Zerbaxa Special Precautions

Impaired renal function: The ZERBAXA dose should be adjusted based on renal function [see Renal Impairment under Dosage & Administration].
In a subgroup analysis of a Phase 3 cIAI trial, clinical cure rates were lower in patients with baseline CrCL of 30 to ≤ 50 mL/min compared to those with CrCL>50 mL/min. The reduction in clinical cure rates was more marked in the ZERBAXA plus metronidazole arm compared to the meropenem arm. A similar trend was also seen in the cUTI trial. Patients with renal impairment at baseline should be monitored frequently for any changes in renal function during treatment and the dose of ZERBAXA should be adjusted as necessary.
Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before initiating therapy with ZERBAXA, make careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or other beta-lactams. If this product is to be given to a patient with a cephalosporin, penicillin, or other beta-lactam allergy, exercise caution because cross sensitivity has been established. If an anaphylactic reaction to ZERBAXA occurs, discontinue the drug and institute appropriate therapy.
Clostridium difficile-associated Diarrhea: Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including ZERBAXA, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile [see Clinical Trials Experience under Adverse Reactions].
C. difficile produces toxins A and B which contribute to the development of CDAD. CDAD must be considered in all patients who present with diarrhea following antibacterial use. 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, discontinue antibacterials not directed against C. difficile, if possible. Manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C. difficile, and institute surgical evaluation as clinically indicated.
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 risks the development of drug-resistant bacteria.
Limitation of the clinical data: Patients who were immunocompromised and patients with severe neutropenia were excluded from clinical trials.
In a trial in patients with complicated intra-abdominal infections, the most common diagnosis was appendiceal perforation or peri-appendiceal abscess (420/970 [43.3%] patients), of which 137/420 (32.6%) had diffuse peritonitis at baseline. Approximately 82% of all patients in the trial had APACHE II (Acute Physiology and Chronic Health Evaluation II) scores of <10 and 2.3% had bacteraemia at baseline. In the clinically evaluable (CE) patients, the clinical cure rates for ceftolozane/tazobactam were 95.9% in 293 patients aged less than 65 years and 87.8% in 82 patients aged 65 years or more.
Clinical efficacy data in patients with complicated lower urinary tract infection are limited. In a randomised active-controlled trial 18.2% (126/693) of microbiologically evaluable (ME) patients had complicated lower urinary tract infection (cLUTI), including 60/126 patients who were treated with ceftolozane/tazobactam. One of these 60 patients had bacteraemia at baseline.
Patients with Renal Impairment: Dosage adjustment is required in patients with moderate (CrCL 30 to 50 mL/min) or severe (CrCL 15 to 29 mL/min) renal impairment and in patients with ESRD on HD [see Renal Impairment under Dosage & Administration and Impaired renal function as previously mentioned].
Use in Children: The safety and efficacy of ZERBAXA in children and adolescents below 18 years of age have not yet been established.
Use in the Elderly: In a population pharmacokinetic analysis of ceftolozane and tazobactam, no clinically relevant differences in exposure were observed with regard to age. No dose adjustment of ZERBAXA based on age alone is recommended.
ZERBAXA is substantially excreted by the kidney and the risk of adverse reactions to ZERBAXA may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. Adjust dosage for elderly patients based on renal function [see Renal Impairment under Dosage & Administration].