Brand name: Teflaro
Drug class: Fifth Generation Cephalosporins
VA class: AM119
Chemical name: 4-[2-[[(6R,7R)-2-Carboxy-7-[[(2Z)-(ethoxyimino)[5-(phosphonoamino)-1,2,4-thiadiazol-3-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]thio]-4-thiazolyl]-1-methyl-pyridinium, inner salt, monoacetate, monohydrate
Molecular formula: C₂₂H₂₁N₈O₈PS₄.C₂H₄O₂.H₂O
CAS number: 866021-48-9

Medically reviewed by Drugs.com on Sep 24, 2024. Written by ASHP.

Introduction

Antibacterial; β-lactam antibiotic; fifth generation cephalosporin.

Uses for Ceftaroline

Community-acquired Pneumonia

Treatment of community-acquired bacterial pneumonia (CABP, CAP) caused by susceptible Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains only), Haemophilus influenzae, Klebsiella pneumoniae, K. oxytoca, or Escherichia coli.

For information regarding treatment of CAP, consult current IDSA clinical practice guidelines available at [Web].

Skin and Skin Structure Infections

Treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible S. aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus, ORSA], S. pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), E. coli, K. pneumoniae, or K. oxytoca.

Some clinicians state that ceftaroline is one of several options for treatment of skin and skin structure infections caused by MRSA, including empiric treatment of surgical site infections in patients at high risk for MRSA (e.g., nasal colonization, prior MRSA infection, recent hospitalization, recent anti-infective therapy).

For information regarding treatment of skin and skin structure infections, including infections caused by MRSA, consult current IDSA clinical practice guidelines available at [Web].

Ceftaroline Dosage and Administration

Administration

Administer by IV infusion.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Do not admix with or add to solutions containing other drugs.

Reconstitution and Dilution

Must be reconstituted and further diluted prior to IV infusion.

Reconstitute 400- or 600-mg single-use vials of ceftaroline fosamil by adding 20 mL of sterile water for injection, 0.9% sodium chloride, 5% dextrose, or lactated Ringer's injection to provide solution containing approximately 20 or 30 mg/mL, respectively. Mix vial gently to ensure complete dissolution; reconstitution should take <2 minutes.

Dilute appropriate dose of reconstituted solution in 50–250 mL of the same diluent used for reconstitution, unless drug was reconstituted with sterile water, in which case use any compatible IV infusion solution (see Solution Compatibility under Stability) for further dilution.

To prepare 600-mg dose in 50-mL infusion bag for use in adults, remove 20 mL of diluent from bag prior to injecting entire reconstituted contents of 600-mg vial; final concentration of infusion solution is approximately 12 mg/mL.

To prepare 400-mg dose in 50-mL infusion bag for use in adults or pediatric patients 2 months of age or older weighing >33 kg, remove 20 mL of diluent from bag prior to injecting entire reconstituted contents of 400-mg vial; final concentration of infusion solution is approximately 8 mg/mL.

To prepare dose in 50-mL infusion bag for use in pediatric patients 2 months of age or older weighing ≤33 kg, amount of diluent to be removed from bag and amount of reconstituted drug solution to be withdrawn from vial and added to diluent vary depending on child's age and weight. Final concentration should not exceed 12 mg/mL.

Reconstituted and diluted solutions appear clear and light to dark yellow.

Final solution in IV infusion bag should be used within 6 hours when stored at room temperature or within 24 hours when stored in refrigerator at 2–8°C.

Rate of Administration

Administer by IV infusion over 5–60 minutes.

Dosage

Available as ceftaroline fosamil monoacetate monohydrate; dosage expressed in terms of anhydrous ceftaroline fosamil.

Pediatric Patients

Community-acquired Pneumonia

IV

2 months to <2 years of age: 8 mg/kg every 8 hours.

2 years to <18 years of age weighing ≤33 kg: 12 mg/kg every 8 hours.

2 years to <18 years of age weighing >33 kg: 400 mg every 8 hours or 600 mg every 12 hours.

Manufacturer recommends treatment duration of 5–14 days in pediatric patients; duration depends on site and severity of infection and patient’s clinical and bacteriologic progress.

Skin and Skin Structure Infections

IV

2 months to <2 years of age: 8 mg/kg every 8 hours.

2 years to <18 years of age weighing ≤33 kg: 12 mg/kg every 8 hours.

2 years to <18 years of age weighing >33 kg: 400 mg every 8 hours or 600 mg every 12 hours.

Manufacturer recommends treatment duration of 5–14 days in pediatric patients; duration depends on site and severity of infection and patient’s clinical and bacteriologic progress.

Adults

Community-acquired Pneumonia

IV

600 mg every 12 hours for 5–7 days.

Duration depends on site and severity of infection and patient’s clinical and bacteriologic progress.

Skin and Skin Structure Infections

IV

600 mg every 12 hours for 5–14 days.

Duration depends on site and severity of infection and patient’s clinical and bacteriologic progress.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations; hepatic impairment not expected to have a clinically important effect on systemic clearance of the drug.

Renal Impairment

Adults: Adjust dosage in those with Cl_cr ≤50 mL/minute, including patients undergoing hemodialysis. (See Table 1.)

Pediatric patients: Dosage adjustments not needed if Cl_cr >50 mL/minute per 1.73 m². Data insufficient to make dosage recommendations for those with Cl_cr <50 mL/minute per 1.73 m².

Geriatric Patients

Dosage adjustment not required based on age; may be required based on age-related changes in renal function. (See Renal Impairment under Dosage and Administration.)

Cautions for Ceftaroline

Contraindications

• Known serious hypersensitivity to ceftaroline or other cephalosporins. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Serious, sometimes fatal, hypersensitivity (anaphylactic) reactions and serious skin reactions reported in patients receiving β-lactam antibiotics. Anaphylaxis reported with ceftaroline.

If hypersensitivity reaction occurs, discontinue the drug and initiate appropriate treatment and supportive measures.

Cross-hypersensitivity

Partial cross-sensitivity occurs among β-lactam antibiotics.

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to ceftaroline, other cephalosporins, penicillins, or carbapenems. Contraindicated in patients hypersensitive to the drug or other cephalosporins; closely monitor patient if used in those allergic to penicillin or other β-lactams.

Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.

C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all systemic anti-infectives, including ceftaroline, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after anti-infective therapy and manage accordingly. Obtain a careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible. Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Hematologic Effects

Neutropenia, leukopenia, and agranulocytosis reported during postmarketing experience.

Seroconversion from negative to positive direct antiglobulin (Coombs’) tests reported in clinical trials in about 11% of adults and about 18% of pediatric patients receiving ceftaroline; no evidence of hemolytic anemia in these adult or pediatric patients.

Consider drug-induced hemolytic anemia in patients who develop anemia during or after ceftaroline treatment; perform diagnostic studies, including direct antiglobulin test. If drug-induced hemolytic anemia is suspected, consider discontinuing ceftaroline and administer supportive treatment (e.g., transfusion) as clinically indicated.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftaroline and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Specific Populations

Pregnancy

Adequate data not available regarding use in pregnant women.

Lactation

Not known whether distributed into human milk; possible effects of the drug on breast-fed infant or on milk production unknown.

Consider benefits of breast-feeding and the importance of ceftaroline to the woman; also consider potential adverse effects on breast-fed infant from the drug or from underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients <2 months of age.

Safety and efficacy established for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in pediatric patients 2 months to <18 years of age. Use for treatment of these indications in this age group supported by evidence from adequate and well-controlled studies in adults and additional pharmacokinetic and safety data from pediatric trials.

Data indicate clinical cure rates reported for treatment of community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections in children 2 months to <18 years of age are similar to those reported in adults ≥18 years of age. In addition, adverse effects reported in pediatric trials are similar to those reported in adult trials.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.

Substantially eliminated by kidneys; consider age-related decreases in renal function, select dosage with caution, and consider monitoring renal function. (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not established; systemic clearance not expected to be altered by hepatic impairment.

Renal Impairment

Dosage adjustments necessary in adults with Cl_cr ≤50 mL/minute, including those undergoing hemodialysis. Data insufficient to date to make dosage recommendations for pediatric patients with Cl_cr <50 mL/minute per 1.73 m². (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Adults: GI effects (diarrhea, nausea, vomiting, constipation ), headache, rash, pruritus, hypokalemia, increased transaminases, phlebitis.

Children 2 months to <18 years of age: GI effects (diarrhea, nausea, vomiting ), pyrexia, rash.

Drug Interactions

Does not inhibit CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4 in vitro; does not induce CYP1A2, 2B6, 2C8, 2C9, 2C19, or 3A4/5. Pharmacokinetic interactions with drugs metabolized by these isoenzymes unlikely.

No formal drug interaction studies to date. Interactions unlikely with CYP substrates, inhibitors, or inducers or drugs that undergo active renal secretion or alter renal blood flow.

Specific Drugs

Ceftaroline Pharmacokinetics

Absorption

Ceftaroline is administered as ceftaroline fosamil, a prodrug that is inactive until converted in vivo to ceftaroline by a plasma phosphatase.

Plasma Concentrations

In healthy adults, peak plasma concentrations and AUC increase approximately in proportion to dose following single IV doses of 50–1000 mg of ceftaroline fosamil.

No appreciable accumulation reported when 600-mg doses are given by IV infusion over 1 hour every 12 hours for up to 14 days in adults with normal renal function.

Following 600-mg doses in 50 mL of compatible infusion solution given by IV infusion every 8 hours for 5 days in healthy adults, mean peak plasma concentrations were 32.5 mcg/mL when given as a 5-minute infusion and 17.4 mcg/mL when given as a 60-minute infusion; time to peak plasma concentrations and AUC were similar for both infusion rates.

Special Populations

In healthy adolescents 12–17 years of age, peak plasma concentrations and AUC after a single 8-mg/kg IV dose (600 mg in those weighing >75 kg) are 10 and 23% lower, respectively, compared with healthy adults who received a single 600-mg IV dose.

Distribution

Extent

Limited data available regarding tissue distribution; animal data indicate ceftaroline is distributed into kidneys, skin, and lungs.

Not known whether distributed into milk.

Plasma Protein Binding

Approximately 20%; decreases slightly with increasing concentrations >1–50 mcg/mL.

Elimination

Metabolism

Ceftaroline fosamil is rapidly converted in vivo to ceftaroline by a plasma phosphatase, principally during IV infusion. In addition, the β-lactam ring of ceftaroline is hydrolyzed to an inactive, open-ring metabolite (ceftaroline M-1).

Ceftaroline is not a substrate of CYP isoenzymes.

Elimination Route

Ceftaroline and its metabolites principally eliminated in urine by glomerular filtration. Following a single 600-mg IV dose of ceftaroline fosamil, approximately 88% is eliminated in urine (approximately 64% as unchanged drug, and 2% as ceftaroline M-1) and 6% is eliminated in feces within 48 hours.

Removed by hemodialysis.

Half-life

Adults: 2.7 hours.

Following 600-mg doses of ceftaroline fosamil in 50 mL of compatible infusion solution given by IV infusion over 5 or 60 minutes every 8 hours for 5 days, terminal elimination half-life of ceftaroline was similar for both infusion rates.

Special Populations

Pediatric patients 2 months to <18 years of age: Pharmacokinetics are similar to pharmacokinetics reported in adults.

Hepatic impairment: Pharmacokinetics not established.

Renal impairment: AUC and half-life increased.

Stability

Storage

Parenteral

Powder for IV Infusion

25°C (may be exposed to 15–30°C).

Following reconstitution and dilution, may be stored in IV infusion bag for up to 6 hours at room temperature or up to 24 hours when refrigerated at 2–8°C.

Compatibility

Parenteral

Solution Compatibility1 HID

Drug CompatibilityHID

Actions and Spectrum

• Based on spectrum of activity, classified as a fifth generation cephalosporin.

• Like third and fourth generation cephalosporins, ceftaroline has an expanded spectrum of activity that includes both gram-positive and gram-negative bacteria. Unlike first, second, third, and fourth generation cephalosporins, ceftaroline has activity against methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant Staphylococcus aureus, ORSA).

• Usually bactericidal.

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.

• Spectrum of activity includes many gram-positive and gram-negative aerobic bacteria and some anaerobic bacteria.

• Gram-positive aerobes: Active in vitro against S. aureus (including MRSA, vancomycin-resistant S. aureus [VRSA], and daptomycin-nonsusceptible S. aureus), coagulase-negative staphylococci (including methicillin-resistant [oxacillin-resistant] strains), Streptococcus pneumoniae (including penicillin- or cefotaxime-resistant S. pneumoniae or multidrug-resistant S. pneumoniae [MDRSP]), S. pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), viridans streptococci, and S. dysgalactiae. Has only limited activity against Enterococcus faecalis; E. faecium are resistant.

• Gram-negative aerobes: Active in vitro against some Escherichia coli, Klebsiella pneumoniae, K. oxytoca, and Haemophilus influenzae (including β-lactamase-producing strains). Also active in vitro against some Citrobacter freundii, C. koseri, Enterobacter aerogenes, E. cloacae, Moraxella catarrhalis (including β-lactamase-producing strains), Morganella morganii, Pasteurella multocida, Proteus mirabilis, and H. parainfluenzae. Inactive against Pseudomonas aeruginosa.

• MRSA with reduced susceptibility or resistance to ceftaroline have been produced in vitro and reported in clinical isolates.

• Gram-negative bacteria that produce extended-spectrum β-lactamases (ESBLs) from the TEM, SHV or CTX-M families, AmpC cephalosporinases, class B metallo-β-lactamases, or serine carbapenemases are resistant.

• Although cross-resistance may occur between ceftaroline and other cephalosporins, some bacteria resistant to other cephalosporins may be susceptible to ceftaroline.

Advice to Patients

• Advise patients that antibacterials (including ceftaroline) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

• Importance of completing full course of therapy, even if feeling better after a few days.

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftaroline or other antibacterials in the future.

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually resolves when the drug is discontinued. Importance of contacting a clinician if watery or bloody diarrhea occurs.

• Importance of informing clinicians of prior hypersensitivity reactions to ceftaroline, other cephalosporins, other β-lactam antibiotics, or other allergens. Importance of discontinuing the drug and immediately informing clinician if an allergic or hypersensitivity reaction occurs.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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