EXBLIFEP Solution for injection Ref.[108537] Active ingredients: Cefepime Cefepime and Enmetazobactam

2.1. Recommended Dosage and Administration

The recommended dosage of EXBLIFEP is 2.5 grams (2 grams cefepime and 0.5 grams enmetazobactam) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older with an estimated glomerular filtration rate (eGFR) between 60 and 129 mL/min. The duration of treatment is 7 days and up to 14 days for patients with concurrent bacteremia.

2.2. Recommended Dosage in Patients (18 Years of Age and Older) Based on Renal Function

The recommended dosage of EXBLIFEP in patients 18 years of age and older with varying degrees of renal function is described in Table 1 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. For patients with changing renal function, monitor serum creatinine concentrations and eGFR at least daily and adjust the dosage of EXBLIFEP accordingly [see Use in Specific Populations (8.6)].

Table 1. Recommended Dosage of EXBLIFEP in Patients (18 Years of Age and Older) Based on Renal Function:

^a As calculated using the Modification of Diet in Renal Disease (MDRD) formula
^b The total duration of treatment is for 7 to 14 days.
^c In patients requiring intermittent hemodialysis, complete the hemodialysis session before the start of EXBLIFEP dosing. Whenever possible, administer cefepime and enmetazobactam at the same time each day.

2.3. Preparation of EXBLIFEP for Intravenous Infusion Administration

Preparation

EXBLIFEP is supplied as a dry powder in a single-dose vial that must be reconstituted and further diluted prior to intravenous infusion as outlined below. EXBLIFEP does not contain preservatives. Aseptic technique must be used for reconstitution and dilution. Prepare the required dose for intravenous infusion using the steps described below:

1. Reconstitute the powder in the EXBLIFEP vial, with 10 mL of 0.9% Sodium Chloride Injection, or 5% Dextrose Injection, or 2.5% Dextrose and 0.45% Sodium Chloride Injection, from a 250 mL infusion bag.

2. Mix gently to dissolve. The reconstituted EXBLIFEP solution will have a resultant concentration of 0.2 grams/mL (cefepime 0.16 grams/mL and enmetazobactam 0.04 grams/mL). The final volume is approximately 13 mL. The reconstituted solution is not for direct injection.

3. The reconstituted solution must immediately be diluted further in the 250 mL infusion bag used in Step 1. The same injection solution should be used for both reconstitution and dilution (e.g., if reconstitution in Step 1 is performed with 5% dextrose, the dilution in Step 3 should be performed with a 250 mL infusion bag of 5% dextrose). To dilute the reconstituted solution, withdraw the full or partial reconstituted vial contents and add it back into the infusion bag in accordance with Table 2 below.

Table 2. Preparation of EXBLIFEP Doses:

4. Store the prepared diluted solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 4 hours prior to administration. The intravenous infusion administration of the diluted solution must be completed within 6 hours of dilution.

5. Visually inspect the diluted EXBLIFEP solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The color of the EXBLIFEP infusion solution for administration is clear to yellowish. Discard unused portion after use.

2.4. Drug Compatibility

EXBLIFEP is compatible with 0.9% Sodium Chloride Injection, 5% Dextrose injection, and 2.5% Dextrose and 0.45% Sodium Chloride.

Compatibility of EXBLIFEP solution for administration with other drugs has not been established.

Patients who receive an overdose should be carefully observed and given supportive treatment.

Cefepime and enmetazobactam can be removed by hemodialysis [see Clinical Pharmacology (12.3)]. No clinical information is available on the use of hemodialysis to treat EXBLIFEP overdosage.

Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus [see Warnings and Precautions (5.2), Adverse Reactions (6.2), and Dosage and Administration (2.2)].

Store EXBLIFEP vials refrigerated at 2°C to 8°C (36°F to 46°F); excursions are permitted to 15°C to 25°C (59°F to 77°F) [see USP, Controlled Room Temperature (CRT)]. Keep the vials in the outer carton to protect from light.

Storage conditions for reconstituted and diluted solutions of EXBLIFEP for injection are described in another section of labeling [see Dosage and Administration (2.3)].