Consumer medicine information

Ceftazidime Juno

Ceftazidime

BRAND INFORMATION

Brand name

Ceftazidime Juno

Active ingredient

Ceftazidime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ceftazidime Juno.

What is in this leaflet

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

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

All medicines have risks and benefits. Your doctor has weighed the risks of you being given Ceftazidime Juno against the benefits this medicine is expected to have for you.

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

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

What Ceftazidime Juno is used for

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

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

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

Your doctor may have prescribed ceftazidime for another reason

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

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

Before you are given Ceftazidime Juno

When you must not be given it

Ceftazidime Juno if you have an allergy to:

  • ceftazidime
  • other cephalosporins
  • any of the ingredients listed at the end of this leaflet.
  • lignocaine

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 if you have had a serious allergic reaction to penicillin antibiotics.

Ceftazidime should not be mixed with lignocaine and given to you if you have had an allergic reaction to lignocaine.

Sometimes Ceftazidime Juno is mixed with lignocaine hydrochloride so that the injection into the muscle is less painful.

Before you are given it

Tell your doctor if you have any types of allergies to penicillin antibiotics. You may have an increased chance of being allergic to Ceftazidime if you are allergic to penicillins.

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you have or have ever had any other health problems or medical conditions, including:

  • kidney disease
  • liver disease.
  • stomach or bowel illness (eg colitis)
  • blood clotting disorder
  • prolonged antibiotic use.
  • central nervous system disorders

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant. Like most cephalosporin medicines, ceftazidime is not recommended for use during pregnancy. If there is a need to consider ceftazidime during your pregnancy, your doctor or pharmacist will discuss with you the benefits and risks of using it.

Tell your doctor or pharmacist if you are breast-feeding or plan to breast-feed. Like most cephalosporin medicines, ceftazidime is not recommended while you are breast-feeding. If there is a need to consider ceftazidime while you are breast feeding, your doctor or pharmacist will discuss the possible risks and benefits of using it.

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

Taking other medicines

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

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

  • chloramphenicol, an antibiotic used to treat bacterial infections
  • diuretics, medicines which help to reduce the amount of excess fluid in the body by increasing the amount of urine produced
  • aminoglycosides, antibiotics used to treat serious bacterial infections.

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

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

Your doctor or pharmacist may have more information on medicines to be careful with or avoid while being given ceftazidime

How Ceftazidime Juno is given

How much is given

Ceftazidime Juno is given as a slow injection or infusion (intravenous drip) into a vein. Alternatively, it can be given as a deep injection into a large muscle.

Ceftazidime Juno should only be given by a doctor or nurse.

Your doctor will decide what dose you will receive and how long you will receive Ceftazidime Juno for. This depends on your infection and other factors, such as your weight. For most infections, Ceftazidime Juno is usually given in divided doses throughout the day.

Sometimes only a single dose of Ceftazidime Juno is required for the treatment of certain infections.

If you take too much (overdose)

As ceftazidime is given under medical supervision, it is very unlikely that you will receive too much.

However, if you experience severe side effects after being given ceftazidime, tell your doctor or nurse immediately or telephone your doctor or the poisons Information Centre (13 11 26) for advice or go to Accident and Emergency at the nearest hospital. Do this even if there are no signs of discomfort or poisoning.

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

You may need urgent medical attention.

Ask your doctor if you have any concerns.

While you are being given Ceftazidime Juno

Things you must do

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

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

If you get a sore, white mouth or tongue while you are being treated with, or soon after stopping treatment with ceftazidime, tell your doctor. Also tell your doctor if you get vaginal itching or discharge. Sometimes the use of ceftazidime allows fungi to grow and the above symptoms to occur. Ceftazidime does not work against fungi.

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

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

If you have to test your urine for sugar while you are being treated with ceftazidime, make sure the doctor knows what type of test you use. Cefoxitin may affect the results of some of these tests.

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

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

Side effects

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

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

Treatment with ceftazidime, particularly in elderly patients with serious kidney or nervous system problems may rarely cause brain or nervous system disorders.

There have been reports of decreased consciousness, abnormal movements, confusion, agitation, and convulsions or seizures.

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

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

While using it

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

  • nausea or vomiting
  • diarrhoea
  • pain or tenderness near the injection site
  • headache
  • stomach pain
  • dizziness
  • numbness or tingling
  • oral thrush - white, furry, sore tongue and mouth
  • bad taste
  • vaginal thrush - sore and itchy vagina and/or discharge
  • hot flushes

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

  • severe abdominal cramps or stomach cramps
  • severe persistent diarrhoea (which may develop during treatment or up to several weeks after you stop ceftazidime)
  • 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
  • tremors, fits or seizures
  • signs of anaemia, such as tiredness, being short of breath when exercising, looking pale, or yellowing of the eyes or skin
  • high temperature (fever)
  • severe diarrhoea
  • light-headedness or dizziness
  • yellowing of the skin and/or eyes
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • decreased consciousness, abnormal movements, confusion, agitation, convulsions or seizures.

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

After finishing it

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

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

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

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

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

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

After being given Ceftazidime Juno

Storage

Ceftazidime Juno will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light and moisture where the temperature stays below 25°C.

Product description

What it looks like

Ceftazidime Juno is a white or cream coloured powder in a glass vial.

Ingredients

Ceftazidime Juno contains ceftazidime (as pentahydrate), equivalent to 1 g or 2 g of Ceftazidime.

It also contains the active ingredient sodium carbonate.

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

Sponsor

Australian Sponsor:

Juno Pharmaceuticals Pty Ltd
15 – 17 Chapel Street,
Cremorne,
VIC 3121

Ceftazidime Juno is available in the following strengths:

This leaflet was prepared in: February 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Ceftazidime Juno

Active ingredient

Ceftazidime

Schedule

S4

 

1 Name of Medicine

Ceftazidime (as pentahydrate).

2 Qualitative and Quantitative Composition

Ceftazidime Juno powder for injection is a cephalosporin antibiotic for use by injection only. Ceftazidime pentahydrate is slightly soluble in water and in methanol, practically insoluble in acetone and in ethanol. It dissolves in acid and alkali solutions.
Ceftazidime Juno is in vials containing 1 g and 2 g ceftazidime (as pentahydrate). For the full list of excipients, see Section 6.1 List of Excipients.
For laboratory tests associated with ceftazidime administration, ceftazidime pentahydrate should be used.

3 Pharmaceutical Form

Ceftazidime Juno is a powder for injection and is a white or cream coloured powder.
On the addition of water for injections, Ceftazidime Juno powder for injection dissolves with effervescence to produce a clear, colourless solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Ceftazidime Juno powder for injection 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

General dosage recommendations.

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 IV or IM 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 immuno-compromised or who suffer from cystic fibrosis.

Neonates and infants up to 12 months.

25 to 100 mg/kg/day in two divided doses. In neonates the serum half-life of ceftazidime can be 3 to 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 the table above 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:
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 haemo-dialysis period. Continuous ambulatory peritoneal dialysis (CAPD) removed approximately 10% of the antibiotic when the dwell time was 4-6 hours.

Administration.

Ceftazidime Juno powder for injection 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 Juno powder for injection may be reconstituted with Water for Injections or, for intramuscular injection, with 1.0% or 0.5% Lignocaine. See Table 2 for addition volumes and solution concentrations.
To reduce microbiological hazard, use as soon as practicable after reconstitution. If storage is necessary, hold at 2 to 8°C for not more than 24 hours. Protect from light.
Following reconstitution, use in one patient on one occasion only and discard any residue.
Vials of Ceftazidime Juno as supplied are under reduced pressure; a positive pressure is produced on reconstitution due to the release of carbon dioxide. For ease of use, it is recommended that the following techniques of reconstitution are adopted.

1 g IM/IV and 2 g IV 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 obtained in about 1 to 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 IV 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. The vacuum may assist entry of the diluent. Remove the syringe needle.
2. Shake to dissolve; carbon dioxide is released and a clear solution obtained in about 1 to 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 Juno powder for injection reconstituted in water for injections retain satisfactory potency for up to 24 hours if kept refrigerated (2 to 8°C).
Ceftazidime is also compatible with the intravenous fluids, 0.9% Sodium Chloride Injection BP and/or 5% Glucose Injection BP. Solutions in these infusion fluids may be stored for up to 24 hours if refrigerated (2 to 8°C).
Ceftazidime Juno powder for injection may be reconstituted for intramuscular administration using 0.5% and 1.0% Lignocaine Hydrochloride Injection BP; the resultant solutions may be stored for up to 24 hours under refrigeration (2 to 8°C).
Some increase in the colour of prepared solutions of Ceftazidime Juno powder for injection may occur on storage. It is, however, advisable to use the reconstituted product as soon as possible.
Sodium bicarbonate injection is not recommended as a diluent.
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.

4.3 Contraindications

Ceftazidime Juno powder for injection 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.
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).

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 tabletsi, Benedict's solution, or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix) be used.
Ceftazidime does not interfere in the alkaline picrate assay for creatinine.

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 furosemide. 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 aminoglycosidic 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 B11)
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.
1Category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformations or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

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.

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 http://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: disc susceptibility test.

Dilution or diffusion techniques.

Either quantitative (minimum inhibitory concentration (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.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

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.

Absorption.

Absorption of ceftazidime after oral administration is negligible, therefore Ceftazidime Juno powder for injection is intended for parenteral use only.
The mean peak serum concentrations of ceftazidime in man following a single intramuscular (IM) administration of ceftazidime are shown in Table 3.
The mean serum levels of ceftazidime after an intravenous (IV) bolus injection are shown in Table 4.
The serum half life in adults with normal renal function is about 1.8 hours (1.2 to 2.9 hours). This may be prolonged to 20 to 35 hours in anuric patients. In neonates, the serum half life of ceftazidime can be 3 to 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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium carbonate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
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

Vials of unreconstituted Ceftazidime Juno powder for injection should be stored at a temperature below 25°C and protected from light.
Vials of the reconstituted Ceftazidime Juno powder for injection can be stored for up to 24 hours at 2 to 8°C and protected from light with:
WFI; 0.5% Lignocaine Injection; 1.0% Lignocaine Injection; 0.9% Sodium Chloride Injection; 0.5% Glucose Injection.

6.5 Nature and Contents of Container

See Table 5.
The glass vials are Type III glass vials sealed with a dark grey bromobutyl rubber stopper and aluminium flip-off cap.
*Currently not marketed.

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-[[(2Z)-2-(2-Aminothiazol-4-yl)-2-[(1-carboxy-1 methylethoxy)imino]acetyl]amino]-8-oxo-3-[(pyridin-1-ium-1-yl)methyl]-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylate pentahydrate.
Molecular formula: C22H22N6O7S2, 5H2O.
Molecular weight: 636.6.

CAS number.

78439-06-2.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes