cefazolin- Cefazolin injection, powder, for solution

Drug Labeling and Warnings

Drug Details [pdf]

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg cefazolin to test the susceptibility of microorganisms to cefazolin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 mcg cefazolin disk should be interpreted according to the following criteria:

For Enterobacteriaceae using the 30 mcg cefazolin disk

Zone diameter (mm)Interpretation
> 18Susceptible (S)
15 to 17Intermediate (I)
< 14Resistant (R)

For Staphylococcus spp, using the 30 mcg cefazolin or the 30 mcg cephalothin disks

Zone diameter (mm)Interpretation
> 18Susceptible (S)
15 to 17Intermediate (I)
< 14Resistant (R)

Interpretation should be as stated above for results using dilution techniques.

Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cefazolin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 mcg cefazolin disk should provide the following zone diameter in this laboratory test quality control strain:

Microorganism Zone diameter (mm)
S. aureusATCC 2592329 to 35
E. coliATCC 2592223 to 29
  • 2 National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests – Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA January 2000.
  • INDICATIONS AND USAGE

    Cefazolin for injection is indicated in the treatment of the following serious infections due to susceptible organisms:

    Respiratory Tract Infections due to S. pneumoniae, Klebsiella species, H. influenzae, S. aureus (penicillin-sensitive and penicillin-resistant), and group A beta-hemolytic streptococci.

    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 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.

    Urinary Tract Infections due to E. coli, P. mirabilis, Klebsiella species, and some strains of enterobacter and enterococci.

    Skin and Skin Structure Infections due to S. aureus (penicillin-sensitive and penicillin-resistant), group A beta-hemolytic streptococci, and other strains of streptococci.

    Biliary Tract Infections due to E. coli, various strains of streptococci, P. mirabilis, Klebsiella species, and S. aureus.

    Bone and Joint Infections due to S. aureus.

    Genital Infections (i.e., prostatitis, epididymitis) due to E. coli, P. mirabilis, Klebsiella species, and some strains of enterococci.

    Septicemia due to S. pneumoniae, S. aureus (penicillin-sensitive and penicillin-resistant), P. mirabilis, E. coli, and Klebsiella species.

    Endocarditis due to S. aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci.

    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 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.)

    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.

  • CONTRAINDICATIONS

    CEFAZOLIN FOR INJECTION IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.

  • WARNINGS

    BEFORE THERAPY WITH CEFAZOLIN FOR INJECTION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS 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 OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, IV FLUIDS, IV ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

    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.”

    After the diagnosis of 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.

  • PRECAUTIONS

    General

    Prolonged use of Cefazolin for injection may result in the overgrowth of nonsusceptible organisms. Careful clinical observation of the patient is essential.

    When Cefazolin for injection is administered to patients with low urinary output because of impaired renal function, lower daily dosage is required (see DOSAGE AND ADMINISTRATION).

    As with other β-lactam antibiotics, seizures may occur if inappropriately high doses are administered to patients with impaired renal function (see DOSAGE AND ADMINISTRATION).

    Cefazolin for injection, as with all cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

    Cephalosporins 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.

    Prescribing Cefazolin for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increase the risk of the development of drug-resistant bacteria.

    Drug Interactions

    Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels.

    Drug/Laboratory Test Interactions

    A false positive reaction for glucose in the urine may occur with Benedict's solution, Fehling’s solution or with CLINITEST® tablets, but not with enzyme-based tests such as CLINISTIX®.

    Positive direct and indirect antiglobulin (Coombs) tests have occurred; these may also occur in neonates whose mothers received cephalosporins before delivery.

    Information for Patients

    Patients should be counseled that antibacterial drugs including Cefazolin for injection, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefazolin for injection is prescribed to treat a 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 for injection or other antibacterial drugs in the future.

    Carcinogenesis/Mutagenesis

    Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of Cefazolin for injection have not been performed.

    Pregnancy

    Teratogenic Effects

    Pregnancy Category B

    Reproduction studies have been performed in rats, mice and rabbits at doses up to 25 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Cefazolin for injection. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

    Labor and Delivery

    When cefazolin has been administered prior to caesarean section, drug levels in cord blood have been approximately one quarter to one third of maternal drug levels. The drug appears to have no adverse effect on the fetus.

    Nursing Mothers

    Cefazolin for injection is present in very low concentrations in the milk of nursing mothers. Caution should be exercised when Cefazolin for injection is administered to a nursing woman.

    Pediatric Use

    Safety and effectiveness for use in premature infants and neonates have not been established. See DOSAGE AND ADMINISTRATION for recommended dosage in pediatric patients older than 1 month.

    Geriatric Use

    Of the 920 subjects who received Cefazolin for injection 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 PRECAUTIONS, General and DOSAGE and ADMINISTRATION).

  • ADVERSE REACTIONS

    The following reactions have been reported:

    Gastrointestinal

    Diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia, and pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS). Nausea and vomiting have been reported rarely.

    Allergic

    Anaphylaxis, eosinophilia, 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.  As with other cephalosporins, reports of hepatitis have been received.

    Renal

    As with other cephalosporins, reports of increased 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. Some induration has occurred.

    Other Reactions

    Genital and anal pruritus (including vulvar pruritus, genital moniliasis, and vaginitis).

    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 antibiotics:

    Adverse Reactions: Allergic reactions, urticaria, serum sickness-like reaction, erythema multiforme, toxic epidermal necrolysis, colitis, renal dysfunction, toxic nephropathy, abdominal pain, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, and superinfection.

    Altered Laboratory Tests: Prolonged prothrombin time, positive direct Coombs’ test, false-positive test for urinary glucose, elevated bilirubin, elevated LDH, increased creatinine, pancytopenia, and agranulocytosis.

    Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. 

  • DOSAGE AND ADMINISTRATION

    Usual Adult Dosage

    Type of InfectionDoseFrequency
  • * ln rare instances, doses of up to 12 grams of Cefazolin for injection per day have been used.
    		•
    Moderate to severe infections500mg to 1gramevery 6 to 8 hrs.
    Mild infections caused by susceptible gram-positive cocci250 mg to 500 mgevery 8 hours
    Acute, uncomplicated urinary tract infections1 gramevery 12 hours
    Pneumococcal pneumonia500 mgevery 12 hours
    Severe, life-threatening infections
     (e.g., endocarditis, septicemia)*    		1 gram to 1.5 gramsevery 6 hours

    Perioperative Prophylactic Use

    To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are:

    1. 1 gram IV administered 1/2 hour to 1 hour prior to the start of surgery.
    2. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV during surgery (administration modified depending on the duration of the operative procedure).
    3. 500 mg to 1 gram IV every 6 to 8 hours for 24 hours postoperatively.

    It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior to the start of surgery so that adequate antibiotic 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 antibiotic 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 for injection may be continued for 3 to 5 days following the completion of surgery.

    Dosage Adjustment for Patients with Reduced Renal Function

    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 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.

    Pediatric Dosage

    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.

    Pediatric Dosage Guide
    Weight25 mg/kg/day
    Divided into 3 Doses    		25 mg/kg/day
    Divided into 4 Doses
    LbsKgApproximate Single Dose mg/q8hVol.(mL)
    needed with
    dilution of 125 mg/mL    		Approximate Single Dose mg/q6hVol.(mL)
    needed with dilution of 125 mg/mL
    104.540 mg0.35 mL30 mg0.25 mL
    20975 mg0.6 mL55 mg0.45 mL
    3013.6115 mg0.9 mL85 mg0.7 mL
    4018.1150 mg1.2 mL115 mg0.9 mL
    5022.7190 mg1.5 mL140 mg1.1 mL
    Weight
         		50 mg/kg/day
    Divided into 3 Doses    		50 mg/kg/day
    Divided into 4 Doses
    LbsKgApproximate Single Dose mg/q8hVol.(mL)
    needed with dilution of 225 mg/mL    		Approximate Single Dose mg/q6hVol.(mL)
    needed with dilution of 225 mg/mL
    104.575 mg0.35 mL55 mg0.25 mL
    209150 mg0.7 mL110 mg0.5 mL
    3013.6225 mg1 mL170 mg0.75 mL
    4018.1300 mg1.35 mL225 mg1 mL
    5022.7375 mg1.7 mL285 mg1.25 mL

    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.

    RECONSTITUTION

    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.

    Reconstituted solutions may range in color from pale yellow to yellow without a change in potency.

    Directions for Proper Use of a Pharmacy Bulk Package

    Not for direct infusion. This Pharmacy Bulk Package is for use in a hospital pharmacy admixture service, only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container may be penetrated only one time using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial closure entry is permitted to complete fluid transfer operations. This time limit should begin with the introduction of the solvent or diluent into the Pharmacy Bulk Package. DISCARD ANY UNUSED PORTION AFTER 4 HOURS.

    THIS PHARMACY BULK PACKAGE IS NOT INTENDED TO BE DISPENSED AS A UNIT

    Pharmacy Bulk Package

    Add Sterile Water for Injection, Bacteriostatic Water for Injection, or Sodium Chloride Injection according to the table below. SHAKE WELL. Use promptly. (Discard vial within 4 hours after initial entry.)

    Vial
     Size    		Amount of
    Diluent    		Approximate
    Concentration    		Approximate
    Available
    Volume
    10 grams45 mL1 gram/5 mL51 mL
     96 mL1 gram/10 mL102  mL 

     ADMINISTRATION

    Intravenous Administration

    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

    When reconstituted or diluted according to the instructions above, Cefazolin for injection is stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5°C or 41 °F). 

    Prior to administration parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.

  • HOW SUPPLIED

    Cefazolin for injection, USP

    Each Pharmacy Bulk Package contains cefazolin sodium equivalent to 10 grams of cefazolin.

    Cefazolin for injection is available as follows:

    10 vials 10 grams/100 mL vials per carton (NDC: 63304-941-10).

    As with other cephalosporins, Cefazolin for injection tends to darken depending on storage conditions; within the stated recommendations, however, product potency is not adversely affected.

    Store dry powder at 20° to 25° C (68° to 77°F) [See USP Controlled Room Temperature]. Before reconstitution PROTECT FROM LIGHT.

  • REFERENCES

    1. National Committee for Clinical Laboratory Standards, Method for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically – Fifth Edition. Approved Standard NCCLS Document M7-A4, Vol. 20, No.2, NCCLS, Wayne, PA, January 2000.
    2. National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests – Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA January 2000.

    CLINITEST is registered trademark of Miles, Inc.

    CLINISTIX is a registered trademark of Bayer Corporation.

    Manufactured for:

    Ranbaxy Pharmaceuticals Inc.

    Jacksonville, FL 32257 USA

    by: Orchid Healthcare

    (A Division of Orchid Chemicals & Pharmaceuticals Ltd.)

    Irungattukottai, India 602 105

    DATE OF ISSUANCE: SEPTEMBER 2006

    948025510

  • INGREDIENTS AND APPEARANCE
    CEFAZOLIN 
    cefazolin injection, powder, for solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 63304-941
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    Cefazolin sodium (UNII: P380M0454Z) (Cefazolin - UNII:IHS69L0Y4T) 10 g
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 63304-941-1010 in 1 CARTON
    11 in 1 VIAL, PHARMACY BULK PACKAGE
    Labeler - ORCHID HEALTHCARE (A DIVISION OF ORCHID CHEMICALS AND PHARMACEUTICALS LTD.)
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