Clinical Pharmacology Corner: FDA Approves BREXAFEMME (Ibrexafungerp)

FDA Approves BREXAFEMME (Ibrexafungerp) for Adult and Post-Menarchal Pediatric Females with Vulvovaginal Candidiasis On June 1, 2021, the U.S. Food and Drug Administration (FDA) approved BREXAFEMME (ibrexafungerp) for the treatment of adult and post-menarchal pediatric females with vulvovaginal candidiasis (VVC). The recommended dosage of BREXAFEMME is 300 mg (two 150 mg tablets) 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). BREXAFEMME may be taken with or without food. Verify the pregnancy status in females of reproductive potential prior to initiating treatment with BREXAFEMME. Additional information regarding dosage and administration as well as warnings and precautions about fetal toxicity can be found in the full prescribing information linked below. Mechanism of Action (MOA) and Pharmacokinetics (PK) MOA: Ibrexafungerp is a triterpenoid antifungal drug. General PK: Ibrexafungerp AUC and Cmax increased approximately dose-proportionally following single doses of 10 to 1600 mg (0.02 to 2.67 times the approved recommended daily dose) and multiple doses of 300 to 800 mg (0.50 to 1.33 times the approved recommended daily dose) in healthy subjects. 300 mg twice a day for 2 doses is predicted to achieve a mean (%CV) AUC0-24 of 6832 (15%) ng•hr/mL and Cmax of 435 (15%) ng/mL under fasted conditions, and a mean AUC0-24 of 9867 (15%) ng•h/mL and Cmax of 629 (15%) ng/mL under fed conditions. Absorption: Ibrexafungerp generally reaches maximum plasma concentrations 4 to 6 hours. Distribution: The mean steady state volume of distribution of ibrexafungerp is approximately 600 L. Ibrexafungerp is greater than 99% protein bound, predominantly to albumin. Animal studies demonstrate a 9-fold higher exposure in vaginal tissue than in blood. Elimination: Ibrexafungerp is eliminated mainly via metabolism and biliary excretion. The elimination half-life of ibrexafungerp is approximately 20 hours. Metabolism: Ibrexafungerp undergoes hydroxylation by CYP3A4, followed by glucuronidation and sulfation, in vitro. Excretion: Following 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% in urine. Drug Interactions Strong CYP3A Inhibitors: Reduce the BREXAFEMME dosage to 150 mg twice daily for one day approximately 12 hours apart. Concomitant use of strong CYP3A inhibitors increases ibrexafungerp concentration, which may increase the risk of BREXAFEMME adverse reactions. Strong or Moderate CYP3A Inducers: Avoid concomitant administration of BREXAFEMME. Concomitant use with a strong or moderate CYP3A inducer may decrease ibrexafungerp concentration, which may reduce BREXAFEMME efficacy. Use in Specific Populations There were no clinically significant differences in ibrexafungerp pharmacokinetics based on age (20 to 45 years and 65 to 76 years). Efficacy and Safety Efficacy of BREXAFEMME was demonstrated in two randomized placebo-controlled clinical trials of a single day of BREXAFEMME 600 mg (two 150 mg tablets per dose, administered 12 hours apart) for the treatment of VVC. Efficacy was assessed by clinical outcome at the test of cure (TOC) visit. A complete clinical response was defined as the complete resolution of signs and symptoms (vulvovaginal signs and symptoms (VSS) score of 0). Additional information regarding the efficacy trials can be found in the full prescribing information linked below. The most frequent adverse reactions (≥ 2%) reported with BREXAFEMME in clinical trials of vulvovaginal candidiasis treatment were diarrhea, nausea, abdominal pain, dizziness, and vomiting. Full prescribing information is available at https://go.usa.gov/x64SQ. Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval. A non-comprehensive list of examples of clinical substrates, inhibitors and inducers for metabolic and transporter system related interactions may be found at https://go.usa.gov/xXY9C. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by completing a form online at https://www.fda.gov/safety/medwatch/default.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088). The Office of Clinical Pharmacology (OCP) is pleased to offer the e-mail subscription service Clinical Pharmacology Corner. This is a free service from FDA to provide occasional updates from OCP regarding newly approved therapies, new regulatory and scholarly publications, upcoming events and other items of interest. Subscribe today at https://public.govdelivery.com/accounts/USFDA/subscriber/topics and select Clinical Pharmacology Corner under Drugs. We always welcome your thoughts regarding the format, content, and utility of this communication. Comments may be sent via email to ocp@fda.hhs.gov. This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

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