Drug Detail:Zerbaxa (Ceftolozane and tazobactam [ sef-tol-oh-zane-and-taz-oh-bak-tam ])
Generic Name: ceftolozane sulfate 1g in 10mL, tazobactam sodium 0.5g in 10mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: Cephalosporins / beta-lactamase inhibitors
2.1 Recommended Dosage in Adult Patients
The recommended dosage of ZERBAXA in adult patients 18 years and older with creatinine clearance (CrCl) greater than 50 mL/min is 1.5 gram (g) (ceftolozane 1 g and tazobactam 0.5 g for cIAI and cUTI and 3 g (ceftolozane 2 g and tazobactam 1 g) for HABP/VABP administered every 8 hours by intravenous infusion over 1 hour The duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress as shown in Table 1.
| Infection | Dose | Frequency | Infusion Time | Duration of Treatment |
|---|---|---|---|---|
|
||||
| Complicated Intra-abdominal Infections† | 1.5 g | Every 8 Hours | 1 hour | 4 to 14 days |
| Complicated Urinary Tract Infections, Including Pyelonephritis | 1.5 g | Every 8 Hours | 1 hour | 7 days |
| Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) | 3 g | Every 8 Hours | 1 hour | 8 to 14 days |
2.2 Recommended Dosage in Pediatric Patients with cIAI or cUTI (birth to less than 18 years of age)
The recommended dosage regimen of ZERBAXA in pediatric patients from birth to less than 18 years of age with cIAI and cUTI with an estimated glomerular filtration rate (eGFR) greater than 50 mL/min/1.73 m2 is described in Table 2. ZERBAXA is administered every 8 hours by intravenous infusion over 1 hour. The duration of treatment should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress as shown in Table 2. For the treatment of cIAI, metronidazole should be given concurrently.
ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73m2 or less [see Use in Specific Populations (8.4)].
There is insufficient information to recommend a dosage regimen for pediatric patients with HABP/VABP [see Use in Specific Populations (8.4)].
| Infection | Dose | Frequency | Infusion time | Duration of treatment |
|---|---|---|---|---|
|
||||
| Complicated Intra-abdominal Infections† | 30 mg/kg up to a maximum dose of 1.5 g‡ | Every 8 hours |
1 hour | 5 to 14 days |
| Complicated Urinary Tract Infections including Pyelonephritis |
30 mg/kg up to a maximum dose of 1.5 g‡ | Every 8 hours |
1 hour | 7 to 14 days |
Dosage Adjustments in Adult Patients with Renal Impairment
Dose adjustment is required for adult patients (18 years and older) with CrCl 50 mL/min or less (Table 3). All doses of ZERBAXA are administered over 1 hour. For patients with changing renal function, monitor CrCl at least daily and adjust the dosage of ZERBAXA accordingly [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
| Estimated CrCl (mL/min)* |
Complicated Intra-abdominal Infections and Complicated Urinary Tract Infections, Including Pyelonephritis | Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) |
|---|---|---|
|
||
| 30 to 50 | 750 mg (500 mg and 250 mg) intravenously every 8 hours | 1.5 g (1 g and 0.5 g) intravenously every 8 hours |
| 15 to 29 | 375 mg (250 mg and 125 mg) intravenously every 8 hours | 750 mg (500 mg and 250 mg) intravenously every 8 hours |
| End-stage renal disease (ESRD) on hemodialysis (HD) | A single loading dose of 750 mg (500 mg and 250 mg) followed by a 150 mg (100 mg and 50 mg) maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis) | A single loading dose of 2.25 g (1.5 g and 0.75 g) followed by a 450 mg (300 mg and 150 mg) maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis) |
Dosage Adjustments in Pediatric Patients with Renal Impairment
Dosage adjustment of ZERBAXA in pediatric patients (birth to less than 18 years of age) with eGFR 50 mL/min/1.73 m2 or less has not been determined.
ZERBAXA is not recommended in pediatric patients who have an eGFR 50 mL/min/1.73m2 or less [see Use in Specific Populations (8.4)].
Preparation of Solutions
ZERBAXA does not contain a bacteriostatic preservative. Aseptic technique must be followed in preparing the infusion solution.
Preparation of doses:
Constitute each vial of ZERBAXA with 10 mL of sterile water for injection or 0.9% Sodium Chloride for Injection, USP and gently shake to dissolve. The final volume is approximately 11.4 mL per vial. Caution: The constituted solution is not for direct injection.
To prepare the required dose, withdraw the appropriate volume determined from Table 4 from the reconstituted vial(s). Add the withdrawn volume to an infusion bag containing 100 mL of 0.9% Sodium Chloride for Injection, USP or 5% Dextrose Injection, USP. For doses above 1.5 g, reconstitute a second vial in the same manner as the first one, withdraw an appropriate volume (per Table 4), and add to the same infusion bag. Discard unused portion.
| ZERBAXA (ceftolozane and tazobactam) Dose | Volume to Withdraw from Reconstituted Vial(s) |
|---|---|
| 3 g (2 g and 1 g) | Two vials of 11.4 mL each (entire contents from two vials) |
| 2.25 g (1.5 g and 0.75 g) | 11.4 mL from one vial (entire contents) and 5.7 mL from a second vial |
| 1.5 g (1 g and 0.5 g) | 11.4 mL (entire contents from one vial) |
| 750 mg (500 mg and 250 mg) | 5.7 mL |
| 450 mg (300 mg and 150 mg) | 3.5 mL |
| 375 mg (250 mg and 125 mg) | 2.9 mL |
| 150 mg (100 mg and 50 mg) | 1.2 mL |
Inspect drug products visually for particulate matter and discoloration prior to use. ZERBAXA infusions range from clear, colorless solutions to solutions that are clear and slightly yellow. Variations in color within this range do not affect the potency of the product.
Compatibility
Compatibility of ZERBAXA with other drugs has not been established. ZERBAXA should not be mixed with other drugs or physically added to solutions containing other drugs.
Storage of Constituted Solutions
Upon constitution with sterile water for injection or 0.9% sodium chloride injection, reconstituted ZERBAXA solution may be held for 1 hour prior to transfer and dilution in a suitable infusion bag.
Following dilution of the solution with 0.9% sodium chloride or 5% dextrose, ZERBAXA is stable for 24 hours when stored at room temperature or 7 days when stored under refrigeration at 2 to 8°C (36 to 46°F). Discard unused portion.
Constituted ZERBAXA solution or diluted ZERBAXA infusion should not be frozen.
