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Ceftaroline Fosamil

Medically reviewed by Drugs.com. Last updated on Sep 1, 2020.

Pronunciation

(sef TAR oh leen FOS a mil)

Index Terms

  • Ceftaroline Fosamil Acetate
  • PPI-0903
  • PPI-0903M
  • T-91825
  • TAK-599

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Teflaro: 400 mg (1 ea); 600 mg (1 ea)

Brand Names: U.S.

  • Teflaro

Pharmacologic Category

  • Antibiotic, Cephalosporin (Fifth Generation)

Pharmacology

Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) 1 through 3. This action blocks the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls and inhibits cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysis and murein hydrolases) while cell wall assembly is arrested. Ceftaroline has a strong affinity for PBP2a, a modified PBP in MRSA, and PBP2x in S. pneumoniae, contributing to its spectrum of activity against these bacteria.

Distribution

Vd: Median: 20.3 L (range: 18.3 to 21.6 L)

Metabolism

Ceftaroline fosamil (inactive prodrug) undergoes rapid conversion to bioactive ceftaroline in plasma by phosphatase enzyme; ceftaroline is hydrolyzed to form inactive ceftaroline M-1 metabolite

Excretion

Urine (~88%); feces (~6%)

Time to Peak

~1 hour

Half-Life Elimination

1.6 ± 0.38 hours (single dose); 2.66 ± 0.4 hours (multiple dose)

Protein Binding

~20%

Special Populations: Renal Function Impairment

AUC increased 52% in moderate renal impairment (CrCl >30 to 50 mL/minute) and 115% in severe renal impairment (CrCl 15 to 30 mL/minute) as compared to patients with normal renal function. Following a 4-hour hemodialysis session, 21.6% of a single 400 mg IV dose (administered prior to hemodialysis) was recovered in the dialysate.

Special Populations: Elderly

The AUC was approximately 33% higher in elderly patients, mainly because of changes in renal function.

Use: Labeled Indications

Pneumonia, community-acquired: Treatment of community-acquired bacterial pneumonia in adults and pediatric patients ≥2 months of age caused by Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.

Skin and skin structure infections: Treatment of acute bacterial skin and skin structure infections in adults and pediatric patients (≥34 weeks gestational age and 12 days postnatal age) caused by S. aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, E. coli, K. pneumoniae, and K. oxytoca.

Contraindications

Known serious hypersensitivity to ceftaroline, other members of the cephalosporin class, or any component of the formulation

Dosing: Adult

Pneumonia, community acquired: Inpatients without risk factors for Pseudomonas aeruginosa: IV: 600 mg every 12 hours as part of an appropriate combination regimen. Duration of therapy is for a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (ATS/IDSA [Metlay 2019]).

Skin and skin structure infection: IV: 600 mg every 12 hours for 5 to 14 days.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Cystic fibrosis (CF) pulmonary exacerbation, MRSA: Very limited data available: Children ≥6 years and Adolescents: IV: 15 mg/kg/dose every 8 hours; maximum dose: 600 mg/dose. Dosing based on a prospective pharmacokinetic study in CF patients ≥6 years (n=7; total treatment courses: 10; age: mean: 20.3 ± 8 years; 43% of patients were <18 years old) receiving ceftaroline for MRSA-positive respiratory secretions; the dosing regimen resulted in achievement of MIC ≥1 mcg/mL for >60% of the time (Barsky 2018).

Pneumonia, community acquired: Treatment duration is dependent on severity of infection and clinical response.

Infants ≥2 months and Children <2 years: IV: 8 mg/kg/dose every 8 hours for 5 to 14 days.

Children ≥2 years and Adolescents <18 years:

≤33 kg: IV: 12 mg/kg/dose every 8 hours for 5 to 14 days.

>33 kg: IV: 400 mg every 8 hours or 600 mg every 12 hours for 5 to 14 days.

Adolescents ≥18 years: 600 mg every 12 hours for 5 to 7 days.

Skin and skin structure infection: Treatment duration is variable (5 to 14 days); dependent on severity of infection and clinical response.

Infants <2 months: IV: 6 mg/kg/dose every 8 hours.

Infants ≥2 months and Children <2 years: IV: 8 mg/kg/dose every 8 hours.

Children ≥2 years and Adolescents <18 years:

≤33 kg: IV: 12 mg/kg/dose every 8 hours.

>33 kg: IV: 400 mg every 8 hours or 600 mg every 12 hours.

Adolescents ≥18 years: IV: 600 mg every 12 hours.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Reconstitute 400 mg or 600 mg vial with 20 mL SWFI, NS, D5W, or LR. Mix gently to reconstitute (<2 minutes). Reconstituted solution (400 mg vial = 20 mg/mL, 600 mg vial = 30 mg/mL) should be further diluted for IV administration in a compatible solution not to exceed a final concentration of 12 mg/mL. To prepare a 400 or 600 mg dose, withdraw 20 mL of diluent from 50 mL IV bag; inject the entire contents of the ceftaroline vial (also 20 mL) to achieve a total volume of 50 mL; resulting concentration is 12 mg/mL (600 mg vial) or 8 mg/mL (400 mg vial). Use the same solution as used for reconstitution (Note: If SWFI was used for reconstitution, then appropriate infusion solutions include NS, 1/2NS, D5W, D2.5W, or LR). Color of infusion solutions ranges from clear and light to dark yellow depending on concentration and storage conditions; potency is not affected.

Administration

IV: Administer by slow IV infusion over 5 to 60 minutes.

Storage

Store unused vials at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Diluted solutions in D2.5W, 1/2NS, D5W, LR, or NS (in infusion bags or Mini-Bag Plus) should be used within 6 hours when stored at room temperature or within 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F).

Drug Interactions

Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Probenecid: May increase the serum concentration of Cephalosporins. 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. 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. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Hematologic & oncologic: Positive direct Coombs test (10% to 18%; no evidence of hemolysis)

1% to 10%:

Cardiovascular: Phlebitis (adults: 2%), bradycardia (adults: <2%), palpitations (adults: <2%)

Central nervous system: Headache (infants, children, and adolescents: <3%), dizziness (adults: <2%), seizure (adults: <2%)

Dermatologic: Skin rash (3% to 7%), pruritus (infants, children, and adolescents: <3%), urticaria (adults: <2%)

Endocrine & metabolic: Hypokalemia (adults: 2%), hyperglycemia (adults: <2%), hyperkalemia (adults: <2%)

Gastrointestinal: Diarrhea (5% to 8%), vomiting (2% to 5%), nausea (3% to 4%), constipation (adults: 2%), abdominal pain (adults: <2%), Clostridioides difficile colitis (adults: <2%)

Hematologic & oncologic: Anemia (adults: <2%), eosinophilia (adults: <2%), neutropenia (adults: <2%), thrombocytopenia (adults: <2%)

Hepatic: Increased serum alanine aminotransferase (infants, children, and adolescents: <3%), increased serum aspartate aminotransferase (infants, children, and adolescents: <3%), increased serum transaminases (adults: 2%), hepatitis (adults: <2%)

Hypersensitivity: Anaphylaxis (adults: <2%), hypersensitivity reaction (adults: <2%)

Renal: Renal failure syndrome (adults: <2%)

Miscellaneous: Fever (≤3%)

Postmarketing: Agranulocytosis, Clostridioides difficile associated diarrhea, eosinophilic pneumonia, leukopenia

Warnings/Precautions

Concerns related to adverse effects:

• Hemolytic anemia: Seroconversion from a negative to a positive direct Coombs’ test has been reported. Hemolytic anemia was not reported in clinical studies; however, if anemia develops during or after treatment, consider drug-induced hemolytic anemia. Diagnostic tests should include a direct Coombs’ test. If hemolytic anemia is suspected, discontinue the drug and institute supportive care as clinically indicated.

• Hypersensitivity: Serious hypersensitivity (anaphylactic) and skin reactions have occurred with ceftaroline. Use with caution in patients with a history of penicillin, cephalosporin, or carbapenem allergy. Maintain clinical supervision if given to penicillin or beta-lactam allergic patients; cross sensitivity among beta-lactam antibacterial agents has been reported. If a serious reaction occurs, discontinue the drug and institute supportive measures as clinically indicated.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis (including fatalities); CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment (CrCl ≤50 mL/minute); dosage adjustments recommended.

Monitoring Parameters

Obtain specimen for culture and susceptibility prior to the first dose. Monitor for signs of anaphylaxis during first dose. Monitor renal function.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Vomiting

• Nausea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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