Version July 2025
Dosage guidance:
Dosing: Doses are expressed as amount of ceftobiprole medocaril (prodrug), consistent with US labeling; in some other countries, dosing may be expressed as ceftobiprole (active drug). Ceftobiprole medocaril 667 mg is equivalent to ceftobiprole 500 mg.
Bloodstream infection (alternative agent): Pathogen-directed therapy for S. aureus, including methicillin-resistant S. aureus:
IV: Ceftobiprole medocaril 667 mg every 6 hours for 8 days, followed by ceftobiprole medocaril 667 mg every 8 hours thereafter (Ref); treat uncomplicated S. aureus bacteremia for ≥14 days starting from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (Ref).
Pneumonia:
Community-acquired pneumonia: IV: Ceftobiprole medocaril 667 mg every 8 hours (Ref) as part of an appropriate combination regimen (Ref). Total duration (including oral step-down therapy) is a minimum of 5 days (or 7 days if methicillin-resistant S. aureus [MRSA] is isolated); patients should be clinically stable with normal vital signs prior to discontinuation (Ref).
Hospital- acquired pneumonia (alternative agent) (off-label use): Note: Not recommended for patients with ventilator-associated pneumonia based on lower cure rate (Ref).
IV: Ceftobiprole medocaril 667 mg every 8 hours (Ref). Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: IV:
Note: Doses are expressed as amount of ceftobiprole medocaril (prodrug), consistent with US labeling; in some other countries, dosing may be expressed as ceftobiprole (active drug). Ceftobiprole medocaril 667 mg is equivalent to ceftobiprole 500 mg. Ceftobiprole medocaril 333 mg is equivalent to ceftobiprole 250 mg.
If recommended dose is ceftobiprole medocaril 667 mg every 6 hours:
CrCl 50 to 150 mL/minute: No dosage adjustment necessary.
CrCl 30 to <50 mL/minute: Ceftobiprole medocaril 667 mg every 8 hours.
CrCl 15 to <30 mL/minute: Ceftobiprole medocaril 333 mg every 8 hours.
CrCl <15 mL/minute: Ceftobiprole medocaril 333 mg every 24 hours.
If recommended dose is ceftobiprole medocaril 667 mg every 8 hours:
CrCl 50 to 150 mL/minute: No dosage adjustment necessary.
CrCl 30 to <50 mL/minute: Ceftobiprole medocaril 667 mg every 12 hours.
CrCl 15 to <30 mL/minute: Ceftobiprole medocaril 333 mg every 12 hours.
CrCl <15 mL/minute: Ceftobiprole medocaril 333 mg every 24 hours.
Augmented renal clearance (CrCl >150 mL/minute): IV:
US labeling: Ceftobiprole medocaril 667 mg every 6 hours.
Canadian labeling: No dosage adjustment necessary; however, duration of infusion should be extended to 4 hours.
Hemodialysis, intermittent (thrice weekly): Dialyzable (~70%) (Ref): IV: Ceftobiprole medocaril 333 mg every 24 hours; administer after hemodialysis on dialysis days.
Peritoneal dialysis: IV: Ceftobiprole medocaril 333 mg every 24 hours (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment unlikely as ceftobiprole is minimally metabolized.
No dosage adjustment necessary based on body weight (Ref).
Refer to adult dosing.
(For additional information see "Ceftobiprole: Pediatric drug information")
Dosage guidance:
Dosing: Doses are expressed as amount of ceftobiprole medocaril (prodrug), consistent with US labeling; in some other countries, dosing may be expressed as ceftobiprole (active drug). Ceftobiprole medocaril sodium 667 mg is equivalent to ceftobiprole 500 mg.
Pneumonia, community acquired: Note: In clinical trials, patients were treated for minimum of 7 days and up to 14 days total (including ≥3 days of IV therapy) (Ref). For uncomplicated pneumonia, the usual total duration of therapy is 5 to 10 days (including any oral step-down therapy); complicated infection (eg, empyema, necrotizing infection, pulmonary abscess) may require longer duration (Ref).
Infants ≥3 months and Children <12 years: IV: 20 mg ceftobiprole medocaril/kg/dose every 8 hours; maximum dose: 667 mg ceftobiprole medocaril/dose.
Children ≥12 years and Adolescents <18 years: IV: 13.3 mg ceftobiprole medocaril/kg/dose every 8 hours; maximum dose: 667 mg ceftobiprole medocaril/dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Doses are expressed as amount of ceftobiprole medocaril (prodrug), consistent with US labeling; in some other countries, dosing may be expressed as ceftobiprole (active drug). Ceftobiprole medocaril sodium 667 mg is equivalent to ceftobiprole 500 mg.
Altered kidney function:
Infants ≥3 months and Children <2 years: IV: There are no dosage adjustments provided in the manufacturer's labeling; dosage adjustment likely necessary based on data in older pediatric patients; data are insufficient to recommend specific adjustments.
Children 2 to <6 years:
eGFR ≥50 mL/minute/1.73 m2: IV: No dosage adjustment necessary.
eGFR 30 to <50 mL/minute/1.73 m2: IV: 13.3 mg ceftobiprole medocaril/kg/dose every 12 hours; maximum dose: 667 mg ceftobiprole medocaril/dose.
eGFR 15 to <30 mL/minute/1.73 m2: IV: 13.3 mg ceftobiprole medocaril/kg/dose every 24 hours; maximum dose: 333 mg ceftobiprole medocaril/dose.
eGFR <15 mL/minute/1.73 m2: IV: Dosage adjustment likely necessary due to predicted increased exposure; however, data are not sufficient to recommend specific dosage adjustments.
Children 6 to <12 years:
eGFR ≥50 mL/minute/1.73 m2: IV: No dosage adjustment necessary.
eGFR 30 to <50 mL/minute/1.73 m2: IV: 10 mg ceftobiprole medocaril/kg/dose every 12 hours; maximum dose: 667 mg ceftobiprole medocaril/dose.
eGFR 15 to <30 mL/minute/1.73 m2: IV: 10 mg ceftobiprole medocaril/kg/dose every 24 hours; maximum dose: 333 mg ceftobiprole medocaril/dose.
eGFR <15 mL/minute/1.73 m2: IV: Dosage adjustment likely necessary due to predicted increased exposure; however, data are not sufficient to recommend specific dosage adjustments.
Children ≥12 years and Adolescents <18 years:
eGFR ≥50 mL/minute/1.73 m2: IV: No dosage adjustment necessary.
eGFR 30 to <50 mL/minute/1.73 m2: IV: 10 mg ceftobiprole medocaril/kg/dose every 12 hours; maximum dose: 667 mg ceftobiprole medocaril/dose.
eGFR 15 to <30 mL/minute/1.73 m2: IV: 10 mg ceftobiprole medocaril/kg/dose every 12 hours; maximum dose: 333 mg ceftobiprole medocaril/dose.
eGFR <15 mL/minute/1.73 m2: IV: Dosage adjustment likely necessary due to predicted increased exposure; however, data are not sufficient to recommend specific dosage adjustments.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, dosage adjustments are unlikely necessary because ceftobiprole is minimally metabolized.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Gastrointestinal: Nausea (10% to 11%)
Hematologic & oncologic: Anemia (12%)
1% to 10%:
Cardiovascular: Hypertension (4% to 5%; including hypertensive crisis), phlebitis (4%), thrombosis (<2%)
Dermatologic: Pruritus (<2%), skin rash (2% to 5%)
Endocrine & metabolic: Hypokalemia (9%), hyponatremia (>2%), increased lactate dehydrogenase (<2%), increased serum triglycerides (<2%)
Gastrointestinal: Abdominal pain (3% to 4%), diarrhea (6% to 7%), dysgeusia (2%), dyspepsia (<2%), dysphagia (<2%), vomiting (2% to 9%)
Genitourinary: Pollakiuria (<2%)
Hematologic & oncologic: Leukopenia (4%), prolonged prothrombin time (<2%), thrombocytopenia (<2%), thrombocytosis (<2%)
Hepatic: Increased liver enzymes (≤10%; including hyperbilirubinemia, increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase)
Hypersensitivity: Facial swelling (<2%), hypersensitivity reaction (<2%; including anaphylactic shock, anaphylaxis, angioedema, severe hypersensitivity reaction)
Infection: Fungal infection (3%; including mucocutaneous fungal infection [<2%])
Local: Injection-site reaction (2%; including infusion-related reaction, infusion-site pain [<2%], infusion-site reaction)
Nervous system: Anxiety (<2%), chills (<2%), dizziness (3%), fatigue (<2%), headache (3% to 7%), insomnia (5%), irritability (<2%), seizure (>2%)
Renal: Increased serum creatinine (7%)
Respiratory: Bronchospasm (<2%), dyspnea (2%), wheezing (<2%)
Miscellaneous: Fever (4%)
Frequency not defined: Dermatologic: Urticaria
Postmarketing: Gastrointestinal: Clostridioides difficile colitis
Severe hypersensitivity to ceftobiprole medocaril, other members of the cephalosporins class, or any component of the formulation.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Immediate and severe hypersensitivity (eg, anaphylaxis) to any other type of beta-lactams (eg, penicillins, carbapenems).
Concerns related to adverse effects:
• CNS effects: Seizures and other adverse CNS reactions have been reported during treatment with ceftobiprole medocaril and other cephalosporins. Nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with cephalosporins, particularly in patients with a history of epilepsy or when recommended doses were exceeded due to kidney impairment. Continue anticonvulsant therapy in patients with known seizure disorders. If adverse CNS reactions including seizures occur, perform a neurological evaluation to determine if ceftobiprole medocaril should be discontinued.
• Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis, were observed in patients treated with ceftobiprole medocaril. Serious, sometimes fatal, hypersensitivity reactions and serious skin reactions have been reported with beta-lactams. Question patients about previous hypersensitivity reactions to other cephalosporins, penicillins, and other beta-lactams. Cross-sensitivity has been established. If administered to a patient with penicillin or other beta-lactam allergy, use with caution; if a hypersensitivity reaction occurs, discontinue and institute supportive therapy.
• Superinfection: Use may result in fungal or bacterial superinfection. Clostridioides difficile–associated diarrhea (CDAD) and pseudomembranous colitis have been reported with use; consider this diagnosis in patients who develop diarrhea during or after administration.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment. Dosage adjustment is required with CrCl <50 mL/minute.
• Ventilator-associated pneumonia: Safety and effectiveness have not been established for treatment of ventilator-associated pneumonia and ceftobiprole medocaril is not approved for this use. An increase in mortality was seen in the subgroup of patients with ventilator-associated pneumonia treated with ceftobiprole medocaril. The cause of increased mortality has not been established; generally, deaths were associated with infectious complications or underlying comorbidities.
Other warnings/precautions:
• Precipitation: May occur when mixed with calcium-containing solutions in the same IV administration line. Do not mix or simultaneously administer ceftobiprole and calcium-containing solutions (except lactated Ringer [Canadian labeling]) in the same IV line.
Zevtera: FDA approved April 2024; anticipated availability currently unknown. Zevtera is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infection, including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates; treatment of adult patients with acute bacterial skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, and Klebsiella pneumoniae; and treatment of adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia caused by Staphylococcus aureus (methicillin[1]susceptible isolates), Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, and Klebsiella pneumoniae.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [strength expressed as base, preservative free]:
Zevtera: 500 mg (1 ea)
No
Solution (reconstituted) (Zevtera Intravenous)
500 mg (per each): $282.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [strength expressed as base]:
Zevtera: 500 mg (1 ea)
IV: Administer by IV infusion over 2 hours. Canadian labeling recommends infusing usual recommended dose over 4 hours in patients with a CrCl >150 mL/minute. Refrigerated infusions should be brought to room temperature prior to administration.
IV: Administer by IV infusion over 2 hours. Refrigerated infusions should be brought to room temperature prior to administration.
Bloodstream infection (bacteremia): Treatment of Staphylococcus aureus bloodstream infection (bacteremia) in adults, including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.
Pneumonia, community- acquired: Treatment of community-acquired bacterial pneumonia in adult and pediatric patients ≥3 months of age, caused by susceptible isolates of S. aureus (methicillin-susceptible isolates), Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, and Klebsiella pneumoniae.
Skin and soft tissue infection: Treatment of acute bacterial skin and skin structure infections in adults, caused by susceptible isolates of S. aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, and K. pneumoniae.
