Brexafemme
Brexafemme Uses, Dosage, Side Effects, Food Interaction and all others data.
Brexafemme, also known as SCY-078 or MK-3118, is a novel enfumafungin derivative oral triterpene antifungal approved for the treatment of vulvovaginal candidiasis (VVC), also known as a vaginal yeast infection. It was developed out of a need to treat fungal infections that may have become resistant to echinocandins or azole antifungals. Brexafemme is orally bioavailable compared to the echinocandins caspofungin, micafungin, and anidulafungin; which can only be administered parenterally. Similar to echinocandins, ibrexafungerp targets the fungal β-1,3-glucan synthase, which is not present in humans, limiting the chance of renal or hepatic toxicity.
Brexafemme was granted FDA approval on 1 June 2021.
Brexafemme is an enfumafungin derivative oral triterpene antifungal approved for the treatment of vulvovaginal candidiasis. It has a moderate duration of action, as it is taken twice daily, and a wide therapeutic index as patients took more than the recommended dose in clinical trials without severe adverse effects. Patients should be counselled regarding the risk of fetal toxicity.
| Trade Name | Brexafemme |
| Availability | Prescription only |
| Generic | Ibrexafungerp |
| Ibrexafungerp Other Names | Ibrexafungerp |
| Related Drugs | fluconazole, nystatin topical, clotrimazole topical, Diflucan, itraconazole, miconazole topical |
| Type | Tablets |
| Formula | C44H67N5O4 |
| Weight | Average: 730.051 Monoisotopic: 729.519305657 |
| Protein binding | Ibrexafungerp is 99.5-99.8% protein bound in plasma, mainly to albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Brexafemme is a triterpene antifungal indicated in the treatment of vulvovaginal candidiasis in post-menarchal patients.
Brexafemme is indicated in the treatment of vulvovaginal candidiasis in post-menarchal patients.
Brexafemme is also used to associated treatment for these conditions: Vulvovaginal Candidiasis
How Brexafemme works
β-1,3-glucan synthase is composed of a catalytic subunit, FKS1 or FKS2, and a GTP-binding regulatory subunit, Rho1. This synthase is involved in the synthesis of β-1,3-glucan, a fungal cell wall component.
Brexafemme acts similarly to the echinocandin antifungals, by inhibiting the synthesis of β-1,3-glucan synthase. While echinocandins bind to the FKS1 domain of β-1,3-glucan synthase, enfumafungin and its derivatives bind at an alternate site which allows them to maintain their activity against fungal infections that are resistant to echinocandins.
Brexafemme has been shown in animal studies to distribute well to vaginal tissue, making it a favourable treatment for vulvovaginal candidiasis.
Toxicity
Data regarding overdoses of ibrexafungerp are not readily available, however patients did take higher than recommended doses in clinical trials without significant adverse effects. Patients experiencing an overdose of ibrexafungerp may experience and increased risk and severity of adverse effects. Patients should be treated with symptomatic and supportive measures.
Food Interaction
- Take with or without food. A high fat meal increases the AUC by 38% and Cmax by 32%, which is not considered significant.
[Moderate] GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of ibrexafungerp.
The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
In healthy subjects receiving the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily for 15 days), ibrexafungerp peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.5-fold and 5.8-fold, respectively.
Increased plasma concentrations of ibrexafungerp may increase the risk for adverse effects such as diarrhea, nausea, abdominal pain, dizziness, and vomiting.
When administered to healthy volunteers with a high-fat meal (800 to 1000 calories; 50% fat), ibrexafungerp Cmax and AUC increased 32% and 38%, respectively, compared to fasted conditions.
MANAGEMENT: Brexafemme may be administered with or without food.
However, avoiding consumption of grapefruit or grapefruit juice during treatment with ibrexafungerp may be advisable.
Volume of Distribution
The volume of distribution at steady state is approximately 600 L.
Elimination Route
Brexafemme given at a dose of 300 mg twice daily reaches a Cmax of 435 ng/mL, with a Tmax of 4-6 hours, and an AUC0-24 of 6832 h*ng/mL.
Half Life
The elimination half life of ibrexafungerp is approximately 20 hours.
Clearance
Clearance values of 53.6 L/h and 56.1 L/h have been reported.
Elimination Route
90% of a radiolabelled oral dose of ibrexafungerp is recovered in the feces, with 51% as the unchanged parent drug. 1% of a radiolabelled oral dose is recovered in the urine.
Innovators Monograph
You find simplified version here Brexafemme
