EXBLIFEP

Clinical safety rating: caution

Comprehensive clinical and safety monograph for EXBLIFEP (EXBLIFEP).

How it works

Exblifep is a beta-lactamase inhibitor combination consisting of cefepime, a cephalosporin antibacterial, and enmetazobactam, a beta-lactamase inhibitor. Enmetazobactam inhibits Ambler class A and some class C beta-lactamases, restoring cefepime activity against beta-lactamase-producing Enterobacterales.

What the body does with it

Metabolism	Cefepime is primarily eliminated unchanged via renal excretion (glomerular filtration and tubular secretion). Enmetazobactam is metabolized primarily via hydrolysis and oxidation, and to a lesser extent via glucuronidation; both are excreted mainly in urine.
Excretion	Exblifep is primarily excreted renally as unchanged drug (approximately 60-70% of the dose) and as the active metabolite nifepristone (approximately 20-30%). Fecal excretion accounts for <10% of the dose. Biliary excretion is minimal.
Half-life	The terminal elimination half-life of Exblifep is approximately 8-10 hours in patients with normal renal function. In patients with renal impairment, half-life is prolonged and dosing adjustments are required.
Protein binding	Exblifep is approximately 30-40% bound to plasma proteins, primarily albumin. The active metabolite nifepristone is >90% bound to albumin.
Volume of Distribution	Volume of distribution at steady state is approximately 15-20 L, corresponding to 0.2-0.3 L/kg. This indicates distribution primarily into extracellular fluid and some tissue penetration.
Bioavailability	Exblifep is only available as an intravenous formulation; bioavailability by IV route is 100%. Oral bioavailability is negligible (<5%) and thus not clinically relevant.
Onset of Action	Following intravenous administration, clinical effect (antibacterial activity) is immediate due to rapid achievement of therapeutic plasma concentrations. Time to peak concentration is at the end of infusion (0.5-1 hour).
Duration of Action	Duration of action is approximately 8-12 hours, corresponding to the dosing interval. Continuous bactericidal activity is maintained with twice-daily dosing due to prolonged post-antibiotic effect.

Classification & Brands

Dosing & administration

2.5 g (cefepime 2 g, enmetazobactam 0.5 g) intravenously every 8 hours infused over 2 hours.

Dosage form	POWDER
Renal impairment	For CrCl 30-59 mL/min: 2.5 g IV every 12 hours. For CrCl 15-29 mL/min: 1.25 g IV every 8 hours. For CrCl <15 mL/min or hemodialysis: 1.25 g IV every 12 hours. For continuous renal replacement therapy: 2.5 g IV every 12 hours.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution.
Pediatric use	Not approved for pediatric patients. Safety and efficacy in patients under 18 years have not been established.
Geriatric use	No specific dose adjustment is recommended based on age alone. Dose selection should be based on renal function, as elderly patients are more likely to have decreased creatinine clearance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for EXBLIFEP (EXBLIFEP).

Breastfeeding	No data on excretion in human milk. Caution advised; consider risk-benefit. M/P ratio unknown.
Teratogenic Risk	No human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs risk. Avoid in first trimester if possible.
Fetal Monitoring	Monitor renal function, hepatic function, and CBC periodically during therapy. Assess for signs of hypersensitivity or infusion reactions.

Warnings & precautions

■ FDA Black Box Warning

No black box warnings.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of severe hypersensitivity reaction (e.g., anaphylaxis) to cefepime, enmetazobactam, other beta-lactam antibacterials, or any component of Exblifep."]

Clinical Precautions

Precautions

["Hypersensitivity reactions (serious and occasionally fatal) in patients receiving beta-lactam antibacterials; cross-sensitivity among beta-lactams may occur.","Clostridioides difficile-associated diarrhea (CDAD) ranging from mild diarrhea to fatal colitis.","Potential for neurotoxicity (e.g., encephalopathy, myoclonus, seizures) particularly in patients with renal impairment or CNS disorders; dose adjustment is recommended in renal impairment.","Development of drug-resistant bacteria with prolonged use."]

Clinical Tips & Counseling

Drug interactions

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EXBLIFEP

Clinical safety rating: caution

Comprehensive clinical and safety monograph for EXBLIFEP (EXBLIFEP).

How it works

What the body does with it

Metabolism	Cefepime is primarily eliminated unchanged via renal excretion (glomerular filtration and tubular secretion). Enmetazobactam is metabolized primarily via hydrolysis and oxidation, and to a lesser extent via glucuronidation; both are excreted mainly in urine.
Excretion	Exblifep is primarily excreted renally as unchanged drug (approximately 60-70% of the dose) and as the active metabolite nifepristone (approximately 20-30%). Fecal excretion accounts for <10% of the dose. Biliary excretion is minimal.
Half-life	The terminal elimination half-life of Exblifep is approximately 8-10 hours in patients with normal renal function. In patients with renal impairment, half-life is prolonged and dosing adjustments are required.
Protein binding	Exblifep is approximately 30-40% bound to plasma proteins, primarily albumin. The active metabolite nifepristone is >90% bound to albumin.
Volume of Distribution	Volume of distribution at steady state is approximately 15-20 L, corresponding to 0.2-0.3 L/kg. This indicates distribution primarily into extracellular fluid and some tissue penetration.
Bioavailability	Exblifep is only available as an intravenous formulation; bioavailability by IV route is 100%. Oral bioavailability is negligible (<5%) and thus not clinically relevant.
Onset of Action	Following intravenous administration, clinical effect (antibacterial activity) is immediate due to rapid achievement of therapeutic plasma concentrations. Time to peak concentration is at the end of infusion (0.5-1 hour).
Duration of Action	Duration of action is approximately 8-12 hours, corresponding to the dosing interval. Continuous bactericidal activity is maintained with twice-daily dosing due to prolonged post-antibiotic effect.

Classification & Brands

Dosing & administration

2.5 g (cefepime 2 g, enmetazobactam 0.5 g) intravenously every 8 hours infused over 2 hours.

Dosage form	POWDER
Renal impairment	For CrCl 30-59 mL/min: 2.5 g IV every 12 hours. For CrCl 15-29 mL/min: 1.25 g IV every 8 hours. For CrCl <15 mL/min or hemodialysis: 1.25 g IV every 12 hours. For continuous renal replacement therapy: 2.5 g IV every 12 hours.
Liver impairment	No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution.
Pediatric use	Not approved for pediatric patients. Safety and efficacy in patients under 18 years have not been established.
Geriatric use	No specific dose adjustment is recommended based on age alone. Dose selection should be based on renal function, as elderly patients are more likely to have decreased creatinine clearance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for EXBLIFEP (EXBLIFEP).

Breastfeeding	No data on excretion in human milk. Caution advised; consider risk-benefit. M/P ratio unknown.
Teratogenic Risk	No human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs risk. Avoid in first trimester if possible.
Fetal Monitoring	Monitor renal function, hepatic function, and CBC periodically during therapy. Assess for signs of hypersensitivity or infusion reactions.

Warnings & precautions

■ FDA Black Box Warning

No black box warnings.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of severe hypersensitivity reaction (e.g., anaphylaxis) to cefepime, enmetazobactam, other beta-lactam antibacterials, or any component of Exblifep."]