Pneumonia, hospital-acquired
Ceftobiprole may be confused with ceftaroline or ceftibuten.
Substrate of OAT1/3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Cephalosporins may increase nephrotoxic effects of Aminoglycosides. Cephalosporins may decrease serum concentration of Aminoglycosides. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Furosemide: May increase nephrotoxic effects of Cephalosporins. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Ceftobiprole Medocaril may increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Probenecid: May increase serum concentration of Cephalosporins. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Vitamin K Antagonists: Cephalosporins may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Adverse events were not observed in animal reproduction studies.
It is not known if ceftobiprole is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Renal function; signs/symptoms of hypersensitivity
Prodrug converted in vivo to active drug with bactericidal activity by inhibiting bacterial cell wall synthesis through binding to one or more of the penicillin-binding proteins (PBPs), including PBP2a in methicillin-resistant S. aureus (MRSA) and PBP2b and PBP2x in penicillin-resistant S. pneumoniae.
Note: Ceftobiprole systemic clearance is 40% greater in patients with CrCl >150 mL/minute and Vd is 30% larger.
Distribution: Vdss: Ceftobiprole:
Children 2 to <12 years: Median: 0.46 L/kg (range: 0.187 to 1.28 L/kg) (Rubino 2021).
Children ≥12 years and Adolescents <18 years: Median: 0.365 L/kg (range: 0.226 to 0.615 L/kg) (Rubino 2021).
Adults: 18 L.
Protein binding: 16% (concentration independent).
Metabolism: Ceftobiprole medocaril sodium (prodrug) rapidly metabolized by plasma esterases to ceftobiprole (active drug), which undergoes minimal metabolism to an inactive metabolite.
Half-life elimination: Ceftobiprole:
Children ≥2 years and Adolescents <18 years: ~2 hours (range: 1.28 to 5.77 hours) (Rubino 2021).
Adults: 3.3 hours.
Excretion: Urine: 89% (83% as active drug, 5% as inactive metabolite, <1% as unchanged prodrug).
Altered kidney function: Ceftobiprole AUC is 2.5- and 3.3-fold higher in patients with CrCl 30 to <50 mL/minute and CrCl <30 mL/minute, respectively.
Anti-infective considerations:
Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC); goal: ≥25 to 65% fT > MIC (Azanza Perea 2019; Craig 2008).
Organism specific:
Staphylococcus aureus: Goal: 29.3 ± 4.6% T > MIC (2-log kill) (Craig 2008).
Streptococcus pneumoniae: Goal: 25.8 ± 4.8% T > MIC (2-log kill) (Craig 2008).
Gram-negative bacilli: Goal: 64.5 ± 25.1% T > MIC (2-log kill) (Craig 2008).
Expected drug exposure in normal kidney function:
Cmax (peak): IV: Note: Doses and serum concentrations are in mg or mg/L ceftobiprole.
Neonates (GA ≥28 weeks) and infants ≤3 months: Single dose: 7.5 mg ceftobiprole/kg (infused over 4 hours): 11.2 mg/L; range: 8.68 to 32.6 mg/L (Rubino 2021).
Children 2 to <6 years: 20 mg ceftobiprole/kg/dose every 8 hours: 32.4 mg/L; range: 20 to 50.8 mg/L (Rubino 2021).
Children 6 to <12 years: 15 mg ceftobiprole/kg/dose every 8 hours: 26.6 mg/L; range: 7.44 to 62.8 mg/L (Rubino 2021).
Children ≥12 years and Adolescents <18 years: 10 mg ceftobiprole/kg/dose every 8 hours: 17.9 mg/L; range: 12.1 to 27.4 mg/L (Rubino 2021).
Adults:
Single dose: 500 mg ceftobiprole: 29.2 to 35.5 mg/L (Azanza Perea 2019; Schmitt-Hoffmann 2024).
Multiple dose: 500 mg ceftobiprole every 8 hours : 33 ± 4.83 mg/L.
Postantibiotic effect: Bacterial killing may continue after ceftobiprole concentration falls below the MIC of targeted pathogen and may vary based on the organism (Craig 2008).
Staphylococcus aureus: 3.8 to 4.8 h (Craig 2008).
Streptococcus pneumoniae, drug-resistant: 0 to 0.8 h (Craig 2008).
