CEFAZOLIN

Cefazolin for Injection USP is a semi-synthetic cephalosporin for parenteral administration. It is the sodium salt of 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]-methyl}-8-oxo-7-[2-(1 H -tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo [4.2.0]oct‑2-ene-2-carboxylic acid. Structural Formula: C 14 H 13 N 8 NaO 4 S 3 M.W. 476.5 Cefazolin for Injection is supplied as a sterile powder in single-dose vials. The 2 g/vial Cefazolin for Injection contains 2 grams of cefazolin (equivalent to 2.097 g of cefazolin sodium). The 3 g/vial Cefazolin for Injection contains 3 grams of cefazolin (equivalent to 3.144 grams of cefazolin sodium). Each vial contains 48 mg of sodium per gram of cefazolin sodium. After reconstitution with sterile water for injection, the drug product solution has a pH of 4.0 to 6.0. Cefazolin for Injection is intended for intravenous infusion. structural formula cefazolin

Cefazolin for Injection is a cephalosporin antibacterial indicated for perioperative prophylaxis in adult patients (1.1). To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefazolin for Injection and other antibacterial drugs, Cefazolin for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (1.2) 1.1 Perioperative Prophylaxis Cefazolin for Injection is indicated for perioperative prophylaxis in adult patients [see Dosage and Administration (2.1, 2.2, 2.3, 2.4) . The perioperative use of Cefazolin for Injection is indicated in adult surgical patients in whom infection at the operative site would present a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty). The prophylactic administration of Cefazolin for Injection preoperatively, intraoperatively and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures which are classified as contaminated or potentially contaminated (e.g., vaginal hysterectomy, and cholecystectomy in high-risk patients such as those older than 70 years, with acute cholecystitis, obstructive jaundice or common duct bile stones). Pediatric use information is approved for B. Braun Medical’s Cefazolin for Injection and Dextrose for Injection. However, due to B. Braun Medical’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefazolin for Injection USP and other antibacterial drugs, Cefazolin for Injection USP 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.

• For intravenous infusion only administered over approximately 30 minutes. (2.1) • Not for intravenous bolus administration or intramuscular administration. (2.1) Table 1: Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr Equal to 55 mL/min or Greater (2.2) Dose administered ½ hour to 1 hour prior to the start of surgery Additional dose during lengthy operative procedures (e.g., 2 hours or more) Dose for 24 hours postoperatively 1 gram (g) to 2 g 500 mg to 1 g 500 mg to 1 g every 6 hours to 8 hours • Dosage adjustment is required for adult patients with CLcr that is less than 55 mL/min. (2.3 and 8.6) • See full prescribing information for preparation and administration instructions. (2.4) 2.1 Important Administration Instructions Administer Cefazolin for Injection via intravenous infusion only over approximately 30 minutes. Not for intravenous bolus administration or intramuscular administration. 2.2 Dosage for Perioperative Prophylaxis Dosage for Perioperative Prophylaxis in Adults with Creatinine Clearance (CLcr) Equal to 55 mL/min or Greater To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended dosages are described in Table 1 below. Table 1: Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr Equal to 55 mL/min or Greater Dose administered ½ hour to 1 hour prior to the start of surgery Additional dose during lengthy operative procedures (e.g., 2 hours or more) Dose for 24 hours postoperatively 1 gram (g) to 2 g 500 mg to 1 g 500 mg to 1 g every 6 hours to 8 hours It is important that (i) the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibacterial concentrations are present in the serum and tissues at the time of initial surgical incision and (ii) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient concentrations of the antibacterial drug at the anticipated moments of greatest exposure to infective organisms. The perioperative prophylactic administration of cefazolin should usually be discontinued within a 24-hour period after the surgical procedure. In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin may be continued for 3 to 5 days following the completion of surgery. Pediatric use information is approved for B. Braun Medical’s Cefazolin for Injection and Dextrose for Injection. However, due to B. Braun Medical’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 2.3 Preparation of Cefazolin for Injection Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter is evident in reconstituted fluids, the drug solutions should be discarded. Reconstituted solutions may range in color from pale yellow to yellow. Reconstitution and Dilution For intravenous infusion, reconstitute Cefazolin for Injection single-dose vials with Sterile Water for Injection according to Table 3 below and shake well . After reconstitution further dilute according to Table 3 using the following diluents: For intermittent or continuous infusion: Dilute reconstituted Cefazolin for Injection in one of the following solutions: • 0.9% Sodium Chloride Injection, USP • 5% Dextrose Injection, USP Discard unused portion. Table 3: Volumes for Reconstitution and Dilution and Final Concentrations Cefazolin for Injection Vial Contents Amount of Sterile Water for Injection for Reconstitution Approximate Reconstituted Concentrations Recommended Diluent Volume Approximate Final Concentrations 2 grams 5 mL 317 mg/mL 50 mL 40 mg/mL 100 mL 20 mg/mL 3 grams 7.5 mL 319 mg/mL 100 mL 30 mg/mL Storage of Reconstituted and Diluted Solutions When reconstituted or diluted according to the instructions above, Cefazolin for Injection is stable for 4 hours at room temperature or for 3 days if stored under refrigeration at 2°C to 8°C (36°F to 46°F).

• Hypersensitivity to cefazolin or other cephalosporin class antibacterial drugs, penicillins, or other beta-lactams (4.1) 4.1 Hypersensitivity to Cefazolin or the Cephalosporin Class of Antibacterial Drugs, Penicillins, or Other Beta-lactams Cefazolin for Injection is contraindicated in patients who have a history of immediate hypersensitivity reactions (e.g., anaphylaxis, serious skin reactions) to cefazolin or the cephalosporin class of antibacterial drugs, penicillins, or other beta-lactams [see Warnings and Precautions (5.1)] .

The following serious adverse reactions to cefazolin for injection are described below and elsewhere in the labeling: • Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams [see Warnings and Precautions (5.1)] • Seizures in Patients with Renal Impairment [see Warnings and Precautions (5.2)] • Clostridioides difficile -associated Diarrhea [see Warnings and Precautions (5.3)] • Adult Patients : Most common adverse reactions: gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash). (6) To report SUSPECTED ADVERSE REACTIONS, contact WG Critical Care, LLC at 1-866-562-4708 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following adverse reactions were reported from clinical trials: Gastrointestinal: Diarrhea, oral candidiasis (oral thrush), mouth ulcers, vomiting, nausea, stomach cramps, epigastric pain, heartburn, flatus, anorexia and pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.3)] . Allergic: Anaphylaxis, eosinophilia, urticaria, itching, drug fever, skin rash, Stevens-Johnson syndrome. Hematologic: Neutropenia, leukopenia, thrombocytopenia, thrombocythemia. Hepatic: Transient rise in SGOT, SGPT, and alkaline phosphatase levels has been observed. Reports of hepatitis have been received. Renal: Reports of increased BUN and creatinine levels, as well as renal failure, have been received. Local Reactions: Instances of phlebitis have been reported at site of injection. Some induration has occurred. Other Reactions: Pruritus (including genital, vulvar and anal pruritus, genital moniliasis, and vaginitis). Dizziness, fainting, lightheadedness, confusion, weakness, tiredness, hypotension, somnolence and headache. Pediatric use information is approved for B. Braun Medical’s Cefazolin for Injection and Dextrose for Injection. However, due to B. Braun Medical’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of cefazolin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders: Serum sickness-like reaction Renal and urinary disorders: Acute tubulointerstitial nephritis (ATIN) Skin and subcutaneous tissue disorders: Acute generalized exanthematous pustulosis (AGEP) 6.3 Cephalosporin-class Adverse Reactions In addition to the adverse reactions listed above that have been observed in patients treated with cefazolin, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterials: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal impairment, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, a fall in prothrombin activity, hepatic impairment including cholestasis, and pancytopenia.

The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin for Injection is not recommended. • Probenecid: The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin for Injection is not recommended. (7)