choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. cefazolin for injection is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin for injection in the subsequent prevention of rheumatic fever are not available at present. 1.2 urinary tract infections urinary tract infections due to escherichia coli , and proteus mirabilis , klebsiella species, and some strains of enterobacter and enterococci. 1.3 skin and skin structure infections skin and skin structure infections due to s. aureus (penicillin-sensitive and penicillin-resistant), group a beta-hemolytic streptococci, and other strains of streptococci. 1.4 biliary tract infections biliary infections due to e. coli , various strains of streptococci, p. mirabilis, klebsiella species, and s. aureus . 1.5 bone and joint infections bone and joint infections due to s. aureus . 1.6 genital infections genital infections (i.e., prostatitis, epididymitis) due to e. coli, p. mirabilis, klebsiella species, and some strains of enterococci. 1.7 septicemia septicemia due to s. pneumoniae, s. aureus (penicillin-sensitive and penicillin-resistant), p. mirabilis, e. coli , and klebsiella species. 1.8 endocarditis endocarditis due to s. aureus (penicillin-sensitive and penicillin-resistant) and group a beta-hemolytic streptococci. 1.9 perioperative prophylaxis 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). the perioperative use of cefazolin for injection may also be effective in 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 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. if there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism so that appropriate therapy may be instituted [ see dosage and administration (2.1) ]. 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 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. cefazolin for injection, usp is a cephalosporin antibacterial indicated in the treatment of the following infections caused by susceptible isolates of the designated microorganisms: respiratory tract infections. (1.1) urinary tract infections. (1.2) skin and skin structure infections. (1.3) biliary tract infections. (1.4) bone and joint infections. (1.5) genital infections. (1.6) septicemia. (1.7) endocarditis. (1.8) perioperative prophylaxis. (1.9)

with other β-lactam antibiotics, seizures may occur if inappropriately high doses are administered to patients with impaired renal function (creatinine clearance less than 55 ml/min.) [ see dosage and administration (2.3) ]. 5.3 clostridium difficile -associated diarrhea clostridium difficile-associated diarrhea (cdad) or pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefazolin, and may range in severity from mild to life-threatening. therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. studies indicate that a toxin produced by clostridium difficile is a primary cause of “antibiotic-associated colitis.” cefazolin for injection, as with all cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. after the diagnosis of cdad or pseudomembranous colitis has been established, therapeutic measures should be initiated. mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. in moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an oral antibacterial drug clinically effective against c. difficile colitis. 5.4 risk of development of drug-resistant bacteria prescribing cefazolin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. as with other antimicrobials, prolonged use of cefazolin for injection may result in overgrowth of nonsusceptible microorganisms. repeated evaluation of the patient's condition is essential. should superinfection occur during therapy, appropriate measures should be taken. 5.5 drug/laboratory test interactions urinary glucose the administration of cefazolin may result in a false-positive reaction for glucose in the urine with benedict's solution, fehling's solution or with clinitest® tablets. it is recommended that glucose tests based on enzymatic glucose oxidase reactions (e.g., clinistix® ) be used. coombs’ test positive direct coombs' tests have been reported during treatment with cefazolin. in hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in coombs' testing of newborns whose mothers have received cephalosporin antibacterial drugs before parturition, it should be recognized that a positive coombs' test may be due to the drug. hypersensitivity reactions: cross-hypersensitivity may occur in up to 10% of patients with a history of penicillin allergy. if an allergic reaction occurs, discontinue the drug. (5.1) use in patients with renal impairment: dose adjustment required for patients with crcl less than 55 ml/min. (5.2) clostridium difficile -associated diarrhea: may range from mild diarrhea to fatal colitis. evaluate if diarrhea occurs. (5.3)

if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic drug at the anticipated moments of greatest exposure to infective organisms. 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. 2.3 patients with renal impairment cefazolin for injection may be used in patients with reduced renal function with the following dosage adjustments: patients with a creatinine clearance of 55 ml/min. or greater or a serum creatinine of 1.5 mg % or less can be given full doses. patients with creatinine clearance rates of 35 to 54 ml/min. or serum creatinine of 1.6 to 3.0 mg % can also be given full doses but dosage should be restricted to at least 8 hour intervals. patients with creatinine clearance rates of 11 to 34 ml/min. or serum creatinine of 3.1 to 4.5 mg % should be given 1/2 the usual dose every 12 hours. patients with creatinine clearance rates of 10 ml/min. or less or serum creatinine of 4.6 mg % or greater should be given 1/2 the usual dose every 18 to 24 hours. all reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. patients undergoing peritoneal dialysis: [ see clinical pharmacology (12.3) ]. 2.4 pediatric population in pediatric patients, a total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections. total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight for severe infections. since safety for use in premature infants and in neonates has not been established, the use of cefazolin for injection in these patients is not recommended. in pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 ml/min.), 60 percent of the normal daily dose given in equally divided doses every 12 hours should be sufficient. in patients with moderate impairment (creatinine clearance of 40 to 20 ml/min.), 25 percent of the normal daily dose given in equally divided doses every 12 hours should be adequate. pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 ml/min.) may be given 10 percent of the normal daily dose every 24 hours. all dosage recommendations apply after an initial loading dose. 2.5 preparation of parenteral solution parenteral drug products should be shaken well when reconstituted , and inspected visually for particulate matter prior to administration. if particulate matter is evident in reconstituted fluids, the drug solutions should be discarded. when reconstituted or diluted according to the instructions below, cefazolin for injection is stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5°c or 41°f). reconstituted solutions may range in color from pale yellow to yellow without a change in potency. single-dose vials for intramuscular injection, intravenous direct (bolus) injection or intravenous infusion, reconstitute with sterile water for injection according to the following table. shake well. 2.6 intramuscular administration reconstitute vials with sterile water for injection according to the dilution table above. shake well until dissolved. cefazolin should be injected into a large muscle mass. pain on injection is infrequent with cefazolin for injection. 2.7 intravenous administration direct (bolus) injection: following reconstitution according to the above table, further dilute vials with approximately 5 ml sterile water for injection. inject the solution slowly over 3 to 5 minutes, directly or through tubing for patients receiving parenteral fluids (see list below). intermittent or continuous infusion: dilute reconstituted cefazolin for injection in 50 to 100 ml of 1 of the following solutions: sodium chloride injection, usp 5% or 10% dextrose injection, usp 5% dextrose in lactated ringer’s injection, usp 5% dextrose and 0.9% sodium chloride injection, usp 5% dextrose and 0.45% sodium chloride injection, usp 5% dextrose and 0.2% sodium chloride injection, usp lactated ringer’s injection, usp invert sugar 5% or 10% in sterile water for injection ringer’s injection, usp 5% sodium bicarbonate injection, usp for intravenous or intramuscular use. (2) *in rare instances, doses of up to 12 grams of cefazolin per day have been used. recommended dosing schedule in adult patients with crcl greater than or equal to 55 ml/min. (2.1) type of infection dose frequency moderate to severe infections 500 mg to 1 gram every 6 to 8 hours mild infections caused by susceptible gram-positive cocci 250 mg to 500 mg every 8 hours acute, uncomplicated urinary tract infections 1 gram every 12 hours pneumococcal pneumonia 500 mg every 12 hours severe, life-threatening infections (e.g., endocarditis, septicemia)* 1 gram to 1.5 grams every 6 hours image1.jpg image2.jpg image3.jpg image4.jpg

ncreased bun and creatinine levels, as well as renal failure, have been received. local reactions: rare instances of phlebitis have been reported at site of injection. pain at the site of injection after intramuscular administration has occurred infrequently. some induration has occurred. other reactions: genital and anal pruritus (including vulvar pruritus, genital moniliasis, and vaginitis). 6.2 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, hepatic impairment including cholestasis, and pancytopenia. most common adverse reactions: gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash). (6) to report suspected adverse reactions, contact apotex corp. at 1-800-706-5575 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

ates have not been established. see dosage and administration (2.4) for recommended dosage in pediatric patients older than 1 month. 8.5 geriatric use of the 920 subjects who received cefazolin in clinical studies, 313 (34%) were 65 years and over, while 138 (15%) were 75 years and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [ see dosage and administration (2.3) and warnings and precautions (5.2) ]. 8.6 patients with renal impairment when cefazolin for injection is administered to patients with low urinary output because of impaired renal function (creatinine clearance less than 55 ml/min.), lower daily dosage is required [ see dosage and administration (2.3) and warnings and precautions (5.2) ]. pediatric use: safety and effectiveness for use in premature infants and neonates have not been established. see dosage and administration (2.4) for recommended dosage in pediatric patients older than 1 month. (8.4) renal impairment: lower daily dosage of cefazolin for injection is required in patients with impaired renal function (creatinine clearance less than 55 ml/min). (8.6) see 17 for patient counseling information. revised: 5/2019

ith dosages of 3.5 mg/kg for 1 hour (approximately 250 mg) and 1.5 mg/kg the next 2 hours (approximately 100 mg), cefazolin for injection produced a steady serum level at the third hour of approximately 28 mcg/ml. studies in patients hospitalized with infections indicate that cefazolin for injection produces mean peak serum levels approximately equivalent to those seen in normal volunteers. bile levels in patients without obstructive biliary disease can reach or exceed serum levels by up to 5 times; however, in patients with obstructive biliary disease, bile levels of cefazolin for injection are considerably lower than serum levels (< 1 mcg/ml). in synovial fluid, the level of cefazolin for injection becomes comparable to that reached in serum at about 4 hours after drug administration. studies of cord blood show prompt transfer of cefazolin for injection across the placenta. cefazolin for injection is present in very low concentrations in the milk of nursing mothers. cefazolin for injection is excreted unchanged in the urine. in the first 6 hours approximately 60% of the drug is excreted in the urine and this increases to 70% to 80% within 24 hours. cefazolin for injection achieves peak urine concentrations of approximately 2,400 mcg/ml and 4,000 mcg/ml respectively following 500 mg and 1 gram intramuscular doses. in patients undergoing peritoneal dialysis (2 l/hr.), cefazolin for injection produced mean serum levels of approximately 10 and 30 mcg/ml after 24 hours' instillation of a dialyzing solution containing 50 mg/l and 150 mg/l, respectively. mean peak levels were 29 mcg/ml (range 13 to 44 mcg/ml) with 50 mg/l (3 patients), and 72 mcg/ml (range 26 to 142 mcg/ml) with 150 mg/l (6 patients). intraperitoneal administration of cefazolin for injection is usually well tolerated. controlled studies on adult normal volunteers, receiving 1 gram 4 times a day for 10 days, monitoring cbc, sgot, sgpt, bilirubin, alkaline phosphatase, bun, creatinine, and urinalysis, indicated no clinically significant changes attributed to cefazolin for injection. 12.4 microbiology mechanism of action cefazolin is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. resistance predominant mechanisms of bacterial resistance to cephalosporins include the presence of extended-spectrum beta-lactamases and enzymatic hydrolysis. antimicrobial activity cefazolin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [ see indications and usage (1) ]. gram-positive bacteria staphylococcus aureus staphylococcus epidermidis streptococcus agalactiae streptococcus pneumoniae streptococcus pyogenes methicillin-resistant staphylococci are uniformly resistant to cefazolin. gram-negative bacteria escherichia coli proteus mirabilis most isolates of indole positive proteus ( proteus vulgaris ), enterobacter spp., morganella morganii, providencia rettgeri, serratia spp., and pseudomonas spp. are resistant to cefazolin. susceptibility testing for specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by fda for this drug, please see: https://www.fda.gov/stic.