Consumer medicine information

Hospira Ceftazidime Powder for Injection

Ceftazidime

BRAND INFORMATION

Brand name

Hospira Ceftazidime Powder for Injection

Active ingredient

Ceftazidime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Hospira Ceftazidime Powder for Injection.

What is in this leaflet

This leaflet answers some common questions about HOSPIRA™ Ceftazidime Powder for Injection. 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 HOSPIRA™ Ceftazidime Powder for Injection 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 HOSPIRA™ Ceftazidime Powder for Injection 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 HOSPIRA™ Ceftazidime Powder for Injection

When you must not be given it

HOSPIRA™ Ceftazidime Powder for Injection should not be given to you if you have an allergy to:

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

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.

Ceftazidime should not be given to you if you have had a major allergic reaction to penicillins.

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

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

If you are not sure whether you should be given HOSPIRA™ Ceftazidime Powder for Injection, talk to your doctor.

Before you are given it

Tell your doctor if you have had any type of allergic reaction to penicillin medicines.

You may have an increased chance of being allergic to ceftazidime if you are allergic to penicillins.

Tell you doctor If you have any allergies to any other medicines or 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.

Tell your doctor 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 will discuss with you the benefits and risks of using it.

Tell your doctor 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 will discuss the possible risks and benefits of using it.

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

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. 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 medicine, 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 HOSPIRA™ Ceftazidime Powder for Injection is given

HOSPIRA™ Ceftazidime Powder for Injection 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.

HOSPIRA™ Ceftazidime Powder for Injection should only be given by a doctor or nurse.

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

Sometimes only a single dose of HOSPIRA™ Ceftazidime Powder for Injection is required for the treatment of certain infections.

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 (telephone 13 11 26 in Australia, or call 0800 764 766 in New Zealand) 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 HOSPIRA™ Ceftazidime Powder for Injection

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 or nurse immediately. Do this even if it occurs several weeks after ceftazidime has been stopped. Do not take any diarrhoea medicine without first checking with your doctor.

Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care.

If you get a sore white mouth or tongue while being given or soon after stopping 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 ceftazidime, tell your doctor immediately.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are being given ceftazidime.

If you have to test your urine for sugar while you are being given ceftazidime, make sure your doctor knows which type of test you use.

Ceftazidime 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.

Ceftazidime may affect the results of some blood tests.

Tell all the doctors, dentists and pharmacist who are treating you that you are being given ceftazidime.

Side effects

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

Ceftazidime 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 treatment if you get some of the side-effects.

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

While using it

Tell your doctor or nurse 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 mouth or tongue
  • bad taste
  • vaginal thrush - discharge, genital itching
  • 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)
  • 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. These 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 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.

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

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

Tell your doctor if you notice any other effects.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After being given HOSPIRA™ Ceftazidime Powder for Injection

Storage

HOSPIRA™ Ceftazidime Powder for Injection will be stored in the pharmacy or on the ward. The powder for injection is kept in the dark, in a cool dry place where the temperature stays below 25°C.

Product description

What it looks like

A white to pale yellow crystalline powder in a glass vial.

Ingredients

HOSPIRA™ Ceftazidime Powder for Injection contains the active ingredient:

  • ceftazidime (as pentahydrate), equivalent to 1 g or 2 g of ceftazidime.

It also contains the inactive ingredient:

  • sodium carbonate.

HOSPIRA™ Ceftazidime Powder for Injection does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Sponsor

Australian Sponsor:

Hospira Pty Ltd
ABN 13 107 058 328
Level 3
500 Collins Street
Melbourne VIC 3000
Australia

New Zealand Sponsor:

Hospira NZ Limited
58 Richard Pearse Drive,
Airport Oaks, Mangere 2022
Auckland
New Zealand

HOSPIRA™ Ceftazidime Powder for Injection is available in the following strengths:

  • 1 g AUST R 177029
  • 2 g AUST R 177030

This leaflet was prepared in: July 2015.

BRAND INFORMATION

Brand name

Hospira Ceftazidime Powder for Injection

Active ingredient

Ceftazidime

Schedule

S4

 

Name of the medicine

Ceftazidime (as ceftazidime pentahydrate).

Excipients.

Sodium carbonate anhydrous (117 mg per g of ceftazidime).

Description

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. MW: 636.6. CAS: 78439-06-2.
Hospira Ceftazidime Powder for Injection is a cephalosporin antibiotic for use by injection only. It is supplied as a white to cream coloured crystalline powder in vials containing 1 g and 2 g ceftazidime (as pentahydrate) with sodium carbonate anhydrous (117 mg per gram of ceftazidime). On the addition of water for injections, Hospira Ceftazidime Powder for Injection dissolves with effervescence to produce a light yellow to amber coloured solution for injection.
Ceftazidime pentahydrate is slightly soluble in water and in methanol, practically insoluble in acetone and in ethanol (96 per cent). It dissolves in acid and alkali solutions. Ceftazidime pentahydrate decomposes at about 150°C.
Ceftazidime pentahydrate is hygroscopic and crystalline in nature. No potential polymorphism is reported.
Hospira Ceftazidime Powder for Injection contains approximately 51 mg (2.17 mEq) of sodium per g of ceftazidime. 116 mg ceftazidime pentahydrate is equivalent to 100 mg ceftazidime anhydrous. For laboratory tests associated with ceftazidime administration, ceftazidime pentahydrate should be used.

Pharmacology

Pharmacokinetics.

Absorption of ceftazidime after oral administration is negligible, therefore Hospira Ceftazidime Powder for Injection 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. (See Table 1.)
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. (See Table 2.)
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%.
Ceftazidime is not metabolised in the body and 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 mean maximum concentrations of ceftazidime in bone, heart, bile, sputum, aqueous humour, synovial and pleural and peritoneal fluids were in excess of the in vitro minimum inhibitory levels for susceptible organisms (see Susceptibility tests). Transplacental transfer of the antibiotic readily occurs. Ceftazidime penetrates the intact blood brain barrier poorly and low levels are achieved in the CSF.
The pharmacokinetics of ceftazidime are similar whether it is administered by a single or by repeat dosage.
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.

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 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.

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 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.

Indications

Hospira Ceftazidime 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 the following.
Severe infections in general: for example septicaemia, including neonatal sepsis, bacteraemia, and in patients in intensive care units with specific problems, for example infected burns.
Respiratory tract infections: for example, pneumonia, bronchopneumonia, 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.

Contraindications

Hospira Ceftazidime 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.

Precautions

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 no 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.
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.

Patients with impaired renal function.

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 Dosage and 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 patients with impaired liver function.

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.

Carcinogenesis, mutagenesis, impairment of fertility.

Long-term studies in animals have not been performed to evaluate carcinogenic potential. However, a mouse micronucleus test and Ames test were both negative for mutagenic effects.

Use in pregnancy.

(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 malformations 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 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.

Use in lactation.

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.

Paediatric use.

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

Interactions

Chloramphenicol.

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 literature that concurrent use of two beta-lactam antibiotics may exhibit antagonism.

Aminoglycoside antibiotics and/or diuretics.

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

Effect 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.

Adverse Effects

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

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.

Genitourinary.

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.

Dosage and Administration

Note.

Vials of Hospira Ceftazidime Powder for Injection as supplied are under reduced pressure, a positive pressure is produced on reconstitution due to the release of carbon dioxide.

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.

Impaired renal function.

Adults.

Ceftazidime is excreted by the kidneys almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function it is recommended that the dosage of ceftazidime should be reduced to compensate for its slower excretion, except in mild impairment, i.e. glomerular filtration rate (GFR) greater than 50 mL/min. In patients with suspected renal insufficiency, an initial loading dose of 1 g of ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dose. (See Table 3.)
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 3 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.

Administration.

Hospira Ceftazidime 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.

Hospira Ceftazidime Powder for Injection may be reconstituted with water for injections or, for intramuscular injection, with 1.0% or 0.5% lignocaine. See Table 4 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.
All sizes of vials are supplied 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.

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. Additional pressure that may develop in the vial especially after, storage should be relieved prior to administration to the patient.

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 Hospira Ceftazidime Powder for Injection reconstituted in water for injections retains satisfactory potency for up to 24 hours if kept refrigerated (2 to 8°C).
Ceftazidime is also compatible with the following intravenous fluids: 0.9% Sodium Chloride Injection BP, 5% Glucose Injection BP, 0.9% Sodium Chloride with 5% Glucose Injection BP (1:1, V/V), M/6 Sodium Lactate Injection BP, M/6 Compound Sodium Lactate Injection BP (Hartmann's Solution), Dextran 40 Injection BP 10% in 0.9% Sodium Chloride Injection, Dextran 40 Injection BP 10% in 5% Glucose, Dextran 70 Injection BP 6% in 0.9% Sodium Chloride, Dextran 70 Injection BP 6% in 5% Glucose Injection BP.
Solutions in these infusion fluids may be stored for up to 24 hours if refrigerated (2 to 8°C).
Hospira Ceftazidime 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 Hospira Ceftazidime 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.
Ceftazidime 2 g injection may be stored for up to 24 hours under refrigeration (2 to 8°C) at concentrations between 0.05 mg/mL and 0.25 mg/mL in Intraperitoneal Dialysis Fluid (Lactate) BPC 1973.
Ceftazidime 2 g injection has been found compatible for 24 hours under refrigeration (2 to 8°C) when admixture at 4 mg/mL with potassium chloride 10 mEq/L or 40 mEq/L in 0.9% Sodium Chloride Injection BP, or heparin (10 and 50 units/mL) in 0.9% sodium chloride.
Ceftazidime 2 g injection (4 mg/mL) has been found compatible for 24 hours when refrigerated (2 to 8°C, do not freeze) when admixed with cloxacillin.
Ceftazidime 2 g injection (5 mg/mL) is compatible for 24 hours when refrigerated (2 to 8°C, do not freeze) when admixed with metronidazole.
Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe.
Precipitation has been reported when vancomycin has been added to ceftazidime in solution. Therefore, it would be prudent to flush giving sets and intravenous lines between the administration of these two agents.
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.

Overdosage

Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma. Ceftazidime can be removed by haemodialysis.
In case of overdose, immediately contact the Poisons Information Centre on 131 126 (Australia) for advice on management.

Presentation

Powder for injection (white to off white or cream, crystalline) 1 g (20 mL vial, AUST R 177029), 2 g (100 mL vial, AUST R 177030): 1's (clear glass moulded Type 1 vial, sealed with a grey bromo butyl rubber stopper and flip-off seal).

Storage

Vials of unreconstituted Hospira Ceftazidime Powder for Injection should be stored at a temperature below 25°C and protected from light.
Vials of the reconstituted Hospira Ceftazidime 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; M/6 Sodium Lactate Injection BP; M/6 Compound Sodium Lactate Injection BP (Hartmann's solution); Dextran 40 Injection BP 10% in 0/9% Sodium Chloride Injection BP; Dextran 40 Injection BP 10% in 5% Glucose Injection BP; Dextran 70 Injection BP 6% in 0.9% Sodium Chloride; Dextran 70 Injection BP 6% in 5% Glucose Injection BP.

Poison Schedule

S4.