GMP Certified Best Quality Cefotaxime Sodium Powder for Injection,
0.5g 1g, 2g/vial, 50vials/box, Antibiotic, Anti-infective
1. Name of the medicinal product
Cefotaxime 2g Powder for solution for injection or infusion
2. Qualitative and quantitative composition
Each vial contains cefotaxime sodium equivalent to 2g of
Each gram of cefotaxime contains approximately 48mg (2.09mmol) of
For a full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder for solution for injection or infusion (Powder for injection
White to slightly yellow powder.
4. Clinical particulars
4.1 Therapeutic indications
1. Cefotaxime is indicated in the treatment of serious infections,
either before the infecting organism has been identified or when
caused by bacteria of established sensitivity, including
and other serious bacterial infections suitable for parenteral
2. Cefotaxime may be used for pre-operative prophylaxis in patients
undergoing surgical procedures, that may be classified as
contaminated or potentially so.
4.2 Posology and method of administration
Cefotaxime may be administered intravenously, by bolus injection or
by infusion, or by intramuscular injection. The dosage, route and
frequency of administration should be determined by the severity of
infection, the sensitivity of causative organisms and condition of
the patient. Therapy may be initiated before the results of
sensitivity tests are known.
The recommended dosage for mild to moderate infections is 1g 12
hourly. However, dosage may be varied according to the severity of
the infection, sensitivity of causative organisms and condition of
the patient. Therapy may be initiated before the results of
sensitivity tests are known.
In severe infections dosage may be increased up to 12g daily given
in three or four divided doses. For infections caused by sensitive
Pseudomonas species daily doses of greater than 6g will usually be
The usual dosage range is 100-150mg/kg/day in two to four divided
doses. However, in very severe infection doses of up to
200mg/kg/day may be required.
Neonates: The recommended dosage is 50mg/kg/day in two to four
divided doses. In severe infections 150-200mg/kg/day, in divided
doses, have been given.
Dosage in renal impairment: Because of extra-renal elimination, it
is only necessary to reduce the dosage of cefotaxime in severe
renal failure (GFR <5ml/min = serum creatinine approximately 751
micromol/litre). After an initial loading dose of 1g, daily dose
should be halved without change in the frequency of dosing, i.e. 1g
twelve hourly becomes 0.5g twelve hourly, 1g eight hourly becomes
0.5g eight hourly, 2g eight hourly becomes 1g eight hourly etc. As
in all other patients, dosage may require further adjustment
according to the course of the infection and the general condition
of the patient.
Dosage in hepatic impairment: No dosage adjustment is required.
Intravenous and Intramuscular Administration: Reconstitute cefotaxime with Water for Injections PhEur as
directed in Section 6.6 (Instructions for use/handling). Shake well
until dissolved and then withdraw the entire contents of the vial
into the syringe.
Intravenous administration (Injection or Infusion): Cefotaxime may be administered by intravenous infusion using the
fluids stated in Section 6.6 (Instructions for use/handling). The
prepared infusion may be administered over 20-60 minutes.
For intermittent I.V. injections, the solution must be injected
over a period of 3 to 5 minutes. During post-marketing
surveillance, potentially life-threatening arrhythmia has been
reported in a very few patients who received rapid intravenous
administration of cefotaxime through a central venous catheter.
Cefotaxime and aminoglycosides should not be mixed in the same
syringe or perfusion fluid.
Hypersensitivity to cephalosporins.
In patients with a history of hypersensitivity to Cefotaxime and/or
to any component of Cefotaxime 2g Powder for solution for injection
or infusion, a penicillin or to any other type of beta-lactam drug.
Allergic cross reactions can exist between penicillins and
cephalosporins (see section 44.).
For pharmaceutical forms containing lidocaine:
• known history of hypersensitivity to lidocaine or other local
anaesthetics of the amide type
• non-paced heart block
• severe heart failure
• administration by the intravenous route
• infants aged less than 30 months of age.
