DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION If dose of cefazolin injection is required that does not equal gram or grams, this product is not recommended for use and as an alternative formulation of cefazolin should be considered. (2.1)For intravenous use only over approximately 30 minutes. (2)Recommended Dosing Schedule in Adult Patients with CLcr Greater Than or Equal To 55 L/min. (2.1)Site and Type of InfectionDoseFrequencyModerate to severe infections500 mg to gramevery to hoursMild infections caused by susceptible gram-positive cocci250 mg to 500 mgevery hoursAcute, uncomplicated urinary tract infections1 gramevery 12 hoursPneumococcal pneumonia500 mgevery 12 hoursSevere, life-threatening infections (e.g., endocarditis, septicemia)In rare instances, doses of up to 12 grams of cefazolin per day have been used. gram to 1.5 gramsevery hoursPerioperative prophylaxis1 gram to grams 1/2 to hour prior to start of surgery500 mg to gramduring surgery for lengthy procedures500 mg to gramevery to hours for 24 hours postoperatively Recommended Dosing Schedule in Pediatric Patients with CLcr Greater than or Equal to 70 mL/min. (2.1, 2.2, and 2.3) Site and Type of Infection Dose Frequency Moderate to severe infectionsFor the treatment indications (1.1 to 1.8) 25 to 50 mg per kg divided into or equal doses Severe infections May increase to 100 mg per kg divided into or equal doses. Recommended Dosing Schedule in Pediatric Patients with CLcr Greater than or Equal to 70 mL/min. (2.1, 2.2, and 2.3). Site and Type of Infection. Dose. Frequency. Moderate to severe infectionsFor the treatment indications (1.1 to 1.8). 25 to 50 mg per kg. divided into or equal doses. Severe infections. May increase to 100 mg. per kg. divided into or equal doses. 2.1 Important Administration Instructions If dose of cefazolin injection is required that does not equal gram or grams, this product is not recommended for use and as an alternative formulation of cefazolin should be considered.Administer cefazolin injection intravenously over approximately 30 minutes. 2.2 Dosage for the Treatment of Infections. Dosage for the Treatment of Infections in Adults with Creatinine Clearance (CLcr) Equal to 55 mL/min or GreaterThe recommended adult dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8)] are outlined in Table below. Administer cefazolin injection intravenously over approximately 30 minutes.Table 1: Recommended Dosing Schedule in Adult Patients with CLcr Greater Than or Equal To 55 mL/minIf dose of cefazolin Injection is required that does not equal gram or grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered..Site and Type of InfectionDoseFrequencyModerate to severe infections500 mg to gramevery to hoursMild infections caused by susceptible gram-positive cocci250 mg to 500 mgevery hoursAcute, uncomplicated urinary tract infections1 gramevery 12 hoursPneumococcal pneumonia500 mgevery 12 hoursSevere, life-threatening infections (e.g., endocarditis, septicemia)In rare instances, doses of up to 12 grams of cefazolin per day have been used. gram to 1.5 gramsevery hoursDosage for the Treatment of Infections in Pediatric Patients with CLcr Equal to 70 mL/min or GreaterThe recommended pediatric dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8)] are outlined in Table below. Administer cefazolin injection intravenously over approximately 30 minutes.If dose of cefazolin injection is required that does not equal gram or grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered [see Use in Specific Populations (8.4) ].Table 2: Recommended Dosage in Pediatric Patients with CLcr 70 mL/min or greater for Treatment of Infections [see Indications and Usage (1.1 to 1.8)]Type of SeverityRecommended Total Daily DosageMild to moderate infections25 mg/kg to 50 mg/kg, divided into or equal dosesSevere infectionsMay increase to 100 mg/kg, divided into or equal doses. 2.3 Dosage for Perioperative Prophylaxis 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 below.Table 3: Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr of 55 mL/min or Greater Dose administered 1/2 hour to hour prior to the start of surgery Additional dose during lengthy operative procedures (e.g., hours or more) Dose for 24 hours postoperatively g g 500 mg to g 500 mg to g every hours to hours If dose of cefazolin injection is required that does not equal gram or grams, this product is not recommended and an alternative formulation of cefazolin should be considered. It is important that (i) the preoperative dose be given just prior (1/2 hour to 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 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 to days following the completion of surgery. Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.. 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 below.. Dose administered 1/2 hour to hour prior to the start of surgery. Additional dose during lengthy operative procedures (e.g., hours or more). Dose for 24 hours postoperatively. g. g. 500 mg to g. 500 mg to g every. hours to hours. If dose of cefazolin injection is required that does not equal gram or grams, this product is not recommended and an alternative formulation of cefazolin should be considered.. It is important that (i) the preoperative dose be given just prior (1/2 hour to 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 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 to days following the completion of surgery.. Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.. 2.4 Dosage Recommendations in Adult and Pediatric Patients with Renal Impairment. Dosage Recommendations in Adult Patients with CLcr less than 55 mL/min The dosage recommendation for cefazolin injection in adult patients with renal impairment (CLcr less than 55 mL/min) is outlined in Table below.Table 5: Dosage Recommendation for Adult Patients with CLcr less than 55 mL/min Creatinine Clearance Dose Frequency 35 to 54 mL/min Recommended dose every hours or longer 11 to 34 mL/min Half of recommended doseIf the recommended dose in adult patients with creatinine clearance equal to 35 mL/min or greater is gram, then this product is not recommended for use in patients with creatinine clearance less than 35 mL/min and an alternative formulation of cefazolin should be considered. every 12 hours 10 mL/min or less Half of recommended dose every 18 to 24 hoursDosage Recommendations in Pediatric Patients with CLcr less than 70 mL/min The dosage recommendation for cefazolin injection in pediatric patients with renal impairment (CLcr less than 70 mL/min) is outlined in Table below.Table 6: Recommended Dosage in Pediatric Patients with CLcr less than 70 mL/min Creatinine Clearance Recommended Dosage 40 to 70 mL/min 60% of the normal daily dose given in equally divided doses every 12 hours 20 to 40 mL/min 25% of the normal daily dose given in equally divided doses every 12 hours to 20 mL/min 10% of the normal daily dose every 24 hoursIf dose of cefazolin injection is required that does not equal gram or grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.. Dosage Recommendations in Adult Patients with CLcr less than 55 mL/min. The dosage recommendation for cefazolin injection in adult patients with renal impairment (CLcr less than 55 mL/min) is outlined in Table below.. Creatinine Clearance. Dose. Frequency. 35 to 54 mL/min. Recommended dose. every hours or longer. 11 to 34 mL/min. Half of recommended doseIf the recommended dose in adult patients with creatinine clearance equal to 35 mL/min or greater is gram, then this product is not recommended for use in patients with creatinine clearance less than 35 mL/min and an alternative formulation of cefazolin should be considered.. every 12 hours. 10 mL/min or less. Half of recommended dose. every 18 to 24 hours. The dosage recommendation for cefazolin injection in pediatric patients with renal impairment (CLcr less than 70 mL/min) is outlined in Table below.. Creatinine. Clearance. Recommended Dosage. 40 to 70 mL/min. 60% of the normal daily dose given in equally divided doses every 12 hours. 20 to 40 mL/min. 25% of the normal daily dose given in equally divided doses every 12 hours. to 20 mL/min. 10% of the normal daily dose every 24 hours. 2.5 Preparation for Use of Cefazolin Injection Thawing of Plastic ContaineroThaw frozen container at room temperature 20-25C (68 77F) or under refrigeration 2-8C (36 46F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. oNo further dilution is necessary.oCheck for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.oDo not add supplementary medication.oThe container should be visually inspected. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.oThe thawed solution is stable for 30 days under refrigeration (5C/41F) or 48 hours at 25C/77F. Do not refreeze thawed antibacterial drugs.Preparation for AdministrationoSuspend container from support.oRemove protector from outlet port at bottom of container.oAttach Intravenous administration set to outlet port. Refer to the manufacturers instructions accompanying the administration set for complete directions.. oThaw frozen container at room temperature 20-25C (68 77F) or under refrigeration 2-8C (36 46F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw. oNo further dilution is necessary.. oCheck for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.. oDo not add supplementary medication.. oThe container should be visually inspected. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.. oThe thawed solution is stable for 30 days under refrigeration (5C/41F) or 48 hours at 25C/77F. Do not refreeze thawed antibacterial drugs.. oSuspend container from support.. oRemove protector from outlet port at bottom of container.. oAttach Intravenous administration set to outlet port. Refer to the manufacturers instructions accompanying the administration set for complete directions.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS Injection: gram cefazolin per 50 mL or gram cefazolin per 100 mL in single-dose GALAXY Container supplied as frozen, premixed, iso-osmotic, sterile, nonpyrogenic solution.. o1 gram in 50 mL and grams in 100 mL (3). o1 gram in 50 mL and grams in 100 mL (3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with cefazolin injection is not recommended.. Probenecid: The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with cefazolin injection is not recommended. (7)Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.

