Zevtera ceftobiprole medocaril sodium 667 mg Injection, Powder, For Solution, 10 vials — NDC 68547-578-10 (Billing 68547-0578-10)
This is a package of 10 vials of Zevtera ceftobiprole medocaril sodium 667 mg Injection, Powder, For Solution from La Jolla Pharmaceutical Company, marketed since Apr 2025 and currently FDA-listed. It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 68547-578-10 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 68547 labeler · 578 product · 10 package
- Package marketed since
- Apr 1, 2025
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Billing quantity
- 10 EA per package
- Barcode (UPC-A, from the NDC)
- 3 6854757810 0
- FDA record last changed
- Jul 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 064494
- GCN: 14428
- GPI-14 (Medi-Span): 02500040202115
- HICL (First Databank): 035916
- AHFS class code: 08:12.06.20
- RxCUI (RxNorm): 2703561
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 3, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Cephalosporin Antibacterial class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Ceftobiprole medocaril injection is used to treat certain blood and skin infections and certain types of pneumonia (an infection of the lungs) caused by bacteria. Ceftobiprole medocaril is in a class of medications called cephalosporin antibiotics. It works by killing bacteria. Antibiotics such as ceftobiprole medocaril injection will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 3, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $224.28 | — |
| Medicare Part B allowsASP · J0681 | $1.098 / J0681 unit | — |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 4, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Billing & reimbursement
Where does this data come from?
- CMS ASP NDC-HCPCS crosswalk · refreshed Sep 22, 2026
- DMEPDAC NDC-HCPCS crosswalk
- openFDA NSDE billing units · refreshed Sep 7, 2026
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 68547-0578-10 You're viewing this Main listing | 10 VIAL, GLASS in 1 BOX / 1 INJECTION, POWDER, FOR SOLUTION in 1 VIAL, GLASS | 2025-04-01 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zevtera 667 mgthis 68547-0578-10 | La | 10 vials | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Apr 3, 2029 |
| GAIN | Qualified Infectious Disease Product (+5-year) | Apr 3, 2034 |
Is there a generic version of ZEVTERA 667 MG VIAL?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
-
UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
2 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 3, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
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Manufacturer & labeler
More NDCs from La Jolla Pharmaceutical Company labeler code 68547
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ZEVTERA is a cephalosporin antibacterial indicated for the treatment of: Adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis ( 1.1 ), Adult patients with acute bacterial skin and skin structure infections (ABSSSI) ( 1.2 ), and Adult and pediatric patients (3 months to less than 18 years old) with community-acquired bacterial pneumonia (CABP) ( 1.3 ). 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 bacteria ( 1.4 ).
1.1Staphylococcus aureus Bloodstream Infection (Bacteremia) ZEVTERA is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infection (bacteremia) (SAB), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates .
1.2Acute Bacterial Skin and Skin Structure Infections ZEVTERA is indicated for the treatment of 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.
1.3Community-Acquired Bacterial Pneumonia ZEVTERA is indicated for the treatment of adult and pediatric patients (3 months to less than 18 years old) 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.
1.4Usage 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. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended dosage of ZEVTERA for adult patients with SAB, ABSSSI and CABP is described in the table below ( 2.1 ): Indication in Adults Dose Frequency SAB 667 mg Every 6 hours on Days 1 to 8 Every 8 hours from Day 9 ABSSSI 667 mg Every 8 hours CABP 667 mg Every 8 hours Duration of treatment in adult patients is up to 42 days for SAB and 5 days to 14 days for ABSSSI and CABP ( 2.1 ). Administer each prepared intravenous infusion solution of ZEVTERA over 2 hours at a concentration of 2.67 mg/mL ( 2.1 , 2.6 ).
The recommended dosage of ZEVTERA for pediatric patients (3 months to less than 18 years old) with CABP is described below ( 2.2 ). Pediatric Age Group for CABP Dose Frequency 12 years to less than 18 years old 13.3 mg/kg (up to 667 mg/dose) Every 8 Hours Greater than or equal to 3 months and less than 12 years old 20 mg/kg (up to 667 mg/dose) Every 8 Hours Duration of treatment in pediatric patients is 7 days to 14 days for CABP ( 2.1 ). Administer each prepared intravenous infusion solution of ZEVTERA over 2 hours at a concentration of 2.67 mg/mL for pediatric patients aged 12 years to less than 18 years old and at a concentration of 5.33 mg/mL for pediatric patients aged 3 months to less than 12 years old ( 2.2 , 2.6 ).
Reduce the dosage in adult patients with CL CR less than 50 mL/min, including patients with CL CR less than 15 mL/min on hemodialysis ( 2.3 and 8.6 ). Increase the dosage in adult patients with CL CR greater than 150 mL/min ( 2.3 ). Reduce the dosage in pediatric patients aged 2 years old to less than 18 years old with eGFR less than 50 mL/min/1.73 m 2 and greater than or equal to 15 mL/min/1.73 m 2 ( 2.4 and 8.6 ).
See Full Prescribing Information for instructions for preparation of ZEVTERA solution infusion solution ( 2.5 ).
2.1Recommended Dosage and Administration for SAB, ABSSSI and CABP in Adult Patients The recommended dosage of ZEVTERA for the treatment of adult patients with SAB, ABSSSI and CABP is described in Table 1. The duration of treatment in adult patients is up to 42 days for SAB and 5 days to 14 days for ABSSSI and CABP. Administer each prepared intravenous infusion solution of ZEVTERA over 2 hours at a concentration of 2.67 mg/mL to adult patients [see Dosage and Administration (2.5) ].
Table 1: Recommended Dosage Regimen for SAB, ABSSSI and CABP in Adult Patients Indication Duration of treatment in adult patients is up to 42 days for SAB and 5 days to 14 days for ABSSSI and CABP. Dose Frequency Administer each prepared intravenous infusion solution of ZEVTERA over 2 hours at a concentration of 2.67 mg/mL [see Dosage and Administration (2.5) ] SAB 667 mg 667 mg of ceftobiprole medocaril sodium is equivalent to 500 mg of ceftobiprole. Every 6 hours on Days 1 to 8 Every 8 hours from Day 9 ABSSSI 667 mg Every 8 hours CABP 667 mg Every 8 hours
2.2Recommended Dosage and Administration for CABP in Pediatric Patients (3 months to less than 18 years old) For treatment of pediatric patients with CABP, the recommended dosage of ZEVTERA is described in Table 2, based on patient age and weight [see Clinical Pharmacology (12.3) ] . The duration of treatment for CABP in pediatric patients (3 months to less than 18 years old) is 7 days to 14 days. Administer each prepared intravenous infusion solution of ZEVTERA over 2 hours at a concentration of 2.67 mg/mL for patients 12 years to less than 18 years old and at a concentration of 5.33 mg/mL for patients greater than or equal to 3 months to less than 12 years old [see Dosage and Administration (2.5) ].
Table 2: Recommended Dosage Regimen in Pediatric Patients with CABP Pediatric Age Group Dose Duration of treatment for CABP in pediatric patients is 7 days to 14 days. Frequency 12 years to less than 18 years old 13.3 mg/kg (up to 667 mg/dose 13.3 mg/kg of ceftobiprole medocaril sodium is equivalent to 10 mg/kg of ceftobiprole; 20 mg/kg ceftobiprole medocaril sodium is equivalent to 15 mg/kg of ceftobiprole. 667 mg cefto… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS ZEVTERA (ceftobiprole medocaril sodium for injection) is available in a single-dose vial as a white, yellowish to slightly brownish, cake to broken cake or powder containing 667 mg of ceftobiprole medocaril sodium (equivalent to 500 mg of ceftobiprole) for reconstitution. For injection: 667 mg of ceftobiprole medocaril sodium (equivalent to 500 mg of ceftobiprole) as a lyophilized powder for reconstitution in a single-dose vial ( 3 ).
⛔ Contraindications ▾
4 CONTRAINDICATIONS ZEVTERA is contraindicated in patients with a known history of severe hypersensitivity to ZEVTERA, or to other members of the cephalosporin class [see Warnings and Precautions (5.2) ]. ZEVTERA is contraindicated in patients with a known history of severe hypersensitivity to ZEVTERA, or to other members of the cephalosporin class ( 4 ).
⚠️ Warnings and Cautions ▾
5 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 ( 5.1 ). Hypersensitivity Reactions: Discontinue ZEVTERA if a hypersensitivity reaction occurs, and institute appropriate treatment ( 5.2 ). Seizures and other adverse central nervous system (CNS) reactions have been associated with the use of ZEVTERA.
If seizures or other CNS adverse reactions occur, evaluate patients to determine whether ZEVTERA should be discontinued ( 5.3 ). Clostridioides difficile -associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including ZEVTERA. Evaluate if diarrhea occurs ( 5.4 ).
5.1Increased Mortality with Unapproved Use in Ventilator-Associated Bacterial Pneumonia Patients In Trial 4, an increase in mortality was seen in the subgroup of patients with ventilator-associated bacterial pneumonia (VABP) who were treated with ZEVTERA (35/103 [34%] versus 24/102 [24%] in comparator-treated patients) [see Adverse Reactions (6.1) ] . The cause of this increased mortality has not been established. Generally, deaths were associated with complications of infection or underlying co-morbidities.
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.
5.2Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, were observed in ZEVTERA-treated patients in clinical trials [see Adverse Reactions (6.1) ] . 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.
5.3Seizures and Other Central Nervous System Reactions Seizures and other adverse central nervous system (CNS) reactions have been reported during treatment with ZEVTERA and other cephalosporins [see Adverse Reactions (6.1) ] . Nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with cephalosporins particularly in patients with a history of epilepsy or when recommended dosages of cephalosporins were exceeded due to renal impairment. Adjust ZEVTERA dosing based on creatinine clearance [see Dosage and Administration (2.3 , 2.4) ] .
Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions, including seizures, occur, patients should undergo a neurological evaluation to determine whether ZEVTERA should be discontinued.
5.4Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including ZEVTERA, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in the Warnings and Precautions section: Increased Mortality in Ventilator-Associated Bacterial Pneumonia Patients [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Contraindications (4) and Warning and Precautions (5.2) ] Seizures and Other Central Nervous System Reactions [see Warnings and Precautions (5.3) ] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.4) ] SAB (adult patients): The most common adverse reactions occurring in ≥ 4% of adult patients were anemia, nausea, hypokalemia, vomiting, hepatic enzyme and bilirubin increased, diarrhea, blood creatinine increased, hypertension, leukopenia, and pyrexia ( 6.1 ).
ABSSSI (adult patients): The most common adverse reactions occurring in ≥ 2% of adult patients were nausea, diarrhea, headache, injection site reaction, hepatic enzyme increased, rash, vomiting, and dysgeusia ( 6.1 ). 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 ( 6.1 ).
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 ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact ISTx, LLC at 1-800-651-3861 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of ZEVTERA was evaluated in adults in four controlled comparative phase 3 clinical trials (Trials 1 through 4) which included 1221 patients treated with ZEVTERA 667 mg (equivalent to 500 mg of ceftobiprole) administered by IV infusion over 2 hours every 6 to 8 hours and 1248 patients treated with comparator for a treatment period up to 42 days.
The median age of patients treated with ZEVTERA was 56 years, ranging between 18 and 95 years old. Patients treated with ZEVTERA were predominantly male (64%) and White (82%). The safety of ZEVTERA was also evaluated in pediatric patients aged 3 months to less than 18 years in a controlled phase 3 clinical trial (Trial 5) which included 138 patients with CABP and hospital-acquired bacterial pneumonia (HABP) requiring hospitalization.
Although HABP was included in the safety data, the safety and effectiveness of ZEVTERA for the treatment of HABP has not been established and ZEVTERA is not approved for the treatment of HABP. Adult Patients with Staphylococcus aureus Bloodstream Infection (Bacteremia) ZEVTERA was evaluated in an active-controlled randomized, double-blind, multicenter phase 3 trial (Trial 1) in patients with Staphylococcus aureus bloodstream infection (bacteremia) (SAB) including right-sided infective endocarditis [see Clinical Studies (14.1) ] .
In Trial 1, 191 patients received ZEVTERA 667 mg (equivalent to 500 mg of ceftobiprole) administered as a 2-hour IV infusion every 6 hours from Day 1 to Day 8, and ZEVTERA 667 mg every 8 hours from Day 9 onwards, and 198 patients were treated with a comparator (daptomycin administered as an IV 0.5 hour infusion, 6 mg/kg up to 10 mg/kg every 24 hours, with optional aztreonam). The dose of study drugs were adjusted based on renal function. The median age of patients treated with ZEVTERA was 57 years, ranging between 20-89 years old with approximately 30% aged greater than or equal to 65 years.
Patients treated with ZEVTERA were predominantly male (68%), White (95%), and from Europe (93%). The median duration of treatment was 21 days in both… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Drug-Laboratory Test Interactions Dipstick Tests ZEVTERA may result in false-positive results in dipstick tests (urine protein, ketones, or occult blood). Use alternate clinical laboratory methods of testing to confirm positive tests. Serological Testing Treatment with ZEVTERA has the potential to interfere with serological testing, such as the Coombs test.
In clinical studies there was no evidence of hemolytic anemia in adults or children. However, the possibility that hemolytic anemia may occur cannot be ruled out. Patients experiencing anemia during or after treatment should be investigated for this possibility.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no available data with use of ZEVTERA in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Available data from published observational studies and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes . Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups, and cannot definitively establish the absence of risk.
Intravenous administration of ceftobiprole medocaril to pregnant rats and monkeys during organogenesis showed no evidence of adverse fetal developmental outcomes at doses approximately 1.4 times and 0.9 times, respectively, the maximum recommended human dose (MRHD). Some evidence of maternal toxicity (slight reduction in body weight and food consumption) was noted in pregnant monkeys at 0.9 times the MRHD. Intravenous administration of ceftobiprole medocaril to rats 2-weeks prior to mating, during organogenesis, and through lactation resulted in no adverse fertility or fetal development effects in offspring at doses approximately 1.4 times the MRHD ( see Data ).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Pregnant rats administered ceftobiprole medocaril intravenously at doses up to 360 mg/kg/day (approximately 1.4 times the MRHD based on total body surface area (BSA)-normalized comparisons) during organogenesis on gestation days (GD) 6 to 17 showed no adverse fetal development effects. Maternal body weight gain and food consumption were slightly decreased at 360 mg/kg/day. Pregnant cynomolgus monkeys were administered ceftobiprole medocaril intravenously at doses up to 120 mg/kg/day (approximately 0.9 times the MRHD based on BSA comparison) during organogenesis (GD 20 to 50).
Maternal body weight gain and food consumption were slightly reduced at 120 mg/kg/day. This dose was associated with a slight increase in abortion rate (approximately 10% above historical controls). No other fetal development adverse effects (i.e., no fetal malformations) were observed at the high dose.
In a pre- and post-natal development toxicity study, ceftobiprole medocaril was administered intravenously to pregnant rats during organogenesis starting at GD 6 and continuing to lactation day 21 (L21) at doses up to 360 mg/kg (approximately 1.4 times the MRHD based on BSA comparisons). Maternal toxicity (mortality, reduced food consumption and body weight gain in surviving females during gestation) was observed at the high dose. Effects in the offspring were also observed at the high dose during the post-natal pre-weaning period (decrease in the number of pups born per litter and decreased post-natal survival up to day 4 after birth).
No adverse effects were observed in surviving pups during the post-natal postweaning development period (days 5-22) at doses up to 360 mg/kg.
8.2Lactation Risk Summary There are no data on the presence of ceftobiprole in human milk, the effects of ceftobiprole on the breastfed infant, or the effects of ceftobiprole on milk production. Animal studies have shown that ceftobiprole was excreted in milk of lactating rats at low concentrations (see Data ) . When a drug is present in animal milk, it is likely the drug will be present in human milk.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZEVTERA and any potential adverse effects… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data with use of ZEVTERA in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Available data from published observational studies and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes . Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups, and cannot definitively establish the absence of risk.
Intravenous administration of ceftobiprole medocaril to pregnant rats and monkeys during organogenesis showed no evidence of adverse fetal developmental outcomes at doses approximately 1.4 times and 0.9 times, respectively, the maximum recommended human dose (MRHD). Some evidence of maternal toxicity (slight reduction in body weight and food consumption) was noted in pregnant monkeys at 0.9 times the MRHD. Intravenous administration of ceftobiprole medocaril to rats 2-weeks prior to mating, during organogenesis, and through lactation resulted in no adverse fertility or fetal development effects in offspring at doses approximately 1.4 times the MRHD ( see Data ).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data Pregnant rats administered ceftobiprole medocaril intravenously at doses up to 360 mg/kg/day (approximately 1.4 times the MRHD based on total body surface area (BSA)-normalized comparisons) during organogenesis on gestation days (GD) 6 to 17 showed no adverse fetal development effects. Maternal body weight gain and food consumption were slightly decreased at 360 mg/kg/day. Pregnant cynomolgus monkeys were administered ceftobiprole medocaril intravenously at doses up to 120 mg/kg/day (approximately 0.9 times the MRHD based on BSA comparison) during organogenesis (GD 20 to 50).
Maternal body weight gain and food consumption were slightly reduced at 120 mg/kg/day. This dose was associated with a slight increase in abortion rate (approximately 10% above historical controls). No other fetal development adverse effects (i.e., no fetal malformations) were observed at the high dose.
In a pre- and post-natal development toxicity study, ceftobiprole medocaril was administered intravenously to pregnant rats during organogenesis starting at GD 6 and continuing to lactation day 21 (L21) at doses up to 360 mg/kg (approximately 1.4 times the MRHD based on BSA comparisons). Maternal toxicity (mortality, reduced food consumption and body weight gain in surviving females during gestation) was observed at the high dose. Effects in the offspring were also observed at the high dose during the post-natal pre-weaning period (decrease in the number of pups born per litter and decreased post-natal survival up to day 4 after birth).
No adverse effects were observed in surviving pups during the post-natal postweaning development period (days 5-22) at doses up to 360 mg/kg.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of ZEVTERA have been established for the treatment of CABP in pediatric patients 3 months to less than 18 years. Use of ZEVTERA in this age group is supported by evidence from an adequate and well-controlled trial of ZEVTERA in adults, with additional pharmacokinetic, safety and efficacy data from pediatric trials [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.3) ] . The safety and effectiveness of ZEVTERA have not been established for the treatment of CABP in pediatric patients less than 3 months of age.
The safety and effectiveness of ZEVTERA have not been established for the treatment of ABSSSI and SAB in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 835 adult CABP, ABSSSI, and SAB patients treated with ZEVTERA in the Trials 1, 2 and 3, 210 patients (25%) were 65 years of age and older, including 85 patients (10%) 75 years of age and older. No overall differences in safety or effectiveness of ZEVTERA were observed between patients 65 years of age and older and younger adult patients. No clinically significant changes in the pharmacokinetics of ZEVTERA were observed in patients 65 years of age and older compared to younger adult patients [ see Clinical Pharmacology (12.3) ] .
Dosage adjustment for geriatric patients should be based on renal function [see Dosage and Administration (2.3) , Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ].
🆘 Overdosage ▾
10 OVERDOSAGE There is no information on clinical signs and symptoms associated with an overdose of ZEVTERA. For patients who receive doses greater than the recommended dosage regimen and have unexpected adverse reactions associated with ZEVTERA, discontinue ZEVTERA, treat symptomatically, and institute general supportive treatment. ZEVTERA can be removed by hemodialysis.
However, no information is available on the use of hemodialysis to treat overdose [see Clinical Pharmacology (12.3) ] .
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action ZEVTERA is an antibacterial drug [see Microbiology (12.4) ]
12.2Pharmacodynamics Ceftobiprole exposure-response relationships and the time course of pharmacodynamic response are unknown. Time Above the Minimum Inhibitory Concentration (MIC) The time that the unbound plasma concentration of ceftobiprole exceeds the MIC of Staphylococcus aureus , Streptococcus pneumoniae , and species of Enterobacterales correlates with efficacy in a neutropenic murine thigh infection model [see Clinical Pharmacology (12.4) ] . Cardiac Electrophysiology At a dose 1 to 2 times the maximum recommended dose, ZEVTERA does not prolong the QT interval to any clinically relevant extent.
12.3Pharmacokinetics Ceftobiprole medocaril is the prodrug of the active moiety ceftobiprole. No clinically significant differences in the pharmacokinetics of ceftobiprole were observed with ZEVTERA following single or multiple dose administration. Ceftobiprole exhibits linear and time-independent pharmacokinetics.
The C max and AUC increase proportionally with the dose over a range of 125 mg to 1000 mg (0.25 to 2 times the highest approved recommended adult dosage). The mean pharmacokinetic parameters of ceftobiprole in healthy adults with normal renal function after single and multiple 2-hour IV infusions of ZEVTERA 667 mg (equivalent to 500 mg of ceftobiprole) administered every 8 hours are summarized in Table 11. Pharmacokinetic parameters were similar for single and multiple dose administrations.
Table 11: Mean (Standard Deviation) Pharmacokinetic Parameters of ZEVTERA in Healthy Adults Parameter Multiple doses administered every 8 hours as a 2-hour infusion (n = 27) C max = Maximum plasma concentration; AUC 0-8h = Area under the plasma concentration-time curve from 0 to 8 h; V ss = Volume of distribution at steady state; CL = Clearance. C max (µg/mL) 33.0 (4.83) AUC 0-8h (µg•h/mL) 102 (11.9) Distribution % Bound to human plasma protein 16 % ELF/unbound plasma 15-19 V ss (L) 18 Metabolism (Minimally Metabolized) t 1/2 (h) 3.3 (0.3) CL (L/h) 4.98 (0.582) Excretion Major route of elimination Renal % excreted unchanged in urine 83 Specific Populations No clinically significant differences in the pharmacokinetics of ceftobiprole were observed in adults based on age (18 to 91 years), gender (36% female), or race/ethnicity (88% white, 3% Black, 5% Asian).
The effect of hepatic impairment on ceftobiprole pharmacokinetics is unknown. Patients with Renal Impairment No clinically significant differences in the pharmacokinetics of ceftobiprole were observed in adult subjects and subjects with mild renal impairment (CL CR 50 to 80 mL/min). Ceftobiprole AUC increased 2.5-fold in adult subjects with moderate renal impairment (CL CR 30 to < 50 mL/min) and 3.3-fold in severe renal impairment (CL CR < 30 mL/min).
The effect of any degree of renal impairment in pediatric patients less than 2 years of age or in pediatric patients with CL CR < 15 mL/min/1.73 m 2 on ceftobiprole pharmacokinetics is unknown. End-stage Renal Disease Requiring Dialysis No clinically significant difference in the pharmacokinetics of ceftobiprole were observed in adult patients with ESRD (CL CR < 15 mL/min) compared to healthy adult subjects based on limited PK data and pharmacokinetic modeling and simulation. Ceftobiprole was demonstrated to be removed by hemodialysis in patients receiving ZEVTERA.
Patients with Augmented Renal Clearance A clinically significant reduction in ceftobiprole exposure is predicted in adult patients with augmented renal clearance (CL CR > 150 mL/min) based upon a mechanistic understanding of this drug. The effect of augmented renal clearance (CL CR > 150 mL/min) on ceftobiprole pharmacokinetics in pediatric patients is unknown. Pediatric Use No clinically significant differences in the pharmacokinetics of ceftobiprole were observed between pediatric patients from birth to < 18 years with normal renal function following administ… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action ZEVTERA is an antibacterial drug [see Microbiology (12.4) ]
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied ZEVTERA (ceftobiprole medocaril sodium for injection), a white, yellowish to slightly brownish sterile powder for reconstitution, is supplied in a single-dose clear glass vial sealed with a rubber stopper (not made with natural rubber latex) and an aluminum seal with a flip-off cap. Each vial contains 667 mg ceftobiprole medocaril sodium (equivalent to 500 mg of ceftobiprole) and is supplied in a carton containing 10 single-dose vials (NDC# 68547-578-10).
16.2Storage and Handling Store ZEVTERA vials refrigerated at 2 °C to 8 °C (36 °F to 46 °F) protected from light. Store in carton until time of use. ZEVTERA must be reconstituted and then further diluted prior to administration by intravenous infusion. Store reconstituted and diluted solution of ZEVTERA as described elsewhere in the labeling [see Dosage and Administration (2.7) ].
