ceftaroline (Rx)

1-10% (Adults)

Diarrhea (5%)

Nausea (4%)

Rash (3%)

Constipation (2%)

Vomiting (2%)

Increased transaminases (2%)

Hypokalemia (2%)

Phlebitis (2%)

<2%

• Blood and lymphatic system disorders: Anemia, eosinophilia, neutropenia, thrombocytopenia
• Cardiac disorders: Bradycardia, palpitations
• Gastrointestinal disorders: Abdominal pain
• General disorders and administration site conditions: Pyrexia
• Hepatobiliary disorders: Hepatitis
• Immune system disorders: Hypersensitivity, anaphylaxis
• Infections and infestations: Clostridium difficile colitis
• Metabolism and nutrition disorders: Hyperglycemia, hyperkalemia
• Nervous system disorders: Dizziness, convulsion
• Renal and urinary disorders: Renal failure
• Skin and subcutaneous tissue disorders: Urticaria

1-10% (Pediatrics)

Diarrhea (8%)

Rash (7%)

Vomiting (5%)

Nausea (3%)

Pyrexia (3%)

Increased ALT/AST (<3%)

Headache (<3%)

Pruritus (<3%)

Postmarketing Reports (Pediatrics)

Agranulocytosis

Leukopenia

Eosinophilic pneumonia

Encephalopathy, seizures

Contraindications

Hypersensitivity to drug, excipients or other cephalosporins

Cautions

If anemia develops during or after treatment, consider drug-induced hemolytic anemia; perform diagnostic studies including a direct Coombs’ test; if drug-induced hemolytic anemia suspected, consider discontinuation; administer supportive care to patient (i.e. transfusion) if clinically indicated

Prescribing drug in absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria

Neurological adverse reactions reported during postmarketing surveillance in patients treated with cephalosporins; reactions include encephalopathy and seizures; most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment; if neurological adverse reactions occur, consider discontinuing therapy or making appropriate dosage adjustments in patients with renal impairment

Hypersensitivity reactions

• Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions reported in patients receiving beta-lactam antibacterial drugs
• Before therapy is instituted, make careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems
• Maintain clinical supervision if product is to be given to a penicillin-or other beta-lactam-allergic patient; cross sensitivity among beta-lactam antibacterial agents has been clearly established; if allergic reaction occurs, discontinue therapy and institute appropriate treatment and supportive measures

Clostridium difficile-associated diarrhea (CDAD)

• CDAD reported for nearly all systemic antibacterial agents and may range in severity from mild diarrhea to fatal colitis; treatment with antibacterial agents alters normal flora of colon and may permit overgrowth of C. difficile
• C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
• CDAD must be considered in all patients who present with diarrhea following antibiotic use; careful medical history is necessary because CDAD has been reported to occur more than 2 months after administration of antibacterial agents
• If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible; institute appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation as clinically indicated

Pregnancy

No data in pregnant women are available

Animal studies

• In developmental toxicity studies conducted in animals, no malformations or other adverse developmental effects were observed in offspring of rats exposed at up to 4 times the maximum recommended human dose (MRHD) during the period of organogenesis through lactation
• In rabbits exposed to ceftaroline during organogenesis at levels approximately equal to the MRHD, no drug-induced fetal malformations were observed despite maternal toxicity

Lactation

No data are available regarding presence in human milk, or the effects on breastfed infants or on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Beta-lactam cephalosporin with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria

Demonstrates activity in vivo against resistant methicillin-resistant Staphylococcus aureus (MRSA) strains and in vitro against vancomycin-resistant and linezolid-resistant S aureus

Absorption

Peak plasma concentration: 21.3 mcg/mL

Peak plasma time: 1 hr

Distribution

Vd: 20.3 L

Protein bound: 20%

Metabolism

Ceftaroline fosamil converted to bioactive ceftaroline in plasma by phosphatase enzyme; undergoes hydrolysis

Elimination

Clearance: 9.6 L/hr

Half-life: 2.6 hr

Excretion: urine (88%)

IV Compatibilities

Solution: 0.9% NaCl; D5W; 2.5% dextrose/0.45% NaCl; Lactated Ringer’s solution

IV Preparation

Reconstitute vial by adding 20 mL sterile water for injection, 0.9% NaCl, D5W, or lactated ringer’s injection; mix gently and ensure all powder has dissolved completely

Resulting approximate concentrations: 400 mg vial (20 mg/mL); 600 mg vial (30 mg/mL)

Color of solution ranges from clear to light-to-dark yellow depending on concentration and storage conditions

Dilution of reconstituted solution

• Withdraw total volume from vial and add to 50-250 mL of 0.9% NaCl, D5W, 2.5% dextrose/0.45% NaCl, or lactated ringer’s solution; use the same diluent that was used for reconstituting (unless sterile water for injection was used)

Dilution of the constituted solution in 50 mL infusion bags

• Preparation of 600 mg dose in (for adult patients): Withdraw 20 mL from bag before adding constituted drug; resulting concentration ~12 mg/mL
• Preparation of 400 mg dose (for adult and pediatric patients weighing >33 kg): Withdraw 20 mL from bag before adding constituted drug; resulting concentration ~8 mg/mL

• Preparation for children weighing ≤33 kg

  • Preparation of dose in infusion bag for pediatric patients weighing ≤33 kg: Amount of solution withdrawn from the constituted vial for dilution in the infusion bag will vary according to the weight and age of the child; infusion solution concentration should not exceed 12 mg/mL ceftaroline

IV Administration

Administer IV injection via volumetric infusion pump

Adults and children aged >2 months: Infuse over 5-60 minutes

Children aged <2 months: Infuse over 30-60 minutes

Storage

Unopened vials: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

Stability of diluted drug in infusion bag or 50-mL bag

• Room temperature: 6 hr
• Refrigerated 2-8°C (36-46°F): 24 hr