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. |
| Molecular Weight | Ceftolozane: 764.78 Da; Tazobactam: 300.29 Da |
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 | No human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
| 2nd trimester | No human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
| 3rd trimester | No human data; animal studies show no teratogenicity. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for ZERBAXA (ZERBAXA).
| Placental transfer | In rats, ceftolozane crosses placenta; tazobactam likely similar. Human data not available. |
| Breastfeeding | Unknown if excreted in human milk; however, ceftolozane/tazobactam are unlikely to cause adverse effects due to low oral bioavailability. Caution advised. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to ceftolozane, tazobactam, or other beta-lactam antibacterials
| 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 |
| Food/Dietary | No specific food interactions. However, for patients on hemodialysis, dietary restrictions related to renal function (e.g., potassium, phosphorus, sodium) may apply. Follow your healthcare provider's dietary recommendations. |
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| L3 |
| 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. |
| 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. |
| Clinical Pearls |
| Zerbaxa (ceftolozane/tazobactam) is a beta-lactam/beta-lactamase inhibitor combination with activity against Pseudomonas aeruginosa, including multi-drug resistant strains. It is primarily used for complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI). Dose adjustment based on creatinine clearance is critical; for CrCl 30-50 mL/min, reduce to 750 mg IV every 8 hours; for CrCl 15-29 mL/min, reduce to 375 mg IV every 8 hours; for CrCl <15 mL/min or on hemodialysis, reduce to 375 mg IV every 12 hours. Monitor for hypersensitivity reactions, including anaphylaxis, especially in penicillin-allergic patients. Prolonged use may lead to Clostridioides difficile infection. Administer over 1 hour via IV infusion. |
| Patient Advice | This medication is given intravenously, usually every 8 hours, and must be administered by a healthcare professional. · Inform your healthcare provider if you have any allergies, especially to penicillins, cephalosporins, or other beta-lactam antibiotics. · Report any signs of allergic reaction such as rash, itching, swelling, or difficulty breathing immediately. · You may experience side effects such as nausea, diarrhea, headache, or insomnia. Contact your doctor if diarrhea is severe or persists. · If you have kidney problems, your dose may need adjustment; your healthcare provider will monitor your kidney function. · This medication treats bacterial infections only; it will not work for viral infections like colds or flu. · Finish the entire course of treatment as prescribed, even if you feel better, to prevent the infection from returning or worsening. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |