Consumer medicine information

DBL Cefotaxime Sodium for Injection

Cefotaxime

BRAND INFORMATION

Brand name

DBL Cefotaxime Sodium for Injection

Active ingredient

Cefotaxime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Cefotaxime Sodium for Injection.

What is in this leaflet

This leaflet answers some common questions about DBL Cefotaxime Sodium for Injection. It does not contain all the available information.

It does not take the place of talking to your doctor and pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given DBL Cefotaxime Sodium for Injection against the benefits this medicine is expected to have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet in a safe place. You may need to read it again.

What DBL Cefotaxime Sodium for Injection is used for

Cefotaxime is an antibiotic used to treat infections in different parts of the body caused by bacteria.

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

Cefotaxime will not work against infections caused by viruses such as colds or the flu.

Cefotaxime belongs to a group of antibiotics called cephalosporins (kef-a-loe-SPOR-ins). These antibiotics work by killing the bacteria that are causing your infection.

Your doctor may have prescribed cefotaxime for another reason.

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

This medicine is available only with a doctors prescription.

DBL Cefotaxime Sodium for Injection is not addictive.

Before you are given DBL Cefotaxime Sodium for Injection

When you must not be given it

DBL Cefotaxime Sodium for Injection should not be given to you if you have an allergy to:

  • cefotaxime
  • other cephalosporins
  • any of the ingredients listed at the end of this leaflet

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.

Cefotaxime should not be given to you if you have had a major allergic reaction to penicillins.

Cefotaxime should not be mixed with lignocaine and given to you if you have had an allergic reaction to lignocaine, or if you have heart failure or heart block. Sometimes DBL Cefotaxime Sodium for Injection is mixed with lignocaine hydrochloride so that the injection into the muscle is less painful.

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

Do not use DBL Cefotaxime Sodium for Injection if the packaging is torn or shows signs of tampering.

Before you are given it

Tell your doctor if you have had any type of allergic reaction to penicillin medicines. You may have an increased chance of being allergic to cefotaxime if you are allergic to penicillins.

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

Tell your doctor if you have, or have ever had, any of the following health problems or medical conditions:

  • kidney disease
  • liver disease
  • severe bowel conditions.
  • a low white blood cell count (neutropenia)
  • you are on a low salt diet.

Tell your doctor if you are pregnant or intend to become pregnant. DBL Cefotaxime Sodium for Injection is not recommended for use during pregnancy. If there is a need to consider cefotaxime during your pregnancy, your doctor will discuss with you the benefits and risks of using it.

Tell your doctor if you are breast-feeding or plan to breast-feed. DBL Cefotaxime Sodium for Injection is not recommended while you are breast-feeding. If there is a need to consider cefotaxime while you are breast feeding, your doctor will discuss the possible risks and benefits of using it.

If you have not told your doctor about any of the above, tell them before you are given cefotaxime.

Taking other medicines

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

Some medicines may interfere with cefotaxime. These include:

  • aminoglycoside antibiotics (such as gentamicin)
  • probenecid
  • diuretics (such as frusemide).
  • opiates and diphenoxylate (medicines used to stop diarrhoea).

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

Talk to your doctor about the need for an additional method of contraception while being given DBL Cefotaxime Sodium for Injection. Some antibiotics may decrease the effectiveness of some birth control pills, although this has not been shown with cefotaxime.

Your doctor or pharmacist may have more information on medicines to be careful with or avoid while being given DBL Cefotaxime Sodium for Injection.

How DBL Cefotaxime Sodium for Injection is given

DBL Cefotaxime Sodium for Injection may be given in two ways:

  • as a slow injection or infusion (intravenous drip) into a vein
  • as a deep injection into a large muscle.

DBL Cefotaxime Sodium for Injection should only be given by a doctor or nurse. Your doctor will decide what dose you will receive and how long you will receive DBL Cefotaxime Sodium for Injection for. This depends on your infection and other factors, such as your weight. For most infections, it is usually given in divided doses throughout the day.

Sometimes only a single dose of DBL Cefotaxime Sodium for Injection is required for the treatment of certain infections.

If you are given too much (overdose)

As DBL Cefotaxime Sodium for Injection is given under medical supervision; it is very unlikely that you will receive too much.

Immediately telephone your doctor the Poisons Information Centre 13 11 26 for advice if you think that you or anyone else has taken/used too much DBL Cefotaxime Sodium for Injection. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep these telephone numbers handy.

Symptoms of a cefotaxime overdose may include the side effects listed below in the ‘Side Effects’ section, but are usually of a more severe nature.

Ask your doctor or pharmacist if you have any concerns.

While you are being given DBL Cefotaxime Sodium for Injection

Things you must do

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

If you get severe diarrhoea, tell your doctor or nurse immediately. Do this even if it occurs several weeks after cefotaxime has been stopped. Do not take any diarrhoea medicine without first checking with your doctor. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care.

If you get a sore white mouth or tongue while being given or soon after stopping cefotaxime, tell your doctor. Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal infection called thrush. Sometimes the use of DBL Cefotaxime Sodium for Injection allows fungi to grow and the above symptoms to occur. Cefotaxime does not work against fungi.

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

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are being given cefotaxime.

If you have to test your urine for sugar while you are being given DBL Cefotaxime Sodium for Injection, make sure your doctor knows which type of test you use. This medicine may affect the results of some of these tests.

If you have to have any blood tests, tell your doctor you are being given DBL Cefotaxime Sodium for Injection. This medicine may affect the results of some blood tests.

Tell all the doctors, dentists and pharmacist who are treating you that you are being given DBL Cefotaxime Sodium for Injection.

Things you must not do

Do not give DBL Cefotaxime Sodium for Injection to anyone else, even if they have the same condition as you.

Do not use DBL Cefotaxime Sodium for Injection to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how DBL Cefotaxime Sodium for Injection affects you. Cefotaxime generally does not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, it may cause dizziness, drowsiness, tiredness in some people.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well while you are being treated with DBL Cefotaxime Sodium for Injection.

Cefotaxime helps most people with infections, but it may have unwanted side-effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side-effects.

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

While using it

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

  • a white, furry, sore tongue and mouth (oral thrush)
  • a sore and itchy vagina and/or discharge (vaginal thrush)
  • nausea or diarrhoea
  • pain, swelling, redness or tenderness near the injection site
  • skin rash
  • itchiness.

These side effects are usually mild.

Tell your doctor or nurse immediately if you notice any of the following:

  • severe blisters and bleeding in the lips, eyes, mouth, nose or genitals
  • itchy spots accompanied by fever and feeling unwell
  • ulceration or lesions on the skin or in the mouth
  • fever
  • severe persistent diarrhoea (which may develop during treatment or up to several weeks after you stop cefotaxime)
  • signs of an allergic reaction, such as rash, itching or hives on the skin; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or difficulty breathing
  • changes in the rhythm or rate of the heartbeat.
  • conjunctivitis (inflammation or swelling of the eyes with possibly itchiness and discharge)
  • decreased urine output or fluid retention with swelling of the legs, ankles or feet.

These are very serious side effects. You may need urgent medical attention. These side effects are rare.

After finishing it

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with DBL Cefotaxime Sodium for Injection:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea which may also 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. However, these side effects are rare.

Do not take any diarrhoea medicine without first checking with your doctor. This medicine can change bacteria, which is normally present in the bowel and normally harmless, to multiply and therefore cause the above symptoms. You may need urgent medical attention. However, this side effect is rare.

Tell your doctor if you notice any other effects. Other side effects not listed above may also occur in some patients.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After being given DBL Cefotaxime Sodium for Injection

Storage

DBL Cefotaxime Sodium for Injection may be stored in the pharmacy or in the ward.

Store DBL Cefotaxime Sodium for Injection in a cool dry place where the temperature stays below 25°C. Keep the vial away from light.

Do not store DBL Cefotaxime Sodium for Injection or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep DBL Cefotaxime Sodium for Injection where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or it has passed their expiry date, ask your pharmacist what to do with any vials that are left over.

Product description

What it looks like

A white to pale yellow crystalline powder in a glass vial.

Ingredients

DBL Cefotaxime Sodium for Injection contains the active ingredient

Cefotaxime Sodium, equivalent to 1 g or 2 g of Cefotaxime.

DBL Cefotaxime Sodium for Injection contains 48.2mg of sodium per gram.

DBL Cefotaxime Sodium for Injection does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Sponsor

DBL Cefotaxime Sodium for Injection is supplied by:

Australian Sponsor:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

DBL Cefotaxime Sodium for Injection is available in the following strengths

1 g AUST R 78702

2 g AUST R 78703

This leaflet was updated in June 2019

™ = Trademark

© Copyright

Published by MIMS August 2019

BRAND INFORMATION

Brand name

DBL Cefotaxime Sodium for Injection

Active ingredient

Cefotaxime

Schedule

S4

 

1 Name of Medicine

Cefotaxime sodium.

6.7 Physicochemical Properties

Molecular Formula: C16H16N5NaO7S2. Molecular Weight: 477.4.

Chemical structure.


CAS number.

64485-93-4.

2 Qualitative and Quantitative Composition

Cefotaxime sodium is a semi-synthetic cephalosporin for use by injection only.
DBL Cefotaxime Sodium for Injection is sterile cefotaxime sodium powder for parenteral administration following reconstitution. The pKa value is 3.35. The sodium content of the formulated material is approximately 2.09 mmol (48 mg) per gram of cefotaxime. The pH of the formulated material is 4.5 to 6.5.

3 Pharmaceutical Form

DBL Cefotaxime Sodium for Injection is a white to pale yellow crystalline powder, soluble in water (greater than 20%) and produces a pale yellow solution. Raising the pH (by addition of strong base) will result in an intense yellow colour and possible degradation.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

At plasma concentrations achieved with the recommended therapeutic doses, cefotaxime is active in vitro against the following microorganisms.

Gram positive pathogens.

Staphylococci, including penicillinase producing strains, but not methicillin resistant strains; Streptococcus pyogenes, Streptococcus pneumoniae. Clostridium perfringens and Streptococcus faecalis are resistant.

Gram negative pathogens.

Strains of Enterobacter, Klebsiella and Serratia group, Haemophilus influenzae, Neisseria sp., gonococcus, (including penicillin resistant gonococci), Proteus genera, including P. mirabilis, P. morganii, P. vulgaris, P. rettgeri, Escherichia coli including many cephalothin and gentamicin resistant strains. Approximately 25% of Pseudomonas aeruginosa strains and 43% of Bacteroides strains have an in vitro MIC of < 16 mg/L.
There is in vitro evidence of synergy between cefotaxime and aminoglycoside antibiotics, such as gentamicin, against some species of Gram negative bacteria including some strains of Pseudomonas aeruginosa, Serratia marcescens, E. coli, Klebsiella species, P. mirabilis and Staph. aureus.
Cefotaxime is resistant to many beta-lactamases (penicillinases and cephalosporinases).
Cefotaxime's bactericidal effect is due to inhibition of cell wall synthesis.

Susceptibility tests.

Dilution or diffusion techniques, either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Cefotaxime is administered by intravenous or intramuscular injection. It is not adequately absorbed by mouth.
Following the intramuscular administration of a single 500 milligram and 1 g dose to normal volunteers, the following mean peak plasma concentrations at 30 minutes and 4 hours post administration were obtained (see Table 1).
With a 2 g dose the plasma level is proportionately increased.
Multiple intramuscular doses of 500 milligram every 8 hours for 10 days in 15 healthy volunteers produced plasma levels ranging from 9.2 to 11.9 milligram/L 30 minutes after dosing, and from 0.08 to 0.55 milligram/L measured just before dosing, i.e. at 8 hours.
After intravenous bolus (5 minutes administration) of 0.5 g, 1 g and 2 g to normal volunteers, the following concentrations were obtained, at peak, 1 hour and 4 hours (see Table 2).
After intravenous infusion (over 30 minutes) of 1 g, the following mean plasma levels were achieved after the end of the infusion (see Table 3).
After multiple infusion of 1 g 6 hourly for 14 days, the mean steady-state trough level was 1.33 milligram/L.
There is no evidence of drug accumulation following multidose intravenous and intramuscular administration in subjects with normal renal function. The mean elimination half-life after intramuscular administration was 1.45 hours, 1.06 hours after rapid intravenous injection, and 1.13 hours after a 30 minute intravenous infusion.

Neonatal pharmacokinetics.

In neonates the pharmacokinetics are influenced by birthweight. In low birthweight neonates, the elimination half-life is prolonged. Following an infusion (10 minutes) of 50 milligram/kg, the following mean concentrations were obtained (see Table 4).
Cefotaxime is deacetylated in the body rapidly with measurable levels detectable in the plasma within 5 minutes after administration. Following a single intravenous dose of 15 miligram/kg to normal volunteers, the mean peak serum level for cefotaxime was 100 microgram/mL and for desacetylcefotaxime at 10 minutes post administration was 5.0 microgram/mL.
The desacetyl metabolite is generally less active than the parent compound, but has a similar spectrum of antibacterial activity in vitro. Its activity may range from twice as active to 32 times less active than the parent drug depending on the species. The desacetyl metabolite is further degraded to an open lactone form which is microbiologically inactive.
Cefotaxime is 32% to 44% bound to plasma protein, while the desacetyl derivative is only bound by half of this value. The affinity for plasma proteins is low, as evidenced by the high urinary clearance.
85% of the administered dose is recovered in the urine, while the faeces accounted for 7.5% of the total recovery. 70% of the administered dose is recovered in the first 4 hours after administration. Studies in human volunteers measuring radioactive recovery in the urine have indicated that 20% of administered drug is excreted as unchanged drug, 15% as the desacetyl metabolite and 20% as the open lactone derivative.
Mean peak urinary concentrations obtained after administration of 1 g cefotaxime intravenously, intramuscularly and by intravenous infusion at 4 hours were 1,309 milligram/L, 903 milligram/L, and 599 milligram/L, respectively.
The elimination half-life of cefotaxime is 0.7 to 1.3 hours, while that of the metabolites is approximately 2 hours in patients with normal renal function. In the presence of impaired renal function, the terminal half-life of the desacetyl derivative is prolonged much more than of the unchanged drug; in patients with creatinine clearance of 5 to 10 mL/min, the terminal half-life of cefotaxime is 3.5 hours compared to 13.0 hours for the desacetyl derivative.
Cefotaxime diffuses into the CSF to a significant extent in the presence of inflamed meninges. After intravenous doses of 1 or 2 g, CSF levels achieved are above the minimum inhibitory concentrations of susceptible organisms, i.e. those with MIC values of less than 0.5 microgram/mL.
Following IV administration of 1 g, mean peak concentrations of 35 milligram/L were recorded in the bile after 30 minutes and declined to 3.30 milligram/L after 4 hours.
Following 1 gram intramuscular dosage the mean plasma clearance is 318 mL/min/1.73 m2.
Studies have shown that concomitant use of 0.5% lignocaine solution does not affect the pharmacokinetics or bioavailability of cefotaxime from intramuscular administration.
Interaction studies between parenterally administered cefotaxime and orally ingested probenecid showed that probenecid increased the retention of cefotaxime by 14% to 40%, and decreased the renal clearance by 11% to 32%.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic 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 beta-lactamase producing strains of N. 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 penicillin G) 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 obstetrical 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.

4.3 Contraindications

Cefotaxime should not be used in patients with known hypersensitivity to cephalosporins or with a history of a previous major allergic response to a penicillin, due to the possibility of cross sensitivity.
Lignocaine hydrochloride should not be used to dilute cefotaxime when used by the intravenous route, nor should it be used as diluent for intramuscular use for:
patients with a known history of hypersensitivity to lignocaine or other local anaesthetics of the amide type;
patients with non-paced heart block;
patients with severe heart failure;
infants aged less than 30 months.

4.4 Special Warnings and Precautions for Use

Cefotaxime should be used with caution in patients with known hypersensitivity to penicillin or other beta-lactam antibiotics. The possibility of severe or fatal anaphylactic reactions should be borne in mind and appropriate treatment kept available.
Cephalosporin antibiotics in high doses should be given with caution to patients receiving aminoglycoside antibiotics or potent diuretics such as frusemide.
Potentially life threatening arrhythmias have been reported in very few patients who received rapid intravenous administration through a central venous catheter. Therefore, when administered by intermittent intravenous injection, cefotaxime must be given over a period of 3 to 5 minutes.
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.

Superinfection.

Superinfection with non-susceptible organisms, including fungi, may occur and requires appropriate therapy.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including cefotaxime. A toxin produced with Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, appropriate therapy such as antibacterial agents effective against C. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (e.g. Lomotil) may prolong and/or worsen the condition and should not be used.

Dosage and administration.

Repeated use of lignocaine hydrochloride should be avoided in patients with severe liver disease or decreased hepatic blood flow due to the possibility of lignocaine toxicity (resulting from decreased metabolism and accumulation).

