ZERBAXA®

(ceftolozane and tazobactam) for injection (1.5 g), for intravenous use

Dosage and Administration

Dosage for Patients with Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)

The recommended dose of ZERBAXA in adult patients with HABP/VABP and creatinine clearance (CrCl) greater than 50 mL/min is 3 grams (two 1.5 g vials) over 1-hour period every 8 hours for 8 to 14 days.

Renal Dosing Adjustments for Patients with HABP/VABP per Estimated CrCl (mL/min)a,b

  • 30 to 50 1.5 g (1 g and 0.5 g) intravenously every 8 hours
  • 15 to 29 750 mg (500 mg and 250 mg) intravenously every 8 hours
  • For patients with end-stage renal disease on hemodialysis: 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 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).

aCreatinine clearance (CrCl) estimated using Cockcroft-Gault formula.

bAll doses of ZERBAXA are administered over 1 hour.

3-g Dose Selected Based on Phase 1 PK/PD Study

  • ZERBAXA at 3-g IV dose acheived target concentration above ceftolozane minimum inhibitory concentration (MIC) in the epithelial lining fluid (ELF) over 100% of the dosing interval.

PK/PD Study Design

  • Following 1-hour intravenous infusions of ZERBAXA 3 g (ceftolozane 2 g and tazobactam 1 g) or adjusted based on renal function every 8 hours in ventilated patients with confirmed or suspected pneumonia (N=22), mean pulmonary epithelial lining fluid-to-free plasma AUC ratios of ceftolozane and tazobactam were approximately 50% and 62%, respectively, and are similar to those in healthy subjects (approximately 61% and 63%, respectively) receiving ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g)
  • Minimum ceftolozane and tazobactam epithelial lung lining fluid concentrations in ventilated subjects at the end of the dosing interval were 8.2 mcg/mL and 1.0 mcg/mL, respectively

Dosage for Patients with cIAI and cUTI with CrCl Greater than 50 mL/min

Infection Dose Frequency Infusion Time Duration of Treatment
Complicated lntra-abdominal Infectionsc 1.5 g Every 8 Hours 1 hour 4-14 days
Complicated Urinary Tract Infections, Including Pyelonephritis 1.5 g Every 8 Hours 1 hour 7 days

(c) Used in conjunction with metronidazole 500 mg intravenously every 8 hours

Dosage Adjustments in Patients with Renal Impairment Dose adjustment is required for patients with CrCl 50 mL/min or less. 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.

Renal Dosing Adjustments for Patients with cIAI and cUTI with CrCl 50 mL/min or Less

  • 30 to 50 750 mg (500 mg and 250 mg) intravenously every 8 hours
  • 15 to 29 375 mg (250 mg and 125 mg) intravenously every 8 hours
  • For patients with 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 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).

Indications

ZERBAXA is indicated for the treatment of patients 18 years and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by the following susceptible Gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens.

ZERBAXA is indicated for the treatment of patients 18 years and older with complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa.

ZERBAXA used in combination with metronidazole is indicated for the treatment of patients 18 years and older with complicated intra-abdominal infections (cIAI) caused by the following susceptible Gram-negative and Gram-positive microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs, ZERBAXA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Selected Safety Information

  • Patients with renal impairment: Decreased efficacy of ZERBAXA has been observed in patients with baseline CrCl of 30 to ≤ 50 mL/min. In a clinical trial, patients with cIAIs with CrCl > 50 mL/min had a clinical cure rate of 85.2% when treated with ZERBAXA plus metronidazole vs 87.9% when treated with meropenem. In the same trial, patients with CrCl 30 to ≤ 50 mL/min had a clinical cure rate of 47.8% when treated with ZERBAXA plus metronidazole vs 69.2% when treated with meropenem. A similar trend was also seen in the cUTI trial. Dose adjustment is required for patients with CrCl 50 mL/min or less. All doses of ZERBAXA are administered over 1 hour. Monitor CrCl at least daily in patients with changing renal function and adjust the dose of ZERBAXA accordingly.
  • Hypersensitivity: ZERBAXA is contraindicated in patients with known serious hypersensitivity to the components of ZERBAXA (ceftolozane/tazobactam), piperacillin/tazobactam, or other members of the beta-lactam class. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. Before initiating therapy with ZERBAXA, make careful inquiry about previous hypersensitivity reactions to cephalosporins, penicillins, or other beta-lactams. If an anaphylactic reaction to ZERBAXA occurs, discontinue use and institute appropriate therapy.
  • Clostridioides difficile-associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including ZERBAXA. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible.
  • Development of drug-resistant bacteria: Prescribing ZERBAXA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria.
  • Adverse reactions: The most common adverse reactions occurring in ≥5% of patients in the HABP/VABP trial were hepatic transaminase increased (11.9%), renal impairment/renal failure (8.9%), and diarrhea (6.4%).
  • The most common adverse reactions occurring in ≥5% of patients in the cUTI and cIAI trials were headache (5.8%) in the cUTI trial, and nausea (7.9%), diarrhea (6.2%), and pyrexia (5.6%) in the cIAI trial.

Before prescribing ZERBAXA, please read the accompanying Prescribing Information.

US-ZER-0111310/20