Consumer medicine information

CEFAZOLIN-AFT

Cefazolin

BRAND INFORMATION

Brand name

Cefazolin-AFT

Active ingredient

Cefazolin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

SUMMARY CMI

Cefazolin-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 using Cefazolin-AFT?

Cefazolin-AFT contains the active ingredient cefazolin sodium. Cefazolin-AFT is an antibiotic used to treat infections in different parts of the body caused by bacteria

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

2. What should I know before I use Cefazolin-AFT?

Do not use if you have ever had an allergic reaction to Cefazolin-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 use Cefazolin-AFT? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Cefazolin-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 do I use Cefazolin-AFT?

Cefazolin-AFT must only be given by a doctor or nurse. Your doctor will decide what dose and how long you will receive Cefazolin-AFT.

More instructions can be found in Section 4. How do I use Cefazolin-AFT? in the full CMI.

5. What should I know while using Cefazolin-AFT?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Cefazolin-AFT.
  • If you get a sore white mouth or tongue or if you get a severe diarrhoea, tell your doctor, pharmacist or nurse immediately.
Driving or using machines
  • Cefazolin-AFT may cause dizziness in some people. Make sure you know how you react to Cefazolin-AFT before you drive a car, operate machinery or do anything else that may be dangerous if you are affected.
Looking after your medicine
  • Cefazolin-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 30°C.

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

6. Are there any side effects?

The common side effects of Cefazolin-AFT are oral thrush, vaginal thrush, diarrhoea, nausea and vomiting. The more serious side effects of Cefazolin-AFT are skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty swallowing or breathing, wheezing or shortness of breath, bleeding or bruising more easily than normal, severe abdominal cramps or stomach cramps, watery and severe diarrhoea, which may also be bloody and signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers.

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

Cefazolin-AFT

Active ingredient(s): Cefazolin sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using Cefazolin-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 Cefazolin-AFT

Where to find information in this leaflet:

1. Why am I using Cefazolin-AFT?
2. What should I know before I use Cefazolin-AFT?
3. What if I am taking other medicines?
4. How do I use Cefazolin-AFT?
5. What should I know while using Cefazolin-AFT?
6. Are there any side effects?
7. Product details

1. Why am I using Cefazolin-AFT?

Cefazolin-AFT contains the active ingredient cefazolin sodium.

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

Cefazolin-AFT will not work against infections caused by viruses such as colds or the flu.

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

Ask your doctor if you have any questions about why Cefazolin-AFT has been prescribed for you. Your doctor may have prescribed Cefazolin-AFT for another reason.

Cefazolin-AFT is available only with a doctor's prescription. It is not addictive.

2. What should I know before I use Cefazolin-AFT?

Warnings

Do not use Cefazolin-AFT if:

  • you are allergic to cefazolin sodium, other cephalosporins or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include asthma, wheezing, shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, skin rash, itching or hives. Always check the ingredients to make sure you can use this medicine.
  • you have had a serious allergic reaction to any penicillins. You may be more likely to have an allergic reaction to Cefazolin-AFT if you are allergic to penicillin medicines.
  • the packaging is torn or shows signs of tampering.
  • the expiry date on the pack has passed.

Check with your doctor if you:

  • have had any type of allergic reaction to any cephalosporin or penicillin medicines. You may have an increased chance of being allergic to Cefazolin-AFT if you are allergic to any cephalosporins or penicillins.
  • have any allergies to:
    - any other medicines
    - any other substances, such as foods, preservatives or dyes.
  • if you have or have had any medical conditions, including:
    - kidney disease
    - stomach or bowel problems.
  • If you are not sure whether you should be given Cefazolin-AFT.

If you have not told your doctor about any of the above, tell them before you are given Cefazolin-AFT

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. Cefazolin-AFT may affect your developing baby if you use it during pregnancy. Your doctor will discuss the risks and benefits of using Cefazolin-AFT during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Cefazolin-AFT passes into breast milk and may affect your baby. Your doctor will discuss the risks and benefits of using Cefazolin-AFT when breast-feeding.

Use in Children

Cefazolin-AFT is not recommended for use in premature infants or infants under one month of age. The safety of Cefazolin-AFT in premature infants and infants under one month of age has not been established.

