Zerbaxa Special Precautions

Decreased Efficacy in Patients with Baseline Creatinine Clearance of 30 to ≤50 mL/min: In a subgroup analysis of a Phase 3 cIAI trial, clinical cure rates were lower in patients with baseline creatinine clearance (CrCl) of 30 to ≤50 mL/min compared to those with CrCl >50 mL/min (Table 15). 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. Monitor CrCl at least daily in patients with changing renal function and adjust the dosage of ZERBAXA accordingly [see Patients with Renal Impairment under Dosage & Administration]. (See Table 15.)

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Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse 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, carbapenem or other beta-lactam allergy, exercise caution because cross sensitivity has been established. If an allergic reaction to ZERBAXA occurs, discontinue the drug and institute appropriate alternative 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.
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.
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 Patients with Renal Impairment under Dosage & Administration, Decreased Efficacy in Patients with Baseline Creatinine Clearance of 30 to ≤50 mL/min as previously mentioned and Pharmacology: Pharmacokinetics under Actions].
Use in Children: Safety and effectiveness in pediatric patients have not been established.
Use in the Elderly: Of the 1015 patients treated with ZERBAXA in the Phase 3 cIAI and cUTI clinical trials, 250 (24.6%) were 65 years or older, including 113 (11.1%) 75 years or older. The incidence of adverse events in both treatment groups was higher in older subjects (65 years or older) in the trials for both indications. In the cIAI trial, cure rates in the elderly (aged 65 years and older) in the ZERBAXA plus metronidazole arm were 69/100 (69%) and in the comparator arm were 70/85 (82.4%). This finding in the elderly population was not observed in the cUTI trial.
Of the 361 patients treated with ZERBAXA in the Phase 3 nosocomial pneumonia clinical trial, 160 (44.3%) were 65 years or older, including 83 (23%) 75 years or older. The incidence of adverse events in both treatment groups was higher in older subjects (65 years or older). In the trial, Day 28 all-cause mortality rates in the elderly (aged 65 years and older) were comparable between treatment arms: 50/160 (31.3%) in the ZERBAXA arm and 54/160 (33.8%) in the comparator arm.
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 Patients with Renal Impairment under Dosage & Administration].