Consumer medicine information

Ceftazidime Kabi

Ceftazidime

BRAND INFORMATION

Brand name

Ceftazidime Kabi

Active ingredient

Ceftazidime

Schedule

What is in this leaflet

This leaflet answers some common questions about Ceftazidime Kabi.

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 Ceftazidime Kabi against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may need to read it again.

What Ceftazidime Kabi is used for

Ceftazidime Kabi is used to treat a wide range of infections caused by bacteria. These infections may affect the chest (bronchitis or pneumonia), ears, nose, throat, bladder and urinary tract, skin and soft tissue, stomach or bones.

This medicine belongs to a group of medicines called cephalosporins.

It works by killing the bacteria that cause these infections.

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.

Ceftazidime Kabi is available only with a doctor's prescription.

Ceftazidime Kabi is not addictive.

Before you are given Ceftazidime Kabi

When you must not be given it

You must not be given Ceftazidime Kabi if you have ever had an allergic reaction to:

any medicine containing cephalosporins or penicillins
any of the ingredients listed at the end of this leaflet.

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.

You must not be given 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:

kidney problems
liver problems
colitis or any other stomach or bowel illness.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor can discuss with you the risks and benefits involved.

Tell your doctor if you are breastfeeding. Ceftazidime Kabi is excreted in human milk in low concentrations. Therefore, it should be administered to breastfeeding women only if clearly needed.

Tell your doctor if your baby has any signs of diarrhoea or any other illness, or if you notice anything wrong.

Tell your doctor if you are prescribed some urine or blood tests or if you are going to have a blood transfusion. The results of some tests can be altered by Ceftazidime Kabi.

If you have not told your doctor about any of the above, tell him/ her before you start taking Ceftazidime Kabi.

Taking other medicines

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

Some medicines and Ceftazidime Kabi may interfere with each other. These include:

some antibiotics called aminoglycosides
diuretics, also called fluid or water tablets
another antibiotic called chloramphenicol, since both medicines can stop each other working
oral contraceptives ('the pill').

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

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

How Ceftazidime Kabi is given

How much is given

Ceftazidime Kabi will always be prepared and given to you by a doctor or another healthcare professional.

Depending on the severity and type of infection, your weight, your age and how well your kidneys are working, your doctor will determine a suitable dosage.

How it is given

Ceftazidime Kabi will be injected deep into muscle tissue or into a vein. When it is injected into a vein it may be given directly or through a 'drip'.

How long it is given for

Ceftazidime Kabi should be administered for as long as recommended by your doctor.

If you are given too much (overdose)

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 may have been given too much Ceftazidime Kabi.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are being given Ceftazidime Kabi

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being given Ceftazidime Kabi.

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

If you are about to have any blood or urine tests, tell your doctor that you are being given this medicine. It may interfere with the results of some tests.

If you become pregnant while taking this medicine, tell your doctor immediately.

Things you must not do

Do not use Ceftazidime Kabi to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if their symptoms seem similar to yours. Do not stop using your medicine or lower the dosage without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how Ceftazidime Kabi affects you. Certain side effects, such as dizziness and convulsions, have been reported with ceftazidime, which may affect some patient's ability to drive and use machines.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Ceftazidime Kabi. Like other medicines, Ceftazidime Kabi may have unwanted side effects in some people.

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 list of side effects. You may not experience any of them.

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

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

skin trouble such as a rash, red spots, itching, skin lumps, hives, blisters or peeling
swelling of the eyelids, face or lips
diarrhoea (even several weeks after your Ceftazidime Kabi treatment)
high temperature (fever)
difficulty breathing
bruising or bleeding
shaking or muscle twitches
fits or seizures
altered mental status; acute confusional state
wheezing, swelling of the lips/ mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting. These could be symptoms of an allergic reaction.

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

pain or flaking skin where you had the injection
headache
stomach pain
dizziness
numbness or tingling
nausea (feeling of sickness) or vomiting
bad taste in mouth
sore mouth or tongue
vaginal discharge, genital itching.

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

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

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

After being given Ceftazidime Kabi

Storage

Ceftazidime Kabi will be stored in the pharmacy or on the ward. The vials are kept in a cool dry place where the temperature stays below 25°C.

Product Description

What it looks like

Ceftazidime Kabi looks like a white to pale yellow powder. The powder is reconstituted with sterile water prior to injection. Once made up, the solution should be a clear and light yellow to amber colour.

Ingredients

Ceftazidime Kabi contains the active ingredient ceftazidime pentahydrate.

It also contains sodium carbonate.

Supplier

Ceftazidime Kabi is supplied in Australia by:

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way
Mount Kuring-gai NSW 2080
Australia
Telephone: (02) 9391 5555

Australian Registration Number

1 g: AUST R 223563

2 g: AUST R 223569

® = Registered Trademark

This leaflet was prepared in November 2023.

Published by MIMS April 2024

BRAND INFORMATION

Brand name

Ceftazidime Kabi

Active ingredient

Ceftazidime

Schedule

1 Name of Medicine

Ceftazidime (as pentahydrate).

2 Qualitative and Quantitative Composition

Ceftazidime Kabi powder for injection contains either 1 g or 2 g of ceftazidime (as pentahydrate).
Ceftazidime Kabi contains approximately 52.5 mg (2.3 mEq) of sodium per gram of ceftazidime. 1.164 g ceftazidime pentahydrate is equivalent to 1 g ceftazidime free acid.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
Supplied as a white to pale yellow powder. On the addition of water for injections, Ceftazidime Kabi dissolves with effervescence to produce a solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Ceftazidime Kabi is indicated for the treatment of single and mixed infections caused by susceptible aerobic organisms with suspected or documented resistance to other antimicrobials, but not to ceftazidime, and as an alternative to aminoglycosides in pseudomonal infection in patients in whom aminoglycoside toxicity is a cause for concern and other pseudomonal antibiotics cannot be used.
Indications include:

Severe infections in general.

For example septicaemia (including neonatal sepsis), bacteraemia, patients in intensive care units with specific problems, e.g. infected burns.

Respiratory tract infections.

For example, pneumonia, broncho-pneumonia, infected pleurisy, infected bronchiectasis, bronchitis.

Severe ear, nose and throat infections.

For example, otitis media, mastoiditis.

Urinary tract infections.

For example, acute and chronic pyelonephritis, pyelitis, cystitis, urethritis (bacterial only), infections associated with bladder and renal stones.

Skin and soft tissue infections.

For example, erysipelas, abscesses, cellulitis, infected burns and wounds, mastitis.

Gastrointestinal and abdominal infections.

For example, intra-abdominal abscesses, enterocolitis.

Bone and joint infections.

For example, osteitis, osteomyelitis, septic arthritis, infected bursitis.

4.2 Dose and Method of Administration

Note.

Vials of Ceftazidime Kabi are supplied under reduced pressure; a positive pressure is produced on reconstitution due to the release of carbon dioxide.

Dosage.

Ceftazidime is to be used by the parenteral route, the dosage depending upon the severity, sensitivity and type of infection and the age, weight and renal function of the patient.

Adults.

The adult dosage range for ceftazidime is 1-6 g per day. For instance, 500 mg, 1 g or 2 g given twelve or eight hours by intravenous or intramuscular injection.
In urinary tract infections and in many less serious infections, 500 mg or 1 g every twelve hours is usually adequate.
In the majority of infections, 1 g every eight hours or 2 g every twelve hours should be given. In very severe infections, 2 g every eight or twelve hours should be administered.
Individual doses in excess of 1 g should be administered intravenously.

Children (over 12 months).

The usual dosage range for children aged over 12 months is 25-100 mg/kg/day (up to a maximum of 6 g/day) given as two or three divided doses. The maximum daily dosage (6 g) may be given to children with very serious infections e.g. those who are immunocompromised or who suffer from cystic fibrosis.

Neonates and infants up to 12 months.

25-100 mg/kg/day in two divided doses. In neonates, the serum half-life of ceftazidime can be 3-4 times greater than that measured in adults.

Method of administration.

Ceftazidime may be given intravenously or by deep intramuscular injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh.
Instructions for reconstitution. Ceftazidime Kabi may be constituted with water for injections or, for intramuscular injection, with 1.0% lidocaine injection. See Table 1 for addition volumes and solution concentrations.

All sizes of vials as supplied are under reduced pressure. As the product dissolves, carbon dioxide is released and a positive pressure develops. Small bubbles in the reconstituted solution will resolve and a clear solution obtained in about 1-2 minutes. For ease of use, it is recommended that the following techniques of reconstitution are adopted.

1 g I.M./I.V. and 2 g I.V. bolus vials.

1. Insert the syringe needle through the vial closure and inject the recommended volume of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
2. Shake to dissolve: carbon dioxide is released and a clear solution will be obtained in about 1-2 minutes.
3. Invert the vial. With the syringe plunger fully depressed, insert the needle through the vial closure and withdraw the total volume of solution into the syringe (the pressure in the vial may aid withdrawal). Ensure that the needle remains within the solution and does not enter the headspace. The withdrawn solution may contain small bubbles of carbon dioxide; they may be disregarded.

2 g I.V. infusion vial.

This vial may be reconstituted for short intravenous infusion (i.e. 15-30 minutes) as follows:
1. Insert the syringe needle through the vial closure and inject 10 mL of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
2. Shake to dissolve; carbon dioxide is released and a clear solution will be obtained in about 1-2 minutes.
3. Insert a gas relief needle through the vial closure to relieve the internal pressure and, with the gas relief in position, add a further 40 mL of diluent. Remove the gas relief needle and syringe needle. Shake the vial and set up for infusion use in the normal way.

Note.

To preserve product sterility, it is important that a gas relief needle is not inserted through the vial closure before the product has dissolved.
These solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids.
Solutions of Ceftazidime Kabi reconstituted in water for injections or 1% lidocaine injection retain satisfactory potency for 4 hours if kept below 25°C or for 12 hours if refrigerated (2-8°C).
Ceftazidime is compatible with the intravenous fluids shown below. Solutions at concentrations up to 40 mg/mL in these infusion fluids may be stored for up to 4 hours below 25°C or 12 hours if refrigerated (2-8°C):
0.9% Sodium Chloride Infusion; Compound Sodium Lactate Infusion; 10% Glucose Infusion.
Sodium bicarbonate infusion is not recommended as a diluent.
It is advisable to administer reconstituted product as soon as possible.
The dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter prior to administration. The solution should only be used if it is clear and free from particles.
Solutions range from light yellow to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations.
For use in one patient on one occasion only. Discard any unused solution appropriately. Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe.
Precipitation has been reported when vancomycin has been added to ceftazidime in solution. Therefore, it would be prudent to flush giving sets and intravenous lines between the administration of these two agents. Protect from light.

Dosage in impaired renal function.

Adults.

Ceftazidime is excreted by the kidneys almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function it is recommended that the dosage of ceftazidime should be reduced to compensate for its slower excretion, except in mild impairment i.e. glomerular filtration rate (GFR) greater than 50 mL/min. In patients with suspected renal insufficiency, an initial loading dose of 1 g ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dose.
Recommended maintenance doses are shown in Table 2.

In patients with severe infections who would normally receive 6 g ceftazidime daily were it not for renal insufficiency, the unit dose given in Table 2 may be increased by 50% or the dosing frequency increased appropriately. In such patients, it is recommended that ceftazidime serum levels should be monitored and trough levels should not exceed 40 mg/L.
When only serum creatinine is available, the following formula (Cockcroft's equation) may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function. See Equation 1.

In children the creatinine clearance should be adjusted for body surface area or lean body mass and the dosing frequency reduced in cases of renal insufficiency as for adults.
The serum half-life of ceftazidime during haemodialysis is approximately 3 hours. The appropriate maintenance dose of ceftazidime should be repeated following each haemodialysis period. Continuous ambulatory peritoneal dialysis removed approximately 10% of the antibiotic when the dwell time was 4-6 hours.

