2. Qualitative and quantitative composition
3. Pharmaceutical form
4. Clinical particulars
As with all beta-lactam antibacterial agents, serious and
occasionally fatal hypersensitivity reactions have been reported.
In case of severe hypersensitivity reactions, treatment with
cefuroxime must be discontinued immediately and adequate emergency
measures must be initiated.
Before beginning treatment, it should be established whether the
patient has a history of severe hypersensitivity reactions to
cefuroxime, to other cephalosporins or to any other type of
beta-lactam agent. Caution should be used if cefuroxime is given to
patients with a history of non-severe hypersensitivity to other
Concurrent treatment with potent diuretics or aminoglycosides
Cephalosporin antibiotics at high dosage should be given with
caution to patients receiving concurrent treatment with potent
diuretics such as furosemide or aminoglycosides. Renal impairment
has been reported during use of these combinations. Renal function
should be monitored in the elderly and those with known
pre-existing renal impairment (see section 4.2).
Overgrowth of non-susceptible microorganisms
Use of cefuroxime may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other
non-susceptible microorganisms (e.g. enterococci and Clostridium difficile), which may require interruption of treatment (see section 4.8).
Antibacterial agent–associated pseudomembranous colitis has been
reported with use of cefuroxime and may range in severity from mild
to life threatening. This diagnosis should be considered in
patients with diarrhoea during or subsequent to the administration
of cefuroxime (see section 4.8). Discontinuation of therapy with
cefuroxime and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis
should not be given.
Due to its spectrum of activity, cefuroxime is not suitable for the
treatment of infections caused by Gram-negative non-fermenting
bacteria (see section 5.1)
Interference with diagnostic tests
The development of a positive Coomb's Test associated with the use
of cefuroxime may interfere with cross matching of blood (see
Slight interference with copper reduction methods (Benedict's,
Fehling's, Clinitest) may be observed. However, this should not
lead to false-positive results, as may be experienced with some
As a false negative result may occur in the ferricyanide test, it
is recommended that either the glucose oxidase or hexokinase
methods are used to determine blood/plasma glucose levels in
patients receiving cefuroxime sodium.
Important information about excipients
Cefuroxime powder for solution for injection and infusion contains
sodium. This should be considered for patients who are on a
controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of
Cefuroxime may affect the gut flora, leading to lower oestrogen
reabsorption and reduced efficacy of combined oral contraceptives.
Cefuroxime is excreted by glomerular filtration and tubular
secretion. Concomitant use of probenicid is not recommended.
Concurrent administration of probenecid prolongs the excretion of
the antibiotic and produces an elevated peak serum level.
Potential nephrotoxic drugs and loop diuretics
High-dosage treatments with cephalosporins should be carried out
with caution on patients who are taking strong-acting diuretics
(such as furosemide) or potential nephrotoxic preparations (such as
aminoglycoside antibiotics), since impairment of renal function
through such combinations cannot be ruled out.
Determination of blood/plasma glucose levels: Please refer to
Concomitant use with oral anticoagulants may give rise to increased
international normalised ratio (INR).
4.6. Fertility, pregnancy and lactation
There are limited amounts of data from the use of cefuroxime in
pregnant women. Studies in animals have shown no reproductive
toxicity (see section 5.3). Cefuroxime should be prescribed to
pregnant women only if the benefit outweighs the risk.
Cefuroxime has been shown to cross the placenta and attain
therapeutic levels in amniotic fluid and cord blood after
intramuscular or intravenous dose to the mother.
Cefuroxime is excreted in human milk in small quantities. Adverse
reactions at therapeutic doses are not expected, although a risk of
diarrhoea and fungus infection of the mucous membranes cannot be
excluded. A decision must be made whether to discontinue
breast-feeding or to discontinue/abstain from cefuroxime therapy
taking into account the benefit of breast feeding for the child and
the benefit of therapy for the woman.
There are no data on the effects of cefuroxime sodium on fertility
in humans. Reproductive studies in animals have shown no effects on
4.7 Effects on ability to drive and use machines
No studies on the effects of cefuroxime on the ability to drive and
use machines have been performed. However, based on known adverse
reactions, cefuroxime is unlikely to have an effect on the ability
to drive and use machines.
4.8 Undesirable effects
The most common adverse reactions are neutropenia, eosinophilia,
transient rise in liver enzymes or bilirubin, particularly in
patients with pre-existing liver disease, but there is no evidence
of harm to the liver and injection site reactions.
The frequency categories assigned to the adverse reactions below
are estimates, as for most reactions suitable data for calculating
incidence are not available. In addition the incidence of adverse
reactions associated with cefuroxime sodium may vary according to
Data from clinical trials were used to determine the frequency of
very common to rare adverse reactions. The frequencies assigned to
all other adverse reactions (i.e. those occurring at <1/10,000)
were mainly determined using post-marketing data, and refer to a
reporting rate rather than a true frequency.
Treatment related adverse reactions, all grades, are listed below
by MedDRA body system organ class, frequency and grade of severity.
The following convention has been utilised for the classification
of frequency: 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 and not known (cannot be estimated from the
|System organ class||Common||Uncommon||Not known|
|Infections and infestations||Candida overgrowth, overgrowth of Clostridium difficile|
|Blood and lymphatic system disorders||neutropenia, eosinophilia, decreased haemoglobin concentration||leukopenia, positive Coomb's test||thrombocytopenia, haemolytic anaemia|
|Immune system disorders||drug fever, interstitial nephritis, anaphylaxis, cutaneous
|Gastrointestinal disorders||gastrointestinal disturbance||pseudomembranous colitis|
|Hepatobiliary disorders||transient rise in liver enzymes||transient rise in bilirubin|
|Skin and subcutaneous tissue disorders||skin rash, urticaria and pruritus||erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson
syndrome, angioneurotic oedema|
|Renal and urinary disorders||elevations in serum creatinine, elevations in blood urea nitrogen
and decreased creatinine clearance (see section 4.4)|
|General disorders and administration site conditions||injection site reactions which may include pain and
Description of selected adverse reactions
Cephalosporins as a class tend to be absorbed onto the surface of
red cell membranes and react with antibodies directed against the
drug to produce a positive Coomb's test (which can interfere with
cross matching of blood) and very rarely haemolytic anaemia.
Transient rises in serum liver enzymes or bilirubin have been
observed which are usually reversible.
Pain at the intramuscular injection site is more likely at higher
doses. However it is unlikely to be a cause for discontinuation of
The safety profile for cefuroxime sodium in children is consistent
with the profile in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the
medicinal product is important. It allows continued monitoring of
the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Overdose can lead to neurological sequelae including
encephalopathy, convulsions and coma. Symptoms of overdose can
occur if the dose is not reduced appropriately in patients with
renal impairment (see sections 4.2 and 4.4).
Serum levels of cefuroxime can be reduced by haemodialysis or
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterials for systemic use,
Second-generation cephalosporins, ATC code J01DC02
Mechanism of Action:
Cefuroxime inhibits bacterial cell wall synthesis following
attachment to penicillin binding proteins (PBPs). This results in
the interruption of cell wall (peptidoglycan) biosynthesis, which
leads to bacterial cell lysis and death.
Mechanisms of resistance
Bacterial resistance to cefuroxime may be due to one or more of the
• Hydrolysis by beta-lactamases including (but not limited to)
extended-spectrum beta-lactamases (ESBLs), and Amp-C enzymes, that
may be induced or stably de-repressed in certain aerobic
Gram-negative bacterial species;
• Reduced affinity of penicillin-binding proteins for cefuroxime;
• Outer membrane impermeability, which restricts access of
cefuroxime to penicillin binding proteins in Gram-negative
• Bacterial efflux pumps.
Organisms that have acquired resistance to other injectable
cephalosporins are expected to be resistant to cefuroxime.
Depending on the mechanism of resistance, organisms with acquired
resistance to penicillins may demonstrate reduced susceptibility or
resistance to cefuroxime.
Cefuroxime sodium breakpoints
The Minimum inhibitory concentration (MIC) breakpoints established
by the European Committee on Antimicrobial Susceptibility Testing
(EUCAST) are as follows:
|Streptococcus A, B, C and G||Note4||Note4|
|Non-species related breakpoints1||≤45||>85|
1 The cephalosporin breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms
(including ESBL and plasmid mediated AmpC). Some strains that
produce beta-lactamases are susceptible or intermediate to 3rd or
4th generation cephalosporins with these breakpoints and should be
reported as found, i.e. the presence or absence of an ESBL does not
in itself influence the categorisation of susceptibility. In many
areas, ESBL detection and characterisation is recommended or
mandatory for infection control purposes.
2 Breakpoint relates to a dosage of 1.5 g × 3 and to E. coli, P. mirabilis and Klebsiella spp . only.
3 Susceptibility of staphylococci to cephalosporins is inferred
from the methicillin susceptibility except for ceftazidime and
cefixime and ceftibuten, which do not have breakpoints and should
not be used for staphylococcal infections.
4 The beta-lactam susceptibility of beta-haemolytic streptococci
groups A, B, C and G is inferred from the penicillin
5 Breakpoints apply to daily intravenous dose of 750 mg × 3 and a
high dose of at least 1.5 g × 3.
The prevalence of acquired resistance may vary geographically and
with time for selected species and local information on resistance
is therefore desirable, particularly when treating severe
infections. As necessary, expert advice should be sought when the
local prevalence of resistance is known and the utility of the
agent in at least some types of infections is questionable.
Cefuroxime is usually active against the following microorganisms in vitro.
|Commonly susceptible species|
Staphylococcus aureus (methicillin-susceptible) *
Streptococcus mitis (viridans group)
|Microorganisms for which acquired resistance may be a problem|
Proteus spp. (other than P. vulgaris )
|Inherently resistant microorganisms|
* All methicillin-resistant S. aureus are resistant to cefuroxime.
In vitro the activities of cefuroxime sodium and aminoglycoside antibiotics
in combination have been shown to be at least additive with
occasional evidence of synergy.
5.2 Pharmacokinetic properties
After intramuscular (IM) injection of cefuroxime to normal
volunteers, the mean peak serum concentrations ranged from 27 to 35
μg/mL for a 750 mg dose and from 33 to 40 μg/mL for a 1000 mg dose,
and were achieved within 30 to 60 minutes after administration.
Following intravenous (IV) doses of 750 and 1500 mg, serum
concentrations were approximately 50 and 100 μg/mL, respectively,
at 15 minutes.
AUC and Cmax appear to increase linearly with increase in dose over
the single dose range of 250 to 1000 mg following IM and IV
administration. There was no evidence of accumulation of cefuroxime
in the serum from normal volunteers following repeat intravenous
administration of 1500 mg doses every 8 hours.
Protein binding has been stated as 33 to 50%, depending on the
methodology used. The average volume of distribution ranges from
9.3 to 15.8 L/1.73 m2 following IM or IV administration over the
dosage range of 250 to 1000 mg. Concentrations of cefuroxime in
excess of the minimum inhibitory levels for common pathogens can be
achieved in the tonsilla, sinus tissues, bronchial mucosa, bone,
pleural fluid, joint fluid, synovial fluid, interstitial fluid,
bile, sputum and aqueous humour. Cefuroxime passes the blood-brain
barrier when the meninges are inflamed.
Cefuroxime is not metabolised.
Cefuroxime is excreted by glomerular filtration and renal tubular
secretion. The serum half-life after either intramuscular or
intravenous injection is approximately 70 minutes. There is an
almost complete recovery (85 to 90%) of unchanged cefuroxime in
urine within 24 hours of administration. The majority of the
cefuroxime is excreted within the first 6 hours. The average renal
clearance ranges from 114 to 170 mL/min/1.73 m2 following IM or IV
administration over the dosage range of 250 to 1000 mg.
Special patient populations
No differences in the pharmacokinetics of cefuroxime were observed
between males and females following a single IV bolus injection of
1000 mg of cefuroxime as the sodium salt.
Following IM or IV administration, the absorption, distribution and
excretion of cefuroxime in elderly patients are similar to younger
patients with equivalent renal function. Because elderly patients
are more likely to have decreased renal function, care should be
taken in cefuroxime dose selection, and it may be useful to monitor
renal function (see section 4.2).
The serum half-life of cefuroxime has been shown to be
substantially prolonged in neonates according to gestational age.
However, in older infants (aged >3 weeks) and in children, the
serum half-life of 60 to 90 minutes is similar to that observed in
Cefuroxime is primarily excreted by the kidneys. As with all such
antibiotics, in patients with markedly impaired renal function
(i.e. C1cr <20 mL/minute) it is recommended that the dosage of
cefuroxime should be reduced to compensate for its slower excretion
(see section 4.2). Cefuroxime is effectively removed by
haemodialysis and peritoneal dialysis.
Since cefuroxime is primarily eliminated by the kidney, hepatic
dysfunction is not expected to have an effect on the
pharmacokinetics of cefuroxime.
For cephalosporins, the most important
pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing
interval (%T) that the unbound concentration remains above the
minimum inhibitory concentration (MIC) of cefuroxime for individual
target species (i.e. %T>MIC).
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on
conventional studies of safety pharmacology, repeated dose
toxicity, genotoxicity and toxicity to reproduction and
development. No carcinogenicity studies have been performed;
however, there is no evidence to suggest carcinogenic potential.
Gamma glutamyl transpeptidase activity in rat urine is inhibited by
various cephalosporins, however the level of inhibition is less
with cefuroxime. This may have significance in the interference in
clinical laboratory tests in humans.
6. Pharmaceutical particulars
6.1 List of excipients
Cefuroxime should not be mixed in the syringe or giving set with
aminoglycosides prior to or during administration.
6.3 Shelf life
24 months for the medicinal product as packaged for sale. After
reconstitution the product should be used immediately, but if not
practicable, the diluted product may be stored for 24 hours at 2 -
8 º C, after which time unused material should be discarded.
6.4 Special precautions for storage
Keep at room temperature (below 25 º C), protected from light.
6.5 Nature and contents of container
Type I or III glass vial (15ml) sealed with a butylic rubber
stopper. The vials are boxed individually and in packs of 2, 5, 10,
20, 30, 40 and 100 vials. Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Instruction for constitution
Table 4. Addition volumes and solution concentrations, which may be
useful when fractional doses are required.
|Addition volumes and solution concentrations, which may be useful
when fractional doses are required|
|Vial size||Displacement (ml)||Amount of water to be added (ml)|
Approximate cefuroxime concentration
|250 mg powder for solution for injection|
|750 mg powder for solution for injection|
|1.5 g powder for solution for injection or infusion|
* Reconstituted solution to be added to 35ml of compatible infusion
fluid (see information on compatibility, below)
** The resulting volume of the solution of cefuroxime in
reconstitution medium is increased due the displacement factor of
the drug substance resulting in the listed concentrations in mg/ml.
Cefuroxime sodium (5 mg/ml) in 5% w/v or 10% w/v xylitol injection
may be stored for up to 24 h at 25oC.
Cefuroxime sodium is compatible with aqueous solutions containing
up to 1% lidocaine hydrochloride.
Cefuroxime sodium is compatible with the following infusion fluids.
It will retain potency for up to 24 hours at room temperature in:
Sodium Chloride Injection BP 0.9% w/v
5% Dextrose Injection BP
0.18% w/v Sodium Chloride plus 4% Dextrose Injection BP
5% Dextrose and 0.9% Sodium Chloride Injection
5% Dextrose and 0.45% Sodium Chloride Injection
5% Dextrose and 0.225% Sodium Chloride Injection
10% Dextrose Injection
10% Invert Sugar in Water for Injection
Ringer's Injection USP
Lactated Ringer's Injection USP
M/6 Sodium Lactate Injection
Compound Sodium Lactate Injection BP (Hartmann's Solution).
The stability of cefuroxime sodium in Sodium Chloride Injection BP
0.9% w/v and in 5% Dextrose Injection is not affected by the
presence of hydrocortisone sodium phosphate.
Cefuroxime sodium has also been found compatible for 24 h at room
temperature when admixed in i.v. infusion with:
Heparin (10 and 50 units/ml) in 0.9% Sodium Chloride Injection;
Potassium Chloride (10 and 40 mEqL) in 0.9% Sodium Chloride
Any unused medicinal product or waste material should be disposed
of in accordance with local requirements.