Consumer medicine information

Ceftazidime Sandoz Powder for injection

Ceftazidime

BRAND INFORMATION

Brand name

Ceftazidime Sandoz

Active ingredient

Ceftazidime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ceftazidime Sandoz Powder for injection.

What is in this leaflet

This leaflet answers some common questions about Ceftazidime Sandoz.

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

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

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

What Ceftazidime Sandoz is used for

The name of your medicine is Ceftazidime Sandoz. It contains the active ingredient ceftazidime pentahydrate.

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

Ceftazidime Sandoz belongs to a group of antibiotics called cephalosporins. These antibiotics work by killing the bacteria that are causing your infection.

Your doctor may have prescribed Ceftazidime Sandoz for another reason. Ask your doctor if you have any questions about why Ceftazidime Sandoz has been prescribed for you.

Ceftazidime Sandoz is available only with a doctor’s prescription.

Ceftazidime Sandoz is not addictive.

Before you are given Ceftazidime Sandoz

When you must not be given it

Do not use Ceftazidime Sandoz if:

  1. you have an allergy to ceftazidime, any of the ingredients listed at the end of this leaflet, or any other cephalosporins
Some of the symptoms of an allergic reaction may include wheezing, shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, skin rash, itching or hives.
  1. you have had a serious allergic reaction to any penicillins
You may be more likely to have an allergic reaction to Ceftazidime Sandoz if you are allergic to penicillin medicines.

Do not use Ceftazidime Sandoz if the packaging is torn or shows signs of tampering.

Do not use Ceftazidime Sandoz after the expiry date on the pack has passed.

If you are not sure whether you should be given Ceftazidime Sandoz, talk to your doctor or nurse.

Before you are given it

Tell your doctor if:

  1. you have had any type of allergic reaction to any cephalosporin or penicillin medicines
You may have an increased chance of being allergic to Ceftazidime Sandoz if you are allergic to any cephalosporins or penicillins.
  1. you are allergic to lignocaine or other local anaesthetics:
Lignocaine can be mixed with Ceftazidime Sandoz prior to injection.
  1. you have any allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. you are pregnant, or intend to become pregnant.
Ceftazidime Sandoz may affect your developing baby if you use it during pregnancy. Your doctor will discuss the risks and benefits of using Ceftazidime Sandoz during pregnancy.
  1. you are breast-feeding or intend to breast-feed.
Ceftazidime Sandoz passes into breast milk and may affect your baby. The use of Ceftazidime Sandoz is not recommended while breast-feeding. Your doctor will discuss the risks and benefits of using it when breast-feeding.
  1. if you have or have had any medical conditions, including:
  • kidney problems
  • liver problems
  • stomach or bowel problems.

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

Taking other medicines

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

Some medicines may interfere with Ceftazidime Sandoz. These include:

  • other forms of antibiotics, e.g. aminoglycoside antibiotics, chloramphenicol; and
  • potent diuretics such as frusemide.

These medicines may be affected by Ceftazidime Sandoz, or may affect how well it works. You may need to use different amounts of your medicine, or you may need to use different medicines. Your doctor will advise you.

Talk to your doctor about the need for an additional method of contraception while using Ceftazidime Sandoz. Some antibiotics may decrease the effectiveness of some birth control pills.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using Ceftazidime Sandoz.

How Ceftazidime Sandoz is given

Ceftazidime Sandoz must only be given by a doctor or nurse.

Ceftazidime Sandoz can be given in two ways:

  • as a slow injection into a vein
  • as a deep injection into a large muscle.

Your doctor will decide what dose and how long you will receive Ceftazidime Sandoz. This depends on your condition and whether you are using any other medicines. For most infections, Ceftazidime Sandoz is usually given in divided doses throughout the day.

If you are 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 Sandoz, 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.

If you are given too much Ceftazidime Sandoz you may experience symptoms such as stomach upsets, headache, dizziness or seizures.

While you are using Ceftazidime Sandoz

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

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

If you become pregnant while you are being treated with Ceftazidime Sandoz tell your doctor immediately.

If you are about to start using any new medicine, tell your doctor and pharmacist that you are being treated with Ceftazidime Sandoz.

If you have to test your urine for sugar while you are being given Ceftazidime Sandoz, make sure your doctor knows which type of test you use. Ceftazidime Sandoz may affect the results of some of these tests.

If you have to have any blood tests tell your doctor you are being given Ceftazidime Sandoz. Ceftazidime Sandoz may affect the results of some blood tests.

Tell all the doctors, dentists and pharmacists who are treating you that you are using Ceftazidime Sandoz.

Things you must not do

Do not give Ceftazidime Sandoz to anyone else, even if they have the same condition as you.

