The most common adverse reactions (≥5% of patients) included nausea, headache, diarrhea, and pyrexia.

Adverse reactions occurring in 1% or greater of patients receiving ZERBAXA in phase 3 clinical trials

	cUTIs, including pyelonephritis		cIAIs
	ZERBAXA^a (N=533) n (%)	Levofloxacin (N=535) n (%)	ZERBAXA^a (N=482) n (%)	Meropenem (N=497) n (%)
Nausea	15 (2.8)	9 (1.7)	38 (7.9)	29 (5.8)
Headache	31 (5.8)	26 (4.9)	12 (2.5)	9 (1.8)
Diarrhea	10 (1.9)	23 (4.3)	30 (6.2)	25 (5)
Pyrexia	9 (1.7)	5 (0.9)	27 (5.6)	20 (4)
Constipation	21 (3.9)	17 (3.2)	9 (1.9)	6 (1.2)
Insomnia	7 (1.3)	14 (2.6)	17 (3.5)	11 (2.2)
Vomiting	6 (1.1)	6 (1.1)	16 (3.3)	20 (4)
Hypokalemia	4 (0.8)	2 (0.4)	16 (3.3)	10 (2)
ALT increased	9 (1.7)	5 (0.9)	7 (1.5)	5 (1)
AST increased	9 (1.7)	5 (0.9)	5 (1)	3 (0.6)
Anemia	2 (0.4)	5 (0.9)	7 (1.5)	5 (1)
Thrombocytosis	2 (0.4)	2 (0.4)	9 (1.9)	5 (1)
Abdominal pain	4 (0.8)	2 (0.4)	6 (1.2)	2 (0.4)
Anxiety	1 (0.2)	4 (0.7)	9 (1.9)	7 (1.4)
Dizziness	6 (1.1)	1 (0.2)	4 (0.8)	5 (1)
Hypotension	2 (0.4)	1 (0.2)	8 (1.7)	4 (0.8)
Atrial fibrillation	1 (0.9)	0	6 (1.2)	3 (0.6)
Rash	5 (0.9)	2 (0.4)	8 (1.7)	7 (1.4)

(a) The ZERBAXA for injection dose was 1.5 g (1 g/0.5 g) IV every 8 hours, adjusted to match renal function where appropriate. In the cIAI trials, ZERBAXA was given in conjunction with 500 mg of metronidazole IV every 8 hours.

In the Phase 3 clinical trials, the incidence of adverse events was higher in subjects 65 years or older.
- 24.6% (250/1015) of patients treated with ZERBAXA were 65 years or older, including 11.1% (113/1015) who were 75 years or older.

Definitions

ALT = alanine aminotransferase

AST = aspartate aminotransferase

Indications

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

ZERBAXA used in combination with metronidazole is indicated in adult patients for the treatment of complicated intra-abdominal infections (cIAI) caused by the following 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 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 creatinine clearance (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. 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 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.
Clostridium 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 is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Adverse reactions: The most common adverse reactions occurring in ≥5% of patients 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.

Indications

Usage

Selected Safety Information

Patients with renal impairment: Decreased efficacy of ZERBAXA has been observed in patients with baseline creatinine clearance (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. 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 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.
Clostridium 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 is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Adverse reactions: The most common adverse reactions occurring in ≥5% of patients 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.

AINF-1159589-017904/18