ZEVTERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZEVTERA (ZEVTERA).
Ceftobiprole, the active moiety of ZEVTERA, is a cephalosporin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), including PBP2a in methicillin-resistant Staphylococcus aureus (MRSA), leading to cell death.
| Metabolism | Ceftobiprole is primarily excreted unchanged via the kidneys, with minimal hepatic metabolism. It is not significantly metabolized by cytochrome P450 enzymes. |
| Excretion | Approximately 70% of the dose is excreted unchanged in urine, with 20% recovered in feces via biliary elimination. Minor route: <5% as metabolites. |
| Half-life | Terminal elimination half-life is approximately 3.5 hours in patients with normal renal function. In moderate renal impairment (CrCl 30-50 mL/min), half-life extends to ~6 hours, requiring dose adjustment. |
| Protein binding | Approximately 90% bound primarily to albumin. |
| Volume of Distribution | Volume of distribution is 0.3 L/kg, indicating distribution primarily into extracellular fluid and plasma (total body water). |
| Bioavailability | Only intravenous formulation available; oral bioavailability is not applicable (0% orally). |
| Onset of Action | Intravenous administration: onset of antibacterial effect within 1 hour post-infusion. No other relevant routes available. |
| Duration of Action | Antibacterial activity persists for approximately 8-12 hours based on pharmacokinetic/pharmacodynamic target attainment (T>MIC). Dosing interval is every 8 hours. |
400 mg intravenously every 8 hours
| Dosage form | POWDER |
| Renal impairment | For GFR 30-49 mL/min: 300 mg IV every 8 hours; for GFR 15-29 mL/min: 200 mg IV every 8 hours; for GFR <15 mL/min: not recommended |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; not studied in Child-Pugh C |
| Pediatric use | Not approved for patients under 18 years of age |
| Geriatric use | No specific dose adjustment; use with caution due to age-related renal function decline |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZEVTERA (ZEVTERA).
| Breastfeeding | Ceftobiprole is excreted into human breast milk in small amounts. The milk-to-plasma (M/P) ratio is not established. Based on limited data, levels are low and unlikely to cause adverse effects in the breastfed infant. However, theoretical risks include diarrhea, candidiasis, and allergic sensitization. Caution is warranted, and use only if clearly needed. |
| Teratogenic Risk | ZEVTERA (ceftobiprole) is a cephalosporin antibiotic classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. In the first trimester, risk is considered low based on animal data. During the second and third trimesters, no specific fetal risks have been identified, but caution is advised due to limited human data. Potential risks include alterations in gut flora due to broad-spectrum activity. |
■ FDA Black Box Warning
There is no FDA black box warning for ZEVTERA.
| Serious Effects |
["Known hypersensitivity to ceftobiprole or other cephalosporins, carbapenems, or serious hypersensitivity to other beta-lactam antibiotics."]
| Precautions | ["Hypersensitivity reactions, including anaphylaxis, have been reported. Cross-sensitivity may occur with other beta-lactams.","Clostridioides difficile-associated diarrhea (CDAD) ranging from mild diarrhea to fatal colitis.","Seizures and other CNS adverse reactions (e.g., encephalopathy) may occur, especially with high doses or in patients with renal impairment.","Dose adjustment required in patients with renal impairment (creatinine clearance <50 mL/min).","Use of ZEVTERA may lead to development of drug-resistant bacteria."] |
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| Fetal Monitoring | In pregnant women receiving ZEVTERA, monitor renal function due to pregnancy-induced increases in glomerular filtration rate, which may affect drug clearance. Also monitor for signs of hypersensitivity reactions, Clostridium difficile-associated diarrhea, and superinfections. Fetal monitoring is not specifically required but standard obstetric monitoring should continue. |
| Fertility Effects | There are no data on the effects of ceftobiprole on human fertility. Animal studies have shown no impairment of fertility at clinically relevant doses. |