HIGHLIGHTS OF PRESCRIBING INFORMATION --------------------------CONTRAINDICATIONS---------------------------- These highlights do not include all the information needed to use TEFLARO • Known serious hypersensitivity to ceftaroline or other members of safely and effectively. See full prescribing information for TEFLARO. the cephalosporin class. (4) TEFLARO® (ceftaroline fosamil) injection for intravenous (IV) use -----------------------WARNINGS AND PRECAUTIONS----------------- • Serious hypersensitivity (anaphylactic) reactions have been Initial U.S. Approval: 2010 reported with beta-lactam antibiotics, including ceftaroline. Exercise caution in patients with known hypersensitivity to beta­ To reduce the development of drug-resistant bacteria and maintain the lactam antibiotics. (5.1) effectiveness of Teflaro and other antibacterial drugs, Teflaro should be used only • Clostridium difficile-associated diarrhea (CDAD) has been to treat infections that are proven or strongly suspected to be caused by bacteria. reported with nearly all systemic antibacterial agents, including Teflaro. Evaluate if diarrhea occurs. (5.2) ---------------------------RECENT MAJOR CHANGES --------------------------­ • Direct Coombs’ test seroconversion has been reported with Dosage and Administration (2.3) 10/2012 Teflaro. If anemia develops during or after therapy, a diagnostic Dosage and Administration (2.3) XX/XXXX workup for drug-induced hemolytic anemia should be performed and consideration given to discontinuation of Teflaro. (5.3) --------------------------INDICATIONS AND USAGE-------------------------------- Teflaro® is a cephalosporin antibacterial indicated for the treatment of the -----------------------------ADVERSE REACTIONS------------------------­ following infections caused by designated susceptible bacteria: The most common adverse reactions occurring in >2 % of patients are • Acute bacterial skin and skin structure infections (ABSSSI) (1.1) diarrhea, nausea, and rash. (6.3) • Community-acquired bacterial pneumonia (CABP) (1.2) To report SUSPECTED ADVERSE REACTIONS, contact Forest ------------------------DOSAGE AND ADMINISTRATION------------------------- Pharmaceuticals, Inc., at 1-800-678-1605 or FDA at 1-800-FDA­ • 600 mg every 12 hours by IV infusion administered over 1 hour in adults ≥ 18 1088 or www.fda.gov/medwatch. years of age (2.1) • Dosage adjustment in patients with renal impairment (2.2) ---------------------------USE IN SPECIFIC POPULATIONS------------- • Dosage adjustment is required in patients with moderate or severe Estimated Creatinine renal impairment and in ESRD patients, including patients on # Clearance hemodialysis. (2.2, 12.3) (mL/min) Teflaro Dosage Regimen > 50 No dosage adjustment necessary See 17 for PATIENT COUNSELING INFORMATION > 30 to ≤ 50 400 mg IV (over 1 hour) every 12 hours ≥ 15 to ≤ 30 300 mg IV (over 1 hour) every 12 hours End-stage renal disease (ESRD), including 200 mg IV (over 1 hour) every 12 hours hemodialysis #As calculated using the Cockcroft-Gault formula -----------------------DOSAGE FORMS AND STRENGTHS ----------------------- 600 mg or 400 mg of sterile Teflaro powder in single-use 20 mL vials. (3) Revised: Month/Year FULL PRESCRIBING INFORMATION: CONTENTS* 6.4 Other Adverse Reactions Observed During 1 INDICATIONS AND USAGE Clinical Trials of Teflaro 1.1 Acute Bacterial Skin and Skin Structure 7 DRUG INTERACTIONS Infections 8 USE IN SPECIFIC POPULATIONS 1.2 Community-Acquired Bacterial Pneumonia 8.1 Pregnancy 1.3 Usage 8.3 Nursing Mothers 2 DOSAGE AND ADMINISTRATION 8.4 Pediatric Use 2.1 Recommended Dosage 8.5 Geriatric Use 2.2 Patients with Renal Impairment 8.6 Patients with Renal Impairment 2.3 Preparation of Solutions 10 OVERDOSAGE 2.3.1 Preparation of 600 mg of Teflaro 11 DESCRIPTION dose in 50 mL 12 CLINICAL PHARMACOLOGY 2.3.2 Preparation of 400 mg of Teflaro 12.1 Mechanism of Action dose in 50 mL 12.2 Pharmacodynamics 3 DOSAGE FORMS AND STRENGTHS 12.3 Pharmacokinetics 4 CONTRAINDICATIONS 12.4 Microbiology 5 WARNINGS AND PRECAUTIONS 13 NONCLINICAL TOXICOLOGY 5.1 Hypersensitivity Reactions 13.1 Carcinogenesis, Mutagenesis, Impairment of 5.2 Clostridium difficile-associated Diarrhea Fertility 5.3 Direct Coombs’ Test Seroconversion 14 CLINICAL TRIALS 5.4 Development of Drug-Resistant Bacteria 14.1 Acute Bacterial Skin and Skin Structure 6 ADVERSE REACTIONS Infections 6.1 Adverse Reactions from Clinical Trials 14.2 Community-Acquired Bacterial Pneumonia 6.2 Serious Adverse Events and Adverse 15 REFERENCES Events Leading to Discontinuation 16 HOW SUPPLIED/STORAGE AND HANDLING 6.3 Most Common Adverse Reactions 17 PATIENT COUNSELING INFORMATION TEFLARO® (ceftaroline fosamil) injection for intravenous (IV) use - draft-labeling-text Page 1 of 22 Reference ID: 3422681 *Sections or subsections omitted from the full prescribing information are not listed. TEFLARO® (ceftaroline fosamil) injection for intravenous (IV) use - draft-labeling-text Page 2 of 22 Reference ID: 3422681 1 FULL PRESCRIBING INFORMATION 2 3 1. INDICATIONS AND USAGE 4 5 Teflaro® (ceftaroline fosamil) is indicated for the treatment of patients with the following infections caused 6 by susceptible isolates of the designated microorganisms. 7 8 1.1 Acute Bacterial Skin and Skin Structure Infections 9 10 Teflaro is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused 11 by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus 12 aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus 13 agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca. 14 15 1.2 Community-Acquired Bacterial Pneumonia 16 17 Teflaro is indicated for the treatment of community-acquired bacterial pneumonia (CABP) caused by 18 susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus 19 pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible 20 isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli. 21 22 1.3 Usage 23 24 To reduce the development of drug-resistant bacteria and maintain the effectiveness of Teflaro and other 25 antibacterial drugs, Teflaro should be used to treat only ABSSSI or CABP that are proven or strongly 26 suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination 27 should be obtained in order to isolate and identify the causative pathogens and to determine their 28 susceptibility to ceftaroline. When culture and susceptibility information are available, they should be 29 considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology 30 and susceptibility patterns may contribute to the empiric selection of therapy. 31 32 33 2. DOSAGE AND ADMINISTRATION 34 35 2.1 Recommended Dosage 36 37 The recommended dosage of Teflaro is 600 mg administered every 12 hours by intravenous (IV) infusion 38 over 1 hour in patients ≥ 18 years of age. The duration of therapy should be guided by the severity and site 39 of infection and the patient’s clinical and bacteriological progress. 40 The recommended dosage and administration by infection is described in Table 1. 41 42 43 44 45 46 47 48 TEFLARO® (ceftaroline fosamil) injection for intravenous (IV) use - draft-labeling-text Page 3 of 22 Reference ID: 3422681 49 50 Table 1: Dosage of Teflaro by Infection Recommended Infusion Time Duration of Total Infection Dosage Frequency (hours) Antimicrobial Treatment Acute Bacterial Skin and Skin 600 mg Every 12 hours 1 5-14 days Structure Infection (ABSSSI) Community- Acquired Bacterial 600 mg Every 12 hours 1 5-7 days Pneumonia (CABP) 51 52 2.2 Patients with Renal Impairment 53 54 Table 2: Dosage of Teflaro in Patients with Renal Impairment Estimated CrCla (mL/min) Recommended Dosage Regimen for Teflaro > 50 No dosage adjustment necessary > 30 to ≤ 50 400 mg IV (over 1 hour) every 12 hours ≥ 15 to ≤ 30 300 mg IV (over 1 hour) every 12 hours End-stage renal disease, 200 mg IV (over 1 hour) every 12 hoursc including hemodialysisb 55 a Creatinine clearance (CrCl) estimated using the Cockcroft-Gault formula. 56 b End-stage renal disease is defined as CrCl < 15 mL/min. 57 c Teflaro is hemodialyzable; thus Teflaro should be administered after hemodialysis on hemodialysis days. 58 59 2.3 Preparation of Solutions 60 61 Aseptic technique must be followed in preparing the infusion solution. The contents of Teflaro vial should 62 be constituted with 20 mL Sterile Water for Injection, USP; or 0.9% of sodium chloride injection (normal 63 saline); or 5% of dextrose injection; or lactated ringer’s injection. The preparation of Teflaro solutions is 64 summarized in Table 3. 65 66 Table 3: Preparation of Teflaro for Intravenous Use Approximate Volume of Diluent Dosage Strength Ceftaroline fosamil Amount to Be To Be Added (mg) Concentration Withdrawn (mL) (mg/mL) 400 20 20 Total Volume 600 20 30 Total Volume 67 68 The constituted solution must be further diluted in range between 50 mL to 250 mL before infusion into 69 patients. Use the same diluent for this further dilution, unless sterile water for injection was used earlier. If 70 sterile water for injection was used earlier, then appropriate infusion solutions include: 0.9% Sodium 71 Chloride Injection, USP (normal saline); 5% Dextrose Injection, USP; 2.5% Dextrose Injection, USP, and TEFLARO® (ceftaroline fosamil) injection for intravenous