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

Things to be careful of

Be careful driving or operating machinery until you know how Ceftazidime Sandoz affects you. Ceftazidime Sandoz may cause dizziness in some people. Make sure you know how you react to Ceftazidime Sandoz before you drive a car, operate machinery or do anything else that may be dangerous if you are affected.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being given Ceftazidime Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

While using Ceftazidime Sandoz

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

  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina sometimes with a white discharge
  • pain, swelling or redness at the injection site
  • diarrhoea
  • nausea (feeling sick) or vomiting
  • headache or dizziness
  • abdominal pain
  • tingling or numbness of the hands and feet
  • bad taste
  • hot flushes.

These side effects are usually mild.

Tell your doctor or nurse immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • wheezing, difficulty breathing or shortness of breath
  • skin rash, itching, hives, blisters or peeling skin
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals.
  • tremors
  • fits or seizures
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • signs of anaemia, such as tiredness, headache, dizziness, being short of breath when exercising, looking pale, or yellowing of the skin or eyes
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers.

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

After finishing Ceftazidime Sandoz

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

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

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

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

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

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

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

Storage

Ceftazidime Sandoz will be stored in the pharmacy or on the ward.

The powder for injection is kept in a cool dry place, where the temperature stays below 25°C.

The reconstituted solution must be used immediately and any unused solution should be discarded.

Product description

What it looks like

Ceftazidime Sandoz is a white to cream coloured powder in a glass vial.

It is reconstituted before being injected.

Ceftazidime Sandoz is available in a pack containing 1 vial.

Ingredients

Active ingredient:

Each vial contains 1000 mg ceftazidime (equivalent to 1164.8 mg of ceftazidime pentahydrate).

Inactive ingredient:

  • sodium carbonate anhydrous.

Ceftazidime Sandoz does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

SPONSOR

Ceftazidime Sandoz is supplied in Australia by:

Sandoz Pty Ltd
54 Waterloo Road
Macquarie Park, NSW
Australia
Tel: 1800 726 369

Australian Registration Numbers:

AUST R 90915

CEFTAZIDIME SANDOZ ceftazidime 1g (as pentahydrate) powder for injection vial(single vial)

This leaflet was revised in Jan 2019.

®Registered Trademark

Published by MIMS March 2019

BRAND INFORMATION

Brand name

Ceftazidime Sandoz

Active ingredient

Ceftazidime

Schedule

S4

 

1 Name of Medicine

Ceftazidime (as pentahydrate).

6.7 Physicochemical Properties

The chemical name of ceftazidime pentahydrate is (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. Its molecular formula is C22H22N6O7S2.5H2O (Molecular weight: 636.6).

Chemical structure.

Its chemical structure is:

CAS number.

72558-82-8.

2 Qualitative and Quantitative Composition

Ceftazidime Sandoz is a cephalosphorin antibiotic containing ceftazidime pentahydrate, a white to faintly yellow crystalline powder, soluble in acid and alkali solution; slightly soluble in water and in methanol; practically insoluble in acetone and in alcohol. On addition of water for injections, Ceftazidime Sandoz dissolves with effervescence to produce a solution for use by injection only.
For laboratory tests associated with ceftazidime administration, ceftazidime pentahydrate should be used.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Vial (powder for reconstitution): 1 g (for IM or IV use).

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 organisms.

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

Gram-positive organisms.

Staphylococcus aureus (methicillin sensitive strains), Staph. epidermidis (methicillin sensitive strains), Micrococcus sp., Streptococcus pyogenes, Streptococcus group B, Strep. pneumoniae, Streptococcus sp. (excluding Strep. faecalis).
Ceftazidime is not active in vitro against methicillin resistant Staphylococci, Streptococcus faecalis and many other Enterococci, Listeria monocytogenes, Campylobacter sp. 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.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable, other therapy should be selected.

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

Absorption.

Absorption of ceftazidime after oral administration is negligible; therefore, Ceftazidime Sandoz is intended for parenteral use only.
In humans, 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 four and eight 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 one and four hours respectively with the three doses. 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 three to four times greater than that measured in adults.
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.

Distribution.

The serum protein binding of ceftazidime is low at about 10%.
The mean maximum concentrations of ceftazidime in bone, heart, bile, sputum, aqueous humour and synovial, pleural and peritoneal fluids were in excess of the in vitro minimum inhibitory levels for susceptible organisms (see Section 5.1 Pharmacodynamic Properties, Susceptibility tests). Transplacental transfer of the antibiotic readily occurs. Ceftazidime penetrates the intact blood-brain barrier poorly and low levels are achieved in the cerebrospinal fluid (CSF).

Metabolism.

Ceftazidime is not metabolised in the body.

Excretion.

It 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.

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.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of single and mixed infections caused by susceptible aerobic organisms with suspected or documented resistance to other antimicrobials, but not to ceftazidime; as an alternative to aminoglycosides in pseudomonal infection in patients in whom aminoglycoside toxicity is a cause for concern and other antipseudomonal antibiotics cannot be used.
Indications include the following:
Severe infections in general (e.g. septicaemia including neonatal sepsis, bacteraemia; in patients in intensive care units with specific problems, e.g. infected burns).
Respiratory tract (e.g. pneumonia, bronchopneumonia, infected pleurisy, infected bronchiectasis and bronchitis).
Severe ear, nose and throat infections (e.g. otitis media, mastoiditis).
Urinary tract (e.g. acute and chronic pyelonephritis, pyelitis, cystitis, urethritis (bacterial only); infections associated with bladder and renal stones).
Skin and soft tissue (e.g. erysipelas, abscesses, cellulitis, infected burns and wounds, mastitis).
Gastrointestinal and abdominal (e.g. intra-abdominal abscesses, enterocolitis).
Bone and joint (e.g. osteitis, osteomyelitis, septic arthritis, infected bursitis).

4.3 Contraindications

Hypersensitivity to cephalosporins or 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 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 C. 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.
Drugs that delay peristalsis, e.g. opiates and diphenoxylate with atropine (e.g. Lomotil), may prolong and/or worsen the condition and should not be used.
C. 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 central nervous system, e.g. meningitis, brain abscess, is not advised at present.
Resistance to initially susceptible Enterobacter species and Serratia spp. can develop during treatment with ceftazidime. When clinically appropriate during therapy of such infections, periodic susceptibility testing should be considered.
As with other broad spectrum antibiotics, prolonged use of ceftazidime may result in the overgrowth of nonsusceptible 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 Sandoz injection, as supplied, are under reduced pressure; 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.

Use in hepatic impairment.

Transient rises in hepatic enzymes have been noted in some patients given Ceftazidime Sandoz, so careful monitoring of hepatic function is advised when any dysfunction exists.
Repeated use of lignocaine hydrochloride as a diluent for intramuscular 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). 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.
Ceftazidime does not interfere with enzyme based tests for glycosuria. Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. Ceftazidime does not interfere in the alkaline picrate assay for creatinine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Chloramphenicol is antagonistic in vitro to 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.
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.
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)
Category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have not shown evidence of an increased occurrence of foetal damage.
The safety of Ceftazidime Sandoz 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 doctor, the expected benefits outweigh the possible risks.
 Ceftazidime is excreted in human breast milk in low concentrations, therefore, it is not recommended for breastfeeding mothers unless the expected benefits to the mother greatly outweigh any potential risk to the infant.

4.8 Adverse Effects (Undesirable Effects)

Data from large clinical trials 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 IV 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 (SGOT), 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 IM 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 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.

4.2 Dose and Method of Administration

Dosage.

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

Adults.

The adult dosage range for ceftazidime is 1 to 6 g daily, for instance, 500 mg, 1 g or 2 g given every 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 exceeding 1 g should be administered intravenously.

Children (over 12 months).

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, 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 three to four 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.

Reconstitution.

Ceftazidime for injection may be reconstituted with water for injections or, for intramuscular injection, with 0.5% or 1% lignocaine. See Table 1 for additive volumes and solution concentrations.
Vials of Ceftazidime Sandoz injection as supplied are under reduced pressure; a positive pressure is produced on reconstitution due to the release of carbon dioxide.
Vials as supplied are under reduced pressure. 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.
Insert syringe needle through vial closure and inject recommended volume of diluent. The vacuum may assist entry of the diluent. Remove syringe needle. Shake to dissolve; carbon dioxide is released and a clear solution obtained in about one to two minutes.
Invert the vial. With the syringe plunger fully depressed, insert the needle through 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, which should be expelled from the syringe before injection.

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.
Ceftazidime Sandoz 1 g injection may be reconstituted for intramuscular administration using 0.5% Lignocaine Hydrochloride Injection BP; the resultant solutions may be stored for 24 hours under refrigeration (2 to 8°C). Solutions of Ceftazidime Sandoz 1 g injection reconstituted in 1.0% lignocaine solution retain satisfactory potency for 24 hours if refrigerated (2 to 8°C). Some increase in the colour of prepared solutions of ceftazidime for injection may occur on storage. It is, however, advisable to use the reconstituted product as soon as possible.
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.
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.

Dosage adjustment in renal impairment.

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/minute. In patients with suspected renal insufficiency, an initial loading dose of ceftazidime 1 g 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 ceftazidime 6 g 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.

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.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

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).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium carbonate anhydrous.
Total sodium content of the mixture is approximately 54 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.
For information on interactions with other medicines and other forms of interactions, see Section 4.5.

6.3 Shelf Life

Solutions of Ceftazidime Sandoz 1 g injection reconstituted in water for injections retain satisfactory potency for 24 hours if refrigerated at 2 to 8°C. To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary hold at 2°-8°C for not more than 24 hours. Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

Vial (powder for reconstitution): 1 g (for IM or IV use): 1's, 5's* and 10's*.
* Not currently 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.

Summary Table of Changes