CEFAZOLIN FOR INJECTION (lyophilized)
For Intravenous Administration ADD-Vantage® Vial
cefazolin sodium injection, powder, lyophilized, for solution GlaxoSmithKline
CEFAZOLIN FOR INJECTION (lyophilized)
For Intravenous Administration ADD-Vantage® Vial
To reduce the development of drug-resistant bacteria and
maintain the effectiveness of cefazolin and other antibacterial drugs, cefazolin
should be used only to treat or prevent infections that are proven or strongly
suspected to be caused by bacteria.
Cefazolin for injection is a sterile, semi-synthetic cephalosporin
for intravenous or intramuscular administration. It is the sodium salt of
Its molecular formula is C14H13N8NaO4S3 and
the molecular weight is 476.50.
Each vial contains 48
mg of sodium/1 gram of cefazolin sodium.
injection is supplied as a lyophilized form.
Each ADD-Vantage® vial
of cefazolin for injection is equivalent to 1 gram cefazolin.
After intramuscular administration of cefazolin to normal
volunteers, the mean serum concentrations were 37 mcg/mL at one hour and
mcg/mL at eight hours following a 500 mg dose, and 64 mcg/mL at one hour and
mcg/mL at eight hours following a 1 gram dose.
have shown that following intravenous administration of cefazolin to normal
volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and
were approximately 4 mcg/mL at eight hours for a 1 gram dose.
serum half-life for cefazolin is approximately 1.8 hours following I.V. administration
and approximately 2.0 hours following I.M. administration.
a study (using normal volunteers) of constant intravenous infusion with dosages
of 3.5 mg/kg for one hour (approximately 250 mg) and 1.5 mg/kg the next two
hours (approximately 100 mg), cefazolin produced a steady serum level at the
third hour of approximately 28 mcg/mL.
Studies in patients
hospitalized with infections indicate that cefazolin produces mean peak serum
levels approximately equivalent to those seen in normal volunteers.
levels in patients without obstructive biliary disease can reach or exceed
serum levels by up to five times; however, in patients with obstructive biliary
disease, bile levels of cefazolin are considerably lower than serum levels
(< 1.0 mcg/mL).
In synovial fluid, the cefazolin
level becomes comparable to that reached in serum at about four hours after
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.
is excreted unchanged in the urine. In the first six hours approximately 60%
of the drug is excreted in the urine and this increases to 70%-80% within
24 hours. Cefazolin achieves peak urine concentrations of approximately 2400
mcg/mL and 4000 mcg/mL respectively following 500 mg and 1 gram intramuscular
In patients undergoing peritoneal dialysis (2
L/hr.), cefazolin 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 13-44
mcg/mL) with 50 mg/L (three patients), and 72 mcg/mL (range 26-142 mcg/mL)
with 150 mg/L (six patients). Intraperitoneal administration of cefazolin
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.
In vitro tests demonstrate
that the bactericidal action of cephalosporins results from inhibition of
cell wall synthesis. Cefazolin is active against the following organisms in vitro and in clinical infections:
are uniformly resistant to cefazolin
Group A beta-hemolytic
streptococci and other strains of streptococci (many strains of enterococci
Most strains of indole positive
Proteus (Proteus vulgaris), Enterobactercloacae, Morganella morganii and Providencia rettgeri are resistant. Serratia, Pseudomonas, Mima, Herellea species are almost uniformly resistant to cefazolin.
Disk Susceptibility Tests
Disk diffusion technique
— Quantitative methods that require measurement of
zone diameters give the most precise estimates of antibiotic susceptibility.
One such procedure1 has been recommended for use with disks to
test susceptibility to cefazolin.
Reports from a laboratory
using the standardized single-disk susceptibility test1 with a
30 mcg cefazolin disk should be interpreted according to the following criteria:
organisms produce zones of 18 mm or greater, indicating that the tested organism
is likely to respond to therapy.
Organisms of intermediate
susceptibility produce zones 15 to 17 mm, indicating that the tested organism
would be susceptible if high dosage is used or if the infection is confined
to tissues and fluids (e.g., urine), in which high antibiotic levels are attained.
organisms produce zones of 14 mm or less, indicating that other therapy should
For gram-positive isolates, a zone of 18
mm is indicative of a cefazolin-susceptible organism when tested with either
the cephalosporin-class disk (30 mcg cephalothin) or the cefazolin disk (30
Gram-negative organisms should be tested
with the cefazolin disk (using the above criteria), since cefazolin has been
shown by in vitro tests to have activity
against certain strains of Enterobacteriaceae found resistant when tested with the cephalothin disk. Gram-negative
organisms having zones of less than 18 mm around the cephalothin disk may
be susceptible to cefazolin.
require use of control organisms. The 30 mcg cefazolin disk should give zone
diameter between 23 and 29 mm for E. coli ATCC
25922 and between 29 and 35 mm for S. aureus ATCC 25923.
The cefazolin disk should not
be used for testing susceptibility to other cephalosporins.
— A bacterial isolate may be considered susceptible
if the minimal inhibitory concentration (MIC) for cefazolin is not more than
16 mcg per mL. Organisms are considered resistant if the MIC is equal to or
greater than 64 mcg per mL.
The range of MIC’s
for the control strains are as follows:
aureus ATCC 25923, 0.25 − 1.0 mcg/mL
E. coli ATCC 25922, 1.0 − 4.0 mcg/mL
INDICATIONS AND USAGE
Cefazolin is indicated in the treatment of the following
serious infections due to susceptible organisms:
TRACT INFECTIONS due to Streptococcus pneumoniae, Klebsiella species, Haemophilus influenzae, Staphylococcus
aureus (penicillin-sensitive and penicillin-resistant) and group
A beta-hemolytic streptococci.
penicillin is considered to be the drug of choice in treatment and prevention
of streptococcal infections, including the prophylaxis of rheumatic fever.
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 at present.
TRACT INFECTIONS due to Escherichia coli, Proteus mirabilis, Klebsiella species and some strains of enterobacter and enterococci.
AND SKIN STRUCTURE INFECTIONS due to Staphylococcusaureus (penicillin-sensitive
and penicillin-resistant), group A beta-hemolytic streptococci and other strains
BILIARY TRACT INFECTIONS due to Escherichiacoli, various strains of streptococci, Proteus
mirabilis, Klebsiella species
BONE AND JOINT INFECTIONS due to Staphylococcus aureus.
INFECTIONS (i.e., prostatitis, epididymitis) due to Escherichia
coli, Proteusmirabilis, Klebsiella species and
some strains of enterococci.
SEPTICEMIA due to Streptococcus pneumoniae, Staphylococcus
aureus (penicillin-sensitive and penicillin-resistant), Proteus mirabilis, Escherichia
coli and Klebsiella species.
due to Staphylococcus aureus (penicillin-sensitive
and penicillin-resistant) and group A beta-hemolytic streptococci.
culture and susceptibility studies should be performed to determine susceptibility
of the causative organism to cefazolin.
PROPHYLAXIS: The prophylactic administration of cefazolin 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 over 70 years of age,
with acute cholecystitis, obstructive jaundice or common duct bile stones).
perioperative use of cefazolin 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).
prophylactic administration of cefazolin should usually be discontinued within
a 24-hour period after the surgical procedure. In surgery where the occurrence
of infection may be particularly devastating (e.g., open-heart surgery and
prosthetic arthroplasty), the prophylactic administration of cefazolin may
be continued for 3 to 5 days following the completion of surgery.
there are signs of infection, specimens for cultures should be obtained for
the identification of the causative organism so that appropriate therapy may
(See DOSAGE AND ADMINISTRATION.)
reduce the development of drug-resistant bacteria and maintain the effectiveness
of cefazolin, and other antibacterial drugs, cefazolin should be used only
to treat or prevent infections that are proven or strongly suspected to be
caused by susceptible bacteria. When culture and susceptibility information
are available, they should be considered in selecting or modifying antibacterial
therapy. In the absence of such data, local epidemiology and susceptibility
patterns may contribute to the empiric selection of therapy.
CEFAZOLIN IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY
TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.
WITH CEFAZOLIN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE
WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFTAZIDIME,
CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE 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 OCCURS, DISCONTINUE 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
Treatment with antibacterial
agents alters the normal flora of the colon and may permit overgrowth of clostridia.
Studies indicate that a toxin produced by Clostridiumdifficile is one primary
cause of ‘‘antibiotic-associated colitis.’’
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 antibacterial drug clinically effective against C. difficile colitis.
— Prolonged use of cefazolin may result in the overgrowth
of nonsusceptible organisms. Careful clinical observation of the patient is
When cefazolin is administered to patients
with low urinary output because of impaired renal function, lower daily dosage
(See DOSAGE AND ADMINISTRATION.)
with other beta-lactam antibiotics, seizures may occur if inappropriately
high doses are administered to patients with impaired renal function.
DOSAGE AND ADMINISTRATION.)
Cefazolin, 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.
cefazolin in the absence of a proven or strongly suspected bacterial infection
or a prophylactic indication is unlikely to provide benefit to the patient
and increases the risk of the development of drug-resistant bacteria.
— 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
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, should only be used to treat
bacterial infections. They do not treat viral infections (e.g., the common
cold). When cefazolin 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 or other antibacterial
drugs in the future.
— Mutagenicity studies and long-term studies in animals
to determine the carcinogenic potential of cefazolin have not been performed.
— 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. 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.
— Cefazolin is present in very low concentrations
in the milk of nursing mothers. Caution should be exercised when cefazolin
is administered to a nursing woman.
— Safety and effectiveness for use in premature infants
and neonates have not been established. See DOSAGE AND ADMINISTRATION for
recommended dosage in pediatric patients over one month.
The following reactions have been reported:
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.
Hepatic: Transient rise in SGOT, SGPT and alkaline
phosphatase levels has been observed. As with other cephalosporins, reports
of hepatitis have been received.
As with other cephalosporins, reports of increased BUN and
creatinine levels, as well as renal failure, have been received.
Rare instances of phlebitis have been reported at site of
injection. Pain at the site of injection after intramuscular administration
has occurred infrequently. Some induration has occurred.
Genital and anal pruritus (including vulvar pruritus, genital
moniliasis and vaginitis).
DOSAGE AND ADMINISTRATION
NOTE: Cefazolin for injection
in the ADD-Vantage® Vial is not intended for direct intravenous
or intramuscular injection.
Type of Infection
Moderate to severe infections
500 mg to 1 gram
every 6 to 8 hrs.
Mild infections caused by susceptible
250 mg to 500 mg
every 8 hours
Acute, uncomplicated urinary
every 12 hours
every 12 hours
Severe, life-threatening infections
1 gram to 1.5 grams
every 6 hours
*In rare instances, doses of up to
12 grams of cefazolin per day have been used.
Perioperative Prophylactic Use
prevent postoperative infection in contaminated or potentially contaminated
surgery, recommended doses are:
a. 1 gram I.V. or I.M.
administered 1/2 hour to 1 hour prior to the start of surgery.
For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram
I.V. or I.M. during surgery (administration modified depending on the duration
of the operative procedure).
c. 500 mg to 1 gram I.V.
or I.M. every 6 to 8 hours for 24 hours postoperatively.
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
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.
where the occurrence of infection may be particularly devastating (e.g., open-heart
surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin
may be continued for 3 to 5 days following the completion of surgery.
Dosage Adjustment for Patients with Reduced Renal Function
Cefazolin may be used in patients
with reduced renal function with the following dosage adjustments: Patients
with a creatinine clearance of 55 mL/min. or greater or a serum creatinine
of 1.5 mg% or less can be given full doses. Patients with creatinine clearance
rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3.0 mg% can also be
given full doses but dosage should be restricted to at least 8 hour intervals.
Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine
of 3.1 to 4.5 mg% should be given 1/2 the usual dose every 12 hours. Patients
with creatinine clearance rates of 10 mL/min. or less or serum creatinine
of 4.6 mg% or greater should be given 1/2 the usual dose every 18 to 24 hours.
All reduced dosage recommendations apply after an initial loading dose appropriate
to the severity of the infection. Patients undergoing peritoneal dialysis:
See Human Pharmacology.
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 three or four 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 in these patients is not recommended.
Pediatric Dosage Guide
Divided into 3
Divided into 4
Vol. (mL) needed with
of 125 mg/mL
Approximate Single Dose mg/q6h
Vol. (mL) needed with dilution of 125 mg/mL
Divided into 3
Divided into 4
Vol. (mL) needed with
of 225 mg/mL
Approximate Single Dose mg/q6h
Vol. (mL) needed with dilution of 225 mg/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
Preparation of Parenteral Solution
Parenteral drug products should be SHAKEN WELL when reconstituted,
and inspected visually for particulate matter and discoloration prior to administration.
If particulate matter is evident in reconstituted fluids, the drug solutions
should be discarded.
When reconstituted or diluted according
to the instructions below, cefazolin for injection is stable for 24 hours
at room temperature. Reconstituted solutions may range in color from pale
yellow to yellow without a change in potency.
of cefazolin for injection are to be reconstituted only with 0.9% Sodium Chloride
Injection or 5% Dextrose Injection in the 50 mL or 100 mL ADD-Vantage® Flexible
Diluent Containers or with 0.45% Sodium Chloride Injection in the 50 mL
ADD-Vantage® Flexible Diluent Container. Cefazolin for injection
supplied in single-dose ADD-Vantage® Vials should be prepared
as directed below.
INSTRUCTIONS FOR USE
To Open Diluent Container:
overwrap at corner and remove solution container. Some opacity of the plastic
due to moisture absorption during the sterilization process may be observed.
This is normal and does not affect the solution quality or safety. The opacity
will diminish gradually.
Assemble Vial and Flexible Diluent Container:
(Use Aseptic Technique)
Remove the protective covers from the top of the vial and the vial port on
the diluent container as follows:
a. To remove the breakaway
vial cap, swing the pull ring over the top of the vial and pull down far enough
to start the opening (SEE FIGURE 1), then pull straight up to remove the cap
(SEE FIGURE 2).
the breakaway cap has been removed, do not access vial with syringe.
Fig. 1Fig. 2
To remove the vial port cover, grasp the tab on the pull ring, pull up to
break the three tie strings, then pull back to remove the cover (SEE FIGURE
2. Screw the vial into the vial port until it will
go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This
occurs approximately 1/2 turn (180°) after the first audible click (SEE
FIGURE 4). The clicking sound does not assure a seal; the vial must be turned
as far as it will go.
NOTE: Once vial is seated, do not attempt to remove (SEE FIGURE 4).
Recheck the vial to assure that it is tight by trying to turn it further in
the direction of assembly.
4. Label appropriately.
Fig. 3 Fig. 4
To Reconstitute the Drug:
Squeeze the bottom of the diluent container gently to inflate the portion
of the container surrounding the end of the drug vial.
With the other hand, push the drug vial down into the container telescoping
the walls of the container. Grasp the inner cap of the vial through the walls
of the container (SEE FIGURE 5).
Pull the inner cap from the drug vial (SEE FIGURE 6). Verify that the
rubber stopper has been pulled out, allowing the drug and diluent to mix.
Mix container contents thoroughly and use within the specified time.
Fig. 5 Fig. 6
Preparation for Administration:
(Use Aseptic Technique)
Confirm the activation and admixture of vial contents.
Check for leaks by squeezing container firmly. If leaks are found, discard
unit as sterility may be impaired.
Close flow control clamp of administration set.
Remove cover from outlet port at bottom of container.
Insert piercing pin of administration set into port with a twisting
motion until the pin is firmly seated. NOTE: See
full directions on administration set carton.
Lift the free end of the hanger loop on the bottom of the vial, breaking
the two tie strings. Bend the loop outward to lock it in the upright position,
then suspend container from hanger.
Squeeze and release drip chamber to establish proper fluid level in
Open flow control clamp and clear air from set. Close clamp.
Attach set to venipuncture device. If device is not indwelling, prime
and make venipuncture.
Regulate rate of administration with flow control clamp.
WARNING: Do not use flexible container
in series connections.
Ordinarily ADD-Vantage® Vials
should be reconstituted only when it is certain that the patient is ready
to receive the drug. However, cefazolin for injection in ADD-Vantage® vials
is stable for 24 hours at room temperature when reconstituted as directed
(see RECONSTITUTION, ADD-Vantage® Vials and INSTRUCTIONS FOR
USE). (DO NOT REFRIGERATE OR FREEZE CEFAZOLIN SODIUM IN ADD-VANTAGE® VIALS.)
Cefazolin for injection is supplied in ADD-Vantage® Vials
equivalent to 1 gram of cefazolin in packages of 25 (NDC 0074-4732-03).
with other cephalosporins, cefazolin for injection tends to darken depending
on storage conditions; within the stated recommendations, however, product
potency is not adversely affected.
protect from light and store at Controlled Room Temperature 20° to 25°C
(68° to 77°F).
1Bauer, A.W.; Kirby, W.M.M.; Sherris, J.C., and
Turck, M.: Antibiotic Testing by a Standardized Single Disc Method, Am. J.
Clin. Path. 45:493, 1966. Standardized Disc Susceptibility Test, Federal Register