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 Cefazolin-AFT. These include:

  • probenecid, a medicine used to treat gout
  • warfarin, a medicine used to prevent blood clots
  • other antibiotics such as amikacin, gentamicin, tobramycin
  • typhoid vaccine.

These medicines may be affected by Cefazolin-AFT, 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 Cefazolin-AFT. 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 Cefazolin-AFT.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Cefazolin-AFT.

4. How do I use Cefazolin-AFT?

How much to take / use

Cefazolin-AFT must only be given by a doctor or nurse. Cefazolin-AFT can be given:

  • into a vein via a drip
  • 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 Cefazolin-AFT. This depends on your condition and whether you are taking any other medicines. For most infections, Cefazolin-AFT is usually given in divided doses throughout the day.

Sometimes only a single dose of Cefazolin-AFT is required for the treatment of certain infections.

If you use too much Cefazolin-AFT

In the unlikely event of an overdose, your treating physician will know what to do.

If you are given too much Cefazolin-AFT you may experience redness, pain or inflammation where the injection was given, stomach upset, headaches, chills, dizziness, tingling or numbness of the hands and feet or seizures.

If you think that you have used too much Cefazolin-AFT, you may need urgent medical attention.

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.

5. What should I know while using Cefazolin-AFT?

Things you should 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 Cefazolin-AFT 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 Cefazolin-AFT, 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 Cefazolin-AFT allows fungi to grow and the above symptoms to occur. Cefazolin-AFT does not work against fungi.

If you become pregnant while you are using Cefazolin-AFT, tell your doctor immediately.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are using Cefazolin-AFT. Also tell all the doctors, dentists and pharmacists who are treating you that you are using Cefazolin-AFT.

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

Driving or using machines

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

Cefazolin-AFT may cause dizziness in some people. Make sure you know how you react to Cefazolin-AFT before you drive a car, operate machinery or do anything else that may be dangerous if you are affected.

Looking after your medicine

Cefazolin-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 30°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.

Less serious side effects

Less serious side effectsWhat to do
Body as a whole:
  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina and/or discharge
  • diarrhoea
  • nausea or vomiting
Pain and swelling related:
  • pain, redness and swelling where the injection was given.
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 reactions:
  • skin rash, itching or hives
  • swelling of the face, lips or tongue which may cause difficulty swallowing or breathing
  • wheezing or shortness of breath
Body as a whole:
  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • fever
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal
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.

After finishing Cefazolin-AFT

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

  • 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 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 Cefazolin-AFT contains

Active ingredient
(main ingredient)		Cefazolin sodium
Other ingredients
(inactive ingredients)		Nil
Potential allergensNil

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

What Cefazolin-AFT looks like

Cefazolin-AFT is a white to off-white powder. It is reconstituted before being injected.

Cefazolin 2 g (Aust R 359670).

Who distributes Cefazolin-AFT

AFT Pharmaceuticals Pty Ltd
113 Wicks Road
North Ryde
NSW 2113
Australia
Email: [email protected]

This leaflet was prepared in May 2022.

Published by MIMS July 2022

BRAND INFORMATION

Brand name

Cefazolin-AFT

Active ingredient

Cefazolin

Schedule

S4

 

1 Name of Medicine

Cefazolin sodium.

2 Qualitative and Quantitative Composition

Cefazolin sodium is a white to off-white crystalline powder with a solubility in water of greater than or equal to 100 mg/mL. Cefazolin-AFT powder for injection contains cefazolin sodium as a single ingredient.
The sodium content is 50 mg/g of cefazolin sodium.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

White to almost white powder for injection which reconstitutes with Sterile Water for Injection to give a colourless solution.
This powder for injection is supplied in vials containing cefazolin sodium equivalent to 500 mg and 1 g cefazolin.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of the following serious infections due to susceptible organisms.
Respiratory tract infections due to Strep. pneumoniae, Klebsiella sp., H. influenzae, Staph. aureus (penicillin sensitive and penicillin resistant) and group A beta-haemolytic Streptococci. Injectable benzathine penicillin is considered to be the drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefazolin is effective in the eradication of Streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available at present.
Genitourinary tract infections due to E. coli, P. mirabilis, Klebsiella sp. and some strains of Enterobacter and enterococci.
Skin and skin structure infections due to Staph. aureus (penicillin sensitive and penicillin resistant) and group A beta-haemolytic Streptococci and other strains of Streptococci.
Bone and joint infections due to Staph. aureus.
Septicaemia due to Strep. pneumoniae, Staph. aureus (penicillin sensitive and penicillin resistant), P. mirabilis, E. coli and Klebsiella sp.
Endocarditis due to Staph. aureus (penicillin sensitive and penicillin resistant) and group A beta-haemolytic Streptococci.

4.2 Dose and Method of Administration

Dose.

Adults. Usual dosage for mild Gram positive infections is cefazolin 250 to 500 mg every eight hours.
In mild to moderate infections of the respiratory tract caused by Strep. pneumoniae, or mild to moderate infections of the genitourinary tract caused by susceptible organisms, a dosage of 500 mg to 1 g every 12 hours may be used.
In moderate or severe infections, the usual adult dosage is cefazolin 500 mg to 1 g every six to eight hours. Cefazolin has been administered in dosages of 6 g/day in serious infections such as endocarditis.

Renal impairment.

In patients with renal impairment, cefazolin is not readily excreted. After a loading dose of 500 mg, the recommendations in Table 1 for maintenance dosage may be used as a guide.
Children. A total daily dosage of 25 to 50 mg/kg bodyweight, divided into three or four equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg/kg bodyweight for severe infections.
Since safety for use in premature infants and in infants aged under one month has not been established, the use of cefazolin in these patients is not recommended (see Table 2).

Renal impairment.

In children with mild to moderate impairment of renal function (creatinine clearance of 70 to 40 mL/minute), 60% of the normal daily dose given in divided doses every 12 hours should be sufficient. In patients with moderate impairment (creatinine clearance of 40 to 20 mL/minute), 25% of the normal daily dose given in divided doses every 12 hours should be sufficient. In children with marked impairment (creatinine clearance of 20 to 5 mL/minute), 10% of the normal daily dose given every 24 hours should be adequate. All dosage recommendations apply after an initial loading dose.

Method of administration.

Cefazolin may be administered intramuscularly or intravenously after reconstitution. The intrathecal administration of cefazolin is not an approved route of administration for this antibiotic; in fact, there have been reports of severe CNS toxicity including seizures when cefazolin was administered in this manner.
Intramuscular administration. Reconstitute with water for injections or sodium chloride 0.9% injection according to the dilution table (see Table 3). Shake well until dissolved. To facilitate putting the product into solution, the vial should be warmed in the hands while shaking. Do not use the reconstituted injection solution if there is any sign of turbidity. Cefazolin should be injected into a large muscle mass.
Intravenous administration. Cefazolin may be administered by direct intravenous injection or by intermittent or continuous infusion. Total daily dosages are the same as with intramuscular injection.

Direct intravenous injection.

Dilute the reconstituted 500 mg or 1 g Cefazolin-AFT powder for injection in 5 mL of water for injections and then dilute to 10 mL. Inject solution slowly over three to five minutes. It may be administered directly into a vein or via the giving line for a patient receiving a compatible IV solution. Cefazolin sodium has been reported to be compatible with the following IV fluids: 0.9% sodium chloride intravenous infusion; 5% or 10% glucose intravenous infusion; 5% glucose and 0.9% sodium chloride injection; lactated Ringer's injection.

Intermittent intravenous infusion.

Cefazolin sodium can be administered along with primary IV fluid management programmes in a volume control set or in a separate, secondary IV infusion bag. Reconstituted 500 mg or 1 g Cefazolin-AFT powder for injection may be diluted in 50 to 100 mL of water for injections or a compatible parenteral fluid, and infused over a period of 10 to 15 minutes. If a Y-type administration set is used, it is desirable to discontinue the other solution during the infusion of the solution containing cefazolin sodium.

Continuous intravenous infusion.

The total daily dose of cefazolin, diluted and well mixed with at least 50 mL of water for injections, may be added to an intravenous bottle containing one of the previously listed parenteral fluids. The choice of saline or glucose solution and the volume to be employed are dictated by fluid and electrolyte management.

Stability.

Reconstituted Cefazolin-AFT injection and dilutions of Cefazolin-AFT injection in the recommended IