CEFAZOLIN SANDOZ 0.5 G

Page 1 of 13

SUMMARY OF PRODUCT

CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Cefazol 1g

powder for solution for

injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Cefazol 1g - powder for solution for

injection

Each vial contains 1.048 g cefazolin as sodium salt (equivalent to 1 g

cefazolin

The sodium content of each vial is 2.2 mmol. (48 mg per 1 g cefazolin).

For a full list of excipients see section

6.1.

3.

PHARMACEUTICAL

FORM

Powder for solution for injection

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Treatment of serious infections caused by susceptible organisms and also perioperatively for

prophylaxis.

Treatment Respiratory tract: Respiratory tract infections due to streptococcus pneumoniae

(formerly diplococcus pneumoniae) klebsiella species haemophilus influenzae

staphylococcus aureus (penicillin sensitive and penicillin-resistant) and group A B - hemolytic

streptococci.

Cefazol is effective in the eradication of streptococci from the nasopharynx.

However data establishing the efficacy of cefazol in the subsequent prevention of rheumatic

fever are not available at present.

Urinary tract: Infections due to escherichia coli klebsiella species proteus mirabilis and some

strains of Enterobacter and enterococci.

Skin and skin structure: -hemolytic beta Infections due to Staphylococcus aureus (penicillin-

sensitive and penicillin resistant) group A streptococci and other strains of streptococci.

Biliary tract: Infections due to Escherichia coli various strains of streptococci proteus mirabilis

klebsiella species and staphylococcus aureus.

Bone and joint : Infections due to staphylococcus aureus.

Genital infections (i.e. prostatitis epididymitis) due to escherichia coli proteus mirabilis

klebsiella species and some strains of enterococci.

Septicemia due to streptococcus pneumoniae (formerly diplococcus pneumonia)

staphylococcus aureus (penicillin-sensitive and penicillin-resistant) proteus mirabilis

escherichia coli and klebsiella species.

Endocarditis caused by staphylococcus aureus (penicillin-sensitive and penicillin-resistant)

and group A beta-hemolytic streptococci.

Appropriate culture and susceptibility studies should be performed to determine the

susceptibility of the causative organism to cefazol.

Perioperative prophylaxis: The prophylactic administration of cefazol perioperatively

(preoperatively intraoperatively and postoperatively) may reduce the incidence of certain

postoperative infections in patients undergoing surgical procedures (e.g. hysterectomy

gastrointestinal surgery and transurethral prostatectomy) that are classified as contaminated

or potentially contaminated. The perioperative use of cefazol may also be effective in surgical

patients in whom infection at the operative site would present a serious risk (e.g. open-heart

surgery and prosthetic arthroplasty) .

Page 2 of 13

4.2

Posology and method of

administration

Posology

The dosage depends on pathogen sensitivity and the severity of the disease.

Adults

The recommended dosage for adults is shown in the table

below:

Type of

infection

Dose

Dosing

interval

Total daily

dose

Mild infections (caused by

Gram-positive

pathogens)

500 mg

every 8 hours

every 12 hours

1.5 g

Uncomplicated urinary tract

infections

every 12 hours

Moderately severe to severe

infections (caused by Gram-

negative pathogens)

every 6 - 8 hours

3g-4g

Life-threatening infections

1g - 1.5 g

every 6 hours

4g-6g

In individual cases, dosages of up to 12 g have been given.

In adult patients with renal dysfunction

, the following dosage schedule should be observed:

Creatinine

clearance

(ml/min x 1.73

m

2

)

Serum

creatinine

(mg/100

ml

)

Daily

dose

Dosing interval

>

<1.5

normal

dose

unchanged

35-54

1.6-3.0

normal

dose

12-hour interval

11-34

3.1-4.5

half the normal

dose

12-hour interval

<

>

quarter of the

normal

dose

24-hour interval

patients

undergoing

haemodialysis,

dosage

depends

dialysis

conditions.

In perioperative use to prevent infection, the dose depends on the type and duration of

the surgical procedure. The following dosages are recommended:

30 minutes to one hour before surgery, a starting dose of 1 g to 2 g is administered IV or IM.

For surgery of longer duration (2 hours or more), a further 500 mg to 1 g is administered

IV or IM during the operation. The dose level and time of administration depend on the

nature and duration of the surgical procedure.

Postoperatively,

500 mg to 1 g are given IV or IM over 24 hours at intervals of 6 to 8

hours.

possible infections

might

particularly dangerous for the

patient

(e.g.

following

heart surgery or major orthopaedic procedures such as joint replacement), it is advisable

to continue postoperative administration of cefazolin for 24 to 48 hours after surgery.

Elderly

patients

No dose adjustment is necessary for elderly patients with normal renal function.

Children and

adolescents

A total daily dose of 25 - 50 mg/kg BW, divided in 3 - 4 single

doses,

effective

for most

mild

moderately

severe

infections.

For severe

infections,

the total dose can be

increased

to the

maximum recommended

dose

of 100 mg/kg

Page 3 of 13

Dosage

instructions for infants. toddlers and children (guideline

values)

Body

weight

25 mg/kg daily in 3

doses

25 mg/kg daily in 4

doses

Dosing interval

approx. 8

hours

Volume to

withdrawn

concentration

mg/ml

Dosing interval

approx.

hours

Volume

withdrawn

concentration

mg/ml

0.35

0.25

0.45

13.5

0.7ml

18.0

0.9ml

22.5

Body

weight

50 mg/kg daily in 3

doses

50 mg/kg daily in 4

doses

Dosing interval

approx.

hours

Volume

withdrawn

concentration of

mg/ml

Dosing interval

approx.

hours

Volume to

withdrawn

concentration of

mg/ml

0.35

0.25

0.7ml

13.5

0.75

18.0

300mg

1.35

22.5

285 mg

1.25

Full-term newborn infants: Safety of use in full-term

newborn

infants has not

been

established

(see section

Children with renal

dysfunction

Creatinine clearance

(ml/min

x 1.73 m

Cefazolin

dose

mg/kg

Dosing

interval

>

7 {up to 500

mg/dose)

25-50

10-25

24-36

<

48-72

Children undergoing haemodialysis

are given 7 mg/kg BW at the start of the

therapy.

serum

cefazolin

level is

reduced

by 35% to 65% during

dialysis,

a dose of 3

to 4

mg cefazolin/kg

BW is

administered

subsequent dialysis-free interval

(dialysis

interval =72

hours)

Duration of

treatment

The duration of

treatment depends

on the course of the

disease.

As is

customary with

antibiotic therapy, cefazolin

should be given for a further 2

3 days after the patient

become

afebrile or proof is

obtained

that the

pathogens

have been

eliminated.

Method of administration

The prepared solution is administered deep into the muscle or intravenously (see also

section 6.6

Intramuscular

use

For intramuscular use,

the medicine should be dissolved in 0.5% lidocaine solution.

Intramuscular doses (maximum 1 g) should be injected into a large muscle mass.

administration should be used only for uncomplicated infections

Reconstitution takes place with

0.5% lidocaine solution according to the following dilution

table.

Page 4 of 13

Volume of solvent

Vial size

500 mg

Intravenous

use

For preparation of solutions for IV injection or infusion, the powder is dissolved in water for

injections or 0.9% sodium chloride solution.

Cefazol 1g

powder for

solution

for injection:

For each gram of powder, at least 4 ml of the solvent must be used.

Preparation of solution for IV infusion: The reconstituted solution (prepared as described above)

has to be transferred into a suitable infusion bag or bottle with 50 - 100 ml 0.9% sodium chloride

solution.

Intermittent intravenous

infusion

Higher daily doses

4- 6 g in 2- 3 single doses) are administered by IV infusion (over 20 to

30 minutes).

Direct intravenous

injection

Up to a dose of 1g, cefazol can be administered by slow IV injection (over 3

5 minutes)

directly into a vein or through the cannula.

Solutions of cefazol in lidocaine must not be given intravenously.

4.3

Contraindications

This medicinal product must not be used in cases of known hypersensitivity to cefazolin or other

cephalosporins

patients

have

previously

shown

immediate

and/or

severe

hypersensitivity reactions to penicillin or to any other beta-lactam antibiotic.

For use in children of less than 30 months of age, cefazol must not be dissolved in lidocaine

solutions.

- Hypersensitivity to lidocaine (IM administration).

4.4 Special warnings and precautions for

use

Particular caution is required in patients with an allergic diathesis, with bronchial asthma or hay

fever. Prior to administering cefazol

previous hypersensitivity reactions to other beta-lactams

(penicillins or cephalosporins) must be investigated.

patients

exhibiting

allergic

reactions, the

product

must

discontinued and appropriate

symptomatic therapy instituted. Serious acute hypersensitivity reactions may require adrenaline

(epinephrine) and other emergency measures, including oxygen, i.v. fluids, i.v. antihistamines,

corticosteroids, pressor amines and airway management, as clinically indicated.

Cross-allergy with other cephalosporins and occasional cross-allergies with penicillins must be

borne in mind. In cases of known hypersensitivity to penicillin, cross-allergy with other beta-

lactams, e.g. cephalosporins, must be taken into account. 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.

Severe

hypersensitivity

reactions

(anaphylaxis)

with

occasional

fatal

outcomes

have

been

reported in patients undergoing treatment with beta-lactam antibiotics (see section 4.8). These

reactions are more likely to occur in persons with a history of known hypersensitivity to beta-

lactam antibiotics.

In patients with impaired renal function, the dosage and/or dosing frequency must be adjusted to

the degree of renal

dysfunction

(see section 4.2).

As with other

-lactam antibiotics, seizures may

occur if inappropriately high doses are administered to patients with impaired renal function.

While cefazolin only rarely causes

renal

impairment, monitoring of renal function is nonetheless

recommended, especially ·in severely ill patients receiving maximum doses and patients

Page 5 of 13

under concomitant

treatment

with

other potentially nephrotoxic medicinal products, such

aminoglycosides or potent diuretics (e.g. furosemide).

As with all cephalosporins, Cefazolin should be prescribed with caution in individuals with a history

of gastrointestinal disease, particularly colitis.

Coagulation disorders

may rarely

occur during

treatment with

cefazolin.

At risk are patients

with

risk

factors leading

vitamin K

deficiency or

affecting

other coagulation mechanisms

(parenteral nutrition, malnutrition, impaired hepatic and renal function, thrombocytopenia). The

same

applies to

comorbidities

(e.g.

haemophilia,

gastrointestinal

ulcers)

that

trigger

aggravate haemorrhages

Prothrombin values should therefore be monitored in such cases. If

these values are reduced, vitamin K replacement should be given (10 mg/week).

In the event of severe and persistent diarrhoea, antibiotic-associated pseudomembranous colitis

should be considered, which can be life-threatening. Cefazolin should therefore be discontinued

immediately

such

cases

appropriate

therapy

instituted.

Antiperistaltic

agents

contraindicated.

During long-term use of cefazolin, non-sensitive pathogens may proliferate. Patients

should therefore be carefully monitored. If superinfection occurs, appropriate measures should be

taken. 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.”

In patients with hypertension or heart failure, the sodium content of the solution for injection

must be taken into account (48 mg per 1g cefazolin).

Children and adolescents

Cefazol should not be

administered

to premature and newborn infants of less than one month of

age, as no experience is available and the safety of such use has not been demonstrated.

Athletes should bear in mind that positive results may be obtained in anti-doping tests when

cefazol is dissolved in lidocaine.

Not for intrathecal use.

Prescribing cefazol 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.

4.5 Interaction with other medicinal

products

and other forms of interaction

Concomitant administration

contraindicated

Antibiotics

Cefazol must

administered

together with

antibiotics

with

bacteriostatic

activity (e.g.

tetracyclines, sulphonamides, erythromycin, chloramphenicol), as antagonistic effects have been

observed during in vitro tests.

Concomitant administration not

recommended

Probenecid

Renal clearance of cefazol is reduced when probenecid is co-administered.

Precautions

Vitamin

K1

Some cephalosporins

such

cefamandole, cefazolin and

cefotetan

interfere with the

metabolisation of

vitamin

particularly in

cases

vitamin

deficiency.

Substitution of

vitamin K1 may therefore be necessary.

Page 6 of 13

Anticoagulants

Cephalosporins may, in very rare cases, lead to coagulation disorders (see section 4.4.).

oral

anticoagulants or high heparin doses are adjuvantly administered, coagulation values must be

monitored.

Nephrotoxic

substances

It cannot be ruled out that the nephrotoxic effect of antibiotics (e.g. aminoglycosides, colistin,

polymyxin

diuretics

(e.g.

furosemide) may

aggravated.

co-administered with

cefazolin, renal function tests should be carefully monitored.

Laboratory tests

Laboratory tests may

give a

false-positive response for urine glucose if Benedict's solution,

Fehling's solution or Clinitest® tablets are used, but not when enzyme-based detection methods

are applied.

The indirect and direct Coombs' test can also give false-positive results. This may also apply to

newborn infants whose mothers have been receiving cephalosporins.

Oral

contraceptives

Cefazolin may influence the efficacy of hormonal contraceptives. For this reason, use of

additional birth

control methods besides hormonal contraceptives is

recommended during

course of treatment with cefazol.

4.6 Fertility,

pregnancy

and

lactation

Pregnancy

To date, there. is insufficient experience for the use of cefazol during human

pregnancy.

Hence, cefazol should only be used during pregnancy after careful benefit/risk

assessment.

This applies particularly to the first trimester. Cefazol crosses the

placenta.

Lactation

Cefazol is excreted in human milk at low concentrations. In breast-fed infants,

sensitisation

and changes

in the intestinal

flora and Candida

infections may

occur.

In these

cases,

breast-

feeding should be suspended during

treatment.

4.7 Effects on ability to drive and use

machines

Cefazol has no influence or negligible influence on the ability to drive and

machines.

However, some adverse reactions (e.g. vertigo, headache,

paraesthesia,

agitation, seizures;

see section 4.8) may affect the ability to concentrate and reaction

times

and may therefore

impair the ability to drive or use

machines.

4.8

Undesirable

effects

The undesirable effects are categorised as

follows:

Very

Common: ≥ 1/10

Common: ≥ 1/100 to < 1/10

Uncommon: ≥ 1/1,000 to <1/100

Rare: ≥1/10,000 to <1/1,000

Very rare: < 1/10,000 .

Not known: cannot be estimated from the available

data

System organ

classes

Common

Uncommon

Rare

Very rare

Not known

Infections and

Infestations

Long-term

treatment or

repeated use

lead

superinfections

Page 7 of 13

System organ

classes

Common

Uncommon

Rare

Very rare

Not known

colonisation

with

resistant

bacteria

or yeast-like fungi

(oral

thrush,

vaginal

candidiasis)

Blood and

lymphatic

system

disorders

Thrombocytopenia,

neutropenia,

leukopenia,

eosinophilia,

agranulocytosis,

haemolytic

anaemia

Coagulation

disorders,

haemorrhages

Leukocytosis,

granulocytosis,

monocytosis,

lymphocytopenia,

basophilia,

reduced

haemoglobin

and/or

haematocrit,

aplastic anaemia,

pancytopenia

Immune

system

disorders

Allergic

skin

reactions

such

erythema,

generalized

exanthema,

Urticaria and

pruritus

Serious

hypersensitivity

reactions such

Angioderma and

drug fever

Life-

threatening

anaphylacti

c shock

Erythema

exsudativum

multiform

Interstitial

pneumonia

pneumonitis,

Lyell´s

syndrome,

Stevens-

Johnson

syndrome

Nervous

system

disorders

Headache,

dizziness,

malaise,

tiredness, vertigo,

paraesthesia,

excitation of

central

nervous

system,

hyperactivity,

nervousness or

anxiety,

sleeplessness,

sleepiness,

weakness,

flushes,

colour

perception

changes

confused

states,

myoclonus,

seizures§

convulsive fits§,

aseptic

meningitis,

Gastrointestinal

disorders

Diarrhoea,

nausea, loss

appetite,

flatulence,

abdominal

Pseudomem-

branous colitis+

Page 8 of 13

System organ

classes

Common

Uncommon

Rare

Very rare

Not known

pain#

Hepatobiliary

disorders

Mild,

transient

elevation of

AST,

ALT and

alkaline

phosphatase

Reversible

hepatitis

cholestatic

jaundice

Raised

GGT,

bilirubin

and/or

Renal

and

urinary

disorders

Interstitial

nephritis

other

renal

disorders$

Transient rise

levels

(blood,

urea,

nitrogen)

serum

creatinine

concentrations,

nephrotoxicity$

General

disorders

and

administration

site

conditions

Phlebitis,

thrombophlebitis

Chest

pains,

pleural

effusion,

dyspnoea

respiratory

distress,

cough,

rhinitis, raised

lowered

serum

glucose

concentration,

genital and

anal

pruritus,

genital

moniliasis,

vaginitis,

pain

from

administration.

Photosensitive

phenomena have

been described

* At risk are patients with risk factors leading to vitamin K deficiency or affecting other

coagulation

mechanisms

as well as patients with disorders that can trigger or

aggravate

haemorrhages.

* * Symptom, which may require appropriate immediate emergency

measures.

§

Particularly in the event of an overdose or unadjusted dosage in patients with

renal

impairment.

# In most cases, the symptoms are mild in nature and often resolve, if not during, then after

discontinuation of

treatment.

+ In the event of severe and persistent diarrhoea during or after treatment with cefazol,

doctor must be consulted, as this may a sign of a severe condition

(pseudomembranous

colitis), which must be treated immediately (e.g.

with

vancomycin oral

250 mg

times

daily). The patient must refrain from all self-medication with antiperistaltic

agents.

$ Mostly occurring in severely ill patients receiving several medicinal

products.

Reporting of suspected adverse reactions

Suspected adverse reactions should be reported by the physician or other healthcare provider to

Ministry

Health

according

National

Regulation

using

online

form

(https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic%40

moh.gov.il)

email

(adr@MOH.HEALTH.GOV.IL

Additionally,

should

also

report

to

www.perrigo‐pharma.co.il.

Page 9 of 13

4.9

Overdose

Symptoms of

overdose:

overdose

cause

pain,

inflammatory

reactions

phlebitis

injection

site.

Administration of very high parenteral cephalosporin doses can result in vertigo, paraesthesia

headache. Particularly

patients

with

renal

disease, seizures

occur

following an

overdose with

cephalosporins.

The following abnormal laboratory test results may occur after an overdose:

elevated

creatinine values, BUN, liver enzyme values and bilirubin; positive Coombs'

test;

thrombocytosis and thrombocytopenia, eosinophilia, leukopenia and prolongation of

prothrombin

time.

Treatment of an

overdose:

If seizures occur, the product must be discontinued immediately. Treatment

with

anticonvulsants

may be indicated. Vital body functions and relevant laboratory

parameters

must be very carefully

monitored. In the event of a severe overdose, a combination

haemodialysis and haemoperfusion

beneficial

other

treatments are

unsuccessful,

although

supportive

data to this are

lacking. Peritoneal dialysis is

ineffective.

5.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic

properties

Pharmacotherapeutic group: other beta-lactam antibiotics, 1

-generation

cephalosporins

ATC code:

J01DB04

Mode of

action

The mechanism of action of cefazolin is based on inhibition of bacterial cell wall synthesis

growth phase), due to blockade of penicillin-binding proteins (PBPs),

e.g.

transpeptidases. This

results in a bactericidal

action.

Pharmacokinetic/pharmacodynamic relationship

Efficacy largely depends on the length of time during which the active substance

level

remains

above the minimum inhibitory concentration (MIC) of the

pathogen.

Resistance

mechanisms

Resistance to cefazolin can be due to the following

mechanisms:

Inactivation

by beta-lactamases:

cefazolin is

largely stable against penicillinases

Gram-positive bacteria, although it has only low stability against numerous

plasmid-

encoded

beta-lactamases, e.g. extended-spectrum beta-lactamases (ESBLs)

chromosome-encoded

beta-lactamases of the AmpC

type.

Reduced

affinity

PBPs

cefazolin:

acquired

resistance

pneumococci

other

streptococci is due to modifications of PBPs present as a result of a

mutation.

However, the formation of an additional PBP with reduced affinity for cefazolin

responsible

for resistance in methicillin (oxacillin)-resistant

staphylococci.

In Gram-negative bacteria, insufficient penetration of cefazolin through the outer

cell

wall can lead to insufficient PBP

inhibition.

Cefazolin can be actively transported from the cell by efflux pumps.

Cefazolin is partially or completely cross-resistant with other

cephalosporins

penicillins.

Breakpoints

Cefazolin is tested using the standard dilution series. The following minimum

inhibitory

concentrations for susceptible and resistant germs have been

established:

EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints

(2011-

01-05, version

Page 10 of 13

Pathogen

Susceptibility

Resistance

Staphylococcus

spp.

Streptococcus group A, B, C,

Other streptococci

< 0.5 mg/1

> 0.5 mg/1

Non-species-specific

breakpoints

1 mg/1

> 2 mg/1

* Susceptibility of staphylococci to cefazolin can be derived from their susceptibility to

cefoxitin.

** Beta-lactam susceptibility of. group A, B, C and G beta-haemolytic streptococci can be

derived from their susceptibility to penicillin.

§ For endocarditis, see national or international endocarditis guidelines for Streptococci

viridans breakpoints.

Susceptibility

For individual species, the prevalence of acquired resistance may vary geographically and

over time. Therefore, local information on the resistance situation is required, particularly for

the adequate treatment of severe infections. If, based on the local resistance situation, the

·efficacy of cefazolin is

questionable,

expert

therapeutic

advice should be sought.

Usually susceptible

species

Gram-positive

aerobes

Staphylococcus aureus

(methicillin-sensitive)°

Staphylococcus saprophyticus °

Streptococcus agalactiae°

Streptococcus

pneumoniae

Streptococcus pyogenes

Species, in which acquired resistance may pose a

problem

during

use

Gram-positive

aerobes

Staphylococcus aureus

Staphylococcus epidermidis

Staphylococcus haemolyticus

Staphylococcus hominis

Staphylococcus pneumoniae (penicillin-intermediate)

Gram-negative

aerobes

Escherichia

coli

Haemophilus influenzae

$

Page 11 of 13

Klebsiella

oxytoca

Klebsiella

pneumoniae

Proteus

mirabilis

Naturally resistant species

Gram-positive

aerobes

Enterococcus

spp.

Staphylococcus aureus

(methicillin-sensitive)

Staphylococcus pneumoniae

(penicillin-resistant)

Gram-negative

aerobes

Acinetobacter

baumannii

Citrobacter

freundii

Enterobacter

spp.

Morganella

morganii

Moraxella

catarrhalis

Proteus

vulgaris

Pseudomonas

aeruginosa

Serratia

marcescens

Stenotrophomonas

maltophilia

Anaerobes

Bacteroides

fragilis

Other

micro-organisms

Chlamydia

spp.

Chlamydophila

spp.

Legionella

spp.

Mycoplasma

spp.

° Susceptibility is assumed in the primary literature, standard works and therapeutic

recommendations.

$ Natural susceptibility of most isolates lies within the intermediate range.

+ The rate of resistance is over 50% in at least one region.

No current data available; in studies (more than 5 years old), the proportion of resistant

strains is stated to be> 50%.

Outside the hospital setting, the

resistance

rate is< 10%.

Further

information

Penicillin-resistant Streptococcus pneumoniae is cross-resistant to

cephalosporins

such

cefazolin.

5.2

Pharmacokinetic

properties

Cefazol is administered parenterally. Peak plasma levels

are(reached

after IM

injection

within 30 to 75

minutes.

Plasma concentrations

(µg/ml)

after intramuscular

administration.

Dose

30 min

500 mg 36.2 36.8 37.9 15.5 6.3 3

60.1

63.8

54.3

29.3

13.2

Page 12 of 13

Plasma concentrations

g/ml}

after intravenous administration of 1

5 min 15 min 30 min 1 h 2 h 4h

188.4

135.8

106.8

73.7

45.6

16.5

Approximately 65 - 92% of cefazolin is bound to plasma proteins. Cefazolin has

good

penetration into tissue such as skeletal muscles, myocardium, bone, bile and

gallbladder,

endometrium

and vagina. Cefazolin penetrates the placental barrier and is also excreted

human milk. Diffusion

into cerebrospinal fluid and aqueous humour is

inadequate.

Cefazolin is not metabolised. It is excreted in the microbiologically active form mainly via

kidneys

by means of glomerular filtration. A small moiety is excreted via the bile. The

plasma

elimination half-

life is approximately two hours; in patients with renal insufficiency,

plasma half-life may be

prolonged.

5.3 Preclinical safety

data

Repeated administration of cefazolin to dogs and rats using different routes of injection

over

a period

of one to six months showed no significant effects on biochemical

haematological

values. Signs of neurotoxicity were seen in some

studies.

After IM injection, cefazolin is only poorly tolerated at the injection

site.

In studies on rabbits, the kidney appeared to be the target organ, though not in rats

and dogs.

Cefazolin showed no teratogenic activity and did not affect general reproductive

functions.

No studies

are available concerning mutagenicity and

carcinogenicity.

6.

PHARMACEUTICAL PARTICULARS

6.1 List of

excipients

None.

6.2

Incompatibilities

Cefazolin is incompatible with amikacin disulphate, amobarbital sodium, ascorbic

acid,

bleomycin

sulphate, calcium glucoheptonate, calcium gluconate, cimetidine

hydrochloride,

colistin

methanesulphonate

sodium, erythromycin glucoheptonate, kanamycin

sulphate,

oxytetracycline

hydrochloride, pentobarbital sodium, polymyxin B sulphate and

tetracycline

hydrochloride

6.3

Shelf life

3 years

After reconstitution:

From a microbiological point of view, the ready-to-use solution should be used immediately. If not

used immediately, the observance of storage times and

conditions

prior to administration are the

responsibility of the user. After reconstitution, a period of 24 hours at 2

-

8°C must not be

exceeded, unless the preparation took place

under

controlled and validated aseptic

conditions.

6.4 Special precautions for storage

Powder for solution for injection or infusion:

Store below 25°C. Keep the container in the outer carton in order to protect

from light.

Prepared solution:

Store in a refrigerator

2°C

8°C).

Page 13 of 13

6.5 Nature and contents of container

Nature

15 ml

-clear

glass vials, class Ill (Ph.Eur.), with halogenated isobutene-isoprene rubber stopper with flip-

off crimp cap.

Contents

Vials in packs of: 10 and 25 per box.

6.6 Special precautions for disposal and other handling

Cefazol 1g

powder for solution for injection:

To prepare an IV solution for injection, the powder is dissolved in water for injections or in

0.9% sodium chloride solution. For this, at least 4 ml solvent per gram of powder is used.

Intramuscular injections should be administered into a large muscle mass. For IM administration, the

product should be dissolved in a 0.5% lidocaine solution. 500 mg and 1

powder are dissolved in 2 ml and 4

ml, respectively.

Use only freshly prepared, clear and colourless

solutions.

For single withdrawal only.

Any unused solution should be

discarded.

The prepared solution should be visually inspected for particles and discolouration prior

administration. The prepared solution is

clear.

7.

MANUFACTURER

Sandoz GmbH,

BIOCHEMIESTRASSE 10, A-6250 KUNDL, AUSTRIA

8.

REGISTRATION HOLDER

Perrigo Israel Agencies Ltd. 29 Lehi st., Bnei-Brak 51200

9.

MARKETING

AUTHORISATION NUMBER

Cefazol 1g 141-70-31813-00

General classification for

supply

Medicinal product subject to medical prescription only.

The content of this leaflet was checked and approved by the Ministry of Health in May 2015.

30.07.2015