Children.

In children, the creatinine clearance should be adjusted for body surface area or lean body mass and the dosing frequency reduced in cases of renal insufficiency as for adults.
The serum half-life of ceftazidime during haemodialysis is approximately three hours. The appropriate maintenance dose of ceftazidime should be repeated following each haemodialysis period. Continuous ambulatory peritoneal dialysis (CAPD) removed approximately 10% of the antibiotic when the dwell time was four to six hours.

Dosage adjustment in the elderly.

In view of the reduced clearance of ceftazidime in elderly patients, the daily dosage should be adjusted according to renal function.

4.3 Contraindications

Hypersensitivity to cephalosporins or major allergy to penicillin (anaphylaxis, angioneurotic oedema, urticaria).
Lignocaine should not be used as a diluent for intramuscular injection in patients who are hypersensitive to lignocaine.

4.4 Special Warnings and Precautions for Use

As with other beta-lactam antibiotics, before therapy with ceftazidime is instituted, careful inquiry should be made for a history of hypersensitivity reactions to ceftazidime, cephalosporins, penicillins or other drugs. Ceftazidime should be given only with special caution to patients with mild type I or immediate hypersensitivity reactions to penicillin or other beta-lactams. If an allergic reaction to ceftazidime occurs, discontinue the drug. Serious hypersensitivity reactions may require adrenaline, hydrocortisone, antihistamine or other emergency measures.
Antibiotic-associated pseudomembranous colitis has been reported with many antibiotics including ceftazidime. A toxin produced by 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 with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.
As with other broad spectrum antibiotics, prolonged use may result in the overgrowth of non-susceptible organisms (e.g. Candida, Enterococci) which may require interruption of treatment or appropriate measures. Repeated evaluation of the patient's condition is essential.
As with other extended-spectrum cephalosporins and penicillins, some initially susceptible strains of Enterobacter spp. and Serratia spp. may develop resistance during ceftazidime therapy. When clinically appropriate during therapy of such infections, periodic susceptibility testing should be considered.
Concurrent treatment with high doses of cephalosporins and nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g. frusemide) may adversely affect renal function. Clinical experience has shown that this is not likely to be a problem with ceftazidime at the recommended dose levels. There is no evidence that ceftazidime adversely affects renal function at normal therapeutic doses.
Drugs which delay peristalsis e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
Clostridium difficile infection rarely manifests as diarrhoea in neonates.
Peak concentrations of ceftazidime in the CSF are considerably lower than those in the plasma. Its use in the treatment of infections of the CNS, e.g. meningitis, brain abscess, etc. is not advised at present.
Prescribing ceftazidime in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Inducible type I beta-lactamase resistance has been noted with some organisms (e.g. Enterobacter spp., Pseudomonas spp., and Serratia spp.). As with other extended-spectrum beta-lactam antibiotics, resistance can develop during therapy, leading to clinical failure in some cases. When treating infections caused by these organisms, periodic susceptibility testing should be performed when clinically appropriate. If patients fail to respond to monotherapy, an aminoglycoside or similar agent should be considered.
Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal and hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.
Ceftazidime should be prescribed with caution to individuals with a history of gastrointestinal disease, particularly colitis.
Distal necrosis can occur after inadvertent intra-arterial administration of ceftazidime.

Neurotoxicity.

There have been reports of neurotoxicity associated with cephalosporin treatment. Symptoms of neurotoxicity include encephalopathy, 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.

Use in hepatic impairment.

Transient rises in hepatic enzymes have been noted in some patients given ceftazidime, so careful monitoring of hepatic function is advised when any dysfunction exists.
Repeated use of lignocaine hydrochloride as a diluent for IM use 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 consequent accumulation.
As with other broad spectrum antibiotics, prolonged use of ceftazidime may result in the overgrowth of non-susceptible organisms (e.g. Candida, Enterococci) which may require interruption of treatment or adoption of appropriate measures. Repeated evaluation of the patient's condition is essential.
Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but if concurrent administration of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered. There is some evidence in the literature that concurrent use of two beta-lactam antibiotics may exhibit antagonism.
See Section 4.2 Dose and Method of Administration for recommended techniques of reconstitution.
Ceftazidime should be prescribed with caution to individuals with a history of gastrointestinal disease, particularly colitis.

Use in renal impairment.

Ceftazidime has shown some evidence of renal toxicity in animals. Clinical studies have shown only transient elevations in serum urea and serum creatinine. It is excreted almost entirely by glomerular filtration and its half-life is prolonged in patients with impaired renal function. In such patients, dosage adjustment may be required in order to avoid the clinical consequences of elevated antibiotic levels. Neurological sequelae have occasionally been reported when the dose has not been reduced appropriately (see Section 4.2 Dose and Method of Administration).
Elevated levels of ceftazidime in patients with renal insufficiency can lead to seizures, encephalopathy, asterixis, neuromuscular excitability and myoclonia. Continued dosage should be determined by degree of renal impairment, severity of infection and susceptibility of the causative organism.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

Ceftazidime is effective in the treatment of neonatal infections caused by susceptible organisms.

Effects on laboratory tests.

The development of a positive Coombs' test associated with the use of ceftazidime in about 5% of patients may interfere with the cross-matching of blood.
The administration of ceftazidime may result in a false-positive reaction for glucose in the urine when using Clinitest tablets¹, Benedict's solution, or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix)¹ be used.
¹Clinitest and Clinistix are registered trademarks of Siemens Healthcare Diagnostics Inc.
Ceftazidime does not interfere in the alkaline picrate assay for creatinine.
For laboratory tests associated with ceftazidime administration, ceftazidime pentahydrate should be used.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Aminoglycoside antibiotics and/or diuretics.

Nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as frusemide. Renal function should be carefully monitored, especially if higher dosages of the aminoglycosides are to be administered or if therapy is prolonged, because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Nephrotoxicity and ototoxicity were not noted when ceftazidime was given alone in clinical trials.

Chloramphenicol.

Chloramphenicol has been shown to be antagonistic to beta-lactam antibiotics, including ceftazidime, based on in vitro studies and time kill curves with enteric gram-negative bacilli. Due to the possibility of antagonism in vivo, particularly when bactericidal activity is desired, this drug combination should be avoided.
In common with other antibiotics, ceftazidime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
The safety of ceftazidime in pregnancy has not been established, although animal studies have not produced evidence of embryopathic or teratogenic effects attributable to ceftazidime. Therefore, it may be administered during known or suspected pregnancy only if in the opinion of the treating physician the expected benefits outweigh the possible risks.
Ceftazidime is excreted in human breast milk in low concentrations; therefore, it is not recommended for nursing mothers unless the expected benefits to the mother greatly outweigh any potential risk to the infant.

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.

4.8 Adverse Effects (Undesirable Effects)

Data from large clinical trials (internal and published) were used to determine the frequency of very common to uncommon undesirable effects. The frequencies assigned to all other undesirable effects were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.
The following convention has been used for the classification of frequency:
Very common ≥ 1/10; common ≥ 1/100 to < 1/10; uncommon ≥ 1/1,000 to < 1/100; rare ≥ 1/10,000 to < 1/1,000; very rare < 1/10,000.

Infections and infestations.

Uncommon: Candidiasis (including vaginitis and oral thrush).

Blood and lymphatic system disorders.

Common: eosinophilia and thrombocytosis.
Uncommon: leucopenia, neutropenia, and thrombocytopenia.
Very rare: lymphocytosis, haemolytic anaemia, and agranulocytosis.

Immune system disorders.

Very rare: anaphylaxis (including bronchospasm and/or hypotension).

Nervous system disorders.

Uncommon: headache and dizziness.
Very rare: paraesthesia.
There have been reports of neurological sequelae including tremor, myoclonia, convulsions, encephalopathy, and coma in patients with renal impairment in whom the dose of ceftazidime has not been appropriately reduced.

Vascular disorders.

