Consumer medicine information

Ceftazidime-AFT

Ceftazidime

BRAND INFORMATION

Brand name

Ceftazidime-AFT

Active ingredient

Ceftazidime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

SUMMARY CMI

Ceftazidime-AFT

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I given Ceftazidime-AFT?

Ceftazidime-AFT contains the active ingredient Ceftazidime (as pentahydrate). Ceftazidime-AFT belongs to a group of medicines called cephalosporins. Ceftazidime-AFT is used to treat a wide range of infections caused by bacteria.

For more information, see Section 1. Why am I given Ceftazidime-AFT? in the full CMI.

2. What should I know before I am given Ceftazidime-AFT?

Do not use if you have ever had an allergic reaction to Ceftazidime-AFT or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given Ceftazidime-AFT? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Ceftazidime-AFT and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is Ceftazidime-AFT given?

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

More instructions can be found in Section 4. How is Ceftazidime-AFT given? in the full CMI.

5. What should I know while I am given Ceftazidime-AFT?

Things you should do
  • Tell your doctor if you are allergic to cephalosporins, penicillins or other antibiotics.
  • Tell your doctor if you have kidney or liver problems.
Things you should not do
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use Ceftazidime-AFT to treat any other complaints unless your doctor says to.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Ceftazidime-AFT affects you.

For more information, see Section 5. What should I know while I am given Ceftazidime-AFT? in the full CMI.

6. Are there any side effects?

Like all medicines, Ceftazidime-AFT can cause 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. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Ceftazidime-AFT

Active ingredient(s): Ceftazidime (as pentahydrate)

Consumer Medicine Information (CMI)

This leaflet provides important information about using Ceftazidime-AFT. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Ceftazidime-AFT.

Where to find information in this leaflet:

1. Why am I given Ceftazidime-AFT?
2. What should I know before I am given Ceftazidime-AFT?
3. What if I am taking other medicines?
4. How is Ceftazidime-AFT Given?
5. What should I know while I am given Ceftazidime-AFT?
6. Are there any side effects?
7. Product details

1. Why am I given Ceftazidime-AFT?

Ceftazidime-AFT contains the active ingredient Ceftazidime (as pentahydrate). Ceftazidime-AFT belongs to a group of medicines called cephalosporins.

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

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

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

2. What should I know before I am given Ceftazidime-AFT?

Warnings

You should not be given Ceftazidime-AFT if:

  • you are allergic to ceftazidime (as pentahydrate), cephalosporins, penicillins or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine,
  • the expiry date (EXP) printed on the pack has passed,
  • the packaging is torn or shows signs of tampering.

Check with your doctor if you:

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

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Ceftazidime-AFT is not recommended for use during pregnancy and breastfeeding. If there is a need to consider Ceftazidime-AFT during pregnancy or breastfeeding, your doctor will discuss with you the benefits and risks of using it.

3. What if I am taking other medicines?

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

Some medicines may interfere with Ceftazidime-AFT. These include:

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

These medicines may be affected by Ceftazidime-AFT 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-AFT.

Some antibiotics may decrease the effectiveness of some birth control pills, although this has not been shown with Ceftazidime-AFT

Your doctor or pharmacist may have more information on medicines to be careful with or avoid while being given Ceftazidime-AFT.

4. How is Ceftazidime-AFT given?

How much is given

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

When Ceftazidime-AFT is given

  • Ceftazidime-AFT will be injected deep into muscle tissue or into a vein. When it is injected into a vein it may be given directly or through a 'drip'.
  • DO NOT try to use the injection on your own unless your doctor has told you to do so and given you complete instructions.
  • Ceftazidime-AFT should be administered for as long as recommended by your doctor.

If too much Ceftazidime-AFT is given

As Ceftazidime-AFT 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, you should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should 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 section 6 ‘Are there any side effects?’ but are usually of a more severe nature.

You may need urgent medical attention.

Ask your doctor if you have any concerns.

5. What should I know while I am given Ceftazidime-AFT?

Things you should do

  • Tell your doctor if you are allergic to cephalosporins, penicillins or other antibiotics.
  • Tell your doctor if you have kidney or liver problems.
  • Tell your doctor that you are being given Ceftazidime-AFT before taking any other prescribed medicine or performing any urine or blood tests. Some medicines may affect the way other medicines work.

Things you should not do

  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use Ceftazidime-AFT to treat any other complaints unless your doctor says to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Ceftazidime-AFT affects you.

Looking after your medicine

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

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects. Do not be alarmed by this list of possible side-effects. You may not experience any of them.

Less serious side effects

Less serious side effectsWhat to do
Body as a whole:
  • pain or flaking skin where you had the injection
  • headache
  • dizziness
  • numbness or tingling
  • bad taste in mouth
  • sore mouth or tongue
  • vaginal discharge, genital itching.
Gastrointestinal related:
  • stomach pain
  • nausea (feeling of sickness) or vomiting
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Allergic reaction related:
  • skin trouble such as a rash, red spots, itching, skin lumps, hives, blisters or peeling
  • swelling of the eyelids, face or lips
  • difficulty breathing
  • Wheezing, swelling of the lips/mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting. These could be symptoms of an allergic reaction.
Body as a whole:
  • diarrhoea (even several weeks after your Ceftazidime-AFT treatment)
  • high temperature (fever)
  • bruising or bleeding
  • shaking or muscle twitches
  • Reduced ability to think clearly or concentrate, memory loss, drowsiness, seizures, muscle twitches and personality change. These symptoms may be related to a condition called encephalopathy.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Ceftazidime-AFT contains

Active ingredient
(main ingredient)		Ceftazidime (as pentahydrate)
Other ingredients
(inactive ingredients)		Sodium carbonate

Do not take this medicine if you are allergic to any of these ingredients.

What Ceftazidime-AFT looks like

Ceftazidime-AFT looks like a white or almost white crystalline powder. The powder is reconstituted with sterile water prior to injection. Once made up the solution should be a clear and light yellow to amber colour (Aust R 277679, 277680).

Who distributes Ceftazidime-AFT

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

This leaflet was prepared in December 2023

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Ceftazidime-AFT

Active ingredient

Ceftazidime

Schedule

S4

 

1 Name of Medicine

Ceftazidime (as pentahydrate).

2 Qualitative and Quantitative Composition

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

3 Pharmaceutical Form

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

4 Clinical Particulars

4.1 Therapeutic Indications

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

Severe infections in general.

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

Respiratory tract infections.

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

Severe ear, nose and throat infections.

For example, otitis media, mastoiditis.

Urinary tract infections.

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

Skin and soft tissue infections.

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

Gastrointestinal and abdominal infections.

For example, intra-abdominal abscesses, enterocolitis.

Bone and joint infections.

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

4.2 Dose and Method of Administration

Note.

Vials of Ceftazidime-AFT Injection are supplied with carbon dioxide as a protective gas. A positive pressure is produced on reconstitution due to the release of carbon dioxide.

Dose.

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

Adults.

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

Infants and children.

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

Neonates and infants up to 12 months.

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

Use in the elderly.

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

Dosage in impaired renal function.

Ceftazidime is excreted by the kidneys almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function it is recommended that the dosage of ceftazidime should be reduced to compensate for its slower excretion, except in mild impairment, i.e. glomerular filtration rate (GFR) greater than 50 mL/min. In patients with suspected renal insufficiency, an initial loading dose of 1 g of ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dose.
Recommended maintenance doses are shown in Table 1.
In patients with severe infections who would normally receive 6 g of ceftazidime daily were it not for renal insufficiency, the unit dose given in Table 1 may be increased by 50% or the dosing frequency increased appropriately. In such patients it is recommended that ceftazidime serum levels should be monitored and trough levels should not exceed 40 mg/L.
When only serum creatinine is available, the following formula (Cockcroft's equation) may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function. See Equation 1.
In children the creatinine clearance should be adjusted for body surface area or lean body mass and the dosing frequency reduced in cases of renal insufficiency as for adults.
The serum half-life of ceftazidime during haemodialysis is approximately 3 hours. The appropriate maintenance dose of ceftazidime should be repeated following each haemodialysis period. Continuous ambulatory peritoneal dialysis (CAPD) removed approximately 10% of the antibiotic when the dwell time was 4-6 hours.

Method of administration.

Ceftazidime may be given intravenously or by deep intramuscular injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh.
Instructions for reconstitution. Ceftazidime-AFT may be reconstituted with water for injections or, for intramuscular injection, with 0.5% lignocaine. See Table 2 for addition volumes and solution concentrations.
All sizes of vials as supplied with carbon dioxide as a protective gas. As the product dissolves carbon dioxide is released and a positive pressure develops. For ease of use, it is recommended that the following techniques of reconstitution are adopted.

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

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

2 g I.V. infusion vial.

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

Note.

To preserve product sterility, it is important that a gas relief needle is not inserted through the vial closure before the product has dissolved.
These solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids.
Solutions of Ceftazidime-AFT Injection reconstituted in water for injections retain satisfactory potency for 12 hours if refrigerated (2-8°C). When reconstituted for intramuscular injection in 0.5% Lignocaine Hydrochloride Injection BP the solution can be stored for up to 12 hours under refrigeration (2-8°C). Some increase in the colour of prepared solutions of Ceftazidime-AFT for injection may occur on storage. It is, however, advisable to use the reconstituted product as soon as possible.
Ceftazidime is compatible with the intravenous fluids shown below. Solutions at concentrations between 1 mg/mL and 40 mg/mL in these infusion fluids may be stored for up to 24 hours if refrigerated (2-8°C).
0.9% Sodium Chloride Injection BP; M/6 Sodium Lactate Injection BP; M/6 Compound Sodium Lactate Injection BP (Hartmann's Solution); 5% Dextrose Injection BP; Dextran 40 Injection BP 10% in 0.9% Sodium Chloride Injection BP; Dextran 40 Injection BP 10% in 5% Dextrose Injection BP; Dextran 70 Injection BP 6% in 0.9% Sodium Chloride Injection BP; Dextran 70 Injection BP 6% in 5% Dextrose Injection BP.
Ceftazidime-AFT Injection may be stored for up to 24 hours under refrigeration (2-8°C) at concentrations of between 0.05 mg/mL and 0.25 mg/mL in Intraperitoneal Dialysis Fluid (Lactate) BPC 1973.
Ceftazidime-AFT Injection has been found compatible for 24 hours under refrigeration (2-8°C) when admixed at 4 mg/mL with: Potassium Chloride 10 mEq/L or 40 mEq/L in 0.9% Sodium Chloride Injection BP.
Heparin (10 and 50 units/mL) in 0.9% Sodium Chloride.
Ceftazidime-AFT Injection (5 mg/mL) is compatible for 24 hours when refrigerated (2-8°C do not freeze) when admixed with metronidazole.
Precipitation has been reported when vancomycin has been added to ceftazidime in solution. Therefore, it would be prudent to flush giving sets and intravenous lines between the administration of these two agents. Protect from light.
Solutions range from colourless to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations.

4.3 Contraindications

Ceftazidime-AFT is contraindicated in persons who have shown hypersensitivity to cephalosporins or who have experienced a major allergy to penicillin (anaphylaxis, angioneurotic oedema, urticaria).
Lignocaine should not be used as a diluent for intramuscular injection in patients who are hypersensitive to lignocaine.

4.4 Special Warnings and Precautions for Use

As with other beta-lactam antibiotics, before therapy with ceftazidime is instituted, careful inquiry should be made for a history of hypersensitivity reactions to ceftazidime, cephalosporins, penicillins, or other drugs. Ceftazidime should be given only with special caution to patients with mild type I or immediate hypersensitivity reactions to penicillin. If an allergic reaction to ceftazidime occurs, discontinue the drug. Serious hypersensitivity reactions may require adrenaline, hydrocortisone, antihistamine or other emergency measures.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including ceftazidime. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
Drugs which delay peristalsis e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
Clostridium difficile infection rarely manifests as diarrhoea in neonates.
Peak concentrations of ceftazidime in the CSF are considerably lower than those in the plasma. Its use in the treatment of infections of the CNS, e.g. meningitis, brain abscess, etc. is not advised at present.
Resistance to initially susceptible Enterobacter species can develop during treatment with ceftazidime.
As with other broad spectrum antibiotics, prolonged use of ceftazidime may result in the overgrowth of non-susceptible organisms (e.g. Candida, Enterococci) which may require interruption of treatment or adoption of appropriate measures. Repeated evaluation of the patient's condition is essential.
Vials of Ceftazidime-AFT Injection are supplied with carbon dioxide as a protective gas. A positive pressure is produced on reconstitution due to the release of carbon dioxide. See Section 4.2 Dose and Method of Administration for recommended techniques of reconstitution.
Ceftazidime should be prescribed with caution to individuals with a history of gastrointestinal disease, particularly colitis.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, Ceftazidime-AFT should be discontinued immediately and an alternative treatment should be considered.

Use in hepatic impairment.

Transient rises in hepatic enzymes have been noted in some patients given Ceftazidime-AFT, so careful monitoring of hepatic function is advised when any dysfunction exists.
Repeated use of lignocaine hydrochloride as a diluent for I.M. use should be avoided in patients with severe liver disease or decreased hepatic blood flow due to the possibility of lignocaine toxicity resulting from decreased metabolism and consequent accumulation.

Use in renal impairment.

Ceftazidime has shown some evidence of renal toxicity in animals. Clinical studies have shown only transient elevations in serum urea and serum creatinine. It is excreted almost entirely by glomerular filtration and its half-life is prolonged in patients with impaired renal function. In such patients dosage adjustment may be required in order to avoid the clinical consequences of elevated antibiotic levels. Neurological sequelae have occasionally been reported when the dose has not been reduced appropriately (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

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

Effects on laboratory tests.

The development of a positive Coombs' test associated with the use of ceftazidime in about 5% of patients may interfere with the cross-matching of blood.
Ceftazidime does not interfere with enzyme-based tests for glycosuria. Slight interference with copper reduction methods (Benedict's, Fehlings, Clinitest) may be observed. Ceftazidime does not interfere in the alkaline picrate assay for creatinine.

Neurotoxicity.

There have been reports of neurotoxicity associated with cephalosporin treatment. Symptoms of neurotoxicity include encephalopathy, seizures and/or myoclonus. Risk factors for developing neurotoxicity with cephalosporin treatment include being elderly, renal impairment, central nervous system disorders and intravenous administration. Withdrawal of the medicine should be considered if there are signs of neurotoxicity.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but if concurrent administration of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered. There is some evidence in the literature that concurrent use of two beta-lactam antibiotics may exhibit antagonism.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

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

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

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

Local.

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

Hypersensitivity.

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

Gastrointestinal.

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

Central nervous system.

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

Genito-urinary.

Candidiasis, vaginitis.

Renal.

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

Hepatic.

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

Haematological.

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

Miscellaneous.

Hot flushes, superficial desquamation around injection site.
Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma. Ceftazidime can be removed by haemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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

Gram-negative.

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

Gram-positive.

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

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Absorption of ceftazidime after oral administration is negligible, therefore Ceftazidime-AFT is intended for parenteral use only.
In man after a single intramuscular administration of 500 mg and 1 g, mean peak serum levels of 18 and 37 mg/L respectively are achieved at 1 hour falling to 8 and 2 mg/L and 20 and 5 mg/L at 4 and 8 hours respectively for the two doses. Five minutes after an intravenous bolus injection of 500 mg, 1 g and 2 g, mean serum levels are respectively 46, 87 and 170 mg/L falling to 17 and 6 mg/L, 32 and 10 mg/L and 85 and 15 mg/L at 1 and 4 hours respectively with the three doses. The serum half-life in adults with normal renal function is about 1.8 hours (1.2-2.9 hours). This may be prolonged to 20-35 hours in anuric patients. In neonates, the serum half-life of ceftazidime can be 3-4 times greater than that measured in adults. The serum protein binding of ceftazidime is low at about 10%.

Distribution.

The mean maximum concentrations of ceftazidime in bone, heart, bile, sputum, aqueous humour, synovial and pleural and peritoneal fluids were in excess of the in vitro minimum inhibitory levels for susceptible organisms (see 'Susceptibility tests'). Transplacental transfer of the antibiotic readily occurs. Ceftazidime penetrates the intact blood brain barrier poorly and low levels are achieved in the CSF.

Metabolism.

Ceftazidime is not metabolised in the body.

Excretion.

Ceftazidime is excreted unchanged in the active form into the urine by glomerular filtration. In the presence of normal renal function approximately 80 to 90% of the dose is recovered in the urine within 24 hours. Less than 1% is excreted via the bile.
The pharmacokinetics of ceftazidime are similar whether it is administered by a single or by repeat dosage.
Concurrent oral administration of probenecid did not affect the serum levels or urinary recoveries of ceftazidime. The pharmacokinetics of ceftazidime were not affected when administered intramuscularly with 0.5% lignocaine.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

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

6.2 Incompatibilities

Sodium bicarbonate injection is not recommended as a diluent.
Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

Stored in glass vials with rubber stopper.

Vial (powder for reconstitution).

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

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: (6R,7R)-7-[[(Z)-2-(2-aminothiazol-4-yl)-2-[(1-carboxy-1-methylethoxy) imino]acetyl]amino]-8-oxo-3-[(1-pyridinio) methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate pentahydrate.
Molecular formula: C22H22N6O7S2.5H2O.
Molecular weight: 636.6.

CAS number.

72558-82-8.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes