BREXAFEMME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BREXAFEMME (BREXAFEMME).
BREXAFEMME (ibrexafungerp) inhibits glucan synthase, an enzyme involved in fungal cell wall synthesis, disrupting cell wall integrity and causing fungal cell death.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C8, CYP2D6, and CYP2C19. |
| Excretion | Ibrexafungerp is primarily eliminated via the biliary/fecal route. In clinical studies, approximately 51% of the dose was recovered in feces (as unchanged drug and metabolites) and ~1% in urine. Renal excretion is negligible. |
| Half-life | The terminal elimination half-life of ibrexafungerp is approximately 20-30 hours in healthy subjects, supporting once-daily oral dosing without need for a loading dose. |
| Protein binding | Ibrexafungerp is highly bound to plasma proteins (>99%), primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The volume of distribution is approximately 600 L (10 L/kg for a 60 kg individual), indicating extensive tissue distribution and high penetration into tissues including the vaginal mucosa. |
| Bioavailability | Oral bioavailability is approximately 35-45% under fed conditions (high-fat meal increases exposure by ~2-fold). Administration with food is recommended to enhance absorption and reduce variability. |
| Onset of Action | Oral administration: Clinical effect (symptom relief) may be observed within 24-48 hours of the first dose, based on clinical trial data for vulvovaginal candidiasis. |
| Duration of Action | The pharmacodynamic effect persists throughout the dosing interval (24 hours) due to the long half-life and high tissue concentrations. Clinical cure rates at test-of-cure visit (day 11-14) are used as endpoint. |
200 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for any degree of renal impairment including end-stage renal disease on dialysis. |
| Liver impairment | For Child-Pugh Class B or C (moderate or severe hepatic impairment), reduce dose to 200 mg every 48 hours. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no FDA-approved dosing. |
| Geriatric use | No specific dose adjustment based on age alone; clinical studies included limited number of patients aged ≥65 years, and no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BREXAFEMME (BREXAFEMME).
| Breastfeeding | It is unknown whether ibresafungin is excreted in human milk. In lactating rats, ibresafungin was detected in milk. The M/P ratio has not been determined in humans. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 5 days after the last dose. |
| Teratogenic Risk | Ibresafungin is classified as FDA Pregnancy Category C. In animal studies, ibresafungin was associated with developmental toxicity including increased resorptions and decreased fetal weights at maternal toxic doses. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ibresafungin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Specific trimester risks are not fully characterized; however, caution is advised throughout pregnancy. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to ibrexafungerp or any excipients"]
| Precautions | ["Not indicated for treatment of invasive fungal infections","Use in patients with hepatic impairment not recommended","May cause fetal harm based on animal data; effective contraception advised during treatment","Potential for drug interactions with strong CYP3A inhibitors and inducers"] |
| Food/Dietary | Take with food; avoid grapefruit and grapefruit juice. No other significant dietary restrictions. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor liver function tests (ALT, AST, alkaline phosphatase, bilirubin) periodically during therapy. Assess for signs of hepatotoxicity. Monitor serum creatinine and electrolytes as clinically indicated. Perform pregnancy testing in women of reproductive potential prior to initiation. Fetal ultrasound may be considered if exposure occurs during pregnancy. |
| Fertility Effects | In animal studies, no adverse effects on male or female fertility were observed at clinically relevant exposures. However, effects on human fertility have not been studied. Women of reproductive potential should use effective contraception during treatment and for 5 days after the last dose. |
| BREXAFEMME (ibrexafungerp) is a triterpenoid antifungal used for vulvovaginal candidiasis. It inhibits glucan synthase. Avoid use in pregnancy (based on animal data); obtain pregnancy test before initiating. Monitor for hepatotoxicity; contraindicated in hepatic impairment (Child-Pugh C). May cause diarrhea and nausea. Drug-drug interactions: avoid strong CYP3A4 inducers; reduce dose with strong CYP3A4 inhibitors. |
| Patient Advice | Take with food to improve absorption and reduce GI side effects. · Complete the full 1-day course (2 doses 12 hours apart) even if symptoms improve. · Inform healthcare provider if you are pregnant, planning to become pregnant, or breastfeeding. · Report signs of liver problems: dark urine, yellowing skin/eyes, severe fatigue. · Do not take with grapefruit products. · If you have a history of liver disease, discuss with your doctor before use. |