Common: phlebitis or thrombophlebitis with i.v. administration.

Gastrointestinal disorders.

Common: diarrhoea.
Uncommon: nausea, vomiting, abdominal pain, and colitis.
Very rare: bad taste.
As with other cephalosporins, colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis (see Section 4.4 Special Warnings and Precautions for Use).

Hepatobiliary disorders.

Common: transient elevations in one or more of the hepatic enzymes, ALT (SGPT), AST (SOGT), LDH, GGT and alkaline phosphatase.
Very rare: jaundice.

Skin and subcutaneous tissue disorders.

Common: maculopapular or urticarial rash.
Uncommon: pruritus.
Very rare: angioedema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Not known: DRESS syndrome^#.

General disorders and administration site conditions.

Common: pain and/or inflammation after i.m. injection.
Uncommon: fever.

Investigations.

Common: positive Coombs' test.
Uncommon: as with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen and/or serum creatinine have been observed.
A positive Coombs' test develops in about 5% of patients and may interfere with blood cross-matching.

Other (frequency not known).

Hypersensitivity.

Maculopapular or urticarial rash, fever, pruritus; very rarely angioedema and anaphylaxis (including bronchospasm and hypotension), erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Hot flushes, superficial desquamation around injection site.
^# DRESS syndrome (drug reaction/rash with eosinophilia and systemic symptoms). There have been rare reports where DRESS has been associated with ceftazidime.

Reporting of 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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma.

Treatment.

Ceftazidime can be removed by haemodialysis.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia) or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology. Ceftazidime is bactericidal in action, exerting its effect on target cell wall proteins and causing inhibition of cell wall synthesis. It is stable to most beta-lactamases produced by Gram-positive and Gram-negative organisms and consequently is active against many ampicillin and cephalothin-resistant strains (but not methicillin-resistant strains). Ceftazidime has been shown to have in vitro activity against the following organisms:

Gram-negative.

Pseudomonas aeruginosa, Pseudomonas species (other), Klebsiella pneumoniae, Klebsiella species (other), Proteus mirabilis, Proteus vulgaris, Morganella morganii (formerly Proteus morganii), Proteus rettgeri, Providencia species, Escherichia coli, Enterobacter species, Citrobacter species, Serratia species, Acinetobacter species, Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenza (including ampicillin-resistant strains).

Gram-positive.

Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Micrococcus species, Streptococcus pyogenes, Streptococcus Group B, Streptococcus pneumoniae, Streptococcus species (excluding Streptococcus faecalis).
Ceftazidime is not active in vitro against methicillin-resistant staphylococci, Streptococcus faecalis and many other Enterococci, Listeria monocytogenes, Campylobacter species or Clostridium difficile.
In vitro, the activities of ceftazidime and aminoglycoside antibiotics in combination have been shown to be at least additive; there is evidence of synergy in some strains tested. This property may be important in the treatment of febrile neutropenic patients.
Susceptibility tests. Quantitative methods that require measurement of zone diameters give the most precise estimate of antibiotic susceptibility. One such procedure has been recommended for use with discs to test susceptibility to ceftazidime.
Reports from the laboratory giving results of the standard single-disc susceptibility test with a 30 microgram ceftazidime disc should be interpreted according to the following criteria:
Susceptible organisms produce zones of 18 mm or greater, indicating that the test organism is likely to respond to therapy.
Organisms that produce zones of 15-17 mm are expected to be susceptible if high dosage is used or if the infection is confined to tissues and fluids (e.g. urine) in which high antibiotic levels are attained.
Resistant organisms produce zones of 14 mm or less, indicating that other therapy should be selected.
Organisms should be tested with the ceftazidime disc, since ceftazidime has been shown by in vitro tests to be active against certain strains found resistant when other beta-lactam discs are used.
Standardised procedures require the use of laboratory control organisms. The 30 microgram ceftazidime disc should give zone diameters between 25-32 mm for E. coli ATCC 25922. For P. aeruginosa ATCC 27853, the zone diameters should be between 22-29 mm. For S. aureus ATCC 25923, the zone diameters should be between 16-20 mm.
In other susceptibility testing procedures, e.g. ICS agar dilution or the equivalent, a bacterial isolate may be considered susceptible if the MIC value for ceftazidime is ≤ 16 microgram/mL. Organisms are considered resistant to ceftazidime if the MIC is ≥ 64 microgram/mL. Organisms having an MIC value of < 64 microgram/mL but > 16 microgram/mL are expected to be susceptible if high dosage is used or if the infection is confined to tissues and fluids (e.g. urine) in which high antibiotic levels are attained.
As with the standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard ceftazidime powder should give MIC values in the range of 4-16 microgram/mL for S. aureus ATCC 25923. For E. coli ATCC 25922, the MIC range should be between 0.125-0.5 microgram/mL. For P. aeruginosa ATCC 27853, the MIC range should be between 0.5-2 microgram/mL.
Susceptibility to ceftazidime will vary with geography and time and local susceptibility data should be consulted where available.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Absorption of ceftazidime after oral administration is negligible; therefore, ceftazidime is intended for parenteral use only.

Distribution.

In humans after a single intramuscular administration of 0.5 g and 1 g, mean peak serum levels of 18 and 37 mg/L, respectively, are achieved at 1 hour, falling to 8 and 2 mg/L and 20 and 5 mg/L at 4 and 8 hours, respectively, for the two doses. Five minutes after an intravenous bolus injection of 0.5 g, 1 g and 2 g, mean serum levels are 46, 87 and 170 mg/L respectively, for the three doses, falling to 17, 32 and 85 mg/L at 1 hour and 6, 10 and 15 mg/L at 4 hours respectively, for the three doses.
The mean maximum concentrations of ceftazidime in bone, heart, bile, sputum, aqueous humour, synovial and pleural and peritoneal fluids were in excess of the in vitro minimum inhibitory levels for susceptible organisms (see Susceptibility tests). Transplacental transfer of the antibiotic readily occurs. Ceftazidime penetrates the intact blood brain barrier poorly and low levels are achieved in the CSF.
The pharmacokinetics of ceftazidime are similar whether it is administered by a single or by repeat dosage.

Metabolism.

Ceftazidime is not metabolised in the body and is excreted unchanged in the active form into the urine by glomerular filtration.

Excretion.

The serum half-life in adults with normal renal function is about 1.8 hours (1.2-2.9 hours). This may be prolonged to 20-35 hours in anuric patients. In neonates, the serum half-life of ceftazidime can be 3-4 times greater than that measured in adults. The serum protein binding of ceftazidime is low at about 10%.
In the presence of normal renal function approximately 80-90% of the dose is recovered in the urine within 24 hours. Less than 1% is excreted via the bile.
Concurrent oral administration of probenecid did not affect the serum levels or urinary recoveries of ceftazidime.
The pharmacokinetics of ceftazidime were not affected when administered intramuscularly with 0.5% lignocaine.

5.3 Preclinical Safety Data

Genotoxicity.

A mouse Micronucleus test and Ames test were both negative for mutagenic effects.

Carcinogenicity.

Long-term studies in animals have not been performed to evaluate carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium carbonate.

6.2 Incompatibilities

Sodium bicarbonate injection is not recommended as a diluent.
Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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

Each vial of unreconstituted Ceftazidime Kabi contains a white or pale yellow powder containing 1 g or 2 g ceftazidime (as pentahydrate).
Vials (Type II colourless glass, halobutyl rubber stopper, plastic-aluminium cap): packs of 1, 5 and 10.
Not all strengths and/or pack sizes may be marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Chemical name: (6R,7R)-7-[[(2Z)-2-(2-Aminothiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino] acetyl]amino]-8-oxo-3-[(1-pyridinio) methyl]-5- thia-1-azabicyclo [4.2.0]oct-2-ene-2-carboxylate pentahydrate.
Molecular formula: C₂₂H₂₂N₆O₇S₂.5H₂O.
Molecular weight: 636.65.

CAS number.

78439-06-2.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

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