4.4 Special warnings and precautions for use
As with other antibiotics, the use of cefotaxime, especially if
prolonged, may result in overgrowth of non susceptible organisms,
such as Enterococcus spp, candida, Pseudomonas aeruginosa. Repeated evaluation of the condition of the patient is essential.
If superinfection occurs during treatment with cefotaxime,
appropriate measures should be taken and specific anti-microbial
therapy should be instituted if considered clinically necessary.
Anaphylactic reactions: Preliminary enquiry about hypersensitivity
to penicillin and other β-Lactam antibiotics is necessary before
prescribing cephalosporins since cross allergy occurs in 5–10% of
cases. The use of cefotaxime is strictly contra-indicated in
subjects with a previous history of immediate-type hypersensitivity
to cephalosporins. Since cross allergy exists between penicillins
and cephalosporins, use of the latter should be undertaken with
extreme caution in penicillin sensitive subjects. Serious,
including fatal hypersensitivity reactions have been reported in
patients receiving cefotaxime (see sections 4.3 and 4.8). If a
hypersensitivity reaction occurs, treatment must be stopped.
Serious bullous reactions: Cases of serious bullous skin reactions
like Stevens-Johnson syndrome or toxic epidermal necrolysis have
been reported with cefotaxime (see section 4.8). Patients should be
advised to contact their doctor immediately prior to continuing
treatment if skin and/or mucosal reactions occur.
Patients with renal insufficiency: The dosage should be modified
according to the creatinine clearance calculated (see section 4.2).
Patients with severe renal dysfunction should be placed on the
dosage schedule recommended under “Posology and Method of
Caution should be exercised if cefotaxime is administered together
with aminoglycosides, probenecid or other nephrotoxic drugs (see
section 4.5). Renal function must be monitored in these patients,
the elderly, and those with pre-existing renal impairment.
Haematological reactions: Leukopenia, neutropenia, and more rarely,
agranulocytosis may develop during treatment with cefotaxime,
particularly if given over long periods. For treatment courses
lasting longer than 7-10 days, the blood white cell count should be
monitored and treatment stopped in the event of neutropenia.
Some cases of eosinophilia and thrombocytopenia, rapidly reversible
on stopping treatment, have been reported. Cases of haemolytic
anaemia have also been reported (see section 4.8).
Sodium intake: The sodium content of cefotaxime (2.09mmol/g) should
be taken into account when prescribing to patients requiring sodium
Clostridium difficile associated disease (e.g. pseudomembranous
colitis): Cefotaxime may predispose patients to pseudomembranous
colitis. Although any antibiotic may predispose to pseudomembranous
colitis, the risk is higher with broad spectrum drugs, such as
cephalosporins. This side effect, which may occur more frequently
in patients receiving higher doses for prolonged periods, should be
considered as potentially serious.
Diarrhoea, particularly if severe and/or persistent, occurring
during treatment or in the initial weeks following treatment, may
be symptomatic of Clostridium difficile associated disease (CDAD).
CDAD may range in severity from mild to life threatening, the most
severe form of which is pseudo-membranous colitis.
The diagnosis of this rare but possibly fatal condition can be
confirmed by endoscopy and/or histology.
It is important to consider this diagnosis in patients who present
with diarrhoea during or subsequent to the administration of
If a diagnosis of pseudomembranous colitis is suspected, cefotaxime
should be stopped immediately and appropriate specific antibody
therapy should be started without delay.
Clostridium difficile associated disease can be favoured by faecal
Medicinal products that inhibit peristalsis should not be given.
Neurotoxicity: High doses of beta-lactam antibiotics, including
cefotaxime, particularly in patients with renal insufficiency, may
result in encephalopathy (e.g. impairment of consciousness,
abnormal movements and convulsions) (see section 4.8).
Patients should be advised to contact their doctor immediately
prior to continuing treatment if such reactions occur.
Precautions for administration: During post-marketing surveillance,
potentially life-threatening arrhythmia has been reported in a very
few patients who received rapid intravenous administration of
cefotaxime through a central venous catheter. The recommended time
for injection or infusion should be followed (see section 4.2).
See section 4.3 for contraindications for formulations containing
Effects on Laboratory Tests: As with other cephalosporins a
positive Coombs' test has been found in some patients treated with
cefotaxime. This phenomenon can interfere with the cross-matching
Urinary glucose testing with non-specific reducing agents may yield
false-positive results. This phenomenon is not seen when a
glucose-oxydase specific method is used.
4.5 Interaction with other medicinal products and other forms of
Aminoglycoside antibiotics and diuretics: As with other cephalosporins, cefotaxime may potentiate the
nephrotoxic effects of nephrotoxic drugs such as aminoglycosides or
potent diuretics (e.g. furosemide). Renal function must be
monitored (see section 4.4).
Uricosurics: Probenecid interferes with renal tubular transfer of cefotaxime,
thereby increasing cefotaxime exposure about 2-fold and reducing
renal clearance to about half at therapeutic doses. Due to the
large therapeutic index of cefotaxime, no dosage adjustment is
needed in patients with normal renal function. Dosage adjustment
may be needed in patients with renal impairment (see sections 4.4
Interference with Laboratory Tests:
A false positive Coombs test may be seen during treatment with
cephalosporins. This phenomenon may occur during treatment with
cefotaxime and can interfere with blood cross-matching.
A false positive reaction to urinary glucose may occur with copper
reduction methods (Benedict's, Fehling's or Clinitest) but not with
the use of specific glucose oxidase methods.
There is a potential for mezlocillin and azlocillin to reduce the
clearance of cefotaxime.
4.6 Pregnancy and lactation
Pregnancy: The safety of cefotaxime has not been established in
Animal studies do not indicate direct or indirect harmful effects
with respect to reproductive toxicity. There are, however, no
adequate and well controlled studies in pregnant women.
Cefotaxime crosses the placental barrier. Therefore, cefotaxime
should not be used during pregnancy unless the anticipated benefit
outweighs any potential risks.
Lactation: Cefotaxime passes into human breast milk in small
amounts and is usually compatible with breast feeding, but careful
monitoring of the infant is recommended.
Effects on the physiological intestinal flora of the breast-fed
infant leading to diarrhoea, colonisation by yeast-like fungi, and
sensitisation of the infant cannot be excluded.
Therefore, a decision must be made whether to discontinue
breast-feeding or to discontinue therapy taking into account the
benefit of breast-feeding for the child and the benefit of therapy
for the woman.
4.7 Effects on ability to drive and use machines
Cefotaxime has been associated with dizziness, which may affect the
ability to drive or operate machinery.
There is no evidence that cefotaxime directly impairs the ability
to drive or to operate machines. High doses of cefotaxime,
particularly in patients with renal insufficiency, may cause
encephalopathy (e.g. impairment of consciousness, abnormal
movements and convulsions) (see section 4.8). Patients should be
advised not to drive or operate machinery if any such symptoms
4.8 Undesirable effects
System organ class
(≥ 1/100 to <1/10)
(≥ 1/1,000 to <1/100)
(≥ 1/10,000 to <1/1,000)
Not known (cannot be estimated from available data)*
Infections and infestations
Superinfection (see section 4.4)
Blood and the lymphatic system disorders
Agranulocytosis (see section 4.4)
Immune system disorders
Nervous system disorders
Convulsions (see section 4.4)
Encephalopathy (e.g. impairment of consciousness, abnormal
movements) (see section 4.4)
Arrhythmia following rapid bolus infusion through central venous
Pseudomembranous colitis (see section 4.4)
Increase in liver enzymes (ALAT, ASAT, LDH, gamma-GT and/or
alkaline phosphatise) and/or bilirubin
Hepatitis* (sometimes with jaundice)
Skin and subcutaneous disorders
Toxic epidermal necrolysis (see section 4.4)
Renal and Urinary disorders
Decrease in renal function/increase of creatinine (particularly
when co-prescribed with aminoglycosides)
General disorders and administration site conditions
For IM formulations: Pain at the injection site
Inflammatory reactions at the injection site, including
For IM formulations (since the solvent contains lidocaine):
Systemic reactions to lidocaine
* postmarketing experience
For the treatment of borreliosis, a Jarisch-Herxheimer reaction may
develop during the first days of treatment.
The occurrence of one or more of the following symptoms has been
reported after several week's treatment of borreliosis: skin rash,
itching, fever, leucopenia, increase in liver enzymes, difficulty
of breathing, joint discomfort.
Increase in liver enzymes (ALAT, ASAT, LDH, gamma-GT and/or
alkaline phosphatase) and/or bilirubin have been observed. These
laboratory abnormalities may rarely exceed twice the upper limit of
the normal range and elicit a pattern of liver injury, usually
cholestatic and most often asymptomatic.
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.
Symptoms of overdose may largely correspond to the profile of side
There is a risk of reversible encephalopathy in cases of
administration of high doses of β–lactam antibiotics including
In case of overdose, cefotaxime must be discontinued, and
supportive treatment initiated, which includes measures to
accelerate elimination, and symptomatic treatment of adverse
reactions (e.g. convulsions).
No specific antidote exists. Serum levels of cefotaxime may be
reduced by peritoneal dialysis or haemodialysis.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Beta-lactam antibiotics, cephalosporins.
ATC Code: J01D A10
Mode of action
Cefotaxime is a third generation broad spectrum bactericidal
cephalosporin antibiotic. The bactericidal properties are due to
the inhibitory effect of cefotaxime on bacterial cell wall
Mechanisms of resistance
Resistance to Cefotaxime may be due to production of
extended-spectrum beta-lactamases that can efficiently hydrolyse
the drug, to the induction and/or constitutive expression of AmpC
enzymes, to impermeability or to efflux pump mechanisms. More than
one of these possible mechanisms may co-exist in a single
Current MIC breakpoints used to interpret cefotaxime susceptibility
data are shown below.
European Committee on Antimicrobial Susceptibility Testing (EUCAST)
Clinical MIC Breakpoints (V1.1, 31/03/2006)
Susceptible (<)/Resistant (>)
Streptococcus A, B, C, G
Non-species related breakpoints1
1. Non-species related breakpoints have been determined mainly on
the basis of PK/PD data and are independent of MIC distributions of
specific species. They are for use only for species that have not
been given a species-specific breakpoint and not for those species
where susceptibility testing is not recommended (marked with -- or
IE in the table).
2. The cephalosporin breakpoints for Enterobacteriaceae will detect
resistance mediated by most ESBLs and other clinically important
beta-lactamases in Enterobacteriaceae. However, some ESBL-producing
strains may appear susceptible or intermediate with these
breakpoints. Laboratories may want to use a test which specifically
screens for the presence of ESBL.
3. Susceptibility of staphylococci to cephalosporins is inferred
from the methicillin susceptibility (except ceftazidime which
should not be used for staphylococcal infections).
4. Strains with MIC values above the S/I breakpoint are very rare
or not yet reported. The identification and antimicrobial
susceptibility tests on any such isolate must be repeated and if
the result is confirmed the isolate sent to a reference laboratory.
Until there is evidence regarding clinical response for confirmed
isolates with MIC above the current resistant breakpoint (in
italics) they should be reported resistant.
-- = Susceptibility testing not recommended as the species is a
poor target for therapy with the drug.
IE = There is insufficient evidence that the species in question is
a good target for therapy with the drug.
RD = rationale document listing data used by EUCAST for determining
The prevalence of resistance may vary geographically and with time
for selected species and local information on resistance is
desirable, particularly when treating severe infections. This
information gives only an approximate guidance on the probabilities
whether micro-organisms will be susceptible to cefotaxime or not.
Frequency of resistance ranges in EU (if > 10%) (extreme values)
Group A Streptococci (includingStreptococcus pyogenes) *
Group B Streptococci
β-hemolytic Streptococci (Group C, F, G)
Streptococcus pneumoniae *
Viridans Group Streptococci
Citrobacter spp. *
Escherichia coli *
Haemophilus influenzae *
Haemophilus parainfluenzae *
Klebsiella spp. *
Moraxella catarrhalis *
Neisseria gonorrhoeae *
Neisseria meningitides *
Proteus spp. *
Providencia spp. *
Clostridium spp. (not Clostridium difficile)
Staphylococcus aureus (MRSA)
*Clinical efficacy has been demonstrated for susceptible isolates
in approved clinical indications.
Methicillin-(oxacillin) resistant staphylococci (MRSA) are
resistant to all currently available β-lactam antibiotics including
Penicillin-resistant Streptococcus pneumoniae show a variable
degree of cross-resistance to cephalosporins such as cefotaxime.
5.2 Pharmacokinetic properties
After a 1000mg intravenous bolus, mean peak plasma concentrations
of cefotaxime usually range between 81 and 102 microgram/ml. Doses
of 500mg and 2000mg produce plasma concentrations of 38 and 200
microgram/ml, respectively. There is no accumulation following
administration of 1000mg intravenously or 500mg intramuscularly for
10 or 14 days.
The apparent volume of distribution at steady-state of cefotaxime
is 21.6 litres/1.73m2 after 1g intravenous 30 minute infusion.
Concentrations of cefotaxime (usually determined by non-selective
assay) have been studied in a wide range of human body tissues and
fluids. Cerebrospinal fluid concentrations are low when the
meninges are not inflamed, but are between 3 and 30 microgram/ml in
children with meningitis. Cefotaxime usually passes the blood-brain
barrier in levels above the minimum inhibitory concentration of
common sensitive pathogens when the meninges are inflamed.
Concentrations (0.2-5.4 microgram/ml), inhibitory for most
Gram-negative bacteria, are attained in purulent sputum, bronchial
secretions and pleural fluid after doses of 1 or 2g. Concentrations
likely to be effective against most sensitive organisms are
similarly attained in female reproductive organs, otitis media
effusions, prostatic tissue, interstitial fluid, renal tissue,
peritoneal fluid and gall bladder wall, after usual therapeutic
doses. High concentrations of cefotaxime and desacetyl-cefotaxime
are attained in bile.
Cefotaxime is partially metabolised prior to excretion. The
principal metabolite is the microbiologically active product,
desacetyl-cefotaxime. Most of a dose of cefotaxime is excreted in
the urine - about 60% as unchanged drug and a further 24% as
desacetyl-cefotaxime. Plasma clearance is reported to be between
260 and 390ml/minute and renal clearance 145 to 217 ml/minute.
After intravenous administration of cefotaxime to healthy adults,
the elimination half-life of the parent compound is 0.9 to 1.14
hours and that of the desacetyl metabolite, about 1.3 hours.
In neonates the pharmacokinetics are influenced by gestational and
chronological age, the half-life being prolonged in premature and
low birth weight neonates of the same age.
In severe renal dysfunction the elimination half-life of cefotaxime
itself is increased minimally to about 2.5 hours, whereas that of
desacetyl-cefotaxime is increased to about 10 hours. Total urinary
recovery of cefotaxime and its principal metabolite decreases with
reduction in renal function.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber that
are additional to those included in other sections.
6. Pharmaceutical particulars
.1 List of excipients
Cefotaxime sodium should not be mixed with alkaline solutions such
as sodium bicarbonate injection or solutions containing