ZERBAXA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZERBAXA (ZERBAXA).
Zerbaxa is a combination of ceftolozane, a cephalosporin antibiotic, and tazobactam, a beta-lactamase inhibitor. Ceftolozane inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), particularly PBP3, leading to cell death. Tazobactam protects ceftolozane from degradation by certain beta-lactamases.
| Metabolism | Ceftolozane is primarily excreted unchanged in urine, with minimal metabolism. Tazobactam is partially metabolized to an inactive metabolite, and both are eliminated renally. |
| Excretion | Primarily renal excretion: ceftolozane ~95% unchanged in urine, tazobactam ~80% unchanged in urine; biliary/fecal elimination <1%. |
| Half-life | Ceftolozane: ~3 hours; tazobactam: ~1 hour; prolonged in renal impairment. |
| Protein binding | Ceftolozane: ~16-21%; tazobactam: ~30%; mainly to albumin. |
| Volume of Distribution | Ceftolozane: ~13.5 L (0.19 L/kg for 70 kg adult); tazobactam: ~18.2 L (0.26 L/kg); distributes well into tissues, including lung and abdominal fluid. |
| Bioavailability | Not applicable; administered only intravenously (100% bioavailability via IV route). |
| Onset of Action | Intravenous: immediate (therapeutic concentrations achieved within 30 min of infusion start). |
| Duration of Action | Approximately 8 hours (dosing interval 8h); sustained antibacterial effect due to time-dependent killing. |
1.5 g (ceftolozane 1 g + tazobactam 0.5 g) intravenously every 8 hours infused over 1 hour.
| Dosage form | POWDER |
| Renal impairment | CrCl >50 mL/min: 1.5 g q8h; CrCl 30-50 mL/min: 750 mg q8h; CrCl 15-29 mL/min: 375 mg q8h; CrCl <15 mL/min or hemodialysis: 375 mg q8h (administer after dialysis on dialysis days). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Approved for patients aged 18 years and older; pediatric dosing is not established. |
| Geriatric use | No specific geriatric dose adjustments beyond renal function. Use weight-based dosing is not required; dose based on renal function (CrCl). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZERBAXA (ZERBAXA).
| Breastfeeding | It is not known whether ceftolozane or tazobactam are excreted in human milk. The M/P ratio is unknown. Caution should be exercised when administered to a nursing woman. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for ZERBAXA and any potential adverse effects on the breastfed child from the drug or the underlying maternal condition. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal reproduction studies, intravenous ceftolozane/tazobactam showed no evidence of fetal harm at doses up to 8 times the human dose. However, because animal studies are not always predictive of human response, use during pregnancy only if clearly needed. No fetal risks have been specifically identified in any trimester. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["History of serious hypersensitivity reaction to ceftolozane, tazobactam, other beta-lactams, or any component of the formulation"]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis) in patients with beta-lactam allergy","Clostridioides difficile-associated diarrhea (CDAD)","Reduced efficacy in patients with renal impairment without dose adjustment","Potential for development of drug-resistant bacteria"] |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond standard clinical monitoring for adverse effects such as hypersensitivity reactions, Clostridioides difficile-associated diarrhea, and renal function monitoring. Routine pregnancy monitoring per standard obstetric care is recommended. |
| Fertility Effects | No human data on fertility effects. In animal studies, no impairment of fertility was observed in male and female rats at doses up to 8 times the human dose. |