Consumer medicine information

DBL Cefotaxime Sodium

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.

SUMMARY CMI

DBL™ Cefotaxime Sodium

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I being given DBL Cefotaxime Sodium?

DBL Cefotaxime Sodium contains the active ingredient Cefotaxime Sodium.

DBL Cefotaxime Sodium is an antibiotic used to treat infections of the kidneys and bladder, blood, skin and flesh immediately under the skin, bones, heart valves, brain, abdomen and some sexually transmitted infections (gonorrhoea).

For more information, see Section 1. Why am I being given DBL Cefotaxime Sodium? in the full CMI.

2. What should I know before I am given DBL Cefotaxime Sodium?

Do not use if you have ever had an allergic reaction to DBL Cefotaxime Sodium or any similar medicines known as cephalosporins or if you have had a major allergic reaction to penicillin. Cefotaxime should not be mixed with lignocaine and given if you have had an allergic reaction to lignocaine or other local anaesthetics, if you have heart failure or heart block or to infants less than 30 months old.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given DBL Cefotaxime Sodium? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DBL Cefotaxime Sodium and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How will I be given DBL Cefotaxime Sodium?

DBL Cefotaxime Sodium should only be given by a doctor or nurse. It may be given by direct injection into a vein or as a slow injection or infusion (intravenous drip) into a vein or as a deep injection into a large muscle. Your doctor will decide what dose you will receive and how long you will receive DBL Cefotaxime Sodium for. This depends on your infection and other factors, such as your weight. More instructions can be found in Section 4. How will I be given DBL Cefotaxime Sodium? in the full CMI.

5. What should I know while being given DBL Cefotaxime Sodium?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are being given DBL Cefotaxime Sodium.
  • If your 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.
Things you should not do
  • Do not use if you have ever had an allergic reaction to DBL Cefotaxime Sodium or any similar medicines known as cephalosporins or if you had a major allergic reaction to penicillin or to lignocaine. DBL Cefotaxime Sodium should not be given if you are pregnant or breastfeeding.
Driving or using machines
  • DBL Cefotaxime Sodium may affect your ability to drive a car or operate machinery.
Looking after your medicine
  • DBL Cefotaxime Sodium will be stored in the hospital pharmacy or on the ward in a cool, dry place, protected from heat and light, where the temperature stays below 25°C.

For more information, see Section 5. What should I know while being given DBL Cefotaxime Sodium? in the full CMI.

6. Are there any side effects?

Side effects include white, furry, sore tongue and mouth, a sore and itchy vagina and/or discharge, signs of frequent infections such as fever, sore throat, swollen glands or mouth ulcers, nausea or diarrhoea, pain, swelling, redness or tenderness near the injection site, skin rash and itchiness. Some serious side effects include signs of an allergic reaction, such as rash, itching or hives, swelling of the face and lips, shortness of breath, wheezing or difficulty breathing, severe blisters and bleeding, ulcerations or lesions of the skin or in the mouth, severe stomach cramps, watery and severe diarrhoea, fever in combination with cramps/ diarrhoea. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

DBL™ Cefotaxime Sodium

Active ingredient(s): Cefotaxime sodium.

Consumer Medicine Information (CMI)

This leaflet provides important information about using DBL Cefotaxime Sodium. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using DBL Cefotaxime Sodium.

Where to find information in this leaflet:

1. Why am I being given DBL Cefotaxime Sodium?
2. What should I know before I am given DBL Cefotaxime Sodium?
3. What if I am taking other medicines?
4. How will I be given DBL Cefotaxime Sodium?
5. What should I know while being given DBL Cefotaxime Sodium?
6. Are there any side effects?
7. Product details

1. Why am I being given DBL Cefotaxime Sodium?

DBL Cefotaxime Sodium contains the active ingredient Cefotaxime Sodium. DBL Cefotaxime Sodium is an antibiotic. Cefotaxime belongs to a group of antibiotics called cephalosporins. These antibiotics work by killing the bacteria that are causing your infection. DBL Cefotaxime Sodium is used to treat infections of the:

  • kidneys and bladder
  • blood (septicaemia)
  • skin and flesh immediately under the skin
  • bones
  • heart valves
  • brain (meningitis)
  • abdomen (peritonitis)
  • some sexually transmitted infections (gonorrhoea).

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.

Your doctor may have prescribed cefotaxime for another reason.

2. What should I know before I am given DBL Cefotaxime Sodium?

Warnings

Do not use DBL Cefotaxime Sodium if:

  • you are allergic to cefotaxime or any similar medicines known as cephalosporins
  • you have had a major allergic reaction to penicillins
  • if you are pregnant or breastfeeding

Cefotaxime should not be mixed with lignocaine and given:

  • if you have had an allergic reaction to lignocaine or other local anaesthetics
  • if you have heart failure or heart block
  • to infants less than 30 months old

Sometimes DBL Cefotaxime Sodium is mixed with lignocaine hydrochloride so that the injection into the muscle is less painful.

Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

  • have of the following medical conditions: kidney disease, liver disease, stomach or bowel problems or asthma.
  • Have a low white blood cell count (neutropenia)
  • are on a low salt diet
  • take any medicines for any other condition

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

DBL Cefotaxime Sodium should not be given if you are pregnant or breastfeeding.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

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

Some medicines may interfere with DBL Cefotaxime Sodium and affect how it works. These include:

  • aminoglycoside antibiotics (such as gentamicin)
  • other antibiotic medicines (such as tetracyclines, erythromycin and chloramphenicol)
  • probenecid, a medicine used to treat gout
  • "water" tablets or diuretics (such as furosemide).

Talk to your doctor about the need for an additional method of contraception while being given DBL Cefotaxime Sodium.

Some antibiotics may decrease the effectiveness of some birth control pills, although this has not been shown with cefotaxime.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect DBL Cefotaxime Sodium.

4. How will I be given DBL Cefotaxime Sodium?

How much will be given

DBL Cefotaxime Sodium may be given by:

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

DBL Cefotaxime Sodium should only be given by a doctor or nurse.

Your doctor will decide what dose of DBL Cefotaxime Sodium you will receive and for how long you will receive it. 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 is required for the treatment of certain infections.

If you are given too much DBL Cefotaxime Sodium

As DBL Cefotaxime Sodium is given under medical supervision; it is very unlikely that you will receive too much. If you think that you have been given too much, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while being given DBL Cefotaxime Sodium?

Things you should do

Call your doctor straight away if:

  • the symptoms of your infection do not improve within a few days, or if they become worse
  • you get severe diarrhoea. 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.
  • you get a sore white mouth or tongue while being given or soon after stopping cefotaxime. 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 allows fungi to grow and the above symptoms to occur. Cefotaxime does not work against fungi.
  • you become pregnant while you are being treated with cefotaxime.

If you have to test your urine for sugar while you are being given DBL Cefotaxime Sodium, 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. This medicine may affect the results of some blood tests.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how DBL Cefotaxime Sodium affects you.

DBL Cefotaxime Sodium may cause dizziness, drowsiness, seizures or unusual body movements in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

No information available.

Looking after your medicine

  • DBL Cefotaxime Sodium will be stored in the hospital pharmacy or on the ward.
  • DBL Cefotaxime Sodium 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.

Keep it where young children cannot reach it.

When to discard your medicine

Discard any medicine that has passed the expiry date.

This medicine should only be used in one patient and any unused medicine should be discarded.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Side effects

Side effectsWhat to do
  • signs of frequent infections such as fever, sore throat, swollen glands or mouth ulcers
  • nausea or diarrhoea
  • pain, swelling, redness or tenderness near the injection site
  • skin rash
  • itchiness
Speak to your doctor if you have any of these side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • a white, furry, sore tongue and mouth (oral thrush)
  • a sore and itchy vagina and/or discharge (vaginal thrush)
  • 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
  • loss of appetite
  • 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
  • severe abdominal cramps, severe persistent diarrhoea which may be bloody, fever (with or without cramps/diarrhoea). It may develop during treatment or several weeks after you stop cefotaxime
  • fast or irregular heartbeat
  • changes in the rhythm or rate of the heartbeat
  • chest pain
  • blood in the urine or decreased urine output or fluid retention with swelling of the legs, ankles or feet
  • 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
  • seizures or abnormal movements.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

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

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/safety/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Cefotaxime Sodium contains

Active ingredient
(main ingredient)		Cefotaxime Sodium (equivalent to 1 g of Cefotaxime)
Other ingredients
(inactive ingredients)		Sodium (each gram of Cefotaxime contains 48.2 mg of sodium)

Do not take this medicine if you are allergic to any of these ingredients.

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

What DBL Cefotaxime Sodium looks like

DBL Cefotaxime Sodium is a white to pale yellow crystalline powder. It is supplied in a glass vial with a rubber stopper in packs of 1 vial (AUST R 78702).

Who distributes DBL Cefotaxime Sodium

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

This leaflet was prepared in February 2025.

Published by MIMS April 2025

BRAND INFORMATION

Brand name

DBL Cefotaxime Sodium for Injection

Active ingredient

Cefotaxime

Schedule

S4

 

1 Name of Medicine

Cefotaxime sodium.

