Cefotaxime 2g Powder for solution for injection or infusion

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Cefotaxime sodium
Available from:
Wockhardt UK Limited
ATC code:
J01DD; J01DD01
INN (International Name):
Cefotaxime sodium
Dosage:
2 gram(s)
Pharmaceutical form:
Powder for solution for injection/infusion
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Third-generation cephalosporins; cefotaxime
Authorization status:
Marketed
Authorization number:
PA1339/002/003
Authorization date:
2003-09-19

PACKAGE LEAFLET: INFORMATION FOR THE USER

Cefotaxime 500mg powder for solution for injection or infusion

Cefotaxime 1g powder for solution for injection or infusion

Cefotaxime 2g powder for solution for injection or infusion

Read all of this leaflet carefully before you start to take this medicine.

Keep this leaflet. You may need to read it again while you are receiving your treatment.

If you have any further questions, please ask your doctor or nurse.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their

symptoms are the same as yours.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your

doctor or pharmacist.

The name of your medicine is cefotaxime 500mg, 1g or 2g powder for solution for injection or infusion. In the

rest of this leaflet it is called cefotaxime for injection.

In this leaflet:

1. What cefotaxime for injection is and what it is used for

2. Before you are given cefotaxime for injection

3. How cefotaxime for injection should be given

4. Possible side effects

5. How to store cefotaxime for injection

6. Further information

1. WHAT CEFOTAXIME FOR INJECTION IS AND WHAT IT IS USED FOR

Cefotaxime belongs to a group of medicines called cephalosporins which are antibiotics. These medicines

work by killing bacteria that cause infections.

Cefotaxime for injection is used for the treatment of a range of serious bacterial infections including

infections of the blood stream (septicaemia), bones (osteomyelitis), the heart valves (endocartitis), the

membranes covering the brain (meningitis) and the lining of the abdomen (peritonitis), and to prevent and

treat infections following surgical operations.

2. BEFORE YOU ARE GIVEN CEFOTAXIME FOR INJECTION

Cefotaxime for injection should not be given if:

You are allergic to cefotaxime or any other cephalosporin.

You have previously had a severe allergic reaction to penicillin or any other beta-lactam antibiotic

If any of the above applies to you, you should not be given Cefotaxime for Injection.

Take special care with cefotaxime for injection if:

you have previously had an allergic reaction to penicillin or other antibiotics of this type. Not all people

who are allergic to penicillins are also allergic to cephalosporins. Before you are given this medicine

your doctor should check whether you have previously had an allergic reaction to such drugs.

you have kidney problems. You will be carefully monitored throughout your treatment.

you are on a low salt diet, your doctor should make sure you are not receiving too much salt by way of

cefotaxime injections

you are being treated for longer than 10 days, your doctor should monitor your blood with blood counts

you are going to have a blood transfusion, make sure that the doctor who organises your transfusion

knows that you are having cefotaxime for injection

you are diabetic, you may get false positive results with urine glucose tests, such as Clinitest.

you develop a severe skin reaction such as Stevens-Johnson syndrome. Symptoms may include a rash,

blistering of the skin, wheals or itching. You must stop treatment immediately and contact your doctor.

you are taking aminoglycosides such as streptomycin and gentamicin. Your kidney function will be

carefully monitored.

You should be kept under observation in case you develop another infection, particularly colitis (infection of

the lower bowel), while you are being treated with cefotaxime for injection.

Taking other medicines

Taking other medicines when cefotaxime for injection is being administered can affect how it or the other

medicine works. Make sure that your doctor knows what other medicines you are taking. Do not take any

other medicines while you are being treated with cefotaxime for injection unless you have told your doctor or

pharmacist and asked their advice. This includes medicines you may have bought yourself without a

prescription.

Please check with your doctor if you are taking any of the following (or any other medication):

Penicillin antibiotics such as mezlocillin and azlocillin

Aminoglycoside antibiotics such as streptomycin, neomycin or gentamicin

Furosemide or other strong diuretics, used to get rid of excess water from the body

Probenecid, used to prevent gout

If you have any doubts about whether you should be given this medicine, then talk to your doctor.

Important information about some of the ingredients of cefotaxime for injection

Cefotaxime for injection contains 1.045mmol (or 24mg) for the 500mg vial, 2.09mmol (or 48mg) for the 1g

vial and 4.18mmol (or 96mg) for the 2g vial of sodium per dose. To be taken into consideration by patients

on a controlled sodium diet.

Pregnancy and breast-feeding

You should let your doctor or nurse know if you are pregnant or wish to become pregnant or are breast-

feeding before this medicine is administered.

Driving and using machines

Cefotaxime for injection may cause dizziness. If you are affected you should not drive or operate machinery.

3. HOW CEFOTAXIME FOR INJECTION SHOULD BE GIVEN

Your doctor or nurse will prepare your injection by dissolving the cefotaxime powder in a suitable fluid for

injection. The mixture is usually injected intramuscularly (into a muscle) or given intravenously (into a vein)

either by injection or infusion (drip).

Cefotaxime which has been dissolved in a solution which contains Lidocaine injection BP, (a local

anaesthetic), should not be given intravenously, or to infants under 30 months, or to patients who are allergic

to Lidocaine injection BP, or who have heart block (without a pacemaker), or heart failure.

Adults and the Elderly

The usual adult (including the elderly) dose by intramuscular or intravenous injection is 1g every twelve

hours. Lower doses may be given to patients with severe kidney problems.

Children

The usual dose for children aged one month to twelve years is 100-150mg per kg body weight daily in two to

four divided doses.

The usual dose for infants aged one to four weeks is 50mg per kg body weight in two or four divided doses.

Higher doses may be given, particularly in severe infections.

Your doctor will decide the dose that is best for you. If you do not understand, or are in any doubt, ask your

doctor or nurse.

If you think you have been given too much or too little cefotaxime for injection

Your doctor will decide which dose is best for you. If you think too much or too little medicine has been given

to you contact your doctor, nurse, pharmacist or nearest hospital.

4. POSSIBLE SIDE EFFECTS

Like many medicines, cefotaxime for injection may cause side effects in some patients, particularly when

treatment is first started. You should inform your doctor or nurse immediately if you are unwell.

These include:

Allergic reactions such as rash, itching, fever and, very rarely, peeling skin, swelling of the face and

difficulty breathing. Tell your doctor immediately if you think you are having an allergic reaction to

cefotaxime.

Feeling sick, being sick, stomach pain and diarrhoea, particularly when it is first given.

The injection site may be sore.

Other side effects that some patients have had with cefotaxime for injection, particularly if given over

long periods, include headaches, dizziness, anaemia or other changes in the blood (which can cause

sore throat and mouth ulcers or a tendency to bleed or bruise easily), temporary changes in liver

function, inflammation of the liver, kidney problems, jaundice, painful joints and thrush.

Treatment with high doses of cefotaxime, particularly in patients with kidney problems, has been known

to cause loss of consciousness, abnormal movements and convulsions.

Occasionally, patients have suffered a blood clot in a vein or irregular heart rhythm after intravenous

cefotaxime.

Administration of high doses in patients with kidney problems may cause brain disease.

Antibiotic treatment can affect the normal bacteria in the gut, causing new infection (colitis). You should

tell your doctor immediately if you develop diarrhoea, abdominal cramps or pain, nausea, dehydration,

fever or bloody, watery diarrhoea. Do not take any anti-diarrhoea medicines, such as loperamide.

Occasionally, if you have had an intravenous injection there may be swelling around the area of infection

or inflammation of the vein.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting systems listed

below.

United Kingdom

Yellow Card Scheme

www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

E-mail: medsafety@hpra.ie

By reporting side effects you can help provide more information on the safety of this medicine.

5.

HOW TO STORE CEFOTAXIME FOR INJECTION

Keep this medicine out of the sight and reach of children.

This medicine should not be used after the expiry date (EXP) shown on the vial and carton. The expiry

date refers to the last day of that month.

The vials should not be stored above 25

C.

Keep the vial in the outer carton in order to protect from light.

Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8

C. From a

microbiological point of view, once opened, the product should be used immediately. If not used

immediately, in-use storage times and conditions prior to use are the responsibility of the user and would

normally not be longer than 24 hours at 2-8

C, unless reconstitution has taken place in controlled and

validated aseptic conditions. For single use only. Once reconstituted, any unused portion of solution

should be discarded.

Do not use cefotaxime for injection if the solution contains particles or is cloudy

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to

dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What cefotaxime for injection contains

Cefotaxime for injection contains the active ingredient cefotaxime as cefotaxime sodium. Each vial contains

500mg, 1g or 2g of cefotaxime. The sodium content per vial is approximately 24mg (1.045mmol), 48mg

(2.09mmol) and 96mg (4.18mmol) respectively.

What cefotaxime for injection looks like and contents of the pack

Cefotaxime for injection is an off white to pale yellow powder, which must be made into a solution before

injection. It is available in packs of 1, 10, 25 and 50 vials.

X-PIL information

To listen to or request a copy of the leaflet in Braille, large print or audio please call, free of charge:

0800 198 5000 (UK only)

Please be ready to give the following information:

Product name Reference number

Cefotaxime 500mg powder for solution for

injection or infusion

PL 29831/0030

Cefotaxime 1g powder for solution for

injection or infusion

PL 29831/0030

Cefotaxime 2g powder for solution for

injection or infusion

PL 29831/0029

This is a service provided by the Royal National Institute of Blind People.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: Wockhardt UK Ltd, Ash Road North, Wrexham, LL13 9UF, UK.

Manufacturer: CP Pharmaceuticals Ltd, Ash Road North, Wrexham, LL13 9UF, UK.

This leaflet was last revised in 03/2017

Information for Health Care Professionals

Cefotaxime 500mg powder for solution for injection or infusion

Cefotaxime 1g powder for solution for injection or infusion

Cefotaxime 2g powder for solution for injection or infusion

Dosage and Administration Information Only

Please refer to the Summary of Product Characteristics for further information

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.

Adults:

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 the 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 required.

Children:

The usual dosage rang is 100-150mg/kg/day may be required. 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 (G=FR <5ml/ min = serum creatinine approximately 751 miocromol/litre).

After an initial loading dose of 1g, daily dose should be halved without change in the frequency or dosing, i.e.

1g twelve hourly becomes 0.5g twelve hourly, 1g eight hourly becomes 0.5g eight hourly, 2g eight hourly

become 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

discussed below in the section entitled ‘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 below in the section entitled ‘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 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.

Incompatibilities

Cefotaxime sodium should not be mixed with alkaline solutions such as sodium bicarbonate injection or

solutions containing aminophylline.

Cefotaxime should not be admixed with aminoglycosides. If they are used concurrently they should be

administered in separate sites.

Cefotaxime should not be mixed with other medicinal products except those listed below in in the section

entitled ‘Instructions for use/handling’.

Shelf life and special precautions for storage

Unopened: 2 years. Do not store about 25

C. Keep the vials in the outer carton.

For the reconstituted solution, chemical and physical in-use stability has been demonstrated for 24 hours at

C. From a microbiological point of view, once opened, the product should be used immediately. If not

used immediately, in-use storage times and conditions prior to use are the responsibility of the user and

would normally not be longer than 24 hours at 2-8

C, unless reconstitution has taken place in controlled and

validated aseptic conditions.

Instructions for use/handling

For single use only. Discard any unused contents.

When dissolved in Water for injections PhEur, cefotaxime forms a straw-coloured solution suitable for

intravenous and intramuscular injection. Variations in the intensity of colour of the freshly prepared solutions

do not indicate a change in potency or safety.

Dilution Table: Intravenous Administration

Vial size

Diluent* to be

added

Approx available volume

Approx displacement volume

500mg

2.3ml

0.3ml

4.6ml

0.6ml

10ml

11.4ml

1.4ml

*Water for injection

Dilution Table: Intramuscular Administration

Vial size

Diluent* to be

added

Approx available volume

Approx displacement volume

500mg

2.3ml

0.3ml

4.6ml

0.6ml

10ml

11.4ml

1.4ml

*Water for injection or 1% lidocaine

Reconstituted solution: Whilst it is preferable to use only freshly prepared solutions for both intravenous and

intramuscular injection, cefotaxime is compatible with several commonly used intravenous infusion fluids and

will retain satisfactory potency for up to 24 hours refrigerated in the following:

Water for Injection Ph Eur

Sodium Chloride Intravenous Infusion BP

5% Glucose Intravenous Infusion BP

Sodium Chloride and Glucose Intravenous Infusion BP

Compound Sodium Lactate Intravenous Infusion BP (Ringer-lactate solution for injection)

Intravenous Infusion:

1-2g cefotaxime are dissolved in 40-100ml of infusion fluid.

After 24 hours any unused solution should be discarded.

Cefotaxime is compatible with 1% lidocaine; however freshly prepared solutions should be used.

Cefotaxime is compatible with metronidazole infusion (500mg/100ml) and both will maintain potency when

refrigerated (2

C) for up to 24 hours. Some increase in colour of prepared solutions may occur on storage.

However, provided the recommended storage conditions are observed, this does not indicate change in

potency or safety.

This leaflet was last revised in 03/2017

The information in this leaflet applies only to Cefotaxime Powder for solution for injection or

infusion.

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13 November 2019

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Summary of Product Characteristics

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 cefotaxime.

Each gram of cefotaxime contains approximately 48mg (2.09mmol) of sodium.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for solution for injection or infusion (Powder for injection or infusion).

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

osteomyelitis,

septicaemia,

bacterial endocarditis,

meningitis, and

peritonitis.

and other serious bacterial infections suitable for parenteral antibiotic therapy.

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.

Adults:

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 required.

Children:

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.

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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.

4.3 Contraindications

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 Administration”.

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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 restriction.

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

cefotaxime.

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 stasis.

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 lidocaine.

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 of blood.

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 interactions

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 and 4.2).

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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 Fertility, pregnancy and lactation

Pregnancy: The safety of cefotaxime has not been established in human pregnancy.

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 occur.

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4.8 Undesirable effects

System organ

class

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

available

data)*

Infections and

infestations

Superinfection

(see section

4.4)

Blood and the

lymphatic

system

disorders

Leukopenia

Eosinophilia

Thrombocytopenia

Neutropenia

Granulocyto

penia

Agranulocyto

sis (see

section 4.4)

Haemolytic

anaemia

Immune system

disorders

Jarisch-Herxheimer

reaction

Anaphylactic

reactions

Angioedema

Bronchospas

Anaphylactic

shock

Nervous system

disorders

Convulsions (see section

4.4)

Headache

Dizziness

Encephalopa

thy (e.g.

impairment

consciousnes

s, abnormal

movements)

(see section

4.4)

Cardiac

disorders

Arrhythmia

following

rapid bolus

infusion

through

central

venous

catheter

Gastrointestinal

disorders

Diarrhoea

Nausea

Vomiting

Abdominal

pain

Pseudomem

branous

colitis (see

section 4.4)

Hepato-biliary

disorders

Increase in liver enzymes

(ALAT, ASAT, LDH,

gamma-GT and/or

alkaline phosphatise)

Hepatitis*

(sometimes

with

jaundice)

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System organ

class

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

available

data)*

and/or bilirubin

Skin and

subcutaneous

disorders

Rash

Pruritus

Urticaria

Drug fever

Erythema

multiforme

Stevens-John

syndrome

Toxic

epidermal

necrolysis

(see section

4.4)

Renal and

Urinary

disorders

Decrease in renal

function/increase of

creatinine (particularly

when co-prescribed with

aminoglycosides)

Interstitial

nephritis

Candidiasis

General

disorders and

administration

site conditions

For IM

formulations:

Pain at the

injection site

Fever

Inflammatory reactions at

the injection site,

including

phlebitis/thrombophlebitis

For IM

formulations

(since the

solvent

contains

lidocaine):

Systemic

reactions to

lidocaine

* postmarketing experience

Jarisch-Herxheimer reaction

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.

Hepatobiliary disorders

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.

Website: www.hpra.ie; e-mail: medsafety@hpra.ie

4.9 Overdose

Symptoms of overdose may largely correspond to the profile of side effects.

There is a risk of reversible encephalopathy in cases of administration of high doses of β–lactam antibiotics including

cefotaxime.

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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

General Properties

ATC Classification

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 synthesis.

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 bacterium.

Breakpoints:

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 (≥)

Enterobacteriaceae

Pseudomonas

Acinetobacter

Staphylococcus

Note

Enterococcus

Streptococcus A, B, C, G

0.5/0.5

Streptococcus pneumoniae

0.5/2

Haemophilus influenzae

Moraxella Catarrhalis

0.12/0.12

Neisseria gonorrhoea

0.12/0.12

Neisseria Meningitidis

0.12/0.12

Gram-negative, anaerobes

Non-species related

breakpoints

S</>R

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).

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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 breakpoints.

Susceptibility

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.

Species

Frequency of resistance ranges in EU (if > 10%) (extreme values)

Susceptible

Gram-positive aerobes

Staphylococcus aureus

(Methicillin-susceptible)

Group A Streptococci (including Streptococcus pyogenes)

Group B Streptococci

β-hemolytic Streptococci (Group C, F, G)

Streptococcus pneumoniae

12.7%

Viridans Group Streptococci

Gram-negative aerobes

Citrobacter spp.

