cefazolin 2000 MG Injection

INDICATIONS AND USAGE Cefazolin for Injection is a cephalosporin antibacterial indicated for: Treatment of the following infections caused by susceptible isolates of the designated microorganisms in adult and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved: 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 in adult patients ( 1.9 ) 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 ( 1.10 ) 1.1 Respiratory Tract Infections Cefazolin for Injection is indicated for the treatment of respiratory tract infections due to Streptococcus pneumoniae, Klebsiella species, Hemophilus influenzae, Staphylococcus aureus (methicillin-susceptible), and Group A beta-hemolytic streptococciin adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. Limitations of Use Injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefazolin for Injection is indicated for 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 Cefazolin for Injection is indicated for the treatment of urinary tract infections due to Escherichia coli, Proteus mirabilis, and Klebsiella species (spp.) in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.3 Skin and Skin Structure Infections Cefazolin for Injection is indicated for the treatment of skin and skin structure infections due to S. aureus (methicillin-susceptible) , Group A beta-hemolytic streptococci, and Streptococcus species (spp.) in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.4 Biliary Tract Infections Cefazolin for Injection is indicated for the treatment of biliary tract infections due to E. coli, various isolates of Streptococcus spp. , P. mirabilis, Klebsiella spp., and S. aureus (methicillin-susceptible ) in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.5 Bone and Joint Infections Cefazolin for Injection is indicated for the treatment of bone and joint infections due to S. aureus in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.6 Genital Infections Cefazolin for Injection is indicated for the treatment of genital infections (i.e., prostatitis, epididymitis) due to E. coli, P. mirabilis, and Klebsiella species in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.7 Septicemia Cefazolin for Injection is indicated for the treatment of septicemia due to S. pneumoniae, S. aureus (methicillin-susceptible), P. mirabilis, E. coli, and Klebsiella species in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.8 Endocarditis Cefazolin for Injection is indicated for the treatment of endocarditis due to S. aureus (methicillin-susceptible) and Group A beta-hemolytic streptococci in adults and pediatric patients 1 month of age and older for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1 , 2.2 , 2.4 and 2.5) ]. 1.9 Perioperative Prophylaxis Cefazolin for Injection is indicated for perioperative prophylaxis in adults. 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 is indicated 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 for Injection 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 for Injection 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 (2.3) ] . 1.10 Usage 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.

DOSAGE AND ADMINISTRATION Cefazolin for Injection, 2 grams/vial: For intravenous infusion ( 2.1 ) For intravenous bolus injection ( 2.1 ) Not for intramuscular administration ( 2.1 ) Cefazolin for Injection, 3 grams/vial: For intravenous infusion only ( 2.1 ) Not for intravenous bolus injection administration or intramuscular administration ( 2.1 ) Recommended Dosage in Adult Patients with CLcr that is greater than or equal to 55 mL/min ( 2.2 ) 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 Perioperative prophylaxis 1 gram to 2 grams 1/2 to 1 hour prior to start of surgery 500 mg to 1 gram during surgery for lengthy procedures (e.g., 2 hours or more) 500 mg to 1 gram every 6 to 8 hours for 24 hours postoperatively * In rare instances, doses of up to 12 grams of cefazolin per day have been used. Recommended Dosage in Pediatric Patients with CLcr that is greater than or equal to 70 mL/min ( 2.3 ) Type of Infection Dose Frequency Mild to moderately severe infections 25 mg per kg to 50 mg per kg divided into 3 or 4 equal doses Severe infections May increase to 100 mg per kg divided into 3 or 4 equal doses Dosage adjustment is required for adult patients with CLcr that is less than 55 mL/min and pediatric patients with CLcr that is less than 70 mL/min ( 2.4 ) See full prescribing information for preparation and administration instructions ( 2.6 ) 2.1 Important Administration Instructions Cefazolin for Injection, 2 grams/vial: Cefazolin for Injection, 2 grams/vial, is for intravenous infusion or intravenous bolus injection in adult and pediatric patients [see Dosage and Administration (2.2 , 2.3 , and 2.6 )] . Not for intramuscular administration. Cefazolin for Injection, 3 grams/vial: Cefazolin for Injection, 3 grams/vial, is for intravenous infusion only in adult and pediatric patients [see Dosage and Administration ( 2.2 , 2.3 , 2.5 , and 2.6 )] . Cefazolin for Injection, 3 grams/vial is not for intravenous bolus injection or intramuscular administration [see Dosage and Administration (2.5 , 2.6) ] . 2.2 Recommended Dosage for the Treatment of Infections Recommended Dosage for the Treatment of Infections in Adults with Creatinine Clearance (CLcr) Equal to 55 mL/min or Greater The recommended adult dosages of Cefazolin for Injection for the treatment of infections [see Indications and Usage (1.1 to 1.8) ] are outlined in Table 1 below. Administration instructions are as follows: Cefazolin for Injection, 2 grams/vial is for intravenous infusion or intravenous bolus injection in adult patients [see Dosage and Administration (2.6) ] . Cefazolin for Injection, 3 grams/vial is only for intravenous infusion in adult patients. Cefazolin for Injection, 3 grams/vial is not for intravenous bolus injection in adult patients [see Dosage and Administration (2.6) ] . Cefazolin for Injection 2 grams/vial and 3 grams/vial are not for intramuscular injection. Table 1: Recommended Dosage in Adult Patients with CLcr Equal to 55 mL/min or Greater Site and 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 * ln rare instances, doses of up to 12 grams of Cefazolin for Injection per day have been used. Recommended Dosage for the Treatment of Infections in Pediatric Patients 1 Month of Age and Older with CLcr Equal to 70 mL/min or Greater The recommended pediatric dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8) ] are outlined in Table 2 below. Administration instructions are as follows: Cefazolin for Injection, 2 grams/vial is for intravenous infusion or intravenous bolus injection in pediatric patients [see Dosage and Administration (2.5 , 2.6) ] . Cefazolin for Injection, 3 grams/vial is only for intravenous infusion in pediatric patients. Cefazolin for Injection, 3 grams/vial is not for intravenous bolus injection in pediatric patients [see Dosage and Administration (2.6) ] . Cefazolin for Injection 2 grams/vial and 3 grams/vial are not for intramuscular injection. Table 2: Recommended Dosage in Pediatric Patients 1 Month of Age and Older with CLcr 70 mL/min or Greater for Treatment of Infections [see Indications and Usage (1.1 to 1.8) ] Type of Severity Recommended Total Daily Dosage Mild to moderately severe infections 25 mg/kg to 50 mg/kg, divided into 3 or 4 equal doses Severe infections May increase to 100 mg/kg, divided into 3 or 4 equal doses 2.3 Recommended Dosage for Perioperative Prophylactic Use in Adults Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr Equal to 55 mL/min or Greater To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended dosages are described in Table 3 below. Administration instructions are as follows: Cefazolin for Injection, 2 grams/vial is for intravenous infusion or intravenous bolus injection in adult patients [see Dosage and Administration (2.4 , 2.6) ] . Cefazolin for Injection, 3 grams/vial is only for intravenous infusion in adult patients. Cefazolin for Injection, 3 grams/vial is not for intravenous bolus injection in adult patients [see Dosage and Administration (2.4 , 2.6) ] . Cefazolin for Injection 2 grams/vial and 3 grams/vial are not for intramuscular injection. Table 3: Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr of 55 mL/min or Greater Dose administered 1/2 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 post-operatively 1 gram to 2 grams 500 mg to 1 gram 500 mg to 1 gram every 6 hours to 8 hours It is important that (1) the preoperative dose be given just (1/2 hour to 1 hour) prior to the start of surgery so that adequate antibacterial levels are present in the serum and tissues at the time of initial surgical incision; and (2) Cefazolin for Injection be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels 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 for Injection may be continued for 3 to 5 days following the completion of surgery. 2.4 Recommended Dosage in Adult and Pediatric Patients with Renal Impairment Recommended Dosage in Adult Patients with CLcr less than 55 mL/min The recommended dosage of Cefazolin for Injection in adult patients with renal impairment (CLcr less than 55 mL/min) is outlined in Table 4 below. Table 4: Recommended Dosage in Adult Patients with CLcr Less than 55 mL/min Creatinine Clearance Dose Frequency 35 to 54 mL/min Recommended dose every 8 hours or longer 11 to 34 mL/min Half of recommended dose every 12 hours 10 mL/min or less Half of recommended dose every 18 to 24 hours *All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection. Recommended Dosage in Pediatric Patients 1 Month of Age and Older with CLcr less than 70 mL/min The recommended dosage of Cefazolin for Injection in pediatric patients 1 month of age and older wi

