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ADULT DATA

TEFLARO® ABSSSI trials included a range of complicated cases, including S. aureus bacteremia

For illustrative purposes only. Not an actual patient.

TEFLARO ABSSSI Study Designs1,4
Type of trial: Two identical, randomized, multicenter, multinational, double-blind, noninferiority trials
Study population: 1396 adults with clinically documented complicated skin and skin structure infection
Comparative agents: TEFLARO – 600 mg administered IV over 1 hour every 12 hours for 5-14 days; vancomycin plus aztreonam – 1 g vancomycin administered IV over 1 hour followed by 1 g aztreonam administered IV over 1 hour every 12 hours for 5-14 days
Treatment duration: Treatment duration was 5 to 14 days. A switch to oral therapy was not allowed
TEFLARO Study Populations  
Day 3 Population*
(Clinical response demonstrated 48-72 hours after starting therapy) 		The analysis evaluated patients with lesion size ≥75 cm2 and having one of the following infection types:
  • Major abscess with ≥5 cm of surrounding erythema
  • Wound infection
  • Deep/extensive cellulitis
Test of Cure (TOC) Populations†  
MITT Modified Intent-to-treat All randomized subjects who received any amount of study drug.
CE Clinically Evaluable Patients in the MITT population who demonstrated sufficient adherence to the protocol. Sufficient adherence is defined as patients who met the minimal clinical disease criteria for cSSSI and all evaluability criteria, including subjects who received at least the prespecified minimal amount of the intended dose and duration of study drug therapy, for which sufficient information regarding the cSSSI site is available to determine the subject’s outcome, and for which there were no confounding factors that interfered with the assessment of that outcome.
ME Microbiologically Evaluable This population consists of a subset of subjects from the CE population who had at least one bacterial pathogen identified from a blood culture or culture of an adequate microbiological sample obtained from the cSSSI site at baseline and who had susceptibility testing performed on at least one of the isolated baseline pathogens.
TEFLARO ABSSSI Study Designs1,4
Type of trial:

Two identical, randomized,
multicenter, multinational,
double-blind, noninferiority trials

Study population:

1396 adults with clinically documented complicated skin and skin structure infection

Comparative agents:

TEFLARO – 600 mg administered IV over 1 hour every 12 hours for 5-14 days; vancomycin plus aztreonam – 1 g vancomycin administered IV over 1 hour followed by 1 g aztreonam administered IV over 1 hour every 12 hours for 5-14 days

Treatment duration:

Treatment duration was 5 to 14 days. A switch to oral therapy was not allowed

TEFLARO Study
Populations Day 3 Population*
(Clinical response demonstrated 48-72 hours after starting therapy)

The analysis evaluated patients with lesion size ≥75 cm2 and having one of the following infection types:

  • Major abscess with ≥5 cm of surrounding erythema
  • Wound infection
  • Deep/extensive cellulitis
Test of Cure (TOC) Populations†

MITT Modified Intent-to-treat

All randomized subjects who received any amount of study drug.

CE Clinically Evaluable

Patients in the MITT population who demonstrated sufficient adherence to the protocol. Sufficient adherence is defined as patients who met the minimal clinical disease criteria for cSSSI and all evaluability criteria, including subjects who received at least the prespecified minimal amount of the intended dose and duration of study drug therapy, for which sufficient information regarding the cSSSI site is available to determine the subject’s outcome, and for which there were no confounding factors that interfered with the assessment of that outcome.

ME Microbiologically Evaluable

This population consists of a subset of subjects from the CE population who had at least one bacterial pathogen identified from a blood culture or culture of an adequate microbiological sample obtained from the cSSSI site at baseline and who had susceptibility testing performed on at least one of the isolated baseline pathogens.

To evaluate the treatment effect of ceftaroline, an analysis was conducted in 797 patients with ABSSSI (such as deep/extensive cellulitis or a wound infection [surgical or traumatic]) for whom the treatment effect of antibacterials may be supported by historical evidence. This analysis evaluated responder rates based on achieving both cessation of lesion spread and absence of fever on Trial Day 3.

The protocol-specified analyses included clinical cure rates at the TOC (8 to 15 days after the end of therapy) in the coprimary CE and MITT populations and clinical cure rates at TOC by pathogen in the ME population.