GERIATRIC USE SECTION.

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)].

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following serious adverse reactions to cefazolin injection are described below and elsewhere in the labeling:oHypersensitivity reactions [see Warnings and Precautions (5.1)]oSeizures in Patients with Renal Impairment [see Warnings and Precautions (5.2)]oClostridioides difficile-associated diarrhea [see Warnings and Precautions (5.3)]. oHypersensitivity reactions [see Warnings and Precautions (5.1)]. oSeizures in Patients with Renal Impairment [see Warnings and Precautions (5.2)]. oClostridioides difficile-associated diarrhea [see Warnings and Precautions (5.3)]. Adult and Pediatric Patients: Most common adverse reactions: gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash). (6)To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 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 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.Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that 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 population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Immune system disorders: Serum sickness-like reactionRenal 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, hepatic impairment including cholestasis, and pancytopenia.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity and MutagenesisMutagenicity studies and long-term studies in animals to determine the carcinogenic potential of cefazolin injection have not been performed.Impairment of FertilityFertility studies conducted in rats subcutaneously administered cefazolin at doses of2000 mg/kg/day (approximately times the maximum recommended human dose based on body surface area comparison) showed no impairment of mating and fertility.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Cefazolin is an antibacterial drug [see Microbiology (12.4) ].. 12.2 Pharmacodynamics The pharmacokinetic/pharmacodynamic relationship for cefazolin has not been evaluated in patients.. 12.3 Pharmacokinetics Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately mcg/mL at hours for 1 gram dose.The serum half-life for cefazolin is approximately 1.8 hours following IV administration.In study of constant intravenous infusion with dosages of 3.5 mg/kg for hour (approximately 250 mg) and 1.5 mg/kg the next hours (approximately 100 mg), cefazolin serum concentrations at the third hour of approximately 28 mcg/mL.Plasma pharmacokinetic parameters of cefazolin in healthy volunteers (N=12) following single 15- minute IV infusion of grams of cefazolin injection are summarized in Table 7.Table 7: Mean (Standard Deviation) Plasma Pharmacokinetic Parameters of Cefazolin in Healthy VolunteersNCmax (mcg/mL)Tmax Tmax reported as median (range)(h)AUC0-inf (mcgh/mL)T1/2 (h)CL(L/h)Vz (L)Single grams Dose as 15- Minute IV Infusion12280.9(45.9)0.25(0.25-0.33)509.9(89.3)2.01(0.28)4.03(0.68)11.50(1.53)N= number of subjects observed; Cmax maximum plasma concentration; Tmax time to maximum plasma concentration; AUC0-inf area under the plasma concentration-time curve extrapolated to infinity; t1/2 apparent plasma terminal elimination half-life; CL total clearance; Vz volume of distributionStudies in patients hospitalized with infections indicate that cefazolin produces mean peak serum concentrations approximately equivalent to those seen in healthy volunteers.Bile concentrations in patients without obstructive biliary disease can reach or exceed serum concentrations by up to five times; however, in patients with obstructive biliary disease, bile concentrations of cefazolin are considerably lower than serum concentrations (less than 1.0 mcg/mL).In synovial fluid, the cefazolin concentration becomes comparable to that reached in serum at about hours after drug administration.Studies of cord blood show prompt transfer of cefazolin across the placenta. Cefazolin is present in very low concentrations in the milk of nursing mothers.Cefazolin is excreted unchanged in the urine. In the first hours approximately 60% of the drug is excreted in the urine and this increases to 70% to 80% within 24 hours.Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.. 12.4 Microbiology Mechanism of ActionCefazolin is bactericidal agent that acts by inhibition of bacterial cell wall synthesis.ResistancePredominant mechanisms of bacterial resistance to cephalosporins include the presence of extended- spectrum beta-lactamases and enzymatic hydrolysis.Antimicrobial ActivityCefazolin 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 (1) section. Gram-Positive Bacteria Staphylococcus aureus Staphylococcus epidermidis Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenesMethicillin-resistant staphylococci are uniformly resistant to cefazolin. Gram-Negative Bacteria Escherichia coli Proteus mirabilisMost isolates of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri, Serratia spp., and Pseudomonas spp. are resistant to cefazolin.Susceptibility TestingFor specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see: http://www.fda.gov/STIC. Gram-Positive Bacteria. Staphylococcus aureus. Staphylococcus epidermidis. Streptococcus agalactiae. Streptococcus pneumoniae. Streptococcus pyogenes. Gram-Negative Bacteria. Escherichia coli. Proteus mirabilis.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS oHypersensitivity to cefazolin or other cephalosporin class antibacterial drugs, penicillins, or other beta-lactams (4.1). oHypersensitivity 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 injection is contraindicated in patients who have 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) ].

DESCRIPTION SECTION.

11 DESCRIPTION Cefazolin injection is frozen, premixed, iso-osmotic, sterile, nonpyrogenic, single-dose solution containing either 1g Cefazolin, USP, equivalent to 1.05 Cefazolin Sodium, USP per 50 mL or g Cefazolin, USP, equivalent to 2.10 Cefazolin Sodium, USP per 100 mL GALAXY container (PL 2040 Plastic). Dextrose, USP has been added to adjust osmolality (4 as dextrose hydrous). The approximate osmolality for cefazolin injection is 290 mOsmol/kg.Cefazolin Sodium is semi-synthetic cephalosporin antibacterial for parenteral administration and has the following IUPAC nomenclature: Sodium (6R,7R)-3-[[(5-methyl-1,3,4- thiadiazol-2-yl)thio]methyl]-8-oxo-7-[2-(1H-tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylate. Its molecular formula is C14H13N8O4S3.Na and its molecular weight is 454.51 (free acid).Cefazolin Sodium USP has the following structural formula:The sodium content is 48 mg/g of cefazolin sodium.The pH of cefazolin injection may have been adjusted with sodium bicarbonate, or sodium hydroxide/hydrochloric acid during manufacture. Water for injection, USP is added as drug vehicle. Contains no preservative. The solution is intended for intravenous use after thawing to room temperature.This GALAXY container (PL 2040 Plastic) is fabricated from specially designed multilayer plastic (PL 2040). Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. However, the suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies. Cefazolin Sodium, USP Structural Formula.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING Cefazolin injection is supplied as premixed frozen iso-osmotic solution in 50 mL or 100 mL single-dose GALAXY plastic containers as follows: Code Product Description NDC Number 2G3503 gram cefazolin in 50 mL Supplied as 24 bags per carton NDC 0338-3503-41 2G3508 grams cefazolin in 100 mL Supplied as 12 bags per carton NDC 0338-3508-41Store in freezer capable of maintaining temperature of -20C (-4F) or below [see Dosage and Administration (2.3)].Handle frozen product containers with care. Product containers may be fragile in the frozen state.. Cefazolin injection is supplied as premixed frozen iso-osmotic solution in 50 mL or 100 mL single-dose GALAXY plastic containers as follows:. Code. Product Description. NDC Number. 2G3503. gram cefazolin in 50 mL. Supplied as 24 bags per carton. NDC 0338-3503-41. 2G3508. grams cefazolin in 100 mL. Supplied as 12 bags per carton. NDC 0338-3508-41.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE Cefazolin injection is cephalosporin antibacterial indicated for: oTreatment of the following infections caused by susceptible isolates of the designated microorganisms in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved: (1) 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)oPerioperative prophylaxis in adults for whom appropriate dosing with this formulation can be achieved (1.9) To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin injection and other antibacterial drugs, cefazolin injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (1.10).. oTreatment of the following infections caused by susceptible isolates of the designated microorganisms in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved: (1) 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). 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). oPerioperative prophylaxis in adults for whom appropriate dosing with this formulation can be achieved (1.9) 1.1 Respiratory Tract Infections Cefazolin injection is indicated for the treatment of respiratory tract infections due to Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].Limitations of UseInjectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.Cefazolin injection is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available.. 1.2 Urinary Tract Infections Cefazolin injection is indicated for the treatment of urinary tract infections due to Escherichia coli, and Proteus mirabilis in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].. 1.3 Skin and Skin Structure Infections Cefazolin injection is indicated for the treatment of skin and skin structure infections due to S. aureus, S. pyogenes, and Streptococcus agalactiae in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].. 1.4 Biliary Tract Infections Cefazolin injection is indicated for the treatment of biliary infections due to E. coli, various isolates of streptococci, P. mirabilis, and S. aureus in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].. 1.5 Bone and Joint Infections Cefazolin injection is indicated for the treatment of bone and joint infections due to S. aureus in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].. 1.6 Genital Infections Cefazolin injection is indicated for the treatment of genital infections due to E. coli, and P. mirabilis in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)]. 1.7 Septicemia Cefazolin injection is indicated for the treatment of septicemia due to S. pneumoniae, S. aureus, P. mirabilis, and E. coli in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].. 1.8 Endocarditis Cefazolin injection is indicated for the treatment of endocarditis due to S. aureus and S. pyogenes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)]. 1.9 Perioperative Prophylaxis Cefazolin injection is indicated is indicated for perioperative prophylaxis in adults for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.3, 2.4, 2.5).The perioperative use of cefazolin injection is indicated in adult surgical patients in whom infection at the operative site would present serious risk (e.g., during open-heart surgery and prosthetic arthroplasty).The prophylactic administration of cefazolin 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).Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.. 1.10 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefazolin injection and other antibacterial drugs, cefazolin 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.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Serious Allergic ReactionsAdvise patients that allergic reactions, including serious allergic reactions could occur and that serious reactions require immediate treatment and discontinuation of cefazolin injection. Patients should report to their health care provider any previous allergic reactions to cefazolin, cephalosporins, penicillins, or other similar antibacterials.SeizuresAdvise patients that seizures could occur with cefazolin injection. Instruct patients to inform healthcare provider at once of any signs and symptoms of seizures, for immediate treatment, dosage adjustment, or discontinuation of cefazolin injection.DiarrheaAdvise patients that diarrhea is common problem caused by antibacterials, which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterials. If this occurs, patients should contact physician as soon as possible.Antibacterial ResistancePatients should be counseled that antibacterial drugs, including cefazolin injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefazolin injection is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cefazolin injection or other antibacterial drugs in the future.

LABOR & DELIVERY SECTION.

8.2 Lactation Risk Summary Data from published literature report that cefazolin is present in human milk, but is not expected to accumulate in breastfed infant. There are no data on the effects of cefazolin on the breastfed child or on milk production.The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for cefazolin injection and any potential adverse effects on the breastfed child from cefazolin injection or from the mothers underlying condition.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action Cefazolin is an antibacterial drug [see Microbiology (12.4) ].

MICROBIOLOGY SECTION.

12.4 Microbiology Mechanism of ActionCefazolin is bactericidal agent that acts by inhibition of bacterial cell wall synthesis.ResistancePredominant mechanisms of bacterial resistance to cephalosporins include the presence of extended- spectrum beta-lactamases and enzymatic hydrolysis.Antimicrobial ActivityCefazolin 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 (1) section. Gram-Positive Bacteria Staphylococcus aureus Staphylococcus epidermidis Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenesMethicillin-resistant staphylococci are uniformly resistant to cefazolin. Gram-Negative Bacteria Escherichia coli Proteus mirabilisMost isolates of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri, Serratia spp., and Pseudomonas spp. are resistant to cefazolin.Susceptibility TestingFor specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see: http://www.fda.gov/STIC. Gram-Positive Bacteria. Staphylococcus aureus. Staphylococcus epidermidis. Streptococcus agalactiae. Streptococcus pneumoniae. Streptococcus pyogenes. Gram-Negative Bacteria. Escherichia coli. Proteus mirabilis.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity and MutagenesisMutagenicity studies and long-term studies in animals to determine the carcinogenic potential of cefazolin injection have not been performed.Impairment of FertilityFertility studies conducted in rats subcutaneously administered cefazolin at doses of2000 mg/kg/day (approximately times the maximum recommended human dose based on body surface area comparison) showed no impairment of mating and fertility.

OVERDOSAGE SECTION.

10 OVERDOSAGE Accidental overdosage resulting in seizures may occur in patients with renal impairment who receive doses greater than the recommended dosage of cefazolin injection [see Warnings and Precautions (5.2)]. If seizures associated with accidental overdosage occur, discontinue cefazolin injection and give supportive treatment.

SPL UNCLASSIFIED SECTION.

1.1 Respiratory Tract Infections Cefazolin injection is indicated for the treatment of respiratory tract infections due to Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration (2.1, 2.2, 2.4 and 2.5) and Use in Specific Populations (8.4)].Limitations of UseInjectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.Cefazolin injection is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from published prospective cohort studies, case series and case reports over several decades with cephalosporin use, including cefazolin, in pregnant women have not established drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Cefazolin crosses the placenta.Animal reproduction studies with rats, mice and rabbits administered cefazolin during organogenesis at doses to times the maximum recommended human dose (MRHD) did not demonstrate adverse developmental outcomes. In rats subcutaneously administered cefazolin prior to delivery and throughout lactation, there were no adverse effects on offspring at dose approximately times the MRHD (see Data).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.Data Human DataWhile available studies cannot definitively establish the absence of risk, published data from case-control studies and case reports over several decades have not identified an association with cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.Animal DataReproduction studies have been performed in rats, mice and rabbits administered cefazolin during organogenesis at doses of 2000, 4000 and 240 mg/kg/day (approximately to times the maximum recommended human dose on body surface area comparison). There was no evidence of any adverse effects on embryofetal development due to cefazolin. In peri- postnatal study in rats, cefazolin administered subcutaneously up to 1200 mg/kg/day (approximately times the MRHD based on body surface area comparison) to pregnant dams prior to delivery and through lactation caused no adverse effects on offspring.. 8.2 Lactation Risk Summary Data from published literature report that cefazolin is present in human milk, but is not expected to accumulate in breastfed infant. There are no data on the effects of cefazolin on the breastfed child or on milk production.The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for cefazolin injection and any potential adverse effects on the breastfed child from cefazolin injection or from the mothers underlying condition.. 8.4 Pediatric Use Cefazolin injection is indicated for the treatment of respiratory tract infections, urinary tract infections, skin and skin structure infections, biliary tract infections, bone and joint infections, genital infections, septicemia, and endocarditis in pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1 to 1.8)].Safety and effectiveness of cefazolin injection in premature infants and neonates have not been established and is not recommended for use in this age group of pediatric patients. Dosing for cefazolin in pediatric patients younger than one month old has not been established.Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of cefazolin injection, and to avoid unintentional overdose, this product is not recommended for use if dose of cefazolin injection that does not equal gram or grams is required and an alternative formulation of cefazolin should be considered [see Dosage and Administration (2.2, 2,3, 2.4 and 2.5)].The safety and effectiveness of cefazolin injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.. 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 injection is administered to adult and pediatric patients with low urinary output because of impaired renal function (creatinine clearance less than 55 mL/min and 70 mL/min for adults and pediatric patients, respectively), lower daily dosage is required [see Dosage and Administration (2.4)and Warnings and Precautions (5.2)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oHypersensitivity reactions: Cross-hypersensitivity may occur in up to 10% of patients with history of penicillin allergy. If an allergic reaction occurs, discontinue the drug. (5.1)oClostridioides difficile-associated diarrhea (CDAD): May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. (5.3) oHypersensitivity reactions: Cross-hypersensitivity may occur in up to 10% of patients with history of penicillin allergy. If an allergic reaction occurs, discontinue the drug. (5.1). oClostridioides difficile-associated diarrhea (CDAD): May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. (5.3) 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 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 history of penicillin allergy. If an allergic reaction to cefazolin injection occurs, discontinue the drug.. 5.2 Seizures in Patients with Renal Impairment Seizures may occur with the administration of cefazolin injection, particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue cefazolin 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 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 history of hypersensitivity to corn products.2 5.5 Risk of Development of Drug-resistant Bacteria Prescribing cefazolin injection in the absence of proven or strongly suspected bacterial infection or 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 injection may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patients condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.. 5.6 Drug/Laboratory Test Interactions Urinary GlucoseThe administration of cefazolin may result in false-positive reaction with glucose in the urine when using glucose tests based on Benedicts 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 TestPositive 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 positive Coombs test may be due to the drug.. 5.7 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance As with other dextrose-containing solutions, cefazolin injection should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL Container LabelNDC 0338-3508-41Cefazolin Injection, USP2g 100 mL(20 mg mL)GALAXYSingle-Dose ContainerDiscard unused portionCode 2G3508Sterile NonpyrogenicIso-osmoticEach 100 mL contains: 2g Cefazolin, USP, equivalent to 2.10g Cefazolin Sodium, USP with approx. g Dextrose Hydrous, USP added to adjust osmolality, and Water for Injection, USP. pH may have been adjusted with sodium bicarbonate, or sodium hydroxide/hydrochloric acid. Dosage: For Intravenous Infusion Only. See prescribing information.Caution: Do not add supplemental medication or additives.Rx onlyStore at or below -20C (-4F). Thaw at room temperature 20-25C (68 77F)or under refrigeration 2-8C (36 46F). Product should not be thawed by immersion in waterbaths or by microwave irradiation. Do not force thaw. Thawed solution is stablefor 30 days under refrigeration or 48 hours at room temperature. DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution is stable for 30 days under refrigeration or 48 hours at room temperature. Do not refreeze. Baxter LogoPL 2040 Plastic Baxter and Galaxy are trademarks of Baxter International Inc.Manufactured by Baxter Healthcare Corporation, Deerfield, IL 60015 USAMade in USA07-34-00-0357BAR CODE POSITION ONLY UPC-A303383508416Carton LabelThaw at room temperature 20-25C (68 77F) or under refrigeration 2-8C (36 49F). DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution is stable for 30 days under refrigeration or 48 hours at room temperature. Do not refreeze.Handle frozen product containers with care. Product containers may be fragile in the frozen state.PL 2040 Plastic07-04-00-0112Cegazolin Injection, USP2g 100 mL (20 mg mL)Contains units of Single-Dose bags. Each bag contains 100 mL. Iso-osmoticStore at or below -20C (-4F).Rx onlyNDC 0338-3508-41Code 2G3508FOR BAR CODE POSITION ONLY(01) 20303383508410GALAXY Container Sterile NonpyrogenicEach 100 mL contains: g Cefazolin, USP, equivalent to 2.10 Cefazolin Sodium, USP with approx. g Dextrose Hydrous, USP added to adjust osmolality, and Water for Injection, USP. pH may have been adjusted with sodium bicarbonate, or sodium hydroxide/hydrochloric acid.Dosage: For Intravenous Infusion Only. See prescribing information.Caution: Do not add supplemental medication or additives. Baxter LogoBaxter and Galaxy are registered trademarks of Baxter International Inc. Baxter Healthcare Corporation, Deerfield, IL 60015 USASerialized Shipper LabelCODE: 2G3508LOT: XXXXXXXXXEXP: DD MMM YYQTY: QQSN: CODE: 2G3508LOT: XXXXXXXXXEXP: DD MMM YYQTY: QQSN: FORPLACEMENTONLY.(01) XXXXXXX XXXXX X(21) XXXXXXXXX(17) XXXXX(10) XXXXXXXXXFORPLACEMENTONLY.(01) XXXXXXX XXXXX X(21) XXXXXXXXX(17) XXXXX(10) XXXXXXXXX07-06-77-681Container LabelBaxter Logo Cefazolin Injection, USP1 / 50 mL(20 mg mL)GALAXY Single Dose ContainerDiscard unused portionNDC 0338-3503-41Code 2G3503Sterile NonpyrogenicIso-osmoticEach 50 mL contains: 1g Cefazolin, USP, equivalent to 1.05g CefazolinSodium, USP with approx. g Dextrose Hydrous, USP added to adjustosmolality. pH may have been adjusted with sodium bicarbonate or sodiumhydroxide/hydrochloric acid.Usual Dosage: For Intravenous Infusion Only. See prescribing information.Cautions: Do not add supplementary medication or additives. Must not be used in series connections. Check for minute leaks and solution clarity.See prescribing information.Rx onlyStore at or below -20C (-4F). Thaw at room temperature 20-25C (68 77F) or under refrigeration 2-8C (36 46F). DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution is stable for 30 days under refrigeration or 48 hours at room temperature. Do not refreeze. Baxter and Galaxy are registered trademarks ofBaxter International Inc.Manufactured by Baxter Healthcare Corporation Deerfield, IL 60015 USAMade in USAPL2040 Plastic07-34-00-0356 BAR CODE POSITION ONLY303383503411Carton LabelThaw at room temperature 20-25C (68 77F) or under refrigeration 2-8C (36 41F). DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution is stable for 30 days under refrigeration or 48 hours at room temperature. Do not refreeze. Handle frozen product containers with care. Product containers may be fragile in thefrozen state.Baxter and Galaxy are registered trademarks of Baxter International Inc.PL 2040 Plastic07-04-00-0111Baxter Logo Cefazolin Injection, USP12 50 mL Single Dose Containers Iso-osmoticStore at or below -20C/-4F. Do not refreeze.1 / 50 mL (20 mg mL)Baxter Healthcare CorporationDeerfield, IL 60015 USANDC 0338-3503-41Code 2G3503FOR BAR CODE POSITION ONLY(01) 20303383503415GALAXY Container Sterile NonpyrogenicEach 50 mL contains: 1g Cefazolin, USP, equivalent to 1.05g Cefazolin Sodium, USP withapprox. g Dextrose Hydrous, USP added to adjust osmolality. pH may have been adjustedwith sodium bicarbonate or sodium hydroxide/hydrochloric acid.Usual Dosage: For Intravenous Infusion Only. See prescribing information.Cautions: Do not add supplementary medications or additives. Must not be used in seriesconnections. Check for minute leaks by squeezing thawed bag firmly. If leaks are found,discard bag as sterility may be impaired. Do not use unless solution is clear. Rx only Serialized Shipper LabelCODE: 2G3503LOT: XXXXXXXXXEXP: DD MMM YYQTY: QQSN: FORPLACEMENTONLY. (01) XXXXXXX XXXXX X(21) XXXXXXXXX(17) XXXXXX(10) XXXXXXXXX07-06-77-680. (01) XXXXXXX XXXXX X(21) XXXXXXXXX(17) XXXXXX(10) XXXXXXXXX. Representative Cefazolin Container Label 0338-3508-41 of 2. Representative Cefazolin Container Label 0338-3508-41 of 2. Representative Cefazolin Carton Label 0338-3508-41 of 2. Representative Cefazolin Carton Label 0338-3508-41 of 2. Representative Sample of Serialized lbl. Representative Cefazolin Container Label 0338-3503-41 of 2. Representative Cefazolin Container Label 0338-3503-41 of 2. Representative Cefazolin Carton Label 0338-3503-41 of 2. Representative Cefazolin Carton Label 0338-3503-41 of 2. Representative Cefazolin 1g Shipper Label 0338-3503-41.

PEDIATRIC USE SECTION.

8.4 Pediatric Use Cefazolin injection is indicated for the treatment of respiratory tract infections, urinary tract infections, skin and skin structure infections, biliary tract infections, bone and joint infections, genital infections, septicemia, and endocarditis in pediatric patients for whom appropriate dosing with this formulation can be achieved [see Indications and Usage (1.1 to 1.8)].Safety and effectiveness of cefazolin injection in premature infants and neonates have not been established and is not recommended for use in this age group of pediatric patients. Dosing for cefazolin in pediatric patients younger than one month old has not been established.Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of cefazolin injection, and to avoid unintentional overdose, this product is not recommended for use if dose of cefazolin injection that does not equal gram or grams is required and an alternative formulation of cefazolin should be considered [see Dosage and Administration (2.2, 2,3, 2.4 and 2.5)].The safety and effectiveness of cefazolin injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics The pharmacokinetic/pharmacodynamic relationship for cefazolin has not been evaluated in patients.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately mcg/mL at hours for 1 gram dose.The serum half-life for cefazolin is approximately 1.8 hours following IV administration.In study of constant intravenous infusion with dosages of 3.5 mg/kg for hour (approximately 250 mg) and 1.5 mg/kg the next hours (approximately 100 mg), cefazolin serum concentrations at the third hour of approximately 28 mcg/mL.Plasma pharmacokinetic parameters of cefazolin in healthy volunteers (N=12) following single 15- minute IV infusion of grams of cefazolin injection are summarized in Table 7.Table 7: Mean (Standard Deviation) Plasma Pharmacokinetic Parameters of Cefazolin in Healthy VolunteersNCmax (mcg/mL)Tmax Tmax reported as median (range)(h)AUC0-inf (mcgh/mL)T1/2 (h)CL(L/h)Vz (L)Single grams Dose as 15- Minute IV Infusion12280.9(45.9)0.25(0.25-0.33)509.9(89.3)2.01(0.28)4.03(0.68)11.50(1.53)N= number of subjects observed; Cmax maximum plasma concentration; Tmax time to maximum plasma concentration; AUC0-inf area under the plasma concentration-time curve extrapolated to infinity; t1/2 apparent plasma terminal elimination half-life; CL total clearance; Vz volume of distributionStudies in patients hospitalized with infections indicate that cefazolin produces mean peak serum concentrations approximately equivalent to those seen in healthy volunteers.Bile concentrations in patients without obstructive biliary disease can reach or exceed serum concentrations by up to five times; however, in patients with obstructive biliary disease, bile concentrations of cefazolin are considerably lower than serum concentrations (less than 1.0 mcg/mL).In synovial fluid, the cefazolin concentration becomes comparable to that reached in serum at about hours after drug administration.Studies of cord blood show prompt transfer of cefazolin across the placenta. Cefazolin is present in very low concentrations in the milk of nursing mothers.Cefazolin is excreted unchanged in the urine. In the first hours approximately 60% of the drug is excreted in the urine and this increases to 70% to 80% within 24 hours.Additional pediatric use information is approved for B. Braun Medical Inc.s CEFAZOLIN FOR INJECTION AND DEXTROSE INJECTION. However, due to B. Braun Medical Inc.s marketing exclusivity rights, this drug product is not labeled with that information.

PREGNANCY SECTION.

8.1 Pregnancy Risk Summary Available data from published prospective cohort studies, case series and case reports over several decades with cephalosporin use, including cefazolin, in pregnant women have not established drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Cefazolin crosses the placenta.Animal reproduction studies with rats, mice and rabbits administered cefazolin during organogenesis at doses to times the maximum recommended human dose (MRHD) did not demonstrate adverse developmental outcomes. In rats subcutaneously administered cefazolin prior to delivery and throughout lactation, there were no adverse effects on offspring at dose approximately times the MRHD (see Data).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.Data Human DataWhile available studies cannot definitively establish the absence of risk, published data from case-control studies and case reports over several decades have not identified an association with cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.Animal DataReproduction studies have been performed in rats, mice and rabbits administered cefazolin during organogenesis at doses of 2000, 4000 and 240 mg/kg/day (approximately to times the maximum recommended human dose on body surface area comparison). There was no evidence of any adverse effects on embryofetal development due to cefazolin. In peri- postnatal study in rats, cefazolin administered subcutaneously up to 1200 mg/kg/day (approximately times the MRHD based on body surface area comparison) to pregnant dams prior to delivery and through lactation caused no adverse effects on offspring.

REFERENCES SECTION.

15 REFERENCES 1.Czarny D, Prichard PJ, Fennessy M, Lewis S. Anaphylactoid reaction to 50% solution of dextrose. Med Aust 1980;2:255-258.2.Guharoy, SR, Barajas M. Probably Anaphylactic Reaction to Corn-Derived Dextrose Solution. Vet Hum Toxicol 1991;33:609-610.. 1.Czarny D, Prichard PJ, Fennessy M, Lewis S. Anaphylactoid reaction to 50% solution of dextrose. Med Aust 1980;2:255-258.. 2.Guharoy, SR, Barajas M. Probably Anaphylactic Reaction to Corn-Derived Dextrose Solution. Vet Hum Toxicol 1991;33:609-610.