Ceftolozane and tazobactam
Dosing in kidney impairment
Recommended Dosage in Adult Patients with Renal Impairment The recommended dosage of ZERBAXA in adult patients with renal impairment is based on CrCl as described in Table 3. Administer all doses of ZERBAXA for 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 and Clinical Pharmacology ] . [See table below.] A single loading dose of ZERBAXA 2.25 g Provides 1.5 g ceftolozane and 0.75 g tazobactam. followed by a ZERBAXA 450 mg Provides 300 mg ceftolozane and 150 mg tazobactam. maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on intermittent hemodialysis days, administer the dose at the earliest possible time following completion of dialysis)
Recommended Dosage in Pediatric Patients with Renal Impairment The recommended dosage of ZERBAXA in pediatric patients 2 years of age and older with renal impairment based on an estimated GFR is described in Table 4. For pediatric patients with cUTI, including pyelonephritis, or cIAI, administer all ZERBAXA doses for 1 hour.
For pediatric patients with HABP/VABP, administer all ZERBAXA doses over 2 hours. For patients with changing renal function, monitor eGFR at least daily and adjust the dosage of ZERBAXA accordingly [see Use in Special Populations (8.4 and 8.6) and Clinical Pharmacology ] . ZERBAXA is not recommended in pediatric patients less than 2 years of age with renal impairment [see Use in Specific Populations ]. [See table below.] A single loading dose of ZERBAXA 45 mg/kg Provides 30 mg/kg ceftolozane and 15 mg/kg tazobactam followed by a ZERBAXA 9 mg/kg Provides 6 mg/kg ceftolozane and 3 mg/kg tazobactam maintenance dose administered 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)
| Estimated CrCl (mL/min)Estimated CrCl using the Cockcroft-Gault formula | Complicated Intra-abdominal Infections and Complicated Urinary Tract Infections, Including Pyelonephritis | Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia | ||
|---|---|---|---|---|
| Dosage | Infusion time | Dosage | Infusion time | |
| 51 to less than 90 | ZERBAXA 1.5 gProvides 1 g ceftolozane and 0.5 g tazobactam. intravenously every 8 hours | 1 hour | ZERBAXA 3 gProvides 2 g ceftolozane and 1 g tazobactam. intravenously every 8 hours | 1 hour |
| 30 to 50 | ZERBAXA 750 mgProvides 500 mg ceftolozane and 250 mg tazobactam. intravenously every 8 hours | ZERBAXA 1.5 g intravenously every 8 hours | ||
| 15 to 29 | ZERBAXA 375 mgProvides 250 mg ceftolozane and 125 mg tazobactam. intravenously every 8 hours | ZERBAXA 750 mg intravenously every 8 hours | ||
| Less than 15 (not receiving intermittent hemodialysis) | ZERBAXA dosage not established | ZERBAXA dosage not established | ||
| Receiving Intermittent Hemodialysis | A single loading dose of ZERBAXA 750 mg followed by a ZERBAXA 150 mgProvides 100 mg ceftolozane and 50 mg tazobactam. maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on intermittent hemodialysis days, administer the dose at the earliest possible time following completion of dialysis) | A single loading dose of ZERBAXA 2.25 gProvides 1.5 g ceftolozane and 0.75 g tazobactam. followed by a ZERBAXA 450 mgProvides 300 mg ceftolozane and 150 mg tazobactam. maintenance dose administered intravenously every 8 hours for the remainder of the treatment period (on intermittent hemodialysis days, administer the dose at the earliest possible time following completion of dialysis) | ||
| Estimated GFREstimate eGFR using an equation validated in pediatric patients in the approved age range. (mL/min/1.73 m2) | Complicated Intra-abdominal Infections and Complicated Urinary Tract Infections, including Pyelonephritis | Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia | ||
|---|---|---|---|---|
| Dosage | Infusion time | Dosage | Infusion time | |
| 51 to less than 90 | ZERBAXA 30 mg/kgProvides 20 mg/kg ceftolozane and 10 mg/kg tazobactam. intravenously every 8 hours | 1 hour | ZERBAXA 75 mg/kgProvides 50 mg/kg ceftolozane and 25 mg/kg tazobactam. intravenously every 8 hours | 2 hours |
| 30 to 50 | ZERBAXA 15 mg/kgProvides 10 mg/kg ceftolozane and 5 mg/kg tazobactam. intravenously every 8 hours | ZERBAXA 37.5 mg/kgProvides 25 mg/kg ceftolozane and 12.5 mg/kg tazobactam. intravenously every 8 hours | ||
| 15 to 29 | ZERBAXA 7.5 mg/kgProvides 5 mg/kg ceftolozane and 2.5 mg/kg tazobactam intravenously every 8 hours | ZERBAXA 18.75 mg/kgProvides 12.5 mg/kg ceftolozane and 6.25 mg/kg tazobactam. intravenously every 8 hours | ||
| Less than 15 (not receiving intermittent hemodialysis) | ZERBAXA dosage not established | ZERBAXA dosage not established | ||
| Receiving Intermittent Hemodialysis | A single loading dose of ZERBAXA 15 mg/kg followed by a ZERBAXA 3 mg/kgProvides 2 mg/kg ceftolozane and 1 mg/kg tazobactam. maintenance dose administered 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 ZERBAXA 45 mg/kgProvides 30 mg/kg ceftolozane and 15 mg/kg tazobactam followed by a ZERBAXA 9 mg/kgProvides 6 mg/kg ceftolozane and 3 mg/kg tazobactam maintenance dose administered 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) | ||
Preparation and administration
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 5), and add to the same infusion bag.
Discard unused portion. [See table below.] 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 C to 8°C (36 F to 46°F).
Discard unused portion. Constituted ZERBAXA solution or diluted ZERBAXA infusion should not be frozen.
| Infection | Dose | Frequency | Infusion Time | Duration of Treatment |
|---|---|---|---|---|
| Complicated Intra-abdominal InfectionsUsed in conjunction with metronidazole 500 mg intravenously every 8 hours | ZERBAXA 1.5 gProvides 1 g ceftolozane and 0.5 g tazobactam | Every 8 Hours | 1 hour | 4 to 14 days |
| Complicated Urinary Tract Infections, Including Pyelonephritis | ZERBAXA 1.5 g | Every 8 Hours | 1 hour | 7 days |
| Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia | ZERBAXA 3 gProvides 2 g ceftolozane and 1 g tazobactam | Every 8 Hours | 1 hour | 8 to 14 days |
| Infection | Age Range | Dose | Frequency | Infusion time | Duration of treatment |
|---|---|---|---|---|---|
| Complicated Intra-abdominal InfectionsUsed in conjunction with metronidazole. | All pediatric patients (at least 32 weeks gestational age) | ZERBAXA 30 mg/kgProvides 20 mg/kg ceftolozane and 10 mg/kg tazobactam. up to a maximum dose of 1.5 gFor pediatric patients with cUTI or cIAI weighing greater than 50 kg, do not exceed a maximum dose of 1.5 g.Provides 1 g ceftolozane and 0.5 g tazobactam | Every 8 hours | 1 hour | 5 to 14 days |
| Complicated Urinary Tract Infections, Including Pyelonephritis | ZERBAXA 30 mg/kg up to a maximum dose of 1.5 g | 1 hour | 7 to 14 days | ||
| Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia | Pediatric patients from at least 32 weeks of gestational age to less than 2 years | ZERBAXA 60 mg/kgProvides 40 mg/kg ceftolozane and 20 mg/kg tazobactam. up to a maximum dose of 3 gFor pediatric patients with HABP/VABP weighing greater than 40 kg, do not exceed a maximum dose of 3 g.Provides 2 g ceftolozane and 1 g tazobactam. | 2 hours | 8 to 14 days | |
| Pediatric patients from 2 years and older | ZERBAXA 75 mg/kgProvides 50 mg/kg ceftolozane and 25 mg/kg tazobactam. up to a maximum dose of 3 g |
| Estimated GFREstimate eGFR using an equation validated in pediatric patients in the approved age range. (mL/min/1.73 m2) | Complicated Intra-abdominal Infections and Complicated Urinary Tract Infections, including Pyelonephritis | Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia | ||
|---|---|---|---|---|
| Dosage | Infusion time | Dosage | Infusion time | |
| 51 to less than 90 | ZERBAXA 30 mg/kgProvides 20 mg/kg ceftolozane and 10 mg/kg tazobactam. intravenously every 8 hours | 1 hour | ZERBAXA 75 mg/kgProvides 50 mg/kg ceftolozane and 25 mg/kg tazobactam. intravenously every 8 hours | 2 hours |
| 30 to 50 | ZERBAXA 15 mg/kgProvides 10 mg/kg ceftolozane and 5 mg/kg tazobactam. intravenously every 8 hours | ZERBAXA 37.5 mg/kgProvides 25 mg/kg ceftolozane and 12.5 mg/kg tazobactam. intravenously every 8 hours | ||
| 15 to 29 | ZERBAXA 7.5 mg/kgProvides 5 mg/kg ceftolozane and 2.5 mg/kg tazobactam intravenously every 8 hours | ZERBAXA 18.75 mg/kgProvides 12.5 mg/kg ceftolozane and 6.25 mg/kg tazobactam. intravenously every 8 hours | ||
| Less than 15 (not receiving intermittent hemodialysis) | ZERBAXA dosage not established | ZERBAXA dosage not established | ||
| Receiving Intermittent Hemodialysis | A single loading dose of ZERBAXA 15 mg/kg followed by a ZERBAXA 3 mg/kgProvides 2 mg/kg ceftolozane and 1 mg/kg tazobactam. maintenance dose administered 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 ZERBAXA 45 mg/kgProvides 30 mg/kg ceftolozane and 15 mg/kg tazobactam followed by a ZERBAXA 9 mg/kgProvides 6 mg/kg ceftolozane and 3 mg/kg tazobactam maintenance dose administered 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) | ||