📦 Storage and Handling ▾
16.2Storage and Handling Store ZEVTERA vials refrigerated at 2 °C to 8 °C (36 °F to 46 °F) protected from light. Store in carton until time of use. ZEVTERA must be reconstituted and then further diluted prior to administration by intravenous infusion. Store reconstituted and diluted solution of ZEVTERA as described elsewhere in the labeling [see Dosage and Administration (2.7) ].
📋 Description ▾
11 DESCRIPTION ZEVTERA (ceftobiprole medocaril sodium for injection) contains sodium salt of ceftobiprole medocaril, a semisynthetic, cephalosporin antibacterial, for intravenous use. Chemically, ceftobiprole medocaril is (6 R ,7 R )-7-[[(2 Z )-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-hydroxyiminoacetyl]amino]-3-[( E )-[1-[(3 R )-1-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methoxycarbonyl]pyrrolidin-3-yl]-2-oxopyrrolidin-3-ylidene]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. Its molecular weight is 690.6 g/mol.
The empirical formula is C 26 H 25 N 8 NaO 11 S 2 . Figure 1 Chemical Structure of ceftobiprole medocaril ZEVTERA vials contain 667 mg of ceftobiprole medocaril sodium (equivalent to 500 mg of ceftobiprole). The powder for injection is a white, yellowish to slightly brownish sterile powder.
Each vial includes inactive ingredient citric acid monohydrate (26.3 mg/vial) as a buffer component and sodium hydroxide (q.s.) as a pH adjustment agent. Each vial of ZEVTERA contains approximately 32 mg of sodium. The pH of the reconstituted solution is 4.5–5.5.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Serious Allergic Reactions Advise patients (or caregiver) that hypersensitivity reactions were reported with the use of ZEVTERA, and that serious and occasionally fatal serious allergic reactions could occur and require immediate treatment. Advise patients to discontinue ZEVTERA if a hypersensitivity reaction occurs and inform their healthcare provider about any previous hypersensitivity reactions to ZEVTERA, other beta-lactams (including cephalosporins), or other allergens [see Warnings and Precautions (5.2) ].
Seizures and Central Nervous System Adverse Reactions Advise patients (or caregiver) that seizures and other adverse central nervous system (CNS) reactions have been reported during treatment with ZEVTERA. If CNS adverse reactions, including seizures, occur, advise patients to inform their healthcare provider to determine whether ZEVTERA should be discontinued [see Warnings and Precautions (5.3) ]. Potentially Serious Diarrhea Advise patients (or caregiver) that diarrhea is a common problem caused by antibacterial drugs, including ZEVTERA.
Sometimes, frequent watery or bloody diarrhea may occur and may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, instruct patients to contact their healthcare provider [see Warnings and Precautions (5.4) ]. Antibacterial Resistance Patients should be counseled that antibacterial drugs, including ZEVTERA, should be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold). Patients should be told that the medication should be administered exactly as directed [see Warnings and Precautions (5.5) ].
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Ceftobiprole medocaril is the prodrug of the active moiety ceftobiprole. No clinically significant differences in the pharmacokinetics of ceftobiprole were observed with ZEVTERA following single or multiple dose administration. Ceftobiprole exhibits linear and time-independent pharmacokinetics.
The C max and AUC increase proportionally with the dose over a range of 125 mg to 1000 mg (0.25 to 2 times the highest approved recommended adult dosage). The mean pharmacokinetic parameters of ceftobiprole in healthy adults with normal renal function after single and multiple 2-hour IV infusions of ZEVTERA 667 mg (equivalent to 500 mg of ceftobiprole) administered every 8 hours are summarized in Table 11. Pharmacokinetic parameters were similar for single and multiple dose administrations.
Table 11: Mean (Standard Deviation) Pharmacokinetic Parameters of ZEVTERA in Healthy Adults Parameter Multiple doses administered every 8 hours as a 2-hour infusion (n = 27) C max = Maximum plasma concentration; AUC 0-8h = Area under the plasma concentration-time curve from 0 to 8 h; V ss = Volume of distribution at steady state; CL = Clearance. C max (µg/mL) 33.0 (4.83) AUC 0-8h (µg•h/mL) 102 (11.9) Distribution % Bound to human plasma protein 16 % ELF/unbound plasma 15-19 V ss (L) 18 Metabolism (Minimally Metabolized) t 1/2 (h) 3.3 (0.3) CL (L/h) 4.98 (0.582) Excretion Major route of elimination Renal % excreted unchanged in urine 83 Specific Populations No clinically significant differences in the pharmacokinetics of ceftobiprole were observed in adults based on age (18 to 91 years), gender (36% female), or race/ethnicity (88% white, 3% Black, 5% Asian).
The effect of hepatic impairment on ceftobiprole pharmacokinetics is unknown. Patients with Renal Impairment No clinically significant differences in the pharmacokinetics of ceftobiprole were observed in adult subjects and subjects with mild renal impairment (CL CR 50 to 80 mL/min). Ceftobiprole AUC increased 2.5-fold in adult subjects with moderate renal impairment (CL CR 30 to < 50 mL/min) and 3.3-fold in severe renal impairment (CL CR < 30 mL/min).
The effect of any degree of renal impairment in pediatric patients less than 2 years of age or in pediatric patients with CL CR < 15 mL/min/1.73 m 2 on ceftobiprole pharmacokinetics is unknown. End-stage Renal Disease Requiring Dialysis No clinically significant difference in the pharmacokinetics of ceftobiprole were observed in adult patients with ESRD (CL CR < 15 mL/min) compared to healthy adult subjects based on limited PK data and pharmacokinetic modeling and simulation. Ceftobiprole was demonstrated to be removed by hemodialysis in patients receiving ZEVTERA.
Patients with Augmented Renal Clearance A clinically significant reduction in ceftobiprole exposure is predicted in adult patients with augmented renal clearance (CL CR > 150 mL/min) based upon a mechanistic understanding of this drug. The effect of augmented renal clearance (CL CR > 150 mL/min) on ceftobiprole pharmacokinetics in pediatric patients is unknown. Pediatric Use No clinically significant differences in the pharmacokinetics of ceftobiprole were observed between pediatric patients from birth to < 18 years with normal renal function following administration of an intravenous dose of ZEVTERA.
ZEVTERA is not approved for use in pediatric patients less than 3 months of age [see Use in Specific Populations (8.4) ] . Drug Interaction Studies In Vitro Studies Ceftobiprole does not inhibit or induce CYP450 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Ceftobiprole is an inhibitor of OATP1B1, OATP1B3, MRP2 and BSEP but is not an inhibitor of P-glycoprotein, BCRP, OAT1, OAT3, OCT1, OCT2, or MATE1.
Clinical Studies Pitavastatin : Coadministration of ceftobiprole (500 mg administered intravenously, every 8 hours) and pitavastatin (single oral dose of 2 mg) in healthy adult subjects decreased the AUC 0-last , AUC 0-inf , and Cmax of pitavastatin by 14% [90%CI (6, 21)], 13% [… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Ceftobiprole exposure-response relationships and the time course of pharmacodynamic response are unknown. Time Above the Minimum Inhibitory Concentration (MIC) The time that the unbound plasma concentration of ceftobiprole exceeds the MIC of Staphylococcus aureus , Streptococcus pneumoniae , and species of Enterobacterales correlates with efficacy in a neutropenic murine thigh infection model [see Clinical Pharmacology (12.4) ] . Cardiac Electrophysiology At a dose 1 to 2 times the maximum recommended dose, ZEVTERA does not prolong the QT interval to any clinically relevant extent.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Staphylococcus aureus Bloodstream Infection (Bacteremia) in Adults The efficacy of ZEVTERA in the treatment of adult patients with SAB, including right-sided infective endocarditis, was demonstrated in a randomized, controlled, double-blind, multinational, multicenter trial (Trial 1, NCT03138733). In this trial, adult patients were randomized to either ZEVTERA 667 mg (equivalent to 500 mg of ceftobiprole) IV every 6 hours from study Day 1 to Day 8, and 667 mg IV every 8 hours from study Day 9 onwards) or daptomycin (6 mg/kg up to 10 mg/kg IV every 24 hours) plus optional aztreonam for coverage of gram-negative co-infections (the comparator).
Randomization was stratified by study site, dialysis status, and use of prior antibacterial drugs. The study was performed in two cohorts based on findings in animal studies [see Nonclinical Toxicology (13.2) ] . The initial cohort was enrolled to receive a maximum treatment duration of 28 days.
Based on a safety evaluation of cohort 1, patients could be enrolled in cohort 2 to receive a treatment duration of up to 42 days. The duration of study treatment was based on the investigator's clinical evaluation. Study patients were required to have at least one positive blood culture for S. aureus obtained within 72 hours prior to randomization, signs and symptoms of bacteremia (fever, elevated white blood cell count or immature neutrophils, tachycardia, or hypotension), and at least one of the following conditions of complicated S. aureus bacteremia: chronic dialysis, persistent SAB, acute bacterial skin and skin structure infection, metastatic infections of native tissue, osteomyelitis, epidural or cerebral abscess, or definite native-valve right-sided infective endocarditis by Modified Duke's Criteria.
Patients with uncomplicated S. aureus bacteremia, left-sided infective endocarditis, prosthetic heart valves, foreign body material that could not be removed, severe neutropenia, or pneumonia, were excluded from the study. Upon entry, patients were classified for likelihood of endocarditis using the modified Duke's criteria (definite, possible, or rejected). Echocardiography, including a transesophageal echocardiogram, was to be performed during screening or within 7 days following study enrollment.
Final diagnoses were to be made by the study investigators within 7 days of randomization. The final diagnosis for persistent S. aureus bacteremia was made by an independent treatment-blinded Data Review Committee (DRC). A total of 390 patients (192 ZEVTERA, 198 daptomycin) with SAB were randomized from 60 centers in the USA, Europe, Latin America, and South Africa.
