TEFLARO® Monotherapy: Clinical Response Demonstrated 48-72 Hours After Starting Therapy

Response Identified as Cessation of Lesion Spread With Absence of Fever

TEFLARO Demonstrated Clinical Response at Day 3 in Acute Bacterial Skin and Skin Structure Infections1
CANVAS 1*
Treatment Difference 9.4%
(95% Cl: 0.4, 18.2)
TEFLARO
monotherapy
74.0%
(148/200)
Vancomycin
+ aztreonam
64.6%
(135/209)
CANVAS 2*
Treatment Difference 5.9%
(95% Cl: -3.1, 14.9)
TEFLARO
monotherapy
74.0%
(148/200)
Vancomycin
+ aztreonam
68.1%
(128/188)

CI=confidence interval.   
Clinical responders, % (n/N)

These data demonstrate the noninferiority of TEFLARO vs vancomycin plus aztreonam. These trials were not designed to show superiority. Superiority cannot be inferred from these data.

CANVAS=Ceftaroline vs Vancomycin in Skin and Skin Structure Infection. CANVAS 1=ABSSSI Trial 1, CANVAS 2=ABSSSI Trial 2.

Additional Day 3 Data from
CANVAS Trials:
65% (13/20) of TEFLARO patients
with baseline S. aureus bacteremia
demonstrated a clinical response at
Day 31

In the CANVAS clinical trials, 35% of patients received at least one dose of TEFLARO as OPAT (Outpatient Parenteral Antibiotic Therapy).

Clinical response at Day 3 for ABSSSI caused by MRSA6
81.7%
(85/104)
TEFLARO
monotherapy
77.4%
(65/84)
Vancomycin
+ aztreonam

Pooled clinical response rates in Day 3 population, % (n/N)

No statistically significant differences between treatment groups can be inferred from the above pathogen response rates. Integrated Day 3 clinical data did not demonstrate that TEFLARO was statistically superior to vancomycin plus aztreonam.

Clinical response demonstrated at Day 3 vs the most common
pathogens in ABSSSI6
  Integrated CANVAS Day 3 data, % (n/N)
Pathogen TEFLARO Monotherapy Vancomycin + aztreonam
Gram-positive    
MSSA 71.8 (102/142) 60.1 (92/153)
MRSA 81.7 (85/104) 77.4 (65/84)
S. pyogenes 53.2 (25/47) 57.1 (28/49)
S. agalactiae 69.2 (9/13) 85.7 (6/7)
Gram-negative    
E. coli 62.5 (5/8) 53.8 (7/13)
K. pneumoniae 55.6 (5/9) 14.3 (1/7)
K. oxytoca 75.0 (6/8) 50.0 (3/6)

No statistically significant differences between treatment groups can be inferred from the above pathogen response rates. Integrated Day 3 clinical data did not demonstrate that TEFLARO was statistically superior to vancomycin plus aztreonam.

Clinical response demonstrated at Day 3 vs the most common pathogens in ABSSSI6
Integrated CANVAS Day 3 data, % (n/N)
TEFLARO Monotherapy Vancomycin + aztreonam
Pathogen
Gram-positive
MSSA
71.8 (102/142) 60.1 (92/153)
MRSA
81.7 (85/104) 77.4 (65/84)
S. pyogenes
53.2 (25/47) 57.1 (28/49)
S. agalactiae
69.2 (9/13) 85.7 (6/7)
Gram-negative
E. coli
62.5 (5/8) 53.8 (7/13)
K. pneumoniae
55.6 (5/9) 14.3 (1/7)
K. oxytoca
75.0 (6/8) 50.0 (3/6)

No statistically significant differences between treatment groups can be inferred from the above pathogen response rates. Integrated Day 3 clinical data did not demonstrate that TEFLARO was statistically superior to vancomycin plus aztreonam.

Next: Efficacy at TOC

ABSSSI Patient Cases See Patient Case

These hypothetical case studies present examples of types of patients who may benefit from TEFLARO.

Dosing

The 5-60 minute infusion allows increased flexibility of infusion time

SEE DOSING
INDICATIONS AND USAGE
  • TEFLARO® (ceftaroline fosamil) is indicated in adult and pediatric patients 2 months of age and older for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and ‑resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.
  • TEFLARO is also indicated in adult and pediatric patients 2 months of age and older for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.

IMPORTANT SAFETY INFORMATION

Contraindications

Warnings and Precautions

Hypersensitivity Reactions

Clostridium difficile-Associated Diarrhea

Direct Coombs' Test Seroconversion

Development of Drug-Resistant Bacteria

Adverse Reactions in Adults

Adverse Reactions in Pediatrics

Drug Interactions

Use in Specific Populations

Please also see full Prescribing Information.

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IMPORTANT SAFETY INFORMATION

Contraindications

  • TEFLARO is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis has been reported with ceftaroline.

Warnings and Precautions

Hypersensitivity Reactions

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

Clostridium difficile-Associated Diarrhea

  • Clostridium difficile-Associated Diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including TEFLARO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.

Direct Coombs' Test Seroconversion

  • In adults, seroconversion from a negative to a positive direct Coombs' test result occurred in 120/1114 (10.8%) of patients receiving TEFLARO and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled adult Phase 3 trials.
  • In children, seroconversion from a negative to a positive direct Coombs' test result occurred in 42/234 (17.9%) of patients receiving TEFLARO and 3/93 (3.2%) of patients receiving comparator drugs in the three pooled pediatric trials.
  • No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with TEFLARO, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of TEFLARO should be considered and supportive care should be administered to the patient if clinically indicated.

Development of Drug-Resistant Bacteria

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

Adverse Reactions in Adults

  • In the four pooled adult Phase 3 clinical trials, serious adverse reactions occurred in 98/1300 (7.5%) of patients receiving TEFLARO and 100/1297 (7.7%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 35/1300 (2.7%) of patients receiving TEFLARO and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse reactions leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the TEFLARO group and 0.5% in the comparator group.
  • The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the adult pooled Phase 3 clinical trials were diarrhea (5%) nausea (4%), and rash (3%).

Adverse Reactions in Pediatrics

  • In the three pooled pediatric clinical trials, serious adverse reactions occurred in 10/257 (4%) of patients receiving TEFLARO and 3/102 (3%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 10/257 (3.9%) of patients receiving TEFLARO and 2/102 (2%) of patients receiving comparator drugs with the most common adverse reaction leading to discontinuation being rash in 2/257 (0.8%) of patients treated with TEFLARO.
  • The most common adverse reactions occurring in ≥3% of patients receiving TEFLARO in the pooled pediatric clinical trials were diarrhea (8%), rash (7%), vomiting (5%), pyrexia (3%) and nausea (3%).

Drug Interactions

  • No clinical drug-drug interaction studies have been conducted with TEFLARO. There is minimal potential for drug-drug interactions between TEFLARO and CYP450 substrates, inhibitors, or inducers; drugs known to undergo active renal secretion; and drugs that may alter renal blood flow.

Use in Specific Populations

  • There have been no adequate and well-controlled studies with TEFLARO in pregnant or nursing women. TEFLARO should only be used if the potential benefit justifies the potential risk in these populations.
  • Safety and effectiveness in pediatric patients below the age of 2 months have not been established as no data are available.
  • Because elderly patients, those ≥65 years of age, are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Dosage adjustment for elderly patients should therefore be based on renal function.
  • Dosage adjustment is required in adult patients with moderate (CrCl >30 to ≤50 mL/min) or severe (CrCl ≥15 to ≤30 mL/min) renal impairment and in patients with end-stage renal disease (CrCl <15 mL/min). There is insufficient information to recommend a dosage regimen for pediatric patients with CrCl <50 mL/min/1.73m2.
  • The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established.

Please also see full Prescribing Information.