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Ceftaroline Fosamil Monoacetate

Pronunciation
Pronunciation: sef-TAR-oh-leen FOS-a-mil MON-oh-AS-e-tate
Class: Antibiotic, Cephalosporin

Trade Names

Teflaro
- Injection, powder for solution 400 mg
- Injection, powder for solution 600 mg

Pharmacology

Ceftaroline fosamil is a prodrug of the bioactive ceftaroline, which inhibits mucopeptide synthesis in bacterial cell walls.

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Pharmacokinetics

Absorption

C max is 19 to 21.3 mcg/mL. T max is approximately 1 h. AUC is approximately 56 mcg•h/mL.

Distribution

Vd is 20.3 L. Approximately 20% protein bound.

Metabolism

Ceftaroline fosamil is converted into bioactive ceftaroline by a phosphatase enzyme. Undergoes hydrolysis to inactive metabolite, ceftaroline M-1.

Elimination

Approximately 88% is excreted in the urine (approximately 64% as ceftaroline and 2% as ceftaroline M-1) and 6% in feces; half—life is 1.6 to 2.6 h. Cl is approximately 9.6 L/h.

Special Populations

Renal Function Impairment

AUC increased 52% in moderate renal impairment (CrCl more than 30 to less than or equal to 50 mL/min) and 115% in severe renal impairment (CrCl at least 15 to less than or equal to 30 mL/min). Dosage adjustment is recommended in patients with moderate and severe renal impairment.

Hepatic Function Impairment

The pharmacokinetics have not been established in patients with hepatic impairment; however, they are not expected to be significantly affected.

Elderly

The AUC was approximately 33% higher in elderly patients, mainly because of changes in renal function. Dosage adjustment in elderly patients should be based on renal function.

Children

The mean C max and AUC for ceftaroline in adolescent subjects were 10% and 23% less than in healthy adult subjects.

Gender

There was a trend for higher C max (17%) and AUC (6% to 15%) in women. No dosage adjustment is recommended.

Race

No significant differences in AUC were observed; no dosage adjustment is recommended based on race.

Indications and Usage

Treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia caused by susceptible strains of specific microorganisms.

Contraindications

Hypersensitivity to ceftaroline or other members of the cephalosporin class.

Dosage and Administration

Acute Bacterial Skin and Skin Structure Infection
Adults

IV 600 mg every 12 h for 5 to 14 days.

Community-Acquired Bacterial Pneumonia
Adults

IV 600 mg every 12 h for 5 to 7 days.

Renal Function Impairment
Adults CrCl more than 50 mL/min

No dosage adjustment necessary.

CrCl more than 30 to less than or equal to 50 mL/min

400 mg IV every 12 h.

CrCl at least 15 to less than or equal to 30 mL/min

300 mg IV every 12 h.

ESRD, Including Hemodialysis (CrCl less than 15 mL/min)

200 mg IV every 12 h. Ceftaroline is hemodialyzable; administer after hemodialysis on hemodialysis days.

General Advice

  • Administer by IV infusion over 1 h.
  • For reconstituting the 400 mg vial, add 20 mL of sterile water for injection to make a concentration of 20 mg/mL.
  • For reconstituting the 600 mg vial, add 20 mL of sterile water for injection to make a concentration of 30 mg/mL.
  • Further dilute reconstituted solution in at least 250 mL of one of the following: sodium chloride 0.9% injection, dextrose 5% injection, dextrose 2.5% injection, sodium chloride 0.45% injection, or Ringer's lactate injection.
  • Do not mix reconstituted IV solution with or physically add to solutions containing other drugs.

Storage/Stability

Store vials refrigerated between 36° and 46°F. Reconstituted solution in infusion bag should be used within 6 h when stored at room temperature or within 24 h when stored under refrigeration between 36° and 46°F.

Drug Interactions

None well documented.

Lab Test Interferences

Seroconversion from negative to positive direct Coombs test result occurred in approximately 11% of patients.

Adverse Reactions

Cardiovascular

Bradycardia, palpitations (less than 2%).

CNS

Convulsion, dizziness (less than 2%).

Dermatologic

Rash (3%); urticaria (less than 2%).

GI

Diarrhea (5%); nausea (4%); constipation, vomiting (2%); abdominal pain, Clostridium difficile colitis (less than 2%).

Hematologic

Anemia, eosinophilia, neutropenia, thrombocytopenia (less than 2%).

Hepatic

Increased transaminases (2%); hepatitis (less than 2%).

Hypersensitivity

Anaphylaxis, hypersensitivity (less than 2%).

Metabolic-Nutritional

Hypokalemia (2%); hyperglycemia, hyperkalemia (less than 2%).

Miscellaneous

Phlebitis (2%); pyrexia, renal failure (less than 2%).

Precautions

Monitor

Monitor renal function periodically in patients with compromised renal function and in elderly patients.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy have not been established.

Hypersensitivity

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterials.

Renal Function

Dosage adjustment is necessary in patients with moderate to severe renal impairment and in patients with ESRD, including patients on hemodialysis.

Superinfection

Drug may cause bacterial or fungal overgrowth of nonsusceptible microorganisms.

C. difficile –associated diarrhea

Consider in patients in whom diarrhea develops. May range in severity from mild diarrhea to fatal colitis.

Direct Coombs test seroconversion

Seroconversion from a negative to a positive direct Coombs test result has occurred. Consider possibility of drug-induced hemolytic anemia in patients who develop anemia during or after treatment with ceftaroline.

Overdosage

Symptoms

No overdose reported.

Patient Information

  • Advise patient to report signs of superinfection: black, furry tongue; white patches in mouth; foul-smelling stools; or vaginal itching or discharge.
  • Advise patient to eat/drink 4 oz of yogurt or buttermilk a day as a prophylaxis against intestinal superinfection.
  • Instruct patient to report the following symptoms to health care provider: nausea, vomiting, diarrhea, skin rash, hives, sore throat, bruising, bleeding, muscle or joint pain.
  • Inform patients that diarrhea is a common problem with antibacterial drugs and usually resolves when the drug is discontinued. Frequent watery or bloody diarrhea may occur and may be a sign of more serious intestinal infection. If severe watery or bloody diarrhea develops, contact your health care provider.
  • Advise patients that allergic reactions may occur and that serious reactions require immediate treatment.
  • Tell patient to seek medical care for symptoms and to not treat at home. Instruct patient to seek emergency care if wheezing or difficulty in breathing occurs.

Copyright © 2009 Wolters Kluwer Health.

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