The modified ITT (mITT) population was used for the primary efficacy analysis, comprising 387 patients (189 ZEVTERA, 198 daptomycin ± aztreonam) who received study drugs and had a baseline blood culture positive for S. aureus . Patient demographic and baseline characteristics were balanced between the treatment groups. The median age among the 387 patients in the mITT population was 58 years, ranging from 19 to 91 years), with 31% aged ≥ 65 years, 69% of patients were male, and 96% were White.
Frequent conditions of complicated SAB included acute bacterial skin and skin structure infections (61%), intra-abdominal abscesses (14%), osteoarticular infections (13%), and patients on chronic dialysis (13%). A total of 6.5% of patients had definite right-sided infective endocarditis. A total of 24% had bacteremia caused by methicillin-resistant S. aureus (MRSA).
The primary efficacy outcome in the study was overall success at the post-treatment evaluation (PTE) visit at 70 days post-randomization in the mITT population, as assessed by the independent DRC. Overall success required survival, symptom improvement, S. aureus bacteremia bloodstream clearance, no new S. aureus bacteremia complications, and no use of other potentially effective antibacterial drugs. Overall success rates at the PTE visit in the mITT population… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No animal studies have been performed to evaluate the carcinogenic potential of ZEVTERA as none were warranted. Mutagenesis Ceftobiprole medocaril was negative in a standard bacterial reverse mutation test, however, the test was limited by bactericidal activity. Further genetic toxicology studies performed in vitro in mammalian cells showed that both ceftobiprole medocaril (pro-drug) and ceftobiprole (active metabolite) induced mutations at the TK locus in mouse lymphoma L5178Y TK+/- cells, however the pro-drug did not induce mutations in an in vitro HPRT forward mutation assay in CHO cells.
Ceftobiprole medocaril was positive for structural chromosome aberrations in human peripheral blood lymphocytes. When administered intravenously, ceftobiprole medocaril was negative for clastogenic effects in the in vivo mouse bone marrow micronucleus assay. Impairment of Fertility Administration of repeated doses of intravenous ceftobiprole medocaril at doses up to 360 mg/kg (approximately 1.4 times the MRHD based on BSA comparisons) to male and female rats starting approximately 2 weeks prior to mating, during mating and continuing through implantation (up to GD 7) were without effect on fertility or early fetal development.
13.2Animal Toxicology and/or Pharmacology Both rats and marmosets showed convulsions and thrombi and/or emboli with dosing durations greater than one month. In the 13-week intravenous rat study, clonic convulsions were noted at 500 mg/kg/day (2 times the MRHD based on BSA comparisons) with early deaths seen at 250 mg/kg in the males (1 time the MRHD based on BSA comparison). In the 13-week intravenous marmoset study, convulsions and thrombi were noted at multiple sites distal to the injection site (i.e., lung, and heart) at doses ≥ 50 mg/kg/day (0.1 times the MRHD, based on BSA comparisons).
While dogs did not show convulsions in a 13-week toxicology study, catheter patency could only be maintained between 4 to 11 weeks in most animals at doses up to 32 mg/kg/day (0.4 times the MRHD based on BSA comparisons). Fibrin, erythrocytes and inflammatory cells within the lumens of the catheters were noted in the 13-week dog study, while thrombi were observed at the injection site in all species tested. Kidney findings were also noted in the 13-week studies in rats (tubular/duct eosinophilic bodies and presence of foreign material) at 1 times the MRHD.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No animal studies have been performed to evaluate the carcinogenic potential of ZEVTERA as none were warranted. Mutagenesis Ceftobiprole medocaril was negative in a standard bacterial reverse mutation test, however, the test was limited by bactericidal activity. Further genetic toxicology studies performed in vitro in mammalian cells showed that both ceftobiprole medocaril (pro-drug) and ceftobiprole (active metabolite) induced mutations at the TK locus in mouse lymphoma L5178Y TK+/- cells, however the pro-drug did not induce mutations in an in vitro HPRT forward mutation assay in CHO cells.
Ceftobiprole medocaril was positive for structural chromosome aberrations in human peripheral blood lymphocytes. When administered intravenously, ceftobiprole medocaril was negative for clastogenic effects in the in vivo mouse bone marrow micronucleus assay. Impairment of Fertility Administration of repeated doses of intravenous ceftobiprole medocaril at doses up to 360 mg/kg (approximately 1.4 times the MRHD based on BSA comparisons) to male and female rats starting approximately 2 weeks prior to mating, during mating and continuing through implantation (up to GD 7) were without effect on fertility or early fetal development.
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL - 667 mg Vial Box NDC# 68547-578-10 Rx Only 10 single-dose vials ZEVTERA ® 667 mg/vial* (ceftobiprole medocaril sodium for injection) *equivalent to 500 mg ceftobiprole For intravenous use only. Reconstitute and further dilute before use. Single-dose vial. Discard unused portion. PRINCIPAL DISPLAY PANEL - 667 mg Vial Box
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