Consumer medicine information

Ceftazidime-AFT

Ceftazidime

BRAND INFORMATION

Brand name

Ceftazidime-AFT

Active ingredient

Ceftazidime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ceftazidime-AFT.

What is in this leaflet?

Please read this leaflet carefully before you use Ceftazidime-AFT.

This leaflet answers some common questions about Ceftazidime-AFT. It does not contain all of the available information.

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

All medicines have risks and benefits. Sometimes new risks are found even when a medicine has been used for many years. Your doctor has weighed the expected benefits of you taking Ceftazidime-AFT against the risks this medicine could 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 is Ceftazidime-AFT used for?

Ceftazidime-AFT belongs to a group of medicines called cephalosporins.

Ceftazidime-AFT 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.

Ceftazidime-AFT works by killing the bacteria that cause these infections.

Your doctor may have prescribed Ceftazidime-AFT for another reason.

There is no evidence that Ceftazidime-AFT injection is addictive.

Before you are given Ceftazidime-AFT

When you must not be given it:

You must not be given Ceftazidime-AFT if:

  • you have ever had an allergic reaction to cephalosporins, penicillins or any of the ingredients listed toward the end of this leaflet. (See "Ingredients")
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering

Tell your doctor if:

You must tell your doctor if:

  • you are allergic to foods, dyes, preservatives or any other medicines (in particular cephalosporins, penicillins, chloramphenicol or lignocaine)
  • you are taking any other medicines, including medicines you buy without a prescription
  • you are taking oral contraceptives (birth control pills)
  • you have had to stop taking another medicine for your infection
  • you have kidney or liver problems
  • you have had stomach or bowel illness (for example, colitis)
  • you test your urine for sugar
  • while on Ceftazidime-AFT, you need to have your blood tested for a blood transfusion
  • you are breastfeeding, pregnant or trying to become pregnant.

How Ceftazidime-AFT is given

How much to give

Ceftazidime-AFT will be administered as directed under the supervision of a doctor or nurse. You will not be expected to give yourself this medication.

How it is given

Ceftazidime-AFT 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'.

DO NOT try to use the injection on your own unless your doctor has told you to do so and given you complete instructions.

How long it is given for

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

Do not stop taking Ceftazidime-AFT, or change the dose without first checking with your doctor.

Use in children and elderly patients

Consult your doctor before using Ceftazidime-AFT in children or elderly patients.

What do I do if I am given too much? (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 131126) for advice, if you think you or anyone else may have taken too much Ceftazidime-AFT, even if there are no signs of discomfort or poisoning.

If you are not sure what to do, contact your doctor, pharmacist or nearest hospital.

While you are being given Ceftazidime-AFT

Things you must do

Tell your doctor if you are allergic to cephalosporins, penicillins or other antibiotics.

Tell your doctor if you have kidney or liver problems.

Tell your doctor that you are being given Ceftazidime-AFT before taking any other prescribed medicine or performing any urine or blood tests.

Some medicines may affect the way other medicines work

Things you must not do

Do not give this medicine to anyone else, even if their symptoms seem similar to yours.

Do not use Ceftazidime-AFT to treat any other complaints unless your doctor says to.

Things to be careful of

Be careful driving or operating machinery until you know how Ceftazidime-AFT affects you.

What are the side-effects?

Check with your doctor as soon as possible if you think you are experiencing any side effects or allergic reactions due to taking Ceftazidime-AFT, even if the problem is not listed below.

Like other medicines, Ceftazidime-AFT can cause some side-effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Tell your doctor immediately if you notice any of the following after receiving Ceftazidime- AFT:

  • 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-AFT treatment)
  • high temperature (fever)
  • difficulty breathing
  • bruising or bleeding
  • shaking or muscle twitches
  • 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 if you notice any of the following after receiving Ceftazidime-AFT:

  • 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.

This is not a complete list of all possible side-effects. Others may occur in some people and there may be some side-effects not yet known.

Tell your doctor or pharmacist if you notice any side effects from your medicine which are not mentioned here.

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

How do I store Ceftazidime-AFT?

Keep this medicine where children cannot reach it, such as in a locked cupboard.

Store your Ceftazidime-AFT injection below 25°C.

Do not leave in a car, on a window sill or in the bathroom.

You will find an expiry (or "use by") date on the manufacturer's label of the pack. The injection should not be used after this date.

Product description

What Ceftazidime-AFT looks like

Ceftazidime-AFT looks like a white or almost white crystalline 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-AFT contains the active ingredient Ceftazidime pentahydrate.

Ceftazidime-AFT also contains anhydrous sodium carbonate.

Supplier

AFT Pharmaceuticals Pty Ltd
113 Wicks Road
North Ryde
NSW 2113
Australia

Where to go for further information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition.

This leaflet was revised in September 2017.

Ceftazidime-AFT Injection 1g: AUST R 277680

Ceftazidime-AFT Injection 2g: AUST R 277679

Published by MIMS May 2018

BRAND INFORMATION

Brand name

Ceftazidime-AFT

Active ingredient

Ceftazidime

Schedule

S4

 

1 Name of Medicine

Ceftazidime (as pentahydrate).

2 Qualitative and Quantitative Composition

Ceftazidime-AFT is a cephalosporin antibiotic for use by injection only. It is supplied as a white or almost white crystalline powder in vials containing 1 g and 2 g ceftazidime (as pentahydrate) with sodium carbonate anhydrous (118 mg per gram of ceftazidime). On the addition of water for injections, Ceftazidime-AFT Injection dissolves with effervescence to produce a solution for injection.
Ceftazidime-AFT Injection contains approximately 52 mg (2.3 mEq) of sodium per gram of ceftazidime. 1.16 g ceftazidime pentahydrate is equivalent to 1 g ceftazidime free acid. For laboratory tests associated with ceftazidime administration, ceftazidime pentahydrate should be used.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

The drug product is white or almost white crystalline powder.
Powder for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Ceftazidime-AFT 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, and in patients in intensive care units with specific problems, e.g. infected burns.

Respiratory tract infections.

For example, pneumonia, broncho-pneumonia, infected pleurisy, infected bronchiectasis and 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), and 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-AFT Injection are supplied with carbon dioxide as a protective gas. A positive pressure is produced on reconstitution due to the release of carbon dioxide.

Dose.

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 to 6 g per day. For instance, 500 mg, 1 g or 2 g given 12 or 8 hourly by I.V. or I.M. injection. In urinary tract infections and in many less serious infections, 500 mg or 1 g 12 hourly is usually adequate. In the majority of infections, 1 g 8 hourly or 2 g 12 hourly should be given. In very severe infections, 2 g 8 or 12 hourly should be administered. Individual doses in excess of 1 g should be administered intravenously.

Infants and children.

The usual dosage range for children aged over 12 months is 25 to 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.

Use in the elderly.

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

Dosage in impaired renal function.

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 of ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dose.
Recommended maintenance doses are shown in Table 1.
In patients with severe infections who would normally receive 6 g of ceftazidime daily were it not for renal insufficiency, the unit dose given in Table 1 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 (CAPD) removed approximately 10% of the antibiotic when the dwell time was 4-6 hours.

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-AFT may be reconstituted with water for injections or, for intramuscular injection, with 0.5% lignocaine. See Table 2 for addition volumes and solution concentrations.
All sizes of vials as supplied with carbon dioxide as a protective gas. As the product dissolves carbon dioxide is released and a positive pressure develops. 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. Remove the syringe needle.
2. Shake to dissolve; carbon dioxide is released and a clear solution 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 (e.g. up to 30 minutes) as follows:
1. Insert the syringe needle through the vial closure and inject 10 mL of diluent. Remove the syringe needle.
2. Shake to dissolve; carbon dioxide is released and a clear solution 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-AFT Injection reconstituted in water for injections retain satisfactory potency for 12 hours if refrigerated (2-8°C). When reconstituted for intramuscular injection in 0.5% Lignocaine Hydrochloride Injection BP the solution can be stored for up to 12 hours under refrigeration (2-8°C). Some increase in the colour of prepared solutions of Ceftazidime-AFT for injection may occur on storage. It is, however, advisable to use the reconstituted product as soon as possible.
Ceftazidime is compatible with the intravenous fluids shown below. Solutions at concentrations between 1 mg/mL and 40 mg/mL in these infusion fluids may be stored for up to 24 hours if refrigerated (2-8°C).
0.9% Sodium Chloride Injection BP; M/6 Sodium Lactate Injection BP; M/6 Compound Sodium Lactate Injection BP (Hartmann's Solution); 5% Dextrose Injection BP; Dextran 40 Injection BP 10% in 0.9% Sodium Chloride Injection BP; Dextran 40 Injection BP 10% in 5% Dextrose Injection BP; Dextran 70 Injection BP 6% in 0.9% Sodium Chloride Injection BP; Dextran 70 Injection BP 6% in 5% Dextrose Injection BP.
Ceftazidime-AFT Injection may be stored for up to 24 hours under refrigeration (2-8°C) at concentrations of between 0.05 mg/mL and 0.25 mg/mL in Intraperitoneal Dialysis Fluid (Lactate) BPC 1973.
Ceftazidime-AFT Injection has been found compatible for 24 hours under refrigeration (2-8°C) when admixed at 4 mg/mL with: Potassium Chloride 10 mEq/L or 40 mEq/L in 0.9% Sodium Chloride Injection BP.
Heparin (10 and 50 units/mL) in 0.9% Sodium Chloride.
Ceftazidime-AFT Injection (5 mg/mL) is compatible for 24 hours when refrigerated (2-8°C do not freeze) when admixed with metronidazole.
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.
Solutions range from colourless to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations.

4.3 Contraindications

Ceftazidime-AFT is contraindicated in persons who have shown hypersensitivity to cephalosporins or who have experienced a 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. 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.
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.
Resistance to initially susceptible Enterobacter species can develop during treatment with ceftazidime.
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.
Vials of Ceftazidime-AFT Injection are supplied with carbon dioxide as a protective gas. A positive pressure is produced on reconstitution due to the release of carbon dioxide. 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.

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, Ceftazidime-AFT should be discontinued immediately and an alternative treatment should be considered.

Use in hepatic impairment.

Transient rises in hepatic enzymes have been noted in some patients given Ceftazidime-AFT, so careful monitoring of hepatic function is advised when any dysfunction exists.
Repeated use of lignocaine hydrochloride as a diluent for I.M. 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.

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).

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.
Ceftazidime does not interfere with enzyme-based tests for glycosuria. Slight interference with copper reduction methods (Benedict's, Fehlings, Clinitest) may be observed. Ceftazidime does not interfere in the alkaline picrate assay for creatinine.

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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
The safety of Ceftazidime-AFT 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)

Clinical trial experience has shown that ceftazidime is generally well tolerated. Adverse reactions are infrequent and include:

Local.

Phlebitis or thrombophlebitis with IV administration; pain and/or inflammation after IM injection.

Hypersensitivity.

Maculopapular or urticarial rash, fever, pruritus, and very rarely angioedema and anaphylaxis (including bronchospasm and hypotension), erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Gastrointestinal.

Diarrhoea, nausea, vomiting, abdominal pain, and very rarely oral thrush or colitis.
Pseudomembranous colitis has been reported.

Central nervous system.

Headache, dizziness, paraesthesia and bad taste. There have been reports of neurological sequelae including tremor, myoclonia, convulsions and encephalopathy and coma occurring in patients with renal impairment in whom the dose of ceftazidime has not been appropriately reduced.

Genito-urinary.

Candidiasis, vaginitis.

Renal.

Transient elevations of blood urea, serum urea and/or serum creatinine have been observed occasionally.

Hepatic.

Elevations in one or more of the hepatic enzymes, SGOT, SGPT, LDH, GGT and alkaline phosphatase may occur.

Haematological.

Eosinophilia, positive Coombs' test, thrombocytosis; very rarely, transient leucopenia, haemolytic anaemia, neutropenia, thrombocytopenia and lymphocytosis have been seen.

Miscellaneous.

Hot flushes, superficial desquamation around injection site.
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.

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 https://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma. Ceftazidime can be removed by haemodialysis.
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.

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 influenzae (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 mm to 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.
Standardised procedures require the use of laboratory control organisms. The 30 microgram ceftazidime disc should give zone diameters between 25 mm and 32 mm for E. coli ATCC 25922. For P. aeruginosa ATCC 27853, the zone diameters should be between 22 mm and 29 mm. For S. aureus ATCC 25923, the zone diameters should be between 16 mm and 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 not more than 16 microgram/mL. Organisms are considered resistant to ceftazidime if the MIC is equal to or greater than 64 microgram/mL. Organisms having an MIC value of less than 64 microgram/mL but greater than 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 microgram/mL and 16 microgram/mL for S. aureus ATCC 25923. For E. coli ATCC 25922, the MIC range should be between 0.125 microgram/mL and 0.5 microgram/mL. For P. aeruginosa ATCC 27853, the MIC range should be between 0.5 microgram/mL and 2 microgram/mL.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Absorption of ceftazidime after oral administration is negligible, therefore Ceftazidime-AFT is intended for parenteral use only.
In man after a single intramuscular administration of 500 mg 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 500 mg, 1 g and 2 g, mean serum levels are respectively 46, 87 and 170 mg/L falling to 17 and 6 mg/L, 32 and 10 mg/L and 85 and 15 mg/L at 1 and 4 hours respectively with the three doses. 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%.

Distribution.

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.

Metabolism.

Ceftazidime is not metabolised in the body.

Excretion.

Ceftazidime is excreted unchanged in the active form into the urine by glomerular filtration. In the presence of normal renal function approximately 80 to 90% of the dose is recovered in the urine within 24 hours. Less than 1% is excreted via the bile.
The pharmacokinetics of ceftazidime are similar whether it is administered by a single or by repeat dosage.
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.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Inactive ingredient: sodium carbonate anhydrous.
Total sodium content of the mixture is approximately 52 mg/g.

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.

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 powder for reconstitution below 25°C. Protect from light.

6.5 Nature and Contents of Container

Stored in glass vials with rubber stopper.

Vial (powder for reconstitution).

1 g (for IM or IV use): 1 vial, 5 vials and 10 vials.
2 g (for IV use): 1 vial, 5 vials and 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.


Chemical name: (6R,7R)-7-[[(Z)-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: 636.6.

CAS number.

72558-82-8.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes