Consumer medicine information

Cefotaxime Sandoz® [9079]

Cefotaxime

BRAND INFORMATION

Brand name

Cefotaxime Sandoz Powder for injection

Active ingredient

Cefotaxime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cefotaxime Sandoz® [9079].

What is in this leaflet

This leaflet answers some common questions about Cefotaxime Sandoz.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

Keep this leaflet.

You may need to read it again.

What Cefotaxime Sandoz is used for

This medicine is used to treat infections in different parts of the body caused by bacteria.

Cefotaxime Sandoz is also used to prevent infections before, during and after surgery.

It contains the active ingredient cefotaxime sodium.

Cefotaxime belongs to a group of medicines called cephalosporin antibiotics.

It works by killing bacteria that are causing your infection.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

Before you are given Cefotaxime Sandoz

When you must not be given it

Do not use this medicine if you have an allergy to:

  • cefotaxime, the active ingredient
  • any other similar medicines such as cephalosporins.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not use this medicine if you have or have had a serious allergic reaction to any penicillins.

You may be more likely to have an allergic reaction to Cefotaxime Sandoz if you are allergic to penicillin medicines.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If you are not sure whether you should be given this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • any type of allergic reaction to any cephalosporin or penicillin medicines. You may have an increased chance of being allergic to Cefotaxime Sandoz if you are allergic to any cephalosporins or penicillins.
  • allergies to lignocaine or other local anaesthetics. Lignocaine may be mixed with Cefotaxime Sandoz prior to injection.
  • kidney problems
  • heart problems
  • liver problems
  • stomach or bowel problems
  • asthma.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you are given Cefotaxime Sandoz.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Cefotaxime Sandoz may interfere with each other. These include:

  • aminoglycoside antibiotics, including gentamicin
  • bacteriostatic antibiotic medicines such as tetracyclines, erythromycin and chloramphenicol
  • fluid tablets or diuretic medicines such as frusemide
  • probenecid, a medicine used to treat gout
  • oral contraceptive medicines (birth control medicines).

These medicines may be affected by Cefotaxime Sandoz or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Talk to your doctor about the need for an additional method of contraception while being treated with Cefotaxime Sandoz.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How Cefotaxime Sandoz is given

How much is given

Your doctor will decide what dose and how long you will receive Cefotaxime Sandoz.

This depends on your condition and whether you are using other medicines.

For most infections, Cefotaxime Sandoz is usually given in divided doses throughout the day.

Sometimes only a single dose of Cefotaxime Sandoz is required for the treatment and prevention of certain infections.

How it is given

Cefotaxime Sandoz must only be given by a doctor or nurse.

It is reconstituted before being injected.

Cefotaxime Sandoz can be given in two ways:

  • as a slow injection into a vein
  • as a deep injection into a large muscle.

If you take too much (overdose)

As Cefotaxime Sandoz is given to you under the supervision of your doctor, it is unlikely that you will receive too much.

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else are experiencing severe side effects after being given Cefotaxime Sandoz.

You may need urgent medical attention.

If you are given too much Cefotaxime Sandoz you may experience symptoms such as:

  • stomach upsets
  • headache
  • dizziness
  • seizures.

While you are given Cefotaxime Sandoz

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being treated with Cefotaxime Sandoz.

Tell any other doctors, dentists, and pharmacists who treat you that you are being treated with this medicine.

If you become pregnant while you are being treated with this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are being treated with this medicine.

It may interfere with the results of some tests.

If you have to test your urine for sugar while you are being treated with this medicine, make sure your doctor knows which type of test you use.

Cefotaxime Sandoz may affect the results of some of these tests.

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

If you experience severe diarrhoea, tell your doctor, pharmacist or nurse immediately. Do this even if it occurs several weeks after Cefotaxime Sandoz has been stopped.

Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any diarrhoea medicine without first checking with your doctor.

If you get a sore white mouth or tongue while being treated with or soon after stopping Cefotaxime Sandoz, tell your doctor. Also tell your doctor if you experience vaginal itching or discharge.

This may mean you have a fungal infection called thrush. Sometimes the use of Cefotaxime Sandoz allows fungi to grow and the above symptoms to occur. Cefotaxime Sandoz does not work against fungi.

Things to be careful of

Be careful driving or operating machinery until you know how Cefotaxime Sandoz affects you.

This medicine may cause dizziness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being treated with Cefotaxime Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

While you are given Cefotaxime Sandoz

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina, sometimes with a white discharge
  • pain or swelling at the injection site
  • diarrhoea
  • nausea (feeling sick) or vomiting
  • headache or dizziness.

These are usually mild side effects of the medicine.

If any of the following happen, tell your doctor or nurse immediately or go to Accident and Emergency at your nearest hospital:

  • severe abdominal or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • wheezing or difficulty breathing
  • skin rash, itching, hives, blisters or peeling skin
  • fast or irregular heart beat
  • signs of frequent infections such as fever, sore throat, swollen glands or mouth ulcers
  • unusual bleeding or bruising under the skin
  • signs of anaemia, such as tiredness, headache, dizziness, being short of breath when exercising or looking pale
  • yellowing of the skin or eyes, also known as jaundice
  • blood in the urine
  • seizures or abnormal movements.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. Serious side effects are rare.

After being given Cefotaxime Sandoz

Tell your doctor immediately if you notice any of the following side effects, even if they occur several weeks after stopping treatment with Ceftotaxime Sandoz:

  • severe abdominal or stomach cramps
  • watery and severe diarrhoea, which may be bloody
  • fever, in combination with one or both of the above.

These are rare but serious side effects. You may have a serious condition affecting your bowel. Therefore, you may need urgent medical attention.

Do not take any diarrhoea medicine without first checking with your doctor.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After being given Cefotaxime Sandoz

Storage

This medicine will be stored in the hospital pharmacy or on the ward and will be looked after by your doctor or pharmacist.

Vials of Cefotaxime Sandoz Powder for Injection should be kept in a cool dry place, protected from heat and light, where the temperature stays below 25°C.

The reconstituted solution must be used immediately and any unused solution should be discarded.

Product description

What it looks like

Cefotaxime Sandoz comes in three types of vials:

  • Cefotaxime Sandoz 0.5g - white to slightly yellow powder.
  • Cefotaxime Sandoz 1g - white to slightly yellow powder.
  • Cefotaxime Sandoz 2g - white to slightly yellow powder.

Available in cartons of 1 vial.

Ingredients

  • Cefotaxime Sandoz 0.5g - 0.5g cefotaxime, as cefotaxime sodium
  • Cefotaxime Sandoz 1g - 1g cefotaxime, as cefotaxime sodium
  • Cefotaxime Sandoz 2g - 2g cefotaxime, as cefotaxime sodium

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Cefotaxime Sandoz is supplied in Australia  by:
Sandoz Pty Ltd
ABN 60 075 449 553
19 Harris Street
Pyrmont NSW 2009
Australia
Tel: 1800 634 500

This leaflet was revised in February 2012.

Australian Register Numbers
0.5g powder for injection: AUST R 76431
1g powder for injection: AUST R 76432
2g powder for injection: AUST R 76433

BRAND INFORMATION

Brand name

Cefotaxime Sandoz Powder for injection

Active ingredient

Cefotaxime

Schedule

S4

 

Name of the medicine

Cefotaxime sodium.

Excipients.

The reconstituted powder contains approximately sodium 48 mg (2.09 mmol) per gram of cefotaxime.

Description

Chemical name: sodium (6R,7R)-3-[(acetyloxy) methyl]-7-[[(Z)-2-(2-aminothiazol-4-yl) -2-(methoxyimino) acetyl]amino] -8-oxo-5-thia-1-azabicyclo [4.2.0]-oct-2-ene -2-carboxylate. Molecular formula: C16H16N5NaO7S2. MW: 477.4. CAS: 64485-93-4. Cefotaxime is a white or slightly yellow powder, hygroscopic, freely soluble to very soluble in water, sparingly soluble in methanol and practically insoluble in ether. The pKa is 3.35, with the 10% prepared solution having a pH of 4.5 to 6.5 and a pale yellow colour. The yellow colour of the solution becomes more intense if the pH is raised, and may indicate possible degradation.

