ibrexafungerp

Action and Spectrum

Actions and Spectrum: 

Actions:  

ibrexafungerp works by inhibiting the synthesis of beta-glucan,a component of the fungal cell wall. This leads to weakening of the cell wall and ultimately leads to cell death. ibrexafungerp has shown activity against a broad spectrum of fungal pathogens, including drug-resistant strains. 

Spectrum:  

ibrexafungerp has a broad spectrum of activity against Candida species, including Candida auris, which is an emerging multidrug-resistant fungus. It is also active against Aspergillus species, including some azole-resistant strains.

ibrexafungerp has also demonstrated in vitro activity against other fungal species, including Cryptococcus neoformans, Pneumocystis jirovecii, and some dermatophytes. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Vulvovaginal candidiasis 

• Abdominal pain (11.4%) 
• Diarrhea (16.7%) 
• Nausea (11.9%) 

Recurrent vulvovaginal candidiasis 

• Headache (17%) 

1-10% 

Vulvovaginal candidiasis 

• Back pain (2%) 
• Dysmenorrhea (2%) 
• Vomiting (2%) 
• Elevated transaminases (2%) 
• Dizziness (3.3%) 
• Flatulence (2%) 
• Rash/hypersensitivity reaction (2%) 
• Vaginal bleeding (2%) 

Recurrent vulvovaginal candidiasis 

• Urinary tract infection (3.8%) 
• Abdominal pain (10%) 
• Nausea (5.4%) 
• Diarrhea (7.7%) 
• Fatigue (3.1%) 

Black Box Warning

Black Box Warning: 

ibrexafungerp is not recommended during pregnancy as it may harm the developing fetus, according to studies. If you at reproductive age, it is important to confirm that you are not pregnant before starting treatment.

If you are using this medication on a monthly basis to prevent recurrent vulvovaginal candidiasis, your pregnancy status should be assessed before each dose. It is advised to use effective contraception during treatment and for four days after your final dose. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: ibrexafungerp is contraindicated in patients who have a known hypersensitivity or allergy to the medication. 
• CYP3A4 Substrates: ibrexafungerp may interact with medications that are metabolized by the CYP3A4 enzyme, such as certain statins, calcium channel blockers, and immunosuppressants.  
• Pregnancy and breastfeeding: The safety and efficacy of ibrexafungerp have not been established in pregnant or breastfeeding women.  
• Strong CYP3A4 Inhibitors: ibrexafungerp may interact with medications that inhibit the CYP3A4 enzyme, such as certain antifungal medications, antibiotics, and antiviral medications.  
• Concomitant use with p-glycoprotein substrates: ibrexafungerp may interact with medications that are substrates of p-glycoprotein, a protein that helps remove substances from cells.  

Caution 

• Hepatic impairment: ibrexafungerp is metabolized in the liver, so caution should be taken when administering it to patients with severe hepatic impairment. 
• Renal impairment: ibrexafungerp is eliminated through the kidneys, so caution should be taken when administering it to patients with severe renal impairment. 
• Drug interactions: ibrexafungerp may interact with other medications, such as CYP3A4 inhibitors and substrates, so caution should be taken when using it concomitantly with other medications.  
• Allergic reactions: Allergic reactions to ibrexafungerp have been reported in some patients. If you experience symptoms such as difficulty breathing or swelling of the face, lips, tongue or throat, seek immediate medical attention. 
• Use in pediatric patients: The safety and efficacy of ibrexafungerp have not been established in pediatric patients, so caution should be taken when using it in this population. 
• Use in geriatric patients: Elderly patients may be more susceptible to certain adverse effects of ibrexafungerp, such as hepatic and renal impairment, so caution should be taken when administering it to this population. 
• Use in pregnant and breastfeeding women: The safety and efficacy of ibrexafungerp have not been established in pregnant or breastfeeding women, so caution should be taken when administering it to these populations. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known.  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

Pharmacodynamics: 

Mechanism of Action 

It obstructs the function of glucan synthase, an enzyme crucial in producing 1,3-beta-D-glucan, which is a vital constituent of the fungal cell wall. 

Time-kill studies have indicated that its fungicidal activity against candidal species is contingent on its concentration. It has been demonstrated to exhibit activity against a majority of isolates of the listed microorganisms in both laboratory settings and actual clinical infections 

• Candida dubliniensis 
• Candida krusei 
• Candida lusitaniae 
• Candida auris 
• Candida tropicalis 
• Candida keyfr 
• Candida parapsilosis 
• Candida glabrata 
• Candida guilliermondii

Pharmacokinetics: 

Absorption 

The peak plasma concentration occurs between 4 to 6 hours after administration. When fasted, the concentration is 435 ng/mL, while when fed, it is 629 ng/mL. The AUC is 6832 ng·hr/mL in the fasted state and 9867 ng·hr/mL in the fed state. 

When ibrexafungerp is administered with a high-fat meal containing 800-1000 calories (50% fat), there is a 32% increase in its peak plasma concentration and a 38% increase in its AUC compared to when taken in a fasted state.  

Distribution 

The volume of distribution (steady-state) of the drug is approximately 6000 L. The drug is highly protein-bound, with more than 99% of it being bound to plasma proteins. 

Metabolism 

The drug is primarily metabolized through hydroxylation by the CYP3A4 enzyme. This is followed by glucuronidation and sulfation of a hydroxylated inactive metabolite. 

Elimination and Excretion 

The half-life of the drug is 20 hours. The drug is predominantly eliminated through feces (90%), with 51% of it being unchanged. A small percentage of the drug is eliminated through urine (1%). 

Adminstartion

Administration: 

Oral administration  

ibrexafungerp should be administered as prescribed by a healthcare provider or according to the instructions on the medication label. It is typically taken orally, with or without food, depending on the specific instructions for the formulation being used.

It is important to take the drug at the same time every day to maintain a consistent level in the bloodstream. If a dose is missed, it is recommended to take it as soon as possible, unless it is almost time for the next scheduled dose, in which case it is advisable to skip the missed dose and resume with the regular dosing schedule. 

It is essential to follow the prescribed dosing schedule and not to take more or less than the recommended amount unless directed by a healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: 

Pronounced:  

Why do we use ibrexafungerp? 

ibrexafungerp is an antifungal medication that is used to treat certain types of fungal infections. It is specifically indicated for the treatment of vulvovaginal candidiasis (VVC), otherwise as vaginal yeast infections, caused by Candida species in adult women.

It works by inhibiting the fungal enzyme beta-glucan synthase, which is necessary for the formation of the fungal cell wall. This leads to the disruption of the cell wall and subsequent death of the fungal cell. ibrexafungerp is not effective against bacterial infections or viral infections as common cold or flu.