ZEVTERA (ceftobiprole medocaril sodium for injection) for HCPs home page

why ZEVTERA

Developed to help address the need
for SAB treatment

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UNMET NEED

Timely antimicrobial therapy is critical for successful SAB treatment1,2

Despite antibiotic treatment, persistent SAB occurs and is associated with mortality rates as high as ~30%3

>40% of SAB cases are reported to be caused by MRSA in the US4. Compared to MSSA, patients with MRSA bacteremia have worse outcomes, including:

3x increased risk of persistent bacteremia1

Higher mortality3

Longer length of hospital/clinic stay4

Increased healthcare costs4

Each additional day of persistent bacteremia increases risk of mortality by 16%, compared with those with 1 day of bacteremia1

  • Persistent bacteremia is associated with increased odds of developing infective endocarditis. One study found a 2.4-fold increase in the odds of developing infective endocarditis with persistent bacteremia compared to non-peristent bacteremia (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.14-5.07; P = 0.02).5,*

    • *In a retrospective cohort study evaluating 1703 episodes of SAB in 1610 adult patients who were treated at a hospital in Stockholm, Sweden between 2011 and 2021. ZEVTERA was not used as a treatment for any of the SAB episodes included in this study.5

  • Identifying patients at risk can guide early antimicrobial therapy. Risk factors for SAB include6‑8:

    • <1 year and >70 years of age
    • Male
    • Diabetes
    • Hemodialysis
    • HIV infection
    • Current uses of intravenous drugs
    • Use of medical devices, including intravascular catheters and prosthetic valves

CI, confidence interval; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; OR, odds ratio; SAB, Staphylococcus aureus bacteremia.

MECHANISM OF ACTION

ZEVTERA is the only FDA-approved cephalosporin for the treatment of SAB in adults, including MRSA bacteremia and cases with right-sided infective endocarditis10,11

ZEVTERA is a powerful bactericidal agent with in vitro activity against Staphylococcus aureus, including isolates that are non-susceptible to methicillin, vancomycin, ceftaroline, and daptomycin.12-14

ZEVTERA uniquely binds multiple target sites10,15

Slide table to view more.
ZEVTERA binds to PBPs on bacterial cells, inhibiting transpeptidase activity, blocking cell wall synthesis, and causing bacterial lysis or death

ZEVTERA inhibits bacterial cell wall synthesis by uniquely binding to multiple PBPs, with high affinity for10:

S. aureus PBPs 1-4, including PBP2a in methicillin‑resistant Staphylococcus aureus

PBP, penicillin-binding protein.

In vitro activity

ZEVTERA—demonstrated activity in vitro† against S. aureus isolates that are resistant to other antibiotics14

In an analysis of over 19,000 clinical S. aureus isolates collected from 37 US medical centers between 2016 and 2022, ZEVTERA was active against 99.7% of S. aureus isolates, including 87% of the 433 S. aureus that were non-susceptible to ceftaroline, which remained susceptible to ZEVTERA.14

†Clinical significance cannot be inferred from in vitro data.

Slide table to view more.
groupNumber of IsolatesZEVTERA (% susceptible)a
Allb19,76499.7
MRSA8,18499.3
Ceftaroline-NS (>1mg/L)c43387.3
Clindamycin-NS (>0.5mg/L)2,61898.0
Daptomycin-NS (>1mg/L)8100
Doxycycline-NS (>4mg/L)39398.2
Erythromycin-NS (>0.5mg/L)10,94099.5
Gentamicin-NS (>4mg/L)41998.1
Levofloxacin-NS (>1mg/L)6,47799.1
Tetracycline-NS (>4mg/L)1,18499.1
TMP-SMX-NS (>2mg/L)49099.4
Vancomycin MIC of 2mg/L11798.3

aApplying susceptible breakpoint of ≤2 mg/L (US FDA and EUCAST).14

bSome isolates were non-susceptible to multiple antibiotics.

cApplying susceptible breakpoint of ≤1 mg/L (US FDA, CLSI, and EUCAST).14

MIC, minimum inhibitory concentration; NS, non-susceptible; TMP-SMX, trimethoprim-sulfamethoxazole.

PATIENT PROFILES

Identifying the appropriate patient types for ZEVTERA

  • Current Condition: Critically ill and hospitalized
  • Current Diagnosis: Knee trauma secondary to fall; suspected systemic infection
  • Medical History: Type 2 diabetes; chronic venous insufficiency; recent total knee arthroplasty
  • Antibiotic History: Treated with broad-spectrum antibiotics for urosepsis 3 weeks ago; central line placed during last hospitalization
  • Recent Complications: Developed fever and hypotension in LTC facility, along with knee swelling; blood cultures positive for MRSA, leading to diagnosis of SAB; echocardiogram confirms right-sided infective endocarditis

CBC, complete blood count; ESRD, end-stage renal disease; LTC, long-term care; WBC= white blood cell.

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It's Clear...

...Achieve rapid bloodstream clearance rates* with ZEVTERA.10,16

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*Based on data from the ERADICATE trial, a Phase 3, randomized, double-blind, noninferiority study comparing ZEVTERA with daptomycin ± aztreonam in patients with complicated SAB. The median time to bloodstream clearance was 4 days in both groups.10,16

INDICATIONS & USAGE

Indications

ZEVTERA® (ceftobiprole medocaril sodium for injection), for intravenous use, is indicated for the treatment of:

  • Adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.
  • Adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following gram‑positive and gram‑negative microorganisms: Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, and Klebsiella pneumoniae.
  • Adult and pediatric patients (3 months to less than 18 years) with community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following gram‑positive and gram‑negative microorganisms: Staphylococcus aureus (methicillin- susceptible isolates), Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, and Klebsiella pneumoniae.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZEVTERA and other antibacterial drugs, ZEVTERA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

Important Safety Information

Contraindications:

ZEVTERA is contraindicated in patients with a known history of severe hypersensitivity to ZEVTERA, or to other members of the cephalosporin class.

Warnings and Precautions:

  • Increased mortality with unapproved use in ventilator-associated bacterial pneumonia (VABP) Patients: The safety and effectiveness of ZEVTERA for the treatment of VABP has not been established and the use of ZEVTERA for VABP is not approved.
  • Serious hypersensitivity reactions, including anaphylaxis, were observed in ZEVTERA-treated patients in clinical trials. Serious and occasionally fatal hypersensitivity reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with ZEVTERA is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or other beta-lactam antibacterial drugs should be made. Maintain clinical supervision if this product is to be given to a penicillin- or other beta-lactam-allergic patient, because cross sensitivity among beta-lactam antibacterial agents has been established. Discontinue ZEVTERA if a hypersensitivity reaction occurs, and institute appropriate treatment.
  • Seizures and other adverse central nervous system (CNS) reactions have been reported during treatment with ZEVTERA and other cephalosporins. If CNS adverse reactions, including seizures, occur, evaluate patients to determine whether ZEVTERA should be discontinued.
  • Clostridioides difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including ZEVTERA, and may range in severity from mild diarrhea to fatal colitis. If CDAD is suspected or confirmed, the risk/benefit of continuing treatment with ZEVTERA should be assessed.

Adverse Reactions:

  • SAB (adult patients): The most common adverse reactions occurring in ≥ 2% of adult patients were anemia, nausea, hypokalemia, vomiting, hepatic enzyme and bilirubin increased, diarrhea, blood creatinine increased, hypertension, leukopenia, pyrexia, abdominal pain, fungal infection, headache, and dyspnea.
  • ABSSSI (adult patients): The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, diarrhea, headache, injection site reaction, hepatic enzyme increase, rash, vomiting, and dysgeusia.

  • CABP (adult and pediatric patients 3 months to less than 18 years of age):

    • Adult Patients: The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, hepatic enzyme increased, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, phlebitis, hypertension, and dizziness.
    • Pediatric Patients: The most common adverse reactions occurring in ≥ 2% of pediatric patients were vomiting, headache, hepatic enzyme increased, diarrhea, infusion site reaction, phlebitis, and pyrexia.

You are encouraged to report negative side effects of prescription drugs to the FDA. To report SUSPECTED ADVERSE REACTIONS, please contact:

Innoviva Specialty Therapeutics, Inc.™ 1‑800‑651‑3861 medinfo@istx.com

U.S. Food and Drug Administration 1‑800‑FDA‑1088 www.fda.gov/medwatch

Before administering, please see the Full Prescribing Information for ZEVTERA.