Renal function.

Caution should be exercised if cefotaxime is administered together with aminoglycosides. Renal function must be monitored in all such cases.

Sodium intake.

The sodium content of cefotaxime sodium (48.2 mg/g) should be taken into account in patients requiring sodium restriction.

Neutropenia.

For treatment courses lasting longer than 10 days, the white blood cell count should be monitored and treatment stopped in the event of neutropenia.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, DBL Cefotaxime Sodium for Injection should be discontinued immediately and an alternative treatment should be considered.

Use in hepatic/renal impairment.

Liver and renal disease.

Transient rises in hepatic enzymes, urea and creatinine have been seen in some patients given cefotaxime, therefore careful monitoring of hepatic and renal function is advised where any dysfunction exists. For dosage adjustment in moderate and severe renal impairment (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

Positive Coombs' tests may occur during treatment with cephalosporins. This phenomenon may be encountered during treatment with cefotaxime.
Urinary glucose testing with non-specific reducing agents may yield to a false positive reaction in patients treated with cefotaxime. This phenomenon is not seen when a glucose-oxidase specific method is used.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Cefotaxime exhibits an additive microbiological effect with gentamicin. However, because of physical incompatibility, cefotaxime should not be mixed with an aminoglycoside antibiotic into a single preparation.
Administration of oral probenecid decreases renal clearance slightly and increases total body concentrations (see Section 5.2 Pharmacokinetic Properties).
As with other cephalosporins, cefotaxime may potentiate the nephrotoxic effects of nephrotoxic drugs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
Australian categorisation definition of 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 in pregnancy has not been established. 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 and the expected benefits outweigh any potential risks.
Cefotaxime is excreted in the breast milk. Peak concentrations measured 2 or 3 hours after intravenous administration of 1 g doses ranged from 0.25 to 0.52 microgram/mL (mean 0.32 ± 0.09). These concentrations in breast milk could affect the oropharyngeal flora of the suckling infant. Therefore, cefotaxime is not recommended for nursing mothers unless the expected benefits outweigh any potential risk or if alternative arrangements for feeding the infant can be made.

4.8 Adverse Effects (Undesirable Effects)

Anaphylactic reactions.

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

Blood.

As with some other cephalosporins, leucopenia, granulocytopenia and more rarely agranulocytosis may develop during treatment with cefotaxime. Some patients have developed positive direct Coombs' test and, rarely, haemolytic anaemia during treatment with cefotaxime. Eosinophilia.

Liver.

Increases in serum transaminases and alkaline phosphatase levels have been noted. These laboratory abnormalities, which also may be explained by the infection, may rarely exceed twice the upper limit of the normal range and elicit a pattern of liver injury, usually cholestatic and most often asymptomatic.

Local reactions.

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

Gastrointestinal.

Nausea, diarrhoea. As with other broad spectrum antibiotics, colitis, including rare instances of pseudomembranous colitis, has been reported with cefotaxime (see Section 4.4 Special Warnings and Precautions for Use).

Kidneys.

Elevations in serum creatinine and blood urea have been reported infrequently. As with some other cephalosporins, rare cases of interstitial nephritis and acute kidney failure have been reported in patients treated with cefotaxime.

Neurological.

Administration of 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).

Cardiovascular.

Potentially life-threatening arrhythmias have been reported in a few patients who received rapid intravenous administration of cefotaxime through a central venous catheter.

Skin and other subcutaneous tissue disorders.

Rash, pruritus and urticaria. As with other cephalosporins, isolated cases of bullous eruptions (erythema multiforme) and severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

Other.

Fever, superinfection (see Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Adults.

For urinary tract infections.

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

For prevention of post operative infection.

In 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 8 hourly intervals for a total duration of 24 hours.

In obstetrical surgery (Caesarean section).

1 g should be administered intravenously after the cord has been clamped and thereafter at 6 and 12 hours.

In biliary surgery.

1 g IV at induction.

For the treatment of gonorrhoea.

Uncomplicated gonorrhoea due to non beta-lactamase producing organisms.

One single intramuscular dose of 1 g.

Uncomplicated gonorrhoea due to beta-lactamase producing organisms.

One single intramuscular dose of 0.5 g of cefotaxime plus probenecid 1 g orally given 1 hour earlier.

Paediatrics.

Neonatal meningitis.

The following dosage schedule is recommended.

0 to 1 week of age.

50 mg/kg intravenously every 12 hours.

1 to 4 weeks of age.

50 mg/kg intravenously every 8 hours.

Children.

The usual dosage range is 100 to 150 mg/kg/day in 3 to 4 divided doses. However, in very severe infections, doses of up to 200 mg/kg/day may be required.

Method of administration.

Cefotaxime should be administered only by the intramuscular or intravenous routes.
Product contains no antimicrobial agent. For single use in one patient only. Discard any residue.
The dosage, route of administration and dosage interval will depend on the site and severity of the infection, sensitivity of the pathogens and condition of the patient.

Intravenous injection.

For intravenous injection the contents of one vial of DBL Cefotaxime Sodium for Injection 1 g are dissolved in at least 4 mL Water for Injections and then injected over a period of 3 to 5 minutes, either into a vein or into the distal part of a clamped-off infusion tube.

Intravenous infusion.

For short infusion, two vials of DBL Cefotaxime Sodium for Injection 1 g are dissolved in 40 mL Water for Injections or an infusion solution and then infused over 20 to 30 minutes. For continuous intravenous infusion, two vials of DBL Cefotaxime Sodium for Injection 1 g are dissolved in 100 mL of an isotonic saline or glucose solution and infused over 4 hours. Sodium bicarbonate solutions must not be mixed with DBL Cefotaxime Sodium for Injection.

Intramuscular administration.

Intramuscular injections should be given laterally deep into the gluteus muscle. It is not advisable to inject more than 4 mL in either buttock. The pain of injection can be avoided by dissolving DBL Cefotaxime Sodium for Injection in a 0.5% lignocaine solution (see Section 4.4 Special Warnings and Precautions for Use; Section 4.3 Contraindications). Intravascular injection of this solution must be strictly avoided.
If the daily dose exceeds 2 g, or if DBL Cefotaxime Sodium for Injection 1 g is administered more than twice daily, intravenous injection is preferred.
In administering the 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. It should be continued for at least three days after normalisation of the body temperature.

Compatibility with other medicines.

DBL Cefotaxime Sodium for Injection is compatible with the commonly used intravenous infusion fluids listed below:
Sodium Chloride Injection B.P.
5% Glucose Injection B.P.
Compound Sodium Lactate Injection B.P. (Ringer-Lactate Injection).
DBL Cefotaxime Sodium for Injection is also compatible with 0.5% lignocaine. Freshly prepared solutions should be used. 0.5% Lignocaine solutions are to be used for intramuscular injections only.
To reduce microbiological hazard, the diluted solution should preferably be used immediately and any remaining residue discarded.

Dosage adjustments.

Use in patients with impaired renal function.

The biological half-life of the desacetyl metabolite of cefotaxime increases significantly and progressively below creatinine clearance of 20 mL/minute.
Furthermore, when the creatinine clearance is less than 5 mL/minute the half-life of the parent compound is also increased. Because of these changes in the pharmacokinetics of the drug, it is recommended that dosage adjustments should be made in patients with creatinine clearance of less than 20 mL/minute in order to achieve approximately equal peak serum levels during repeated dosage.
As a guide when creatinine clearance is less than or equal to 20 mL/minute, it is recommended that the current daily dose, for the treatment of the specific infection, be reduced by half and given every 12 hours. When creatinine clearance is less than or equal to 5 mL/minute, the recommended dose is 500 mg every 12 hours (1 g daily).

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Serum levels of cefotaxime may be reduced by haemodialysis.
There is a risk of reversible encephalopathy in cases of administration of high doses of beta-lactam antibiotics including cefotaxime. No specific antidote exists.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Cefotaxime is physically incompatible with aminoglycosides. Where an aminoglycoside antibiotic is administered at the same time as DBL Cefotaxime Sodium for Injection they should be administered separately and not mixed together as a single preparation.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

DBL Cefotaxime Sodium for Injection 1 g is a sterile powder for injection. It is supplied in a 10 mL clear glass vial with rubber stopper, containing a white to pale yellow crystalline powder. Available in packs of 10 vials.
DBL Cefotaxime Sodium for Injection 2 g is a sterile powder for injection. It is supplied in a 20 mL clear glass vial with rubber stopper, containing a white to pale yellow crystalline powder. Available in packs of 10 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes