Version October 2024
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.
(For additional information see "Ceftobiprole: 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 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.
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.
Yes
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. Refrigerated infusions should be brought to room temperature prior to administration.
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.
Intact vials: Store at 2°C to 8°C (36°F to 46°F); store in carton to protect from light.
Reconstituted solution: If unable to dilute reconstituted solution immediately, may store for ≤1 hour at room temperature and ≤24 hours refrigerated.
Diluted solution:
Adults and pediatric patients ≥12 years of age (ceftobiprole medocaril 2.67 mg/mL):
Reconstituted with D5W:
Diluted in NS: May store for 4 hours at 25°C (77°F) (not protected from light) or 24 hours at 2°C to 8°C (36°F to 46°F) (protected from light).
Diluted in D5W: May store for 6 hours at 25°C (77°F) (not protected from light) or 94 hours at 2°C to 8°C (36°F to 46°F) (protected from light).
Reconstituted with SWFI: Diluted in D5W or NS: May store for 6 hours at 25°C (77°F) (not protected from light) or 94 hours at 2°C to 8°C (36°F to 46°F) (protected from light).
Diluted in lactated Ringer's solution [Canadian labeling]: Stable for 24 hours (protected from light) or 8 hours (not protected from light) at 25°C (77°F); do not refrigerate. Storage time includes the 2-hour time frame for infusion to be completed.
Pediatric patients <12 years of age (ceftobiprole medocaril 5.33 mg/mL): Reconstituted and diluted with D5W: May store for 6 hours at 25°C (77°F) (not protected from light) or 24 hours at 2°C to 8°C (36°F to 46°F) (protected from light).
Treatment of community-acquired bacterial pneumonia (FDA approved in ages ≥3 months and adults); treatment of Staphylococcus aureus bacteremia, including those with right-sided infective endocarditis (FDA approved in adults); treatment of acute skin and soft tissue infection (FDA approved in adults).
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.
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
Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect 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 diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect 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 combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Furosemide: May enhance the nephrotoxic effect of Cephalosporins. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Ceftobiprole Medocaril may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect 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 diminish the therapeutic effect 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 (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Adverse events were not observed in animal reproduction studies.
Kidney function; signs/symptoms of hypersensitivity; stool frequency/consistency.
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.
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