WARNINGS AND PRECAUTIONS 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 ) Clostridioides difficile -associated Diarrhea (CDAD): May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. ( 5.3 ) Prothrombin Activity : May be associated with a fall in prothrombin activity. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated ( 5.5 ) 5.1 Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with Cefazolin for Injection and Dextrose Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or carbapenems. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefazolin for Injection and Dextrose Injection occurs, discontinue the drug. 5.2 Seizures in Patients with Renal Impairment Seizures may occur with the administration of Cefazolin for Injection and Dextrose Injection, particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue Cefazolin for Injection and Dextrose Injection if seizures occur or make appropriate dosage adjustments in patients with renal impairment [see Dosage and Administration (2.4) ] . Anticonvulsant therapy should be continued in patients with known seizure disorders. 5.3 Clostridioides difficile -associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefazolin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.4 Hypersensitivity to Dextrose-containing Products Hypersensitivity reactions, including anaphylaxis, have been reported with administration of dextrose-containing products. These reactions have been reported in patients receiving high concentrations of dextrose (i.e. 50% dextrose) 1 . The reactions have also been reported when corn-derived dextrose solutions were administered to patients with or without a history of hypersensitivity to corn products. 2 5.5 Prothrombin Activity Cefazolin for Injection and Dextrose Injection may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated. 5.6 Risk of Development of Drug-resistant Bacteria Prescribing Cefazolin for Injection and Dextrose Injection in the absence of 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 and Dextrose 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. 5.7 Drug/Laboratory Test Interactions Urinary Glucose The administration of cefazolin may result in a false-positive reaction with glucose in the urine when using glucose tests based on Benedict’s copper reduction reaction that determine the amount of reducing substances like glucose in the urine. It is recommended that glucose tests based on enzymatic glucose oxidase 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. 5.8 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance As with other dextrose-containing solutions, Cefazolin for Injection and Dextrose Injection should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

CONTRAINDICATIONS 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 and Dextrose 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) ] .

CLINICAL PHARMACOLOGY After intramuscular administration of Cefazolin for Injection, USP to normal volunteers, the mean serum concentrations were 37 mcg/mL at 1 hour and 3 mcg/mL at 8 hours following a 500-mg dose, and 64 mcg/mL at 1 hour and 7 mcg/mL at 8 hours following a 1-gram dose. Studies have shown that following intravenous administration of Cefazolin for Injection, USP to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1-gram dose. The serum half-life for Cefazolin for Injection, USP is approximately 1.8 hours following IV administration and approximately 2.0 hours following IM administration. In a study (using normal volunteers) of constant intravenous infusion with 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, USP 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, USP 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, USP are considerably lower than serum levels (< 1.0 mcg/mL). In synovial fluid, the level of Cefazolin for Injection, USP 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, USP across the placenta. Cefazolin for Injection, USP is present in very low concentrations in the milk of nursing mothers. Cefazolin for Injection, USP 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, USP 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, USP 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, USP 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, USP. 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 as described in the INDICATIONS AND USAGE section. 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.