2 Qualitative and Quantitative Composition

Each vial of DBL Cefotaxime Sodium contains 1 g cefotaxime sodium.
Each gram of cefotaxime contains approximately 48 mg (2.09 mmol) of sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
DBL Cefotaxime Sodium is a white to pale yellow crystalline powder.
The reconstituted product is a pale yellow solution. Raising the pH (by addition of strong base) will result in an intense yellow colour and possible degradation.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Cefotaxime Sodium 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.

4.2 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 postoperative infections. 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.

Paediatric population.

For meningitis.

Neonatal patients: 0 to 1 week of age: 50 mg/kg IV every 12 hours;
1 to 4 weeks of age: 50 mg/kg IV every 8 hours.

Paediatric patients.

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.

DBL Cefotaxime Sodium should be administered only by intramuscular injection, intravenous injection or intravenous infusion.
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 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 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 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.

Intramuscular injection.

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 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 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 is compatible with the commonly used intravenous infusion fluids listed below:
Water for injection.
Sodium Chloride Injection.
5% Glucose Injection.
Compound Sodium Lactate Injection (Ringer-Lactate Injection).
DBL Cefotaxime Sodium 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.
Product contains no antimicrobial agent. For single use in one patient only. Discard any residue.
To reduce microbiological hazard, the diluted solution should preferably be used immediately and any remaining residue discarded.

Dosage adjustments.

Use in renal impairment.

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).

4.3 Contraindications

DBL Cefotaxime Sodium is contraindicated in patients:
with a history of hypersensitivity to cefotaxime;
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 (see Section 4.4 Special Warnings and Precautions for Use);
in pregnancy and during lactation (see Section 4.6 Fertility, Pregnancy and Lactation).
Lignocaine hydrochloride should not be used to dilute DBL Cefotaxime Sodium:
for intravenous use patients with a known history of hypersensitivity to lignocaine or other local anaesthetics of the amide type;
in patients with non-paced heart block;
in patients with severe heart failure;
in infants aged less than 30 months.

4.4 Special Warnings and Precautions for Use

Anaphylactic reactions.

Before starting therapy with DBL Cefotaxime Sodium, an accurate history must be determined to highlight previous hypersensitivity reactions to cefotaxime, cephalosporin, penicillin or other drugs.
The use of cefotaxime is contraindicated in patients with a previous history of hypersensitivity to cephalosporins.
Some patients receiving treatment with cefotaxime have presented with severe reactions including hypersensitivity reactions with a fatal outcome (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)).
Since cross allergy exists between penicillins and cephalosporins, cefotaxime should be used with caution in patients with known hypersensitivity to penicillin or other beta-lactam antibiotics. Serious, including fatal hypersensitivity reactions have been reported in patients receiving cefotaxime (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)). If a hypersensitivity reaction occurs, treatment must be stopped.
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 furosemide.

Precautions for administration.

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 (see Section 4.2 Dose and Method of Administration).
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.

As with other antibiotics, the use of cefotaxime, especially prolonged use, may lead to increased growth of non-sensitive micro-organisms.
A close examination of the patient's condition is essential. If super-infections arise during therapy, appropriate measures must be taken.
Superinfection with non-susceptible organisms, including fungi, may occur and requires appropriate therapy.
Third-generation cephalosporin, as with other beta-lactams, may induce microbial resistance; this occurrence is more significant with opportunistic organisms, especially Enterobacteriales and Pseudomonas, in immunocompromised patients and probably when combining additional beta-lactams.

Pathologies associated with Clostridium difficile (CDAD).

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including cefotaxime. A toxin produced with C. difficile appears to be the primary cause. The severity of the colitis may range from mild to life-threatening; the most severe form is pseudomembranous colitis.
It is important to take such diagnosis into consideration in patients who present with diarrhoea during therapy with cefotaxime. 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.
If a diagnosis of pseudomembranous colitis is suspected, treatment with cefotaxime must be stopped immediately and an appropriate therapy with a specific antibiotic must be started right away. The pathology associated with C. difficile may be exacerbated by faecal stasis.
Drugs that inhibit peristalsis should not be administered. Treatment with broad spectrum antibiotics alters the normal flora of the colon and this may promote the growth of clostridia.
Cefotaxime must be prescribed with caution in individuals with a history of gastrointestinal diseases, particularly colitis.
Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine may prolong and/or worsen the condition and should not be used.

Sodium intake.

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

Severe cutaneous adverse reactions.

Case of severe bullous rashes and 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 should be discontinued immediately and an alternative treatment should be considered. See Section 4.8 Adverse Effects (Undesirable Effects).

Haematological reactions.

During treatment with cefotaxime, especially when administered for long periods, leucopenia, neutropenia and, more rarely, bone marrow deficiency, pancytopenia and agranulocytosis may develop.
For treatment courses of more than 7-10 days, the white blood cell count should be monitored and in the case of neutropenia, treatment should be discontinued.
Cases of haemolytic anaemia were also reported.
Also see Section 4.8 Adverse Effects (Undesirable Effects).

Neurotoxicity.

There have been reports of neurotoxicity associated with cephalosporin treatment. Symptoms of neurotoxicity include encephalopathy (e.g. loss of consciousness, abnormal movements and convulsions), seizures and/or myoclonus. Risk factors for developing neurotoxicity with cephalosporin treatment include being elderly, renal impairment, central nervous system disorders and intravenous administration. Withdrawal of the medicine should be considered if there are signs of neurotoxicity (see Section 4.8 Adverse Effects (Undesirable Effects)).
Patients should be warned to contact the doctor immediately before continuing with the treatment if reactions of this type occur. Also see Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment.

Use in hepatic impairment.

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).
Transient rises in hepatic enzymes, have been seen in some patients given cefotaxime, therefore careful monitoring of hepatic function is advised where any dysfunction exists. See Section 4.8 Adverse Effects (Undesirable Effects).

Use in renal impairment.

Transient rises in urea and creatinine have been seen in some patients given cefotaxime, therefore, careful monitoring of renal function is advised where any dysfunction exists.
The dosage should be modified based on creatinine clearance (see Section 4.2 Dose and Method of Administration).
The simultaneous use of aminoglycosides or other nephrotoxic drugs (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions) must be undertaken with caution. Renal function should be monitored in these patients, the elderly and in the case of pre-existing kidney failure.

Use in the elderly.

No data available.

Paediatric use.

For use in paediatric patients, see Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

As with other cephalosporins, false positive results on the Coombs test have been reported in some patients receiving treatment with cefotaxime. This phenomenon may interfere with blood compatibility tests.
The administration of cephalosporins may interfere with some laboratory tests causing false positives for glycosuria in methods performed using non-specific reducing agents (such as Benedict or Fehling methods) but this phenomenon does not occur when enzyme methods are used (such as the specific glucose-oxidase method).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Other antibiotics.

Cefotaxime should not be mixed in the same syringe with other antibiotics and other drugs.
Cefotaxime should not be combined with medicines with bacteriostatic action (e.g. tetracycline, erythromycin, chloramphenicol or sulfonamides), as antagonistic effect has been observed regarding the anti-bacterial effect in vitro.
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.

Nephrotoxic drugs and loop diuretics.

As with other cephalosporins, cefotaxime may potentiate the nephrotoxic effects of nephrotoxic drugs (e.g. aminoglycosides) or potent diuretics (e.g. furosemide).
Renal function must be monitored in these patients (see Section 4.4 Special Warnings and Precautions for Use, Neurotoxicity, Use in renal impairment).

Uricosuric agents (e.g. probenecid).

Administration of oral probenecid decreases renal clearance slightly and increases total body concentrations (see Section 5.2 Pharmacokinetic Properties).
Dosage adjustment may be needed in patients with kidney failure (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
The safety of cefotaxime in pregnancy has not been established. However, cefotaxime crosses the placenta and therefore, it should not be used during pregnancy unless the expected benefit outweighs the potential risks.
 Cefotaxime is excreted in the breast milk, it is therefore, advisable to stop breast-feeding when administering the drug. 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). 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, 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.

4.7 Effects on Ability to Drive and Use Machines

In the case of unwanted effects such as dizziness, the patient's ability to concentrate and properly react may be impaired.
Furthermore, high doses of cefotaxime, especially in patients with kidney failure may cause encephalopathies (e.g. loss of consciousness, abnormal movements and convulsions. See Section 4.8 Adverse Effects (Undesirable Effects)). Patients must be warned not to drive or use machines if they show any of these symptoms.

4.8 Adverse Effects (Undesirable Effects)

Infections and infestations.

Super-infection (see Section 4.4 Special Warnings and Precautions for Use), candida vaginitis.

Immune system disorders.

Anaphylactic reactions, Jarisch-Herxheimer reaction. Angioedema, bronchospasm and malaise, possibly culminating in shock, may rarely occur.

Blood and lymphatic system disorders.

As with some other cephalosporins, leucopenia, granulocytopenia, thrombocytopenia, bone marrow deficiency, pancytopenia, neutropenia and more rarely agranulocytosis (see Section 4.4 Special Warnings and Precautions for Use) may develop during treatment with cefotaxime. Some patients have developed positive direct Coombs' test and, rarely, haemolytic anaemia during treatment with cefotaxime. Eosinophilia.