Escherichia coli

Haemophilus influenzae

Haemophilus parainfluenzae

Klebsiella spp.

Moraxella catarrhalis

Neisseria gonorrhoeae

Neisseria meningitides

Proteus spp.

Providencia spp.

Yersinia enterocolitica

Anaerobes

Clostridium spp. (not Clostridium difficile)

Peptostreptococcus spp.

Propionibacterium spp.

Others

Borrelia spp.

Resistant

Gram-positive aerobes

Enterococcus spp.

Enterococcus faecalis

Enterococcus faecium

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Listeria spp.

Staphylococcus aureus (MRSA)

Staphylococcus epidermidis (MRSE)

Gram-negative aerobes

Acinetobacter spp.

Citrobacter spp.

Enterobacter spp.

Morganella morganii

Pseudomonas spp.

Serratia spp.

Xanthomonas maltophilia

Anaerobes

Bacteroides spp.

Clostridium difficile

Others

Clamydiae

Mycoplasma spp.

Legionella pneumophilia

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

cefotaxime.

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/1.73m

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.

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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

6.1 List of excipients

None.

6.2 Incompatibilities

Cefotaxime sodium should not be mixed with alkaline solutions such as sodium bicarbonate injection or solutions containing

aminophylline.

Cefotaxime should not be admixed with aminohlycosides. If they are used concurrently they should be administered in

separate sites.

Cefotaxime should not be mixed with other medicinal products except those listed in section 6.6.

6.3 Shelf life

Unopened: 2years.

For the reconstituted solution, chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C. From a

microbiological point of view, once opened, the product should be used immediately. If not used immediately, in-use storage

times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C,

unless reconstitution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Unopened: Do not store above 25°C. Keep the vials in the outer carton.

For storage times following reconstitution, see section 6.3.

6.5 Nature and contents of container

Cefotaxime is supplied in Type II 15ml glass vials, closed with a Type I rubber stopper (coated or uncoated with Omniflex) and

sealed with an aluminium/plastic cap fitted with a detachable flip top.

The vials are boxed individually and in packs of 10, 25 or 50 vials.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

For single use only. Discard any unused contents.

When dissolved in Water for Injections PhEur, cefotaxime forms a straw-coloured solution suitable for intravenous and

intramuscular injection. Variations in the intensity of colour of the freshly prepared solutions do not indicate a change in

potency or safety.

Dilution Table:Intravenous Administration

Vial size

Diluent* to be added

Approx available volume

Approx displacement volume

10ml

11.4ml

1.4ml

*Water for injection

Dilution Table:Intramuscular Administration:

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Vial size

Diluent* to be added

Approx available volume

Approx displacement volume

10ml

11.4ml

1.4ml

*Water for injection or 1% lidocaine

Reconstituted solution: Whilst it is preferable to use only freshly prepared solutions for both intravenous and intramuscular

injection, cefotaxime is compatible with several commonly used intravenous infusion fluids and will retain satisfactory potency

for up to 24 hours refrigerated in the following:

Water for InjectionsPh Eur

Sodium Chloride Intravenous Infusion BP

5% Glucose Intravenous Infusion BP

Sodium Chloride and Glucose Intravenous Infusion BP

Compound Sodium Lactate Intravenous Infusion BP (Ringer-lactate solution for injection)

Intravenous Infusion:

1-2g cefotaxime are dissolved in 40-100ml of infusion fluid.

After 24 hours any unused solution should be discarded.

Cefotaxime is compatible with 1% lidocaine; however freshly prepared solutions should be used.

Cefotaxime is also compatible with metronidazole infusion (500mg/100ml) and both will maintain potency when refrigerated

(2º-8ºC) for up to 24 hours. Some increase in colour of prepared solutions may occur on storage. However, provided the

recommended storage conditions are observed, this does not indicate change in potency or safety.

7 MARKETING AUTHORISATION HOLDER

Wockhardt UK Limited

Ash Road North

Wrexham

LL13 9UF

United Kingdom

8 MARKETING AUTHORISATION NUMBER

PA1339/002/003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorization: 19 September 2003

Date of last renewal: 02 November 2005

10 DATE OF REVISION OF THE TEXT

September 2017

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