TEFLARO ABSSSI studies: Selected patient demographics and baseline characteristics (integrated MITT)5
Characteristic TEFLARO
(n=693) 		Vancomycin
plus aztreonam
(n=685)
Age, median years (range) 48.0 (18-93) 48.0 (18-96)
Male sex, no. (%) 444 (64.1) 419 (61.2)
BMI    
Median (range) 26.9 (14.1-74.1) 27.4 (16.6-66.5)
>30, no. (%) 222 (32.0) 227 (33.1)
Duration of therapy, mean days ± SD 8.3±3.2 8.4±3.3
Comorbid conditions, no. (%)    
Diabetes mellitus 122 (17.6) 120 (17.5)
Peripheral vascular disease 93 (13.4) 93 (13.6)
Injection drug use 46 (6.6) 59 (8.6)
Site of primary infection, no. (%)    
Lower limb 338 (48.8) 339 (49.5)
Head/neck 45 (6.5) 33 (4.8)
Other 310 (44.7) 313 (45.7)
Prior antimicrobial therapy, no. (%) 276 (39.8) 260 (38.0)
Infection measurements    
Length, median cm (range) 15.00 (0.4-65.0) 15.00 (0.2-99.0)
Width, median cm (range) 10.00 (0.5-55.0) 10.00 (0.2-61.3)
Surgical procedures on primary infection site ≤48 hours after enrollment,* no. (%)    
≥1 procedure 97 (14.0) 108 (15.8)
Incision and drainage 46 (6.6) 51 (7.4)
Debridement 31 (4.5) 29 (4.2)
TEFLARO ABSSSI studies:
Selected patient
demographics and baseline
characteristics
(integrated MITT)5
TEFLARO
(n=693) 		Vancomycin
plus aztreonam
(n=685)
Characteristic
Age, median years (range)
48.0 (18-93) 48.0 (18-96)
Male sex, no. (%)
444 (64.1) 419 (61.2)
BMI
Median (range)
26.9
(14.1-74.1) 		27.4
(16.6-66.5)
>30, no. (%)
222 (32.0) 227 (33.1)
Duration of therapy, mean days days ± SD
8.3±3.2 8.4±3.3
Comorbid conditions, no. (%)
Diabetes mellitus
122 (17.6) 120 (17.5)
Peripheral vascular disease
93 (13.4) 93 (13.6)
Injection drug use
46 (6.6) 59 (8.6)
Site of primary infection,
no. (%)
Lower limb
338 (48.8) 339 (49.5)
Head/neck
45 (6.5) 33 (4.8)
Other
310 (44.7) 313 (45.7)
Prior antimicrobial
therapy, no. (%)
276 (39.8) 260 (38.0)
Infection measurements
Length, median cm (range)
15.00
(0.4-65.0) 		15.00
(0.2-99.0)
Width, median cm (range)
10.00
(0.5-55.0) 		10.00
(0.2-61.3)
Surgical procedures on primary infection site ≤48 hours after enrollment,* no. (%)
≥1 procedure
97 (14.0) 108 (15.8)
Incision and drainage
46 (6.6) 51 (7.4)
Debridement
31 (4.5) 29 (4.2)

BMI=body mass index (calculated as the weight in kilograms divided by the square of height in meters); SD=standard deviation.

Includes patients with surgical procedures performed <24 hours before first dose or randomization and <48 hours after first dose.

Adapted from Corey GR et al. Clin Infect Dis. 2010. Reproduced with permission of the Infectious Diseases Society of America.

S. aureus bacteremia:
In the two ABSSSI studies, 20 of
the 693 patients in the TEFLARO
group had baseline S. aureus
bacteremia (9 MRSA and 11
MSSA).1

Next: Clinical Response

ABSSSI Patient Cases See Patient Case

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

INDICATIONS AND USAGE

IMPORTANT SAFETY INFORMATION

Contraindications

Warnings and Precautions

Hypersensitivity Reactions

Clostridioides difficile-Associated Diarrhea

Neurological Adverse Reactions

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.

References:
  1. TEFLARO® (ceftaroline fosamil) [prescribing information]. Allergan USA, Inc.
  2. Elixhauser A, Owens P. Reasons for being admitted to the hospital through the emergency department, 2003. Healthcare Cost and Utilization Project Statistical Brief #2. February 2006. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb2.pdf. Accessed February 7, 2020.
  3. FDA Guidance ABSSSI. Guidance for industry: acute bacterial skin and skin structure infections: developing drugs for treatment. October 2013. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071185.pdf. Accessed February 7, 2020.
  4. Data on file. Allergan, Inc.
  5. Corey GR, Wilcox M, Talbot GH, et al. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis. 2010;51(6):641-650.
  6. Friedland HD, O'Neal T, Biek D, et al. CANVAS 1 and 2: analysis of clinical response at day 3 in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2015;56(5):2231-2236.
  7. Eckburg PB, Friedland HD, Llorens L, et al. Day 4 clinical response of ceftaroline fosamil versus ceftriaxone for community-acquired bacterial pneumonia. Infect Dis Clin Pract. 2012;20:254-260.
  8. File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, double-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis. 2010;51(12):1395-1405.

TEFLARO® and its design are registered trademarks of Allergan Sales, LLC, an AbbVie company.

© 2023 AbbVie. All rights reserved. US-TEF-230028 06/23

This site is intended for U.S. healthcare professionals only. If you are a patient, and have any questions, please discuss them with your doctor or healthcare professional. For additional information about TEFLARO, call AbbVie Medical Information at 1.800.678.1605.

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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.

Clostridioides difficile-Associated Diarrhea

  • Clostridioides 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.

Neurological Adverse Reactions

  • Neurological adverse reactions have been reported during postmarketing surveillance in patients treated with cephalosporins, including TEFLARO. These reactions include encephalopathy and seizures. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after discontinuation of TEFLARO or after hemodialysis. If neurological adverse reactions associated with TEFLARO therapy occur, consider discontinuing TEFLARO or making appropriate dosage adjustments in patients with renal impairment.

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 or a prophylactic indication 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 of TEFLARO for the treatment of ABSSSI in pediatric patients less than 34 weeks gestational age and less than 12 days postnatal age have not been established. Safety and effectiveness for the treatment of CABP 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 ≤30mL/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.