Included as part of the PRECAUTIONS section.
Hypersensitivity Reactions To Cefazolin, Cephalosporins,
Penicillins, Or Other Beta-lactams
Serious and occasionally fatal hypersensitivity
(anaphylactic) reactions have been reported in patients receiving beta-lactam
antibacterial drugs. Before therapy with cefazolin for injection is instituted,
careful inquiry should be made to determine whether the patient has had
previous immediate hypersensitivity reactions to cefazolin, cephalosporins,
penicillins, or carbapenems. Exercise caution if this product is to be given to
penicillin-sensitive patients because cross-hypersensitivity among beta-lactam
antibacterial drugs has been clearly documented and may occur in up to 10% of
patients with a history of penicillin allergy. If an allergic reaction to
cefazolin for injection occurs, discontinue the drug.
Use In Patients With Renal Impairment
As with other beta-lactam antibacterial drugs, seizures
may occur if inappropriately high doses are administered to patients with
impaired renal function (creatinine clearance less than 55 mL/min.) [see
DOSAGE AND ADMINISTRATION].
Clostridium Difficile-associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD)
has been reported with use of nearly all antibacterial agents, including
cefazolin, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon
leading to overgrowth of C. difficile.
C. difficile produces toxins A and B, which
contribute to the development of CDAD. Hypertoxinproducing 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.
Risk Of Development of Drug-resistant Bacteria
Prescribing cefazolin for injection in the absence of
proven or strongly suspected bacterial infection or a prophylactic indication is
unlikely to provide benefit to the patient and increases the risk of the development
of drug-resistant bacteria.
As with other antimicrobials, prolonged use of cefazolin
for injection may result in overgrowth of nonsusceptible microorganisms.
Repeated evaluation of the patient's condition is essential. Should superinfection
occur during therapy, appropriate measures should be taken.
Drug/Laboratory Test Interactions
The administration of cefazolin may result in a
false-positive reaction with glucose in the urine when using CLINITEST® tablets.
It is recommended that glucose tests based on enzymatic glucose oxidase reactions
(e.g., CLINISTIX®) be used.
Positive direct Coombs' tests have been reported during
treatment with cefazolin. In hematologic studies or in transfusion
cross-matching procedures when antiglobulin tests are performed on the minor
side or in Coombs' testing of newborns whose mothers have received
cephalosporin antibacterial drugs before parturition, it should be recognized
that a positive Coombs' test may be due to the drug.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Mutagenicity studies and long-term studies in animals to
determine the carcinogenic potential of cefazolin for injection have not been
1 Clinical Laboratory Standards Institute (CLSI). Methods
for Dilution Antimi crobial Susceptibility Tests for Bacteria that Grow
Aerobically; Approved Standard-Ninth Edition. CLSI Document M07-A9. CLSI, 940
West Valley Road, Suite 2500, Wayne, PA, 2012.
2 Clinical Laboratory Standards Institute (CLSI). Performance
Standards for Antimicrobial Susceptibility Testing; Twentieth Informational
Supplement. CLSI document M100-S20. CLSI, Wayne, PA, 2010.
3 Clinical Laboratory Standards Institute (CLSI). Performance
Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard-
Eleventh Edition. CLSI Document M02-A11. CLSI, Wayne, PA, 2012.
Use In Specific Populations
Pregnancy Category B
Reproduction studies have been performed in rats, mice
and rabbits at doses of 2000, 4000 and 240 mg/kg/day or 1 to 3 times the
maximum recommended human dose on a body surface area basis. There was no
evidence of impaired fertility or harm to the fetus due to cefazolin.
Labor And Delivery
When cefazolin has been administered prior to caesarean
section, drug concentrations 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 beexercised when cefazolin for
injection 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 older than 1 month.
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 and WARNINGS
Patients With Renal Impairment
When cefazolin for injection is administered to patients
with low urinary output because of impaired renal function (creatinine
clearance less than 55 mL/min.), lower daily dosage is required [see DOSAGE
AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].