DBL™ Cefepime Powder for Injection

New Zealand - English - Medsafe (Medicines Safety Authority)

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Active ingredient:
Cefepime dihydrochloride monohydrate 1 g
Available from:
Pfizer New Zealand Limited
INN (International Name):
Cefepime dihydrochloride monohydrate 1 g
Dosage:
1 g
Pharmaceutical form:
Powder for injection
Composition:
Active: Cefepime dihydrochloride monohydrate 1 g Excipient: Arginine
Units in package:
Vial, glass, single dose, Type I clear glass 20 mL vial with a grey bromobutyl rubber closure and Al flip-off green seal, 1 g
Class:
Prescription
Prescription type:
Prescription
Manufactured by:
Orchid Chemicals and Pharmaceuticals Limited
Therapeutic indications:
Indicated for the treatment of lower respiratory tract infections, including pneumonia and bronchitis, when caused by susceptible bacteria.
Product summary:
Package - Contents - Shelf Life: Vial, glass, single dose, Type I clear glass 20 mL vial with a grey bromobutyl rubber closure and Al flip-off green seal - 1 g - 24 months from date of manufacture stored at or below 25°C protect from light 24 hours reconstituted stored at 2° to 8°C (Refrigerate, do not freeze) protect from light
Authorization number:
TT50-8887
Authorization date:
2011-08-22

Data Sheet – New Zealand

Hospira 3.0

Page 1 of 12

DBL

TM

CEFEPIME POWDER FOR INJECTION

NAME OF THE MEDICINE

Cefepime (as hydrochloride monohydrate) powder for solution for injection

PRESENTATIONS

Cefepime hydrochloride is a semi-synthetic broad spectrum cephalosporin antibiotic for

parenteral

administration.

chemical

name

Pyrrolidinium,

1-[[7-[[2-amino-4-

thiazolyl)(methoxyimino)acetyl]-amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-

3-yl]methyl]-1-methyl-,chloride, monohydrochloride, monohydrate, [6R- [6

(Z)]].

Cefepime hydrochloride is a white to pale yellow powder. It is highly soluble in water. It has

a pH of between 4.0 and 6.0.

Cefepime Powder for Injection is a sterile lyophilised powder for injection containing

the inactive ingredient L-arginine to control the pH of the reconstituted solution at 4.0 to 6.0.

Following reconstitution with Water for Injection as directed in labelling, it results in a pale

yellow to amber coloured, clear solution.

Each 20 mL vial contains either 1.914 g or 3.828 g of sterile cefepime – L-arginine powder,

which is equivalent to 1 g or 2 g of cefepime and approximately 725 mg of arginine per gram

of cefepime. It contains no antimicrobial preservative and is for use in one patient only.

USES

Actions

Cephalosporins act by interfering with bacterial cell-wall synthesis, leading to lysis of the

infectious organism.

Pharmacokinetics

In Adults

Average plasma concentrations of cefepime observed in normal adult males at various

times following single 30-minute infusions of 1 g and 2 g are summarised in Table 1.

Following intramuscular (IM) administration, cefepime is completely absorbed. The average

plasma concentrations of cefepime at various times following a single IM injection are

summarised in Table 1.

Table 1: Mean plasma concentrations of cefepime (microgram/mL)

Cefepime doses

0.5 hr

1 hr

2 hr

4 hr

8 hr

12 hr

1 g IV

66.9

41.8

25.3

11.0

2 g IV

127.6

81.7

45.4

20.1

1 g IM

14.8

25.9

26.3

16.0

2 g IM

36.1

49.9

51.3

31.5

Concentrations of cefepime achieved in specific tissues and body fluids are listed in Table

Table 2: Mean concentrations of cefepime in various body fluids (microgram/mL) and

tissues (microgram/g)

Data Sheet – New Zealand

Hospira 3.0

Page 2 of 12

Tissue or fluid

Dose (IV)

Average time of

sample post-dose

(hr)

Mean concentration

Urine

3120

Bile

Peritoneal fluid

16.4

Blister fluid

24.5

Bronchial mucosa

24.1

Sputum

Prostate

31.5

Appendix

Gallbladder

11.9

The average elimination half-life of cefepime is approximately 2 hours, and the disposition

of cefepime does not vary with respect to dose over the range of 250 mg to 2 g. There is

no evidence of accumulation in healthy subjects receiving doses up to 2 g intravenously

every 8 hours for a period of 9 days. Total body clearance averages 120 mL/min. The

average

renal

clearance

of cefepime is 110 mL/min, demonstrating that cefepime is

eliminated almost exclusively by renal mechanisms, primarily glomerular filtration.

Cefepime is metabolised to N-methylpyrrolidine which is rapidly converted to the N-oxide.

Urinary recovery of unchanged cefepime represents approximately 85% of dose, resulting in

high concentrations of cefepime in the urine. The serum protein binding of cefepime

averages 16.4% and is independent of its concentration in the serum.

Healthy volunteers 65 years old or older, who received a single 1g intravenous (IV) dose of

cefepime had higher AUC and lower renal clearance values compared to younger healthy

adults;

Dosage

adjustments

elderly

recommended

renal

function

compromised

(see

WARNINGS

PRECAUTIONS

DOSAGE

ADMINISTRATION).

The pharmacokinetics of cefepime do not change to a clinically significant degree in cystic

fibrosis patients. The pharmacokinetics of cefepime are unaltered in patients with impaired

hepatic function who received a single 1g dose.

It is not necessary to alter the dosage of

cefepime in these patient populations.

Studies

patients

with

various

degrees

renal

insufficiency

have

demonstrated

prolongation in elimination half-life. There is a linear relationship between total body

clearance and creatinine clearance in patients with abnormal renal function, which serves as

the basis for dosage adjustment recommendations in this group of patients (see DOSAGE

AND ADMINISTRATION).

The average half-life in severely impaired patients requiring dialysis therapy is 13 hours for

haemodialysis or 19 hours for continuous ambulatory peritoneal dialysis.

MICROBIOLOGY

Cefepime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis.

Cefepime has a broad spectrum of in vitro activity that encompasses a wide range of gram-

positive and gram-negative bacteria. Cefepime has a low affinity for chromosomally-

encoded

beta-lactamases.

Cefepime

highly

resistant

hydrolysis

most

beta-

lactamases and exhibits rapid penetration into gram-negative bacterial cells. Within bacterial

cells, the molecular targets of cefepime are the penicillin binding proteins (PBP).

Data Sheet – New Zealand

Hospira 3.0

Page 3 of 12

Cefepime

been

shown

active

against

most

strains

following

microorganisms, both in vitro and in clinical infections as described in the INDICATIONS

section.

Aerobic Gram-Negative Microorganisms

Enterobacter

Escherichia coli

Klebsiella pneumoniae

Proteus mirabilis

Pseudomonas aeruginosa

Aerobic Gram-Positive Microorganisms

Staphylococcus aureus (methicillin-susceptible strains only)

Streptococcus pneumoniae

Streptococcus pyrogenes (Lancefield’s Group A streptococci)

The presence of acquired resistance may vary geographically and with time for selected

species. Information about the local resistance pattern should be obtained from a local

bacteriological laboratory and taken into account in the choice of empiric therapy.

Susceptibility (With % acquired resistance* for susceptible organisms as follows).

Susceptible:

Enterobacter aerogenes* 0%

Enterobacter cloacae* 0%

Escherichia coli * 0%

Haemophilus influenzae 0%

Klebsiella pneumoniae* 0%

Proteus mirabilis* 0%

Pseudomonas aeruginosa* 3%

Staphylococcus aureus (methicillin susceptible) 0.2%

Streptococcus pneumoniae* 3%

Streptococcus pyogenes* 0%

Intermediate:

No organisms listed

Insusceptible:

Staphylococcus aureus (methicillin resistant)

*Clinical

efficacy

been

demonstrated

susceptible isolates in approved clinical

indications.

NOTE: 1-20% of Enterobacteriacae have an acquired resistance mechanism (depressed

synthesis

ampC

beta-lactamase

production

ESBL)

which

decreases

susceptibility to cefepime resulting in MICs in the 1-16 microgram/mL range.

The following in vitro data are available, but the clinical significance is unknown.

Cefepime has been shown to have in vitro activity against most strains of the following

microorganisms; however, the safety and effectiveness of cefepime in treating clinical

infections due to these microorganisms have not been established in adequate and well-

controlled trials.

Aerobic Gram-Positive Microorganisms

Staphylococcus epidermidis (methicillin-susceptible strains only)

Data Sheet – New Zealand

Hospira 3.0

Page 4 of 12

Staphylococcus saprophyticus

Streptococcus agalactiae (Lancefield’s Group B streptococci)

Viridans group streptococci

NOTE: Most strains of entrococci, eg Entercoccus faecalis, and methicillin-resistant

staphylococci are resistant to cefepime.

Aerobic Gram-Negative Microorganisms

Acinetobacter calcoaceticus subsp. lwoffi

Citrobacter diversus

Citrobacter freundii

Enterobacter agglomerans

Haemophilius influenzae (including beta-lactamase producing strains)

Hafnia alvei

Klebsiella oxytoca

Moraxella catarrhalis (including beta-lactamase producing strains)

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

NOTE: Cefepime is inactive against many strains of Stenotrophomonas (formally

Xanthomonas maltophilia and Pseudomonas maltophilia).

Anaerobic Microorganisms

NOTE: Cefepime is inactive against most strains of Clostridium difficile.

Susceptibility testing

Dilution or diffusion techniques – either quantitative (MIC) or breakpoint, should be used

following

regularly

updated,

recognised

standardised

method

(e.g.

NCCLS).

Standardised

susceptibility

test

procedures

require

laboratory

control

microorganisms to control the technical aspects of the laboratory procedures.

report

‘Susceptible’

indicates

that

pathogen

likely

inhibited

antimicrobial compound in the blood reaches the concentration usually achievable. A report

‘Intermediate’

indicates

result

should

considered

equivocal,

microorganism is not fully susceptible to alternative clinically feasible drugs, the test should

be repeated. This category implies possible clinical applicability in body sites where the

drug is physiologically concentrated or in situations where high dosage of drug can be used.

This category also provides a buffer zone, which prevents small uncontrolled technical

factors from causing major discrepancies in interpretation. A report of ‘Resistant’ indicates

that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood

reaches the concentrations usually achievable; other therapy should be selected.

INDICATIONS

Adults

Cefepime Powder

for Injection is indicated in the treatment of the infections listed

below when caused by susceptible bacteria.

Lower respiratory tract infections, including pneumonia and bronchitis.

Urinary

tract

infections,

both

complicated,

including

pyelonephritis,

uncomplicated infections.

Skin and skin structure infections.

Intra-abdominal infections, including peritonitis and biliary tract infections.

Septicaemia

Data Sheet – New Zealand

Hospira 3.0

Page 5 of 12

Empiric

treatment

febrile

neutropenic

patients

(see

WARNINGS

PRECAUTIONS)

Culture and susceptibility studies should be performed when appropriate to determine

susceptibility

the causative organism(s) to cefepime. Empiric therapy with DBL

Cefepime Powder for Injection may be instituted before results of susceptibility studies are

known; however, once these results become available, the antibiotic treatment should be

adjusted accordingly.

Because of its broad spectrum of bactericidal activity against gram-positive and gram-

negative bacteria,

Cefepime Powder

for Injection can be used appropriately as

monotherapy prior to identification of the causative organisms(s). In the treatment of febrile

neutropenia, consideration should be given to the need for other antibiotics in combination

with DBL

Cefepime Powder for Injection. In patients who are at risk of mixed aerobic-

anaerobic infection, including infections in which Bacterioides fragilis may be present,

concurrent initial therapy with an anti-anaerobic agent is recommended before the causative

organism(s) is known.

DOSAGE AND ADMINISTRATION

Adults

usual

adult

dosage

route

administration

cefepime

administered

intravenously or intramuscularly every 12 hours. However, the dosage and route vary

according to the susceptibility of the causative organisms, the severity of the infection, and

the condition and renal function of the patient. Guidelines for dosage of cefepime are

provided in Table 3. The usual duration of therapy is 7-10 days; however, more severe

infections may require longer treatment.

Table 3: Recommended dosage schedule for adults with normal renal function (aged

12 years and over)

Severity of Infection

Dose and

Route of

Administration

Dosing Interval

Mild to moderate urinary tract infection

500 mg – 1 g IV

or IM

q12 hours

Mild to moderate infections other than UTI

1 g IV or IM

q12 hours

Severe infections

2 g IV

q12 hours

Very severe or life threatening infections

2 g IV

q8 hours

Impaired Hepatic Function

No adjustment is necessary for patients with impaired hepatic function.

Impaired Renal Function - Adults

In patients with impaired renal function, the dose of cefepime should be adjusted to

compensate for the slower renal elimination. The recommended initial dose of cefepime in

patients with mild to moderate renal impairment should be the same as in patients with

normal renal function. The recommended maintenance doses of cefepime in patients with

renal insufficiency are presented in Table 4.

When only a serum creatinine measurement is available, the following formula (Cockcroft

and Gault equation) may be used to estimate creatinine clearance. The serum creatinine

should represent a steady state of renal function:

Males: Creatinine clearance (mL/min) =

weight (kg) x (140 - age)

Data Sheet – New Zealand

Hospira 3.0

Page 6 of 12

814 x serum creatinine (mmol/L)

Females: 0.85 x value calculated using formula for males

Table 4: Maintenance Dosing Schedule in Adult Patients With Renal Impairment

Creatine

Clearance

(mL/min)

Recommended Maintenance dosage

> 50

(Usual dose, no adjustment necessary)

2 g q8h 2 g q12h 1 g q12h 500 mg q12h

30 - 50

2 g q12h

2 g q24h

1 g q24h

500 mg q24h

11 - 29

2 g q24h

1 g q24h

500 mg q24h

500 mg q24h

≤ 10

1 g q24h

500 mg q24h

250 mg q24h

250 mg q24h

Haemodialysis*

500 mg q24h

500 mg q24h

500 mg q24h

500 mg q24h

* Pharmacokinetic modelling indicates that reduced dosing for these patients is necessary.

Patients receiving cefepime who are undergoing concomitant haemodialysis should be

dosed as follows: 1 gram loading dose on the first day of cefepime therapy and 500mg per

thereafter.

dialysis

days,

cefepime

should

be administered following dialysis.

Whenever possible cefepime should be administered at the same time each day.

Dialysis Patients

In patients undergoing haemodialysis, approximately 68% of the total amount of cefepime

present in the body at the start of dialysis will be removed during a 3 hour dialysis period. In

patients

undergoing

continuous

ambulatory

peritoneal

dialysis,

cefepime

administered at normally recommended doses, ie: 1g or 2g, depending on infection severity,

at a dosage interval of every 48 hours.

Administration

Cefepime Powder for Injection may be given intravenously or by deep intramuscular

injection into a large muscle mass (such as the upper outer quadrant of the gluteus

maximus). The dosage and route vary according to the susceptibility of the causative

organisms, the severity of the infection, renal function, and overall condition of the patient.

Product is for single use in one patient only.

Intravenous Administration

The IV route of administration is preferable for patients with severe or life-threatening

infections, particularly if the possibility of shock is present.

For direct IV administration, reconstitute DBL

Cefepime Powder for Injection with 10mL of

Sterile 5% Glucose Injection or 0.9% Sodium Chloride, as directed in Table 5. Slowly inject

directly into the vein over a period of three to five minutes or inject into the tubing of an

administration set while the patient is receiving a compatible IV fluid (see Compatibility).

For IV infusion, reconstitute the 1g or 2g vial, as noted above for direct IV administration,

and add an appropriate quantity of the resulting solution to an IV container with one of the

compatible IV fluids (see Compatibility). The resulting solution should be administered over

a period of approximately 30 minutes.

Intramuscular Administration

Cefepime Powder

for Injection should be reconstituted with one of the following

diluents: Sterile water for Injections, 0.9% Sodium Chloride or 5% Glucose Injection (refer to

Table 5). Although DBL

Cefepime Powder for Injection can be constituted with 0.5% or

1.0% lignocaine hydrochloride; it is usually not required because cefepime causes little or

no pain upon IM administration.

Data Sheet – New Zealand

Hospira 3.0

Page 7 of 12

Compatibility

Intravenous

Cefepime Powder

for Injection is compatible at concentrations between 1 and

40mg/mL with the following IV infusion fluids: 0.9% Sodium Chloride, 5% Glucose Injection,

M/6 Sodium Lactate Injection, 5% Glucose and 0.9% Sodium Chloride Injection, Lactated

Ringers and 5% Glucose Injection.

Cefepime Powder for Injection in 0.9% Sodium Chloride or 5% Glucose Injection is

compatible when admixed with heparin (10 or 50 units/mL), potassium chloride (10 or 40

mEq/L) and theophylline (0.8mg/mL in 5% Glucose Injection). Cefepime at a concentration

of 40 mg/mL in 0.9% Sodium Chloride or 5% Glucose Injection was found to be compatible

with Amikacin (amikacin 6mg/mL).

Intramuscular

Cefepime Powder

for Injection should be reconstituted with the following diluents:

Sterile Water for Injections, 0.9% Sodium Chloride, 5% Glucose Injection, or lignocaine

hydrochloride 0.5% or 1%.

NOTE: Solutions of cefepime, like those of most beta-lactam antibiotics, should not

added to solutions of gentamicin, metronidazole, vancomycin, tobramycin sulphate or

netilmicin sulphate because of physical or chemical incompatibility. However, if concurrent

therapy with cefepime and gentamicin is indicated, each of these antibiotics can be

administered separately to the same patient.

Stability

Cefepime should be reconstituted immediately before use, and used as soon as practicable

after reconstitution, any residue being discarded. If there is any delay in use of the

reconstituted Cefepime it should be stored at 2°C-8°C for a maximum of 24 hours.

Reconstituted solutions should be protected from light.

Note:

Parenteral

drugs

should

inspected

visually

particulate

matter

before

administration and not used if particulate matter is present.

As with other cephalosporins, the colour of reconstituted DBL

Cefepime Powder

Injection may darken on storage, however, product potency is not adversely affected.

Table 5: Preparations of solutions of DBL

Cefepime Powder for Injection

Amount of diluent

to

be added (mL)

Approximate

available volume

(mL)

*Approximate

cefepime

concentration

(mg/mL)

Intravenous

1g vial

10.0

11.3

2g vial

10.0

12.6

Intramuscular

1g vial

*Reconstitution of DBL

Cefepime Powder for Injection in a volume of diluent other than

those included in this table will not produce a linear change in concentration.

Data Sheet – New Zealand

Hospira 3.0

Page 8 of 12

CONTRAINDICATIONS

Cefepime

contraindicated

patients

have

shown

immediate

hypersensitivity

reactions to any component of the formulation (including L-arginine), the cephalosporin

class of antibiotics, penicillins or other beta-lactam antibiotics.

WARNINGS AND PRECAUTIONS

Before therapy with cefepime is instituted, careful inquiry should be made to determine

whether the patient has had previous immediate hypersensitivity reactions to cefepime,

cephalosporins,

penicillins,

other

beta-lactam

antibiotics.

Antibiotics

should

administered with caution to any patient who has demonstrated some form of allergy,

particularly to drugs. If an allergic reaction to cefepime occurs, discontinue the drug and

treat the patient appropriately. Serious immediate hypersensitivity reactions may require

adrenalin and other supportive therapy.

Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics

including cefepime; therefore, it is important to consider this diagnosis in patients who

develop diarrhoea in association with the use of antibiotics. Treatment with broad-spectrum

antibiotics 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.

Mild

cases

pseudomembranous

colitis

respond

drug

discontinuation alone. In moderate to severe cases, management should include fluid,

electrolyte

protein

supplementation.

When

colitis

does

improve

after

drug

discontinuation or when it is severe, it should be treated with an antibiotic clinically effective

against Clostridium difficile. Other causes of colitis should also be considered. Drugs which

delay peristalsis may prolong and/or worsen the condition and should not be used.

Prolonged

prothrombin

time

occur

patients

receiving

protracted

antimicrobial

therapy.

In patients at high risk for severe infection (including patients with a history of recent bone

marrow transplantation, with hypotension at presentation, with an underlying haematologic

malignancy, or with severe or prolonged neutropenia), antimicrobial monotherapy may not

be appropriate. Insufficient data exist to support the efficacy of cefepime monotherapy in

such patients.

with

other

antibiotics,

prolonged

cefepime

result

overgrowth

nonsusceptible

organisms.

Should

superinfection

occur

during

therapy,

appropriate

measures should be taken.

Cefepime should be prescribed with caution in individuals with a history of gastrointestinal

disease, particularly colitis.

If neutropenia occurs as a result of prolonged therapy, cefepime should be discontinued

and alternative antibiotic therapy used.

Impaired Renal Function

In patients with impaired renal function, such as reduction of urinary output because of renal

insufficiency (creatinine clearance < 50 mL/min) or other conditions that may compromise

renal function, the dosage of cefepime should be adjusted to compensate for the slower

rate of renal elimination. Because high and prolonged serum antibiotic concentrations can

occur from usual doses in patients with renal insufficiency or other conditions that may

compromise renal function, the maintenance dosage should be reduced when cefepime is

administered to such patients. Continued dosage should be determined by degree of renal

impairment,

severity

infection,

susceptibility

causative

organisms

(see

DOSAGE AND ADMINISTRATION and

USES

). During postmarketing surveillance, the

Data Sheet – New Zealand

Hospira 3.0

Page 9 of 12

following

serious

adverse

events

have

been

reported:

reversible

encephalopathy

(disturbance

consciousness

including

confusion,

hallucinations,

stupor

coma),

myoclonus, seizures (including nonconvulsive status epilepticus), and/or renal failure (see

ADVERSE EFFECTS). Most cases occurred in patients with renal impairment who received

doses of cefepime that exceeded recommendations. In general, symptoms of neurotoxicity

resolved after discontinuation of cefepime and/or after haemodialysis however, some cases

included a fatal outcome.

Renal function should be monitored carefully if drugs with nephrotoxic potential, such as

aminoglycosides and potent diuretics, are administered with cefepime.

Carcinogenicity, mutagenicity, impairment of fertility

Although no long-term studies in animals have been performed to evaluate carcinogenic

potential, a battery of in vitro and in vivo tests for genotoxicity have been conducted. The

overall conclusion of this testing is that cefepime is not genotoxic. Standard tests to assess

fertility in rats show no impairment of fertility at exposure levels nearly two-fold higher than

the calculated maximal daily human exposure.

Use in pregnancy (Category B1)

Reproduction studies performed in mice and rats showed no evidence of impaired fertility or

harm to the foetus at dose levels equivalent to (mouse) or slightly greater (rat) than the

maximum human daily dose when the daily doses are compared to those in humans on a

mg/m

basis. 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.

Use in lactation

Cefepime is excreted in human breast milk in very low concentrations. Although less than

0.01% of a 1 g IV dose is excreted in milk, caution should be used when cefepime is

administered to a nursing woman.

Use in labour and delivery

Cefepime has not been studied for use during labour and delivery. Treatment should only

be given if clearly indicated.

Use in paediatrics

Although

studies

paediatric

patients

ongoing,

safety

effectiveness

cefepime in children have not been established.

Effect on ability to drive or operate machinery

During treatment with cefepime undesirable effects may occur (e.g. dizziness), which may

influence the ability to drive and use machines. Patients should be cautious when driving or

operating machinery.

Use in the elderly

Of the more than 6400 adults treated with cefepime in clinical studies, 35% were 65 years

or older while 16% were 75 years or older. In clinical studies, when geriatric patients

received the usual recommended adult dose, clinical efficacy and safety were comparable

to clinical efficacy and safety in non-geriatric adult patients unless the patients had renal

insufficiency. There was a modest prolongation in elimination half-life and lower renal

Category B1

Drugs

which

have

been

taken

only

limited

number

pregnant women and women of

childbearing age, without an increase in the frequency of malformation or other direct or indirect

harmful effects on the human foetus having been observed.

Studies in animals have not shown evidence of an increased occurrence of foetal damage.

Data Sheet – New Zealand

Hospira 3.0

Page 10 of 12

clearance values compared to those seen in younger persons. Dosage adjustments are

recommended if renal function is compromised (see DOSAGE AND ADMINISTRATION).

Cefepime 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 renal function should be monitored (see WARNINGS AND PRECAUTIONS,

ADVERSE EFFECTS and

USES

). Serious adverse events, including encephalopathy

(disturbance

consciousness

including

confusion,

hallucinations,

stupor

coma),

myoclonus, seizures (including nonconvulsive status epilepticus), and/or renal failure have

occurred in geriatric patients with renal insufficiency given the usual dose of cefepime (see

WARNINGS AND PRECAUTIONS and ADVERSE EFFECTS).

ADVERSE EFFECTS

Cefepime is generally well tolerated. In clinical trials (n=5598) the most common adverse

events were gastrointestinal symptoms and hypersensitivity reactions. Adverse events

considered to be of definite, probable or possible relationship to cefepime are listed below.

Events that occurred at an incidence of >0.1% - 1% (except where noted) were:

Hypersensitivity: rash (1.8%), pruritis, urticaria, cutaneous vasculitis may occur

Gastrointestinal:

nausea,

vomiting,

oral

moniliasis,

diarrhoea

(1.2%),

colitis

(including pseudomembranous colitis)

Central nervous system: headache

Other: fever, vaginitis, erythema

Events that occurred at an incidence of 0.05% - 0.1% were abdominal pain, constipation,

vasodilation, dyspnoea, dizziness, paraesthesia, genital pruritis, taste perversion, chills and

unspecified moniliasis.

Events that occurred at an incidence of <0.05% included anaphylaxis and seizures.

Phlebitis at the site of injection may occur.

Local reactions at the site of IV infusions

occurred in 5.2% of patients; these included phlebitis (2.9%) and inflammation (0.1%).

Intramuscular administration of cefepime was very well tolerated with 2.6% of patients

experiencing pain or inflammation at the injection site.

Laboratory test abnormalities that developed during clinical trials in patients with normal

baseline values were transient. Those that occurred at a frequency between 1% and 2%

(unless

noted)

were:

elevations

alanine

aminotransferase

(3.6%),

aspartate

aminotransferase

(2.5%),

alkaline

phosphatase,

total

bilirubin,

anaemia,

eosinophilia,

prolonged prothrombin time, partial prothrombin time (2.8%), and positive Coombs' test

without haemolysis (18.7%). Transient elevations of serum urea, and/or serum creatinine

and transient thrombocytopenia were observed in 0.5% to 1% of patients. Transient

leukopenia and neutropenia were also seen (< 0.5%).

Postmarketing Experience

During postmarketing experience, encephalopathy (disturbance of consciousness including

confusion, hallucinations, stupor and coma), seizures, myoclonus and/or renal failure have

been reported. Most cases occurred in patients with renal impairment who received doses

of cefepime that exceeded recommendations (see also WARNINGS AND PRECAUTIONS).

Anaphylaxis including anaphylactic shock, transient leukoenia, neutropenia, agranulocytosis

and thrombocytopenia have been reported rarely. Because of the uncontrolled nature of

these spontaneous reports, a causal relationship to cefepime has not been determined.

following

adverse

effects

altered

laboratory

tests

have

been

reported

cephalosporin-class antibiotics: Urticaria, Stevens-Johnson syndrome, erythema multiforme,

Data Sheet – New Zealand

Hospira 3.0

Page 11 of 12

toxic

epidermal

necrolysis,

renal

dysfunction,

toxic

nephropathy,

aplastic

anaemia,

haemolytic anaemia, haemorrhage, hepatic dysfunction including cholestasis, and false

positive tests for urinary glucose.

Paediatrics

The safety profile of cefepime in infants and children is similar to that seen in adults. The

most frequently reported adverse event considered related to cefepime in clinical trials was

rash.

INTERACTIONS

Renal function should be monitored carefully if drugs with nephrotoxic potential, such as

aminoglycosides and potent diuretics, are administered with cefepime. Nephrotoxicity has

been

reported

following

concomitant

administration

other

cephalosporins

with

aminoglycoside antibiotics or potent diuretics such as frusemide.

OVERDOSE

In case of severe overdosage, especially in patients with compromised renal function,

dialysis will aid in the removal of cefepime from the body; peritoneal dialysis is of no value.

Accidental overdosing has occurred when large doses were given to patients with impaired

renal function (see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS

and ADVERSE EFFECTS). Symptoms of overdosage include encephalopathy (disturbance

consciousness

including

confusion,

hallucinations,

stupor,

coma),

myoclonus,

seizures and neuromuscular excitability.

In case of overdose, immediately contact the Poison Information Centre for advice (In New

Zealand, call 0800 764 766).

PHARMACEUTICAL PRECAUTIONS

Cefepime Powder for Injection is a 20 mL vial containing a powder for solution for

injection providing 1 g or 2 g cefepime. Following reconstitution with Water for Injection as

directed in DOSAGE AND ADMINISTRATION, it results in pale yellow to amber coloured,

clear solution.

Cefepime Powder for Injection in original cartons should be stored at below 25°C.

Protect from light.

To avoid the risk of microbial contamination, reconstituted DBL

Cefepime Powder

Injection should be administered as soon as possible after reconstitution.

PACKAGE QUANTITIES

Cefepime Powder for Injection is available in packs containing 1 vial:

1g (20 mL vial)

2g (20 mL vial)

MEDICINE CLASSIFICATION

Prescription Medicine

Data Sheet – New Zealand

Hospira 3.0

Page 12 of 12

FURTHER INFORMATION

Molecular Formula:

Cl.HCl.H

Molecular Weight:

571.5

CAS Registry No.:

123171-59-5

ATC code:

J01DE01

SPONSOR DETAILS

Pfizer New Zealand Limited,

PO Box 3998

Auckland, New Zealand, 1140

Toll Free Number: 0800 736 363

DATE OF PREPARATION

22 February 2017

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