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1- Chemistry
Cefazolin - C14 H13 O4 N8 S3 Na
2- Pharmacolgy
Cefazex® is a first- generation cephalosporin which like other
cephalosporin and penicllins, kills bacteria by interfering in
the synthesis of the bicterial cell wall. Cefazex® binds with
high affinity t o penicllin binding. Proteins (PBPs) in the
baclerial cell wall. this process interferes with peptidoglycan
synthesis. Peptidoglycan is a heteropolymric structure that
provides the cell wall with mechanical stability.
As a resulte bacterial cell wall is weakened, and the call
swells and then ruptures. Cefazex® is bactericidal against a
broad spectrum of bacteria at easily achievable plasmaconcenterations.
The low affinity pencillin- binding protein
PBP’s2a. is responsible for the Cefazex® resistance observed
in some organisms.
3- Toxicology
There is no eidence that Cefazex® is mutagenic. No
embryotoxic effects have been detected in rats, mice or rabbits.
Various degrees of damage to the epithelial cells of the
proximal convoluted tubules may be produced with
500 mg.kg-1 which is equivalent to a single dose of 35g given
to a 70kg adult a dose which far exceeds the dose
recommended for humans.
Carcinogenicity studies have not been performed.
4- Clinical pharmacology
Cefazex® is a bactericldal antibiotic that is active against a
range of bacteria. It is active against ?-hemolytic streptococci,
viridans. Streptococcus pneumoniae, staphylococcus aureus
and staphylococcus epidermidis. The minimum inhibitory
concentration for 50% of isolates (MIC50) is less than 0.5mg
except for staphylococcus epidermidis. Neisseria gonorrhoeae,
Escherrichia coli, Klebsiella spp, Haemophilus influenzae
and Enterrobacter aerogenes are also sensitive at concentrations
of 6mg.l-1 or less. Most starins of Enterobacter cloacae and
indole- positive Proteus and most strains of Enterococci are
resistant, although synergy with gentamicin against Enterococci
has been reported. Pseudomonas, Acinetobacter, and Serratia
spp. are resistant to Cefazex®. Cefazex® has been extensively
evaluated after single and multiple dosing up to 5g daily. The
highest dosage known to have been given is 12g daily. The
normal dose range is 1-4g daily. Cefazex® has no other clinical
pharmacological effects in human.
5- Pharmaco kinetics
Cefazex® has an average plasma half- life of 1.8 h, rising to
15-30h in sever renal impairment and 30-40 h or longer in
anuria.
Renal clearance is about 49.1 ml.min-1 with normal renal
function and decrease to 1.5ml.min-1 in severe renal failure.
Cefazex® is not metabolized. It is excreted unchaged in the
urine primarily by glomerular filtration, and to a lesser extend
by tubular secretion.
Cefazex® is detectabel in concenterations in excess of the
minimum inhibitory concenteration of many common
pathogens in bile, urine, the t onsils, pleural, peritoneal,
synovial fluid and bone.
It does not enter cerebrospinal fluid to any useful extent.
When given to mothers in early pregnancy, Cefazex®
distrbutional was limited t o the fetal body fluids.
Oral adsorption -
Presystemic metabolism -
Plasma half - life
Range 1.6 - 2.2h
Mean 1.8h
Volume of distribution 9.2 1/1.73M2
Plasma proten binding 74 - 86%
6- Metabolism
Cefazex® is not metabolized and is excreted unchanged in
CEFAZEX
Cefazolin
the active form by glomerular filteration and to lesser extent
by tubular secretion.
7- Therapeutic use
Mode of use
Cefazex® is administered only by the parenteral route. The
dosage is dependent upon the severity and site of infection,
the suscceptibility of the infecting microorganisem(s) and the
age, weight, and renal function of the patient. The drug is
adminstered by the intravenous route (by bolus injection or
infusion) or by deep interamuscular injection into a large
muscle mass.
The adult dose range is 1 - 4g daily in doses of 500mg to 1g
twice to four times daily. Many infection can be adequately
treated by a dose of 500mg 8-12 hourly. Urinary tract infecions
can be treated with 500mg to 1g 12-hourly. In severe infactions,
1g 6-hourly recommended.
Indications
1. Respiratory tract infections
Cefazex® has been used in the treatment of a wide variety of
lower respiratory tract infections including infective
exacerbations of chronic bronchitis where daily doses of
2-3g have resulted in good clinical responses and clearance
of sputum purulence.
2- Genitourinary tract infection
One study showed treatment of gonorrhae. One study showed
a treatment failure rate of 42% of a total of 31 men receiving
1g of Cefazex® and 10% of a total of 76 men and 24 women
receiving 2g of the drug. in the case of urinary tract infectione
the limited activity of Cefazex® against uropathogens does
not make it a drug of first choice, although it has been used
and found effective in infections caused by Escherichia Coli,
Klebsiella spp. and Proteus mirabilis.
3- Skin and soft tissue infections
The high activity of Cefazex® against Staphylococus aureus
and Streptococus pyogenes has been confirmed by its effecacy
in treating a wide range of skin and soft tissue infections.
4- Bone and joint infections
Although demonstrating satisfactory concentrations in joint
fluid, bone and capsular materials, Cefazex® is not widely
used in the treatment of bone infection. Although
staphylococcal arthritis has responded satisfactorily.
5-Septicemia
Cefazex® has proved effective in the treatment of a variety
of infection complicated by septicemia, such as staphylococcal.
Pneumococcal, and streptococcal pyoderma.
6-Endocarditis
Cefazex® has been used in the treatment of bacterial
endocarditis although, in general, there is a lack of adequate
comparative data supporting clinical efficacy of the
cephalosporins in bacterial endocarditis.
7- Surgical prophylaxis
Cefazex® has been widely used in the chemoprophylaxis of
biliary tract surgery owing to the high biliary concentrations
achievable.
Contraindications
1- Hypersensivity to cephalosporins
2- History of hypersensivity to penicillins
8- Advers reactions
Potentially life - threatening effects
Anaphylactic reactions and pseudomemdranous colitis may
be occured.
Symptomatic adverse effects
Hypersensivity reactions (5%), hematological effects
(neutropenia, leukopenia, thrombocytopenia, and eosinophilia),
neurological effects such as convulision, gasterointestinal
effects (nausea, diarrhea and anorexia), genital and anal
pruritus.
Interference with clinical pathologys tests
A positive direct indirect coombs test and false-positive
reaction for glucose in urine is recongnized. A transient rise
in AST(SGOT), ALT (SGPT) and blood urea levels has been
reported.
9- High risk groups
Neonates
Cefazex® is not recommended for use in neonate showever,
doses of 40-60 mg.kg-1 daily have been suggested.
Breast milk
Cefazex® is excreted in human milk but unlikely makes
problems in the feeding infants.
Children
Children a total daily dose of 25-50 mg.Kg-1 daily, increased
to 100 mg.kg-1 per day in severe infections, is recommended.
Pregnant woman
Cefazex® is best avoided during this period unless no safer
treatment is available.
The elderly
No spical precaution are required for the use of Cefazex®.
Concurrent disease
In patients with renal impairment Cefazex® is not readily
excreted, therefore doses should be reduced when creatinine
clearance falls below 35 ml.min-1.
10- Drug intractions
Potentially hazarduse interactions
Loop diuretics. Such as furosemide and ethacrynic acid may
increase the risk of renal toxicity.
Aminoglycosides. Caution should be exercised with other
nephrotoxic drugs such as aminoglycosides.
Anticoagolants. The prothrombin time may be prolonged.
Qunolone antibiotics. Caution should be advised when these
agents are combined in patiants at risk of seizures.
Potententially usefull interactions
Probenecid blocks the secretion of Cefazex® thereby increasing
the serum levels and prolonging the half-life.
Storage
Prior to reconstitution, store below 30ºC. Protect from light.
Packaging
Boxes of 12 vials, for injection
60
R CEFAZEX
Cefazolin(as Sodium) Vial
500, 1000 mg
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