Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Advanz Pharma Limited, Unit 17 Northwood House, Northwood Crescent, Dublin 9, D09 V504, Ireland
EXBLIFEP is indicated for the treatment of the following infections in adults (see sections 4.4 and 5.1):
Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
For complicated urinary tract infections (cUTI), including pyelonephritis, the recommended dose for patients with normal renal function is 2 g/0.5 g cefepime/enmetazobactam every 8 hours administered as an intravenous infusion over 2 hours.
In patients with augmented renal clearance (eGFR >150 mL/min) prolongation of the infusion to 4 hours is recommended (see section 5.2).
For hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP), the recommended dose for patients with normal renal function is 2 g/0.5 g cefepime/enmetazobactam every 8 hours administered as an intravenous infusion over 4 hours.
The usual duration of treatment is 7 to 10 days. In general, administration should not be less than 7 days and not longer than 14 days. In patients with bacteraemia treatment up to 14 days may be required.
No dose adjustment is necessary for the elderly based on age alone (see section 5.2).
Dose adjustment is recommended in patients with renal impairment who have an absolute estimated glomerular filtration rate (eGFR) less than 60 mL/min (see section 5.2). The recommended dose in patients with varying degrees of renal function is presented in Table 1.
Patients receiving continuous renal replacement therapy (CRRT) need a higher dose than patients on haemodialysis. For patients receiving continuous renal replacement therapy, the dose should be adjusted guided by the CRRT clearance (CLCRRT in mL/min).
For patients with changing renal function, serum creatinine concentrations and eGFR should be monitored at least daily and the dose of EXBLIFEP adjusted accordingly.
For patients with Hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP), infusion time should be 4 hours regardless of the renal impairment status.
Table 1. Recommended dose of EXBLIFEP in patients with renal impairment:
| Absolute eGFR (mL/min) | Recommended dose regimen for EXBLIFEP (cefepime and enmetazobactam) | Dosing interval |
|---|---|---|
| Mild (60 - <90) | cefepime 2 g and enmetazobactam 0.5 g | Every 8 hours |
| Moderate (30 - <60) | cefepime 1 g and enmetazobactam 0.25 g | Every 8 hours |
| Severe (15 - <30) | cefepime 1 g and enmetazobactam 0.25 g | Every 12 hours |
| End stage renal disease (<15) | cefepime 1 g and enmetazobactam 0.25 g | Every 24 hours |
| Patients requiring hemodialysis | cefepime 1 g and enmetazobactam 0.25 g loading dose on the first day of therapy and cefepime 0.5 g and enmetazobactam 0.125 g thereafter (every 24 hours but after the haemodialysis session on haemodialysis days). | Every 24 hours |
| Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) | cefepime 2 g and enmetazobactam 0.5 g | Every 48 hours |
No dose adjustment is necessary in patients with hepatic impairment (see section 5.2).
The safety and efficacy in children below 18 years of age has not yet been established. No data are available
EXBLIFEP is administered via intravenous infusion.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
Symptoms of overdose include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, and seizures (see section 4.8).
Accidental overdosing has occurred when large doses were given to patients with impaired renal function (see sections 4.2 and 4.4).
In case of severe overdose, especially in patients with compromised renal function, haemodialysis will aid in the removal of cefepime and enmetazobactam from the body; peritoneal dialysis is of no value (see section 5.2).
2 years.
After reconstitution:
The reconstituted vial should be further diluted immediately.
After dilution:
Chemical and physical in-use stability has been demonstrated for 6 hours at 2°C to 8°C followed by 2 hours at 25°C.
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
Store in a refrigerator (2°C–8°C).
Keep the vial in the outer carton in order to protect from light.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
20 mL vial (Type I clear glass) with stopper (bromobutyl rubber) and flip-off seal.
Pack size of 10 vials.
This medicinal product is for intravenous infusion and each vial is for single use only.
Aseptic technique must be followed in preparing the infusion solution.
Cefepime-enmetazobactam is compatible with sodium chloride 9 mg/ml (0.9%) solution for injection, 5% glucose injection solution and a combination of glucose injection solution and sodium chloride injection solution (containing 2.5% glucose and 0.45% sodium chloride).
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.
To prepare the required dose for intravenous infusion, reconstitute the vial as determined from Table 3 below:
1. Withdraw 10 mL from an infusion bag of 250 mL (compatible injection solution) and reconstitute the cefepime-enmetazobactam vial.
2. Mix gently to dissolve. The reconstituted cefepime-enmetazobactam solution will have an approximate cefepime concentration of 0.20 g/mL and an approximate enmetazobactam concentration of 0.05 g/mL. The final volume is approximately 10 mL.
CAUTION: THE RECONSTITUTED SOLUTION IS NOT FOR DIRECT INJECTION.
The reconstituted solution must be diluted further, immediately, in an infusion bag of 250 mL (compatible injection solution) before intravenous infusion. To dilute the reconstituted solution, withdraw the full or partial reconstituted vial content and add it back into the infusion bag according to Table 3 below.
3. The intravenous infusion of the diluted solution must be completed within 8 hours, if stored under refrigerated conditions (i.e., at 2°C to 8°C; where it has been refrigerated for less than 6 hours, prior to being allowed to reach room temperature and then administered at room temperature over a period of 2 or 4 hours).
Table 3. Preparation of cefepime-enmetazobactam doses:
| Cefepime/enmetazobactam dose | Number of vials to reconstitute | Volume to withdraw from each reconstituted vial for further dilution | Final volume of infusion bag |
|---|---|---|---|
| 2.5 g (2 g/0.5 g) | 1 | Entire content (approximately 10 mL) | 250 mL |
| 1.25 g (1 g/0.25 g) | 1 | 5.0 mL (discard unused portion) | 245 mL |
| 0.625 g (0.5 g/0.125 g) | 1 | 2.5 mL (discard unused portion) | 242.5 mL |
Inspect the vial before use. It must only be used if the solution is free from particles. Use only clear solutions.
Like other cephalosporins, cefepime-enmetazobactam solutions can develop a yellow to amber color, depending on storage conditions. However, this has no negative influence on the effect of the product.
The prepared solution should be administered via intravenous infusion.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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