Company: Cerexa Approval Status: November 2010Cerexa

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.

Teflaro™ / ceftaroline fosamil Clinical Application Indications: Indications: – Treatment of acute bacterial skin and skin structure infections (ABSSI) caused by susceptible isolates of MRSA, S. aureus, S. pyogenes, S. agalactiae, E. coli, K. pneumoniae, and K. oxytoca  either a major abscess with greater-than or equal to 5 cm of surrounding erythema, wound infection, or deep/extensive cellulitis requiring – Treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of S. pneumoniae, S. aureus, H. influenzae, K. pneumoniae, K. oxytoca, and E. coli  respiratory symptom (cough, dyspnea, pleuritic chest pain, or sputum(

Teflaro™ / ceftaroline fosamil 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.

Teflaro™ / ceftaroline fosamil Dosage InfectionDosageFrequenc Infusion Time Recommend ed Duration ABSSSI 600 mg Every 12 1 h 5-14 days CABP 600 mg Every 12 1 h 5-7 days

Teflaro™ / ceftaroline fosamil 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

Teflaro™ / ceftaroline fosamil 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%). M Ceftaroline fosamil is converted to bioactive ceftaroline by a phosphatase enzyme. No significant hepatic metabolism by CYP450 enzymes. E Ceftaroline 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 Results Community-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 Conclusions Teflaro™ / ceftaroline fosamil Trial 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

Teflaro™ / ceftaroline fosamil 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

Teflaro™ / ceftaroline fosamil 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 ATTENTION Doaa Hussien Al-Hamed