungerp with cenobamate. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and cenobamate is a moderate CYP3A inducer.
Ceritinib: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ceritinib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Chloramphenicol: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with chloramphenicol. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Clarithromycin: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with clarithromycin. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Cobicistat: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with cobicistat. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Dabrafenib: (Major) Avoid concurrent administration of ibrexafungerp with dabrafenib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Darunavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with darunavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Darunavir; Cobicistat: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with cobicistat. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively. (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with darunavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with cobicistat. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively. (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with darunavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Delavirdine: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with delavirdine. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Efavirenz: (Major) Avoid concurrent administration of ibrexafungerp with efavirenz. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent administration of ibrexafungerp with efavirenz. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent administration of ibrexafungerp with efavirenz. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Elagolix: (Major) Avoid concurrent administration of ibrexafungerp with elagolix. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent administration of ibrexafungerp with elagolix. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with cobicistat. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with cobicistat. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Encorafenib: (Major) Avoid concurrent administration of ibrexafungerp with encorafenib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Major) Avoid concurrent administration of ibrexafungerp with enzalutamide. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and enzalutamide is a strong CYP3A inducer.
Eslicarbazepine: (Major) Avoid concurrent administration of ibrexafungerp with eslicarbazepine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer.
Etravirine: (Major) Avoid concurrent administration of ibrexafungerp with etravirine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and etravirine is a moderate CYP3A inducer.
Fosphenytoin: (Major) Avoid concurrent administration of ibrexafungerp with phenytoin/fosphenytoin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and phenytoin and fosphenytoin are strong CYP3A inducers.
Grapefruit juice: (Major) Advise patients to avoid consuming grapefruit or grapefruit juice while taking ibrexafungerp. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and grapefruit is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Idelalisib: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with idelalisib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Indinavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with indinavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concurrent administration of ibrexafungerp with rifampin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Isoniazid, INH; Rifampin: (Major) Avoid concurrent administration of ibrexafungerp with rifampin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Itraconazole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with itraconazole. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ketoconazole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concomitantly with ketoconazole. In a drug interaction study, the AUC and Cmax of ibrexafungerp increased by 5.8-fold and 2.5-fold, respectively, when coadministered with ketoconazole. Ibrexafungerp is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with clarithromycin. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Levoketoconazole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concomitantly with ketoconazole. In a drug interaction study, the AUC and Cmax of ibrexafungerp increased by 5.8-fold and 2.5-fold, respectively, when coadministered with ketoconazole. Ibrexafungerp is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor.
Lonafarnib: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with lonafarnib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Lopinavir; Ritonavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ritonavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Lorlatinib: (Major) Avoid concurrent administration of ibrexafungerp with lorlatinib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer.
Lumacaftor; Ivacaftor: (Major) Avoid concurrent administration of ibrexafungerp with combination lumacaftor; ivacaftor. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and combination lumacaftor; ivacaftor is a strong CYP3A inducer.
Lumacaftor; Ivacaftor: (Major) Avoid concurrent administration of ibrexafungerp with combination lumacaftor; ivacaftor. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and combination lumacaftor; ivacaftor is a strong CYP3A inducer.
Mavacamten: (Major) Avoid concurrent administration of ibrexafungerp with mavacamten. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Methohexital: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Mifepristone: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with mifepristone. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Mitotane: (Major) Avoid concurrent administration of ibrexafungerp with mitotane. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and mitotane is a strong CYP3A inducer.
Nafcillin: (Major) Avoid concurrent administration of ibrexafungerp with nafcillin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and nafcillin is a moderate CYP3A inducer.
Nefazodone: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with nefazodone. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Nelfinavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with nelfinavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Nirmatrelvir; Ritonavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ritonavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concurrent administration of ibrexafungerp with rifabutin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Pentobarbital: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Pexidartinib: (Major) Avoid concurrent administration of ibrexafungerp with pexidartinib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
Phenobarbital: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenytoin: (Major) Avoid concurrent administration of ibrexafungerp with phenytoin/fosphenytoin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and phenytoin and fosphenytoin are strong CYP3A inducers.
Posaconazole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with posaconazole. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Primidone: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Repotrectinib: (Major) Avoid concurrent administration of ibrexafungerp with repotrectinib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer.
Ribociclib: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ribociclib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ribociclib; Letrozole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ribociclib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Rifabutin: (Major) Avoid concurrent administration of ibrexafungerp with rifabutin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Rifampin: (Major) Avoid concurrent administration of ibrexafungerp with rifampin. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Rifapentine: (Major) Avoid concurrent administration of ibrexafungerp with rifapentine. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ritonavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ritonavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
Saquinavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with saquinavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Secobarbital: (Major) Avoid concurrent administration of ibrexafungerp with barbiturates. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Sotorasib: (Major) Avoid concurrent administration of ibrexafungerp with sotorasib. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and sotorasib is a moderate CYP3A inducer.
St. John's Wort, Hypericum perforatum: (Major) Avoid concurrent administration of ibrexafungerp with St. John's Wort. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and St. John's Wort is a strong CYP3A inducer.
Tipranavir: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with tipranavir. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Tucatinib: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with tucatinib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with clarithromycin. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Voriconazole: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with voriconazole. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrexafungerp is a triterpenoid antifungal agent and acts by inhibiting glucan synthase, an enzyme involved in the formation of beta (1,3)-D-glucan. Beta (1,3)-D-glucan is a major fungal cell wall component, and by disrupting its biosynthesis, ibrexafungerp compromises the integrity of the fungal cell wall resulting in cell lysis. Ibrexafungerp has concentration-dependent fungicidal activity against Candida sp. and fungistatic activity against Aspergillus sp. Ibrexafungerp retains in vitro antifungal activity when tested at pH 4.5 (the normal vaginal pH).
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 sp. No resistance development has been observed after monthly dosing in persons with recurrent vulvovaginal candidiasis. The mechanism of action of ibrexafungerp is similar to the echinocandin antifungals; however, the binding sites on the glucan synthase enzyme are different, but partly overlap resulting in very limited cross-resistance between ibrexafungerp- and echinocandin-resistant strains. In vitro studies have not demonstrated antagonism between ibrexafungerp and azoles or echinocandins.
Ibrexafungerp is administered orally. The mean steady-state Vd of ibrexafungerp is approximately 600 L. Ibrexafungerp is highly protein bound (more than 99%), predominately to albumin. Animal studies demonstrate a 9-fold higher exposure in vaginal tissue than in blood. Ibrexafungerp is eliminated mainly by metabolism and biliary excretion. Metabolism occurs via hydroxylation by CYP3A4, followed by glucuronidation and sulfation of a hydroxylated inactive metabolite. After oral administration of radiolabeled ibrexafungerp to healthy volunteers, a mean of 90% of the radioactive dose (51% as unchanged ibrexafungerp) was recovered in feces and 1% was recovered in urine. The elimination half-life of ibrexafungerp is approximately 20 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C8, CYP3A4, OATP1B3, P-gp
Ibrexafungerp is a substrate of CYP3A4 and P-gp. Concurrent administration with CYP3A4 inducers or inhibitors may alter ibrexafungerp plasma concentrations. Ibrexafungerp is also an inhibitor of CYP2C8, CYP3A4, OATP1B3, or P-gp; however, due to the short treatment duration, ibrexafungerp is not expected to significantly alter the pharmacokinetics of CYP2C8, CYP3A4, OATP1B3, or P-gp substrates.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration, ibrexafungerp generally reaches maximum plasma concentrations at 4 to 6 hours after single and multiple dosing. In a study of healthy volunteers, ibrexafungerp AUC and Cmax increased approximately dose-proportionally after single-dose administration of 10 to 1,600 mg and multiple-dose administration of 300 to 800 mg. Based on a population pharmacokinetic analysis in patients with vulvovaginal candidiasis, the model predicts that 300 mg twice daily for 2 doses achieves a mean AUC0-24 exposure of 6,832 ng x hour/mL and Cmax of 435 ng/mL under fasted conditions and a mean AUC0-24 exposure of 9,867 ng x hour/mL and Cmax of 629 ng/mL under fed conditions. Administration with a high fat meal (800 to 1,000 calories; 50% fat) increased the Cmax and AUC by 32% and 38%, respectively, as compared to fasting conditions; these changes are not considered clinically significant.
-Special Populations
Hepatic Impairment
The pharmacokinetics of ibrexafungerp were not altered in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) when the total AUC estimates were compared to healthy subjects. The impact of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of ibrexafungerp is unknown.
Pediatrics
The pharmacokinetics of ibrexafungerp are not altered in post-menarchal adolescents (ages 13 to 17 years).
Geriatric
A study in geriatric patients (ages 65 to 76 years) found no clinically meaningful differences in the pharmacokinetics of ibrexafungerp when compared to younger adults.