In CABP, TEFLARO® was studied in pediatrics vs ceftriaxone1

TEFLARO CABP study design in the pediatric population1,4
Type of trial: Randomized, multicenter, multinational, parallel-group, active-controlled trial.
Primary endpoint: To evaluate the safety and tolerability of TEFLARO.
Study population: 161 children 2 months to less than 18 years old with a diagnosis of CABP.
Comparative agents: TEFLARO was compared to ceftriaxone (each with optional switch to amoxicillin/clavulanate on Day 4 at up to 90 mg/kg/day divided equally every 12 hours).

The dose of TEFLARO was adjusted for patient age and weight and delivered via a 60-minute infusion every 8 hours; patients less than 6 months of age received 8 mg/kg; patients over 6 months of age received 12 mg/kg for those weighing 33 kg or less; or 400 mg for those weighing more than 33 kg.*

The dose of ceftriaxone 75 mg/kg to a maximum of 4 g/day, IV in equally divided doses, each infused over 30 minutes every 12 hours.
Treatment duration: 5 to 14 days (IV therapy with or without oral therapy).
TEFLARO Study Populations  
Intent-to-treat (ITT): All randomized patients.
Modified Intent-to-treat (MITT): Excluded all patients who did not have a confirmed diagnosis of CABP or those infected with a sole atypical pathogen.
Clinically Evaluable (CE): All patients in the MITT population who met the definition of CABP and evaluability criteria.
Safety: Randomized patients who received any amount of the study drug.

TEFLARO CABP study design in the pediatric population1,4
Type of trial:

Randomized, multicenter, multinational, parallel-group, active-controlled trial.

Primary endpoint:

To evaluate the safety and tolerability of TEFLARO.

Study population:

161 children 2 months to less than 18 years with a diagnosis of CABP.

Comparative agents:

TEFLARO was compared to ceftriaxone (each with optional switch to amoxicillin/clavulanate on Day 4 at up to 90 mg/kg/day divided equally every 12 hours).

The dose of TEFLARO was adjusted for patient age and weight and delivered via a 60-minute infusion every 8 hours; patients less than 6 months of age received 8 mg/kg; patients over 6 months of age received 12 mg/kg for those weighing 33 kg or less; or 400 mg for those weighing more than 33 kg.*

The dose of ceftriaxone 75 mg/kg to a maximum of 4 g/day, IV in equally divided doses, each infused over 30 minutes every 12 hours.

Treatment duration:

5 to 14 days (IV therapy with or without oral therapy).


TEFLARO Study Populations Intent-to-treat (ITT):

All randomized patients.

Modified Intent-to-treat (MITT):

Excluded all patients who did not have a confirmed diagnosis of CABP or those infected with a sole atypical pathogen.

Clinically Evaluable (CE):

All patients in the MITT population who met the definition of CABP and the evaluability criteria.

Safety:

Randomized patients who received any amount of the study drug.

The doses of ceftaroline fosamil were based on pediatric population pharmacokinetic modeling designed to achieve the same antibiotic exposure in children that was shown to be effective in adults.4

Next: CABP Study Demographics

Pediatric Dosing

Learn about TEFLARO dosing in pediatric patients based on age and weight

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.