company: cerexa approval status: november 2010cerexa

Company: CerexaApproval Status:

November 2010

Teflaro™ / ceftaroline fosamil

Pharmacology

Ceftaroline fosamil is a cephalosporin with in vitro bactericidal action against Gram-positive and Gram-negative bacteria

It exerts its bactericidal action through binding to essential penicillin-binding proteins

Ceftaroline inhibits the unique PBP produced by MRSA (PBP2a) for which beta-lactams have little binding affinity

against S. aureus due to its affinity for PBP2a against Streptococcus pneumoniae due to its

affinity for PBP2x.


Clinical Application

Indications:Indications:– Treatment of acute bacterial skin and skin structure Treatment of acute bacterial skin and skin structure

infections (ABSSI) caused by susceptible isolates of infections (ABSSI) caused by susceptible isolates of

MRSAMRSA , , S. aureusS. aureus, , S. pyogenesS. pyogenes, , S. agalactiaeS. agalactiae, , E. coliE. coli, , K. K. pneumoniaepneumoniae, and , and K. oxytocaK. oxytoca

either a major abscess with greatereither a major abscess with greater--than or equal to 5 than or equal to 5 cm of surrounding erythema, wound infection, or cm of surrounding erythema, wound infection, or deepdeep//extensive cellulitis requiring extensive cellulitis requiring

– Treatment of community-acquired bacterial pneumonia Treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of (CABP) caused by susceptible isolates of S. S. pneumoniaepneumoniae, , S. aureusS. aureus, , H. influenzaeH. influenzae, , K. pneumoniaeK. pneumoniae, , K. oxytocaK. oxytoca, and , and E. coliE. coli

respiratory symptom respiratory symptom ((cough, dyspnea, pleuritic chest pain, or cough, dyspnea, pleuritic chest pain, or sputumsputum((


Dosage

Teflaro is supplied as 600 mg or 400 mg of sterile powder for reconstitution into a solution designed for intravenous administration (IV) .

The recommended dosage of Teflaro is 600 mg administered every 12 hours by intravenous (IV) infusion over 1 hour in patients >18 years of age.

The duration of therapy should be guided by the severity and site of infection and the patient’s clinical and bacteriological progress.


Dosage

RecomRecommendemended d DuratioDuration n

InfusiInfusion on TimeTime

FrequeFrequencnc

DosaDosagege

InfectionInfection

5-14 5-14 daysdays

1 h1 hEvery Every 1212

600 600 mgmg

ABSSSIABSSSI

5-7 5-7 daysdays

1 h1 hEvery Every 1212

600 600 mgmg

CABPCABP


Prescription Information

Supplied/Storage and Handling:– Single-use, clear

glass vials– 400 mg or 600 mg– Vials should be

refrigerated at 2 to 8°C


Pharmacokinetics

A100% (given IV)

D

volume of distribution of 0.37 L/kg, serum half-life of 2.6 h, and a relatively low affinity for human proteins (~20%).

MCeftaroline fosamil is converted to bioactive ceftaroline by a phosphatase enzyme. No significant hepatic metabolism by CYP450 enzymes.

ECeftaroline and its metabolites are primarily eliminated by the kidneys by glomerular filtration.

Clinical Results Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Objective: Compare ceftaroline monotherapy with vancomycin plus aztreonam combination therapy for the treatment of adults with complicated skin and skin structure infections (cSSSI)

Trial Design: Phase 3, international, multicenter, randomized, double-blind, comparative efficacy and safety studies

Intervention:–600 mg IV ceftaroline followed by normal

saline placebo or 1 g of vancomycin followed by 1 g of aztreonam over 5 to 14 days

Clinical ResultsCommunity-Acquired Bacterial Pneumonia (CABP)

1. Objective: trials were designed to compare Teflaro

(600 mg administered IV over 1 hour every 12 hours) with ceftriaxone (1 g ceftriaxone administered IV over 30 minutes every 24 hours


Trial ConclusionsTrial Conclusions

Ceftaroline is noninferior to vancomycin plus aztreonam for the treatment of cSSSI

Ceftaroline an efficacious monotherapy for the treatment of cSSSI, including MRSA

Ceftaroline is generally safe and well-tolerated

ceftaroline to be noninferior to ceftriaxone for the treatment of CABP

Contraindications

Known serious hypersensitivity to Teflaro or other members of the cephalosporin class.

Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline.

Side Effects

Diarrhea Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all antibacterial agents including Teflaro

Nausea Rash Vomiting Constipation Hypokalemia


Monitoring Parameters

Efficacy Monitoring:– Resolution of infection, including but not

limited to WBC, temperature, chest x-ray, and repeat cultures

Toxicity Monitoring:– Hypersensitivity reactions and severe

watery or bloody diarrhea


Drug Interactions

No clinical drug-drug interaction studies have been conducted

Unlikely to have CYP450 interactions : Therefore neither ceftaroline fosamil nor

ceftaroline are expected to inhibit or induce the clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner.

THANKS 4 YOUR THANKS 4 YOUR ATTENTIONATTENTION

Doaa Hussien Al-Hamed

company: cerexa approval status: november 2010cerexa

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