Pharmacology

Cefotaxime is a semisynthetic broad spectrum cephalosporin for parenteral use. Cefotaxime's bactericidal effect is due to inhibition of cell wall synthesis.

Microbiology.

Table 1 describes the spectrum of cefotaxime activity under in vivo conditions (at plasma concentrations achieved with the recommended doses).
Some Pseudomonas aeruginosa (approximately 25%) and Bacteroides (approximately 43%) strains have in vitro minimum inhibitory concentrations (MIC) of < 16 mg/L. The in vitro combination of cefotaxime with aminoglycosides (e.g. gentamicin) has shown evidence of synergy against some Gram negative microbial strains, including some strains of Serratia marcescens, E. coli, Pseudomonas aeruginosa, Klebsiella sp., P. mirabilis and Staph. aureus.
Cefotaxime also shows resistance to many β-lactamases (penicillinases and cephalosporinases).

Susceptibility tests.

Dilution or diffusion techniques (either quantitative (MIC) or breakpoint), should be used following a regularly updated, recognised and standardised method (e.g. National Council of Clinical Laboratory Service (NCCLS)). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of susceptible indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of intermediate indicates that the result should be considered equivocal, and if the 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.

Pharmacokinetics.

Absorption.

Cefotaxime is suitable for intramuscular and intravenous injection however due to poor absorption, it is not suitable for oral administration.
Single intramuscular injections of cefotaxime 500 mg and 1 g to normal volunteers gave post-dose mean peak plasma levels of 11.7 and 20.5 mg/L at 30 minutes and 1.4 and 3.36 mg/L at four hours, respectively. Proportionally higher plasma levels are seen with 2 g doses.
Following 8 hourly 500 mg IM injections over ten days in 15 normal volunteers, predose plasma levels of 0.08 to 0.55 mg/L and 30 minutes postdose levels of 9.2 to 11.9 mg/L were recorded.
Please see Table 2 for plasma levels obtained following IV bolus injections (administered over 5 minutes) of cefotaxime 500 mg, 1 g and 2 g to normal volunteers.
When administered as an infusion over 30 minutes, a 1 g dose gives plasma levels of 27.9, 8.81 and 2.62 mg/L, at 30, 90 and 210 minutes postdose, respectively. Steady-state trough levels of 1.33 mg/L are obtained following six hourly 1 g infusions over 14 days. In patients with normal renal function, there is no evidence of cefotaxime accumulation following multiple IV or IM dosing. Following administration via IM, IV bolus and IV infusion, the mean elimination half-lives were 1.45, 1.06 and 1.13 hours, respectively.

Distribution.

Cefotaxime is 32 to 44% bound to plasma protein with the desacetyl metabolite displaying half this binding. High renal clearance indicates that cefotaxime has a low binding affinity.
Urinary and faecal recovery accounts for 85-90% and 7-9.5% of the administered dose, with 70-80% recovered in the first four hours postdose. As evidenced in radioactive labelling studies in normal volunteers, 20-36% of administered drug is excreted in the urine unchanged, 15-25% as the desacetyl derivative, and 20-25% as the opened lactone metabolite. Urinary concentrations vary with route of administration, with 1 g bolus IV, infusion IV and IM injections giving peak levels of 1309, 599 and 903 mg/L, respectively, four hours postdose.
When meninges are inflamed, cefotaxime displays significant diffusion into the cerebrospinal fluid, with concentrations obtained following IV doses of 1 to 2 g being above the MIC for susceptible organisms (i.e. those with MIC < 0.5 mg/L).
Mean peak levels of 35 mg/L are obtained in the bile 30 minutes following a 1 g IV dose, with concentrations reducing to 3.30 mg/L after 4 hours.

Metabolism.

Following administration, cefotaxime is rapidly deacetylated in the body, with measurable plasma levels obtained five minutes postdose. After administration of a single IV dose of 15 mg/kg to normal volunteers, the mean peak serum levels after ten minutes for cefotaxime and desacetylcefotaxime were 100 and 5 microgram/mL, respectively.
The desacetyl derivative has a similar antimicrobial spectrum to cefotaxime in vitro but is generally less active, ranging from twice as active to 32 times less active, depending on the microbial species. Desacetylcefotaxime undergoes further metabolism to a microbiologically inactive open lactone moiety.

Excretion.

In patients with normal renal function, the elimination half-life of cefotaxime is 0.7-1.3 hours, and desacetylcefotaxime approximately two hours. In patients with impaired renal function, the terminal half-life of the desacetylcefotaxime is prolonged to a greater extent than that of cefotaxime (e.g. in patients with creatinine clearance of 5-10 mL/minute, the terminal half-life of cefotaxime is 3.5 versus 13.0 hours for desacetylcefotaxime).
Following IM administration of a 1 g dose the mean plasma clearance is 318 mL/minute/1.73 m2.
Interaction studies have demonstrated that orally administered probenecid decreases the renal clearance of cefotaxime by 11-32%, and increases cefotaxime retention by 14-40%.
The bioavailability and pharmacokinetics of IM administered cefotaxime are not affected by concomitant use of lignocaine 0.5% solution.

Neonatal pharmacokinetics.

Neonatal pharmacokinetics are influenced by birthweight, with elimination half-life prolonged at lower birthweights (see Table 3). Following a ten minute infusion of 50 mg/kg, the mean concentrations shown in Table 3 were obtained.

Indications

Cefotaxime is indicated for the treatment of the following types of infection when caused by susceptible microorganisms.
Infections of the respiratory tract (upper and lower); infections of the urinary tract; septicaemia (concomitant therapy with an aminoglycoside may be instituted prior to isolation of the causative organism); intra-abdominal infection; gonorrhoea (including gonorrhoea caused by β-lactamase producing strains of Neisseria gonorrhoeae); ear, nose and throat infections; skin and skin structure infections; bone and joint infections; meningitis: cefotaxime should be combined with an appropriate alternative antibiotic (ampicillin, chloramphenicol or benzylpenicillin) for initial therapy in children (excluding neonates) pending the availability of culture and sensitivity results. In adults the empirical use of cefotaxime should be restricted to patients suspected of having meningitis caused by Gram negative enteric bacilli.
Cefotaxime may be used for the prevention of postoperative infection in obstetric surgery, vaginal and abdominal hysterectomy and biliary surgery.
In serious cases cefotaxime may be used, if considered appropriate, before the results of sensitivity tests become available.
The emergence of resistance to cefotaxime may complicate treatment.

Contraindications

Known hypersensitivity to cefotaxime or other cephalosporin antibiotics, or history of a previous major allergic response to a penicillin (due to the possibility of cross sensitivity).
Cefotaxime should not be administered via IV injection with lignocaine, nor should lignocaine be used as a diluent in patients with a known history of hypersensitivity to lignocaine or other amide type local anaesthetics; nonpaced heart block; severe heart failure; or infants aged less than 30 months.

Precautions

Potentially life threatening arrhythmia has been reported in a very few patients receiving rapid IV cefotaxime administration via a central venous catheter. Cefotaxime given by intermittent IV injection should, therefore, be administered over a period of 3-5 minutes.
Cefotaxime should be used with caution in patients with known hypersensitivity to penicillin or other β-lactam antibiotics. The possibility of severe or fatal anaphylactic reactions should be borne in mind and appropriate treatment kept available.

Serious bullous reactions.

Cases of serious bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with cefotaxime (see Adverse Effects). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.
High doses of cefotaxime should be used with caution in patients receiving concomitant therapy with aminoglycoside antibiotics or potent diuretics (e.g. frusemide).
Cefotaxime sodium, like other parenteral anti-infective drugs, may be locally irritating to tissues. To minimise the potential for tissue inflammation, infusion sites should be monitored regularly and changed when appropriate.
Cefotaxime should be used with caution in patients with allergic diathesis and asthma.
Superinfection with cefotaxime resistant microorganisms, including fungi, may occur. In such instances appropriate therapy should be implemented.
As the powder for injection contains sodium 48.2 mg per gram of cefotaxime sodium, this should be taken into account in patients requiring sodium restriction.

Haematological reactions.

Leukopenia, neutropenia and, more rarely, agranulocytosis may develop during treatment with cefotaxime, particularly if given over long periods.
White blood cell counts should be performed in patients requiring treatment for in excess of 7 days. If the patient becomes neutropenic, therapy should be ceased.

Pseudomembranous colitis.

If during treatment with broad spectrum antibiotics or in the weeks immediately following cessation of therapy, diarrhoea (particularly if severe and/or persistent) is reported, this may be indicative of disease associated with Clostridium difficile, the most severe form of which is pseudomembranous colitis, a rare and sometimes fatal condition. Diagnosis of Cl. difficile associated disease can be made through faecal screening for the organism and its cytotoxin. Confirmation of a diagnosis of pseudomembranous colitis should be made by endoscopic and/or histological examination.
If pseudomembranous colitis is suspected, cefotaxime should be immediately ceased and appropriate therapy (e.g. oral antibacterial agents effective against Cl. difficile) should be considered. Fluids, electrolytes and protein replacement therapy should be provided as required. Drugs that delay peristalsis, such as opiates and diphenoxylate with atropine (e.g. Lomotil), may prolong and/or worsen the condition and should not be used. Patients with faecal stasis may be at higher risk of developing Cl. difficile associated conditions.

Hepatic disease.

Hepatic function should be monitored in patients with liver disease as transient rises in liver enzymes have been reported following cefotaxime therapy. In patients with severe hepatic insufficiency or reduced hepatic blood flow, the metabolism of lignocaine may be reduced, causing accumulation and toxicity. In these cases, repeated use of lignocaine should be avoided.

Renal disease.

Transient rises in creatinine and urea have been reported during cefotaxime therapy. Renal function should, therefore, be monitored in patients with renal insufficiency. The dosage in such patients may also need to be adjusted (see Dosage and Administration).
The combination of cefotaxime and aminoglycoside antibiotics, probenecid or other nephrotoxic agents should be used with caution, and renal function monitored in all cases.

Use in pregnancy.

(Category B1)
Category B1: drugs which have been taken by only a limited number of 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.
The safety of cefotaxime when used in pregnancy has not been established. Cefotaxime has not been shown to cause any teratogenic or embryotoxic effects in animals. However, cefotaxime crosses the placenta and it should be administered during known or suspected pregnancy only if, in the judgment of the treating clinician, such use is deemed essential to the patient's welfare.

Use in lactation.

Cefotaxime is excreted in the breast milk, with peak concentrations following a 1 g IV dose within the range of 0.25-0.52 microgram/mL (mean 0.32 ± 0.09 microgram/mL) two to three hours postdose. At these cefotaxime concentrations in breast milk the infant's oropharyngeal flora may be affected. Consequently, cefotaxime is not recommended during breastfeeding unless the expected benefits outweigh any potential risk.

Effects on ability to drive and use machines.

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 Adverse Effects). Patients should be advised not to drive or operate machinery if any such symptoms occur.

Interactions

Although cefotaxime and gentamicin have additive microbiological effects, they are physically incompatible and should not be combined in a single preparation (e.g. infusion bag).
Orally administered probenecid causes an increase in cefotaxime levels and slightly delays renal clearance. Due to the large therapeutic index of cefotaxime, no dose adjustment is needed in patients with normal renal function. Dose adjustment may be needed in patients with renal impairment (see Pharmacology and Precautions).
Cefotaxime, as for many cephalosporins, may potentiate the renal toxicity of nephrotoxic drugs.
The efficacy of oral contraceptives may be decreased during concomitant use of cefotaxime. Therefore, during therapy with Cefotaxime Sandoz additional contraceptive methods should be used.
Cefotaxime Sandoz should not be combined with bacteriostatic antibiotics (e.g. tetracycline, erythromycin and chloramphenicol) since an antagonistic effect is possible.

Effects on laboratory tests.

Cephalosporin therapy, including cefotaxime, may cause false positive Coombs' tests.
Urinary glucose testing with nonspecific reducing agents may give a false positive reaction in patients receiving cefotaxime therapy. This is not seen when a glucose oxidase specific method is used.

Adverse Effects

Hypersensitivity reactions.

Angioedema, bronchospasm and malaise, possibly culminating in anaphylactic shock, may rarely occur.

Cardiovascular.

During postmarketing surveillance, potentially life threatening arrhythmia has been reported in a few patients who received rapid intravenous administration of cefotaxime through a central venous catheter.

Dermatological.

Rash, pruritus, urticaria. Isolated cases of bullous eruptions (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported.

Gastrointestinal.

Nausea, diarrhoea, candidiasis, vomiting, abdominal pain, colitis, including rare instances of pseudomembranous colitis (see Precautions).

Haematological.

Leucopenia and granulocytopenia and, more rarely, agranulocytosis may develop during treatment with cefotaxime, as for some other cephalosporins. False positive direct Coombs' tests have been reported. Haemolytic anaemia during treatment with cefotaxime has been reported rarely. Eosinophilia. Rare cases of thrombocytopenia have also been recorded, but these were rapidly reversible on withdrawal of treatment. It is, therefore, recommended that blood count should be monitored if treatment lasts for longer than 7 days.

Hepatobiliary.

Moderate and transient increase in liver enzymes (ALT, AST, LDH, GGT and/or alkaline phosphatase) and/or bilirubin. Increases in serum transaminases and alkaline phosphatase levels have been noted. These laboratory abnormalities, which could also be explained by the infection, may rarely exceed twice the upper limit of the normal range and elicit a pattern of hepatic injury, usually cholestatic and most often asymptomatic. Hepatitis (sometimes with jaundice).

Injection site reactions.

Pain, phlebitis and tenderness have been reported in approximately 4.8% of cases. Inflammatory reactions at the injection site have also been reported.

Neurological.

High doses of β-lactam antibiotics, including cefotaxime, particularly in patients with renal insufficiency, may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions). Patients should be advised to contact their doctor immediately prior to continuing treatment if such reactions occur.

Renal.

Decrease in renal function, elevations in blood urea and serum creatinine have been infrequently reported, particularly when coprescribed with aminoglycosides. Rare cases of interstitial nephritis have been reported in patients treated with cefotaxime.

Jarisch-Herxheimer reaction.

For the treatment of borreliosis (Lyme's disease), 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 weeks treatment of borreliosis: skin rash, itching, fever, leucopenia, increase in liver enzymes, difficulty of breathing, joint discomfort.

Other.

Fever, shivering, headache, dizziness, joint pain, superinfection (see Precautions).

Dosage and Administration

Cefotaxime should be administered only by the IM or IV routes. The dosage, route of administration and dosage interval will depend on the location and severity of the infection, the susceptibility of the pathogens to cefotaxime and the overall condition of the patient.

Adults.

Treatment of gonorrhoea.

Uncomplicated gonorrhoea due to non-β-lactamase producing organisms. A single IM 1 g dose.
Uncomplicated gonorrhoea due to β-lactamase producing organisms. A single IM dose of cefotaxime 0.5 g, plus probenecid 1 g orally given one hour earlier.

Prevention of postoperative infection.

Obstetric surgery (Caesarean section). 1 g should be administered intravenously after the cord has been clamped and thereafter at six and twelve hours.
Vaginal or abdominal hysterectomy. 1 g should be administered intramuscularly 30 to 60 minutes before incision and repeated thereafter on completion of surgery and at intervals of eight hours for a total duration of 24 hours.
Biliary surgery. 1 g intravenously at induction.

Urinary tract infections.

The recommended dose is 2 g daily in two divided doses.

Other infections.

The minimum recommended dosage is 2 g daily in divided doses. This dosage may be increased to 3, 4 or 6 g daily according to the severity of the infection, sensitivity of causative organisms and condition of the patient.

Children.

The usual dosage range is 100 to 150 mg/kg/day in three to four divided doses. In very severe infections doses of up to 200 mg/kg/day may be required.

Neonatal meningitis.

The following dosage schedule is recommended.
0 to 1 week of age. 50 mg/kg intravenously every twelve hours.
1 to 4 weeks of age. 50 mg/kg intravenously every eight hours.

Dosing in impaired renal function.

The biological half-life of desacetylcefotaxime increases significantly and progressively where creatinine clearance is < 20 mL/minute. Furthermore, when the creatinine clearance is < 5 mL/minute the half-life of the parent compound is also increased. Due to these alterations in the pharmacokinetic profile, dosage adjustments should be made in patients with creatinine clearance < 20 mL/minute, in order to achieve approximately equal peak serum levels during repeated dosage.
As a general rule, if creatinine clearance is ≤ 20 mL/minute, the current daily dose should be halved and administered every 12 hours. For creatinine clearance ≤ 5 mL/minute, the recommended dose is 500 mg every twelve hours (1 g daily).

Mode and duration of administration.

Intravenous injection.

The contents of one cefotaxime 1 g vial should be dissolved in at least 4 mL water for injections. The reconstituted solution should be injected over a period of three to five minutes either into a vein or into the distal part of a clamped off infusion tube.

Intravenous infusion.

For a short infusion, two cefotaxime 1 g vials should be dissolved in 40 mL water for injections or an infusion solution (e.g. glucose solution, Rheomacrodex) and then infused over 20 to 30 minutes. For a continuous IV infusion, 2 vials of cefotaxime 1 g should be dissolved in 100 mL of a normal saline or glucose solution and infused over four hours. Sodium bicarbonate solutions must not be mixed with cefotaxime.

Intramuscular injection.

IM injections should be given laterally deep into the gluteus muscle. It is not advisable to inject more than 4 mL into either buttock. The pain of injection can be avoided by dissolving cefotaxime in lignocaine 0.5% solution (see Precautions and Contraindications). Intravascular injection of this solution must be strictly avoided. Where doses greater than 2 g are indicated, or 1 g doses required more than twice daily, the IV injection route should be used. For administration of a 500 mg dose, half the amount of any one of the solutions mentioned above may be used.
The duration of treatment depends on the patient's response, and therapy should be continued for at least three days after body temperature normalisation.

Compatibility.

Cefotaxime is physically incompatible with aminoglycosides. Where combination therapy is required, the drugs should be administered separately and not mixed together as a single preparation.
Cefotaxime is compatible with the following IV infusion fluids which do not contain sodium bicarbonate: Sodium Chloride Injection BP, Glucose 5% Injection BP, Glucose and Sodium Chloride Injection BP, Compound Sodium Lactate Injection BP (Ringer's lactate injection). Cefotaxime is also compatible with lignocaine 0.5% solution.
Cefotaxime contains no antimicrobial preservative. It is for single use in one patient only. The reconstituted solution should be used immediately and any unused solution should be discarded.
Cefotaxime and lignocaine combinations are for IM injections only and must not be injected intravenously.

Overdosage

Contact the Poisons Information Centre on 131 126 for advice on management of overdose.
No cases of cefotaxime overdosage have been reported. Animal evidence suggests that cefotaxime has a very low toxic potential. The LD50 studies in mice and rats administered cefotaxime intravenously have shown no mortality nor associated symptoms of intoxication up to doses of 716 mg/kg and 2000 mg/kg, respectively.
There is a risk of reversible encephalopathy following high doses of β-lactam antibiotics including cefotaxime. No specific antidote exists.
Symptoms of overdose may largely correspond to the profile of side effects.
In the 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). Cefotaxime plasma levels may be reduced by haemodialysis or peritoneal dialysis.
In the case of anaphylactic shock immediate countermeasures are required. Upon first signs of hypersensitivity reactions (e.g. cutaneous reactions, such as skin rashes or urticaria, headache, nausea, restlessness) the administration of Cefotaxime Sandoz should be discontinued. In cases of severe hypersensitivity reactions or anaphylactic reactions, emergency treatment should be initiated, such as administration of epinephrine and/or glucocorticoids. According to the clinical severity, additional therapeutic measures may be required (e.g. artificial breathing, application of histamine receptor antagonists). In cases of circulatory collapse, resuscitation must be initiated according to the current guidelines.

Presentation

Powder for injection (sterile), 500 mg, 1.0 g, 2.0 g: 1's, 5's*, 10's* (vials).
*Not currently marketed in Australia.

Storage

Store below 25°C.
Protect from heat and light.

Poison Schedule

S4.