Zevtera (ceftobiprole medocaril)

Ceftobiprole medocaril is commercially available as ceftobiprole medocaril sodium; dosage is expressed in terms of ceftobiprole medocaril sodium.

Ceftobiprole medocaril is administered by IV infusion.

Store vials containing ceftobiprole medocaril lyophilized powder at 2-8degreesC in the original carton; protect from light.

IV solutions of ceftobiprole medocaril should not be admixed with or addedto solutions containing other drugs. Do not mix or administer simultaneously with calcium-containing solutions.

No dosing information is available for this tab.

In vitro, ceftobiprole does not inhibit or induce cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5.

Ceftobiprole does not appear to be a substrate of CYP enzymes.

Ceftobiprole is an inhibitor of organic anion transporting polypeptide (OATP) 1B1, OATP1B3, multidrug resistance-associated protein (MRP) 2, and bile salt export pump (BSEP) transporters. Ceftobiprole is not an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, or multidrug and toxin extrusion (MATE) 1.

Clinical drug interaction studies of ceftobiprole have not been performed to date.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known serious hypersensitivity to ceftobiprole or other cephalosporins.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Clostridioides difficile infection
• Lower seizure threshold
• Seizure disorder

• Kidney disease with likely reduction in glomerular filtration rate (GFr)

Adverse effects occurring in >=4% of adult patients receiving ceftobiprole medocaril for the treatment of bacteremia and endocarditis include anemia, nausea, hypokalemia, vomiting, increased hepatic enzyme and bilirubin concentrations, diarrhea, increased serum creatinine concentrations, hypertension, leukopenia, and pyrexia.

Adverse effects occurring in >=2% of adult patients receiving ceftobiprole medocaril for the treatment of acute bacterial skin and skin structure infections include nausea, diarrhea, headache, injection site reactions, increased hepatic enzyme concentrations, rash, vomiting, and dysgeusia.

Adverse effects occurring in >=2% of adult patients receiving ceftobiprole medocaril for the treatment of community-acquired pneumonia include nausea, increased hepatic enzyme concentrations, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, phlebitis, hypertension, and dizziness.

Adverse effects occurring in >=2% of pediatric patients 3 months to <18 years of age receiving ceftobiprole medocaril for the treatment of community-acquired pneumonia include vomiting, headache, increased hepatic enzyme concentrations, diarrhea, infusion site reactions, phlebitis, and pyrexia.

Less Frequent

• Abnormal hepatic function tests
• Hyponatremia

Rare or Very Rare

• Agranulocytosis
• Anaphylaxis
• Anemia
• Asthma
• Clostridioides difficile infection
• Eosinophilia
• Hypokalemia
• Leukopenia
• Renal failure
• Seizure disorder
• Thrombocytopenic disorder
• Thrombocytosis

More Frequent

• Diarrhea
• Hyperbilirubinemia
• Hypertension
• Injection site sequelae
• Nausea
• Vomiting

Less Frequent

• Dizziness
• Dysgeusia
• Fever
• Headache disorder
• Phlebitis after infusion
• Skin rash

Rare or Very Rare

• Acute abdominal pain
• Agitation
• Candidiasis
• Drowsy
• Dyspepsia
• Dysphagia
• Dyspnea
• Fatigue
• Hyperglycemia
• Hypertriglyceridemia
• Hypocalcemia
• Insomnia
• Muscle spasm
• Nightmares
• Panic disorder
• Peripheral edema
• Pruritus of skin
• Sore throat
• Symptoms of anxiety

No enhanced messaging available.

Safety and efficacy of ceftobiprole medocaril for the treatment of community-acquired pneumonia (CAP) in pediatric patients 3 months to <18 years of age have been established based on the safety and efficacy of the drug in adults. In addition, use of ceftobiprole in pediatric patients with CAP is supported by pharmacokinetic, safety, and efficacy data from pediatric trials.

Safety and efficacy of ceftobiprole medocaril have not been established for the treatment of CAP in pediatric patients <3 months of age.

Safety and efficacy of ceftobiprole medocaril have not been established for the treatment of acute bacterial skin and skin structure infections or bacteremia with or without endocarditis in pediatric patients.

In pediatric patients <18 years of age with normal renal function, no clinically important differences in the pharmacokinetics of ceftobiprole were observed compared with adults.

There are no available data with use of ceftobiprole medocaril in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. The manufacturer of ceftobiprole medocaril states that while available studies cannot definitively establish the absence of risk, published data from observational studies and case reports over several decades have not identified an association with the use of cephalosporins during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Reproduction studies in rats and monkeys using ceftobiprole medocaril at doses approximately 1.4 and 0.9 times, respectively, the maximum recommended human dose showed no evidence of adverse fetal developmental outcomes. Some evidence of maternal toxicity (slight reduction in body weight and food consumption) was observed in pregnant monkeys receiving 0.9 times the maximum recommended human dose. No adverse effects on fertility or fetal development were observed in rats receiving ceftobiprole medocaril at doses approximately 1.4 times the maximum recommended human dose 2 weeks prior to mating, during organogenesis, and through lactation.

No data are available on the presence of ceftobiprole in human milk or on the effects of the drug on the breastfed infant or on milk production. Ceftobiprole is distributed at low concentrations into milk in rats. When a drug is present in animal milk, it is likely to be present in human milk. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for ceftobiprole and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Dosage adjustments based solely on age are not necessary when ceftobiprole medocaril is used in geriatric patients, but dosage adjustments are indicated in those with renal impairment.

Of the 835 adult patients who received ceftobiprole medocaril in clinical trials, 25% were >=65 years of age while 10% were >=75 years of age. No overall differences in safety or efficacy were observed between geriatric patients and younger adults.

No clinically important differences in the pharmacokinetics of ceftobiprole medocaril were observed in patients >=65 years of age compared to younger adults. Dosage adjustments for geriatric patients should be based on renal function.