Metabolic and nutrition disorders.

Anorexia.

Musculoskeletal and connective tissue disorders.

Arthralgia.

Hepatobiliary disorders.

Increases in serum transaminases (alanine aminotransferase (ALT), aspartate transaminase (AST), blood lactate dehydrogenase (LDH), gamma-glutamyltransferase and alkaline phosphatase and/or bilirubin 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.

General disorders and administration site condition.

Pain at the injection site, phlebitis and tenderness have been reported in approximately 4.8% of cases. Also, inflammatory reactions at the injection site including phlebitis/thrombophlebitis have been reported. Fever, systemic reactions to lidocaine (IM administration, since the solvent contains lidocaine), feeling of tightness in the chest, asthenia.
Other reported reactions were hardening and fragility at the injection site.

Gastrointestinal disorders.

Glossitis, heartburn, nausea, vomiting, abdominal pain and 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).

Other gastrointestinal pathologies.

The occurrence of severe and prolonged diarrhoea has been connected with the use of various classes of antibiotics. In this event, the possibility of enterocolitis must be considered, which is sometimes accompanied by the presence of blood in the stools. Pseudomembranous colitis is a specific form of enterocolitis occurring with the use of antibiotics (most cases are caused by C. difficile). If a colonoscopy investigation confirms this diagnosis, the antibiotics in use must be discontinued immediately and treatment with oral vancomycin must be started. Peristalsis inhibitor drugs are contraindicated.

Renal and urinary disorders.

Decrease in renal function/elevations in serum creatinine (especially when prescribed with aminoglycosides) and blood urea have been reported infrequently. As with some other cephalosporins, rare cases of interstitial nephritis and acute kidney failure (see Section 4.4 Special Warnings and Precautions for Use) have been reported in patients treated with cefotaxime. Increase in azotaemia.

Nervous system and psychiatric disorders.

Headache, dizziness, agitation, confusion and vertigo. 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 (see Section 4.4 Special Warnings and Precautions for Use).

Cardiac disorders.

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 subcutaneous tissue disorders.

Rash, pruritus, urticaria, hives and nocturnal sweating. 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) (see Section 4.4 Special Warnings and Precautions for Use), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

Post-marketing experience.

Hepatobiliary disorders.

Hepatitis (potentially with jaundice).

Nervous system disorders.

Seizures, encephalopathy, myoclonus.

Immune system disorders.

Acute coronary syndrome associated with an allergic reaction (Kounis syndrome) has been observed.

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.

4.9 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).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Cefotaxime sodium is a semi-synthetic cephalosporin for use by injection only.
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 spp., 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 S. 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

Absorption.

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.

Distribution.

Cefotaxime diffuses into the cerebrospinal fluid (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.

Metabolism.

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 milligram/kg to normal volunteers, the mean peak serum level for cefotaxime was 100 microgram/mL and for desacetylcefotaxime at 10 minutes postadministration 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.
Mean peak urinary concentrations obtained after administration of 1 g cefotaxime intravenously, intramuscularly and by intravenous infusion at 4 hours were 1309 milligram/L, 903 milligram/L, 599 milligram/L, respectively.

Excretion.

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.
There is no evidence of drug accumulation following multi dose intravenous and intramuscular administration in subjects with normal renal function. The mean elimination half life after intramuscular administration was 1.45 hour, 1.06 hour after rapid intravenous injection and 1.13 hour after 30 minute intravenous infusion.
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%.

Special population.

Neonatal patients.

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).

Patients with renal impairment.

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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

There are no excipients in DBL Cefotaxime Sodium.

6.2 Incompatibilities

DBL Cefotaxime Sodium should not be mixed with sodium bicarbonate solutions, other antibiotics especially aminoglycosides and other drugs. Cefotaxime is physically incompatible with aminoglycosides. Where an aminoglycoside antibiotic is administered at the same time as DBL Cefotaxime Sodium 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 is supplied in a 10 mL clear glass vial with rubber stopper in packs of 1 or 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.

6.7 Physicochemical Properties

Chemical structure.


Molecular formula: C16H16N5NaO7S2.
Molecular weight: 477.4.
Cefotaxime Sodium is soluble in water (greater than 20%). The pH of the formulated material is 4.5 to 6.5. The pKa value is 3.35.

CAS number.

64485-93-4.

7 Medicine Schedule (Poisons Standard)

Schedule 4, Prescription Only Medicine.

Summary Table of Changes