1.14.1.3 CEFTRIAXONE FOR INJECTION AND DEXTROSE INJECTION DRAFT LABELING TEXT Page 1 of 18 Y36-002-740 LD-104-2 DOSAGE FORMS AND STRENGTHS HIGHLIGHTS OF PRESCRIBING INFORMATION • 1 g in 50 mL and 2 g in 50 mL (3) These highlights do not include all the information needed to use Ceftriaxone for Injection and Dextrose Injection safely and effectively. See full prescribing CONTRAINDICATIONS information for Ceftriaxone for Injection and Dextrose Injection. • Anaphylaxis to ceftriaxone or other cephalosporin class antibacterials, penicillins, or other beta-lactam antibacterials (4.1) CEFTRIAXONE FOR INJECTION AND DEXTROSE INJECTION IN DUPLEX® CONTAINER, for intravenous use WARNINGS AND PRECAUTIONS Initial U.S. Approval: 1993 • Hypersensitivity reactions: Include anaphylaxis and serious skin reactions. Cross-hypersensitivity may occur in up to 10% of patients with a history of To reduce the development of drug-resistant bacteria and maintain the effectiveness penicillin allergy. If an allergic reaction occurs, discontinue the drug. (5.1) of Ceftriaxone for Injection and Dextrose Injection and other antibacterial drugs, • Interaction with Calcium-containing Products: Precipitation can occur. Do not Ceftriaxone for Injection and Dextrose Injection should be used only to treat or prevent administer simultaneously with calcium-containing IV solutions. (5.2) infections that are proven or strongly suspected to be caused by bacteria. • Clostridium difficile-associated diarrhea: May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. (5.3) INDICATIONS AND USAGE • Hemolytic Anemia: Severe cases of hemolytic anemia, including fatalities in Ceftriaxone for Injection and Dextrose Injection is a cephalosporin antibacterial adults and children, have been reported. If anemia is diagnosed, discontinue indicated for the treatment of the following infections caused by susceptible isolates of the drug until the etiology is determined. (5.4) the designated bacteria: Lower Respiratory Tract Infections (1.1); Skin and Skin Structure Infections (1.2); Complicated and Uncomplicated Urinary Tract Infections ADVERSE REACTIONS (1.3); Pelvic Inflammatory Disease (1.4); Bacterial Septicemia (1.5); Bone and Joint The most common adverse reactions occurring in >2% of patients receiving Infections (1.6); Intra-abdominal Infections (1.7); Meningitis (1.8); and Surgical ceftriaxone include diarrhea, eosinophilia, thrombocytosis, leukopenia, and elevations Prophylaxis (1.9). of SGOT and SGPT. DOSAGE AND ADMINISTRATION To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at For intravenous use only over approximately 30 minutes. (2) 1-800-227-2862 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Use this formulation of ceftriaxone only in patients who require the entire 1 or 2 gram dose and not any fraction thereof. (2.1) DRUG INTERACTIONS Recommended Dosing Schedule for Ceftriaxone for Injection and Dextrose • Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically Injection incompatible. (7.1) Site and Type of Dose Frequency Total Daily Dose • Calcium-containing products: precipitation can occur. (7.2) Infection Usual Adult Dose 1 g to 2 g once a day or in should not USE IN SPECIFIC POPULATIONS equally divided exceed 4 g* • Hepatic and renal impairment doses twice a day Surgical 1 gram IV 1/2 to 2 hours Patients with both hepatic and renal impairment should not received more than 2 Prophylaxis once before surgery grams of ceftriaxone per day (5.7) Meningitis 100 mg/kg once a day or Should not divided doses exceed 4 g* Pediatric Patients every 12 hours • Ceftriaxone for Injection and Dextrose Injection in the DUPLEX® Container is Skin and Skin 50 mg/kg to 75 once a day or in should not designed to deliver a 1 g or 2 g dose of ceftriaxone. To prevent unintentional Structure Infections mg/kg equally divided exceed 2 g overdose, this product should not be used in pediatric patients who require doses twice a day less than the full adult dose of ceftriaxone. (2.2, 8.4) Serious Infections 50 mg/kg to 75 every 12 hours should not other than mg/kg exceed 2 g See 17 for PATIENT COUNSELING INFORMATION Meningitis Revised: XX/20XX * Patients with hepatic impairment and significant renal impairment should not receive more than 2 grams per day of ceftriaxone. Reference ID: 3274090 1.14.1.3 CEFTRIAXONE FOR INJECTION AND DEXTROSE INJECTION DRAFT LABELING TEXT Page 2 of 18 FULL PRESCRIBING INFORMATION: CONTENTS* 5.9 Development of Drug-resistant Bacteria 1 INDICATIONS AND USAGE 5.10 Patients with Overt or Known Subclinical Diabetes 1.1 Lower Respiratory Tract Infections Mellitus or Carbohydrate Intolerance 1.2 Skin and Skin Structure Infections 5.11 Alterations in Prothrombin Time 1.3 Complicated and Uncomplicated Urinary Tract 6 ADVERSE REACTIONS Infections 6.1 Clinical Trials Experience 1.4 Pelvic Inflammatory Disease 6.2 Postmarketing Experience 1.5 Bacterial Septicemia 6.3 Cephalosporin-class Adverse Reactions 1.6 Bone and Joint Infections 7 DRUG INTERACTIONS 1.7 Intra-abdominal Infections 7.1 Vancomycin, Amsacrine, Aminoglycosides, and 1.8 Meningitis Fluconazole 1.9 Surgical Prophylaxis 7.2 Calcium-containing Products 2 DOSAGE AND ADMINISTRATION 8 USE IN SPECIFIC POPULATIONS 2.1 Adult Population 8.1 Pregnancy 2.2 Pediatric Patients 8.3 Nursing Mothers 2.3 Preparation for Use of Ceftriaxone for Injection and 8.4 Pediatric Use Dextrose Injection in DUPLEX® Container 8.5 Geriatric Use 3 DOSAGE FORMS AND STRENGTHS 10 OVERDOSAGE 4 CONTRAINDICATIONS 11 DESCRIPTION 4.1 Anaphylaxis to Ceftriaxone or the Cephalosporin 12 CLINICAL PHARMACOLOGY Class of Antibacterials, Penicillins, or Other Beta­ 12.1 Mechanism of Action lactam Antibacterials 12.3 Pharmacokinetics 5 WARNINGS AND PRECAUTIONS 12.4 Microbiology 5.1 Hypersensitivity Reactions to Ceftriaxone, 13 NONCLINICAL TOXICOLOGY Cephalosporins, Penicillins, or Other Drugs 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.2 Interaction with Calcium-containing Products 13.2 Animal Toxicology and/or Animal Pharmacology 5.3 Clostridium difficile-associated Diarrhea 15 REFERENCES 5.4 Hemolytic Anemia 16 HOW SUPPLIED/STORAGE AND HANDLING 5.5 Hypersensitivity to Dextrose Products 17 PATIENT COUNSELING INFORMATION 5.6 Gallbladder Sonogram Abnormalities 5.7 Patients with Hepatic and Renal Impairment * Sections or subsections omitted from the full prescribing 5.8 Pancreatitis information are not listed. Reference ID: 3274090 1.14.1.3 CEFTRIAXONE FOR INJECTION AND DEXTROSE INJECTION DRAFT LABELING TEXT Page 3 of 18 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ceftriaxone for Injection and Dextrose Injection and other antibacterial drugs, Ceftriaxone for Injection and Dextrose Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Ceftriaxone for Injection and Dextrose Injection is indicated for the treatment of the following infections when caused by susceptible bacteria. 1.1 Lower Respiratory Tract Infections Lower respiratory tract infections caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis or Serratia marcescens. 1.2 Skin and Skin Structure Infections Skin and skin structure infections caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Viridans group streptococci, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii*, Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis* or Peptostreptococcus species. * The efficacy for these organisms in this organ system were studied in fewer than ten infections. 1.3 Complicated and Uncomplicated Urinary Tract Infections Complicated and uncomplicated urinary tract infections caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae. 1.4 Pelvic Inflammatory Disease Pelvic inflammatory disease caused by Neisseria gonorrhoeae. Ceftriaxone sodium, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and Chlamydia trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added. 1.5 Bacterial Septicemia Bacterial septicemia caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae or Klebsiella pneumoniae. 1.6 Bone and Joint Infections Bone and joint infections caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae or Enterobacter species. 1.7 Intra-abdominal Infections Intra-abdominal infections caused by Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis, Clostridium species or Peptostreptococcus species. 1.8 Meningitis Meningitis caused by Haemophilus influenzae, Neisseria meningitidis or Streptococcus pneumoniae. Ceftriaxone sodium has also been used successfully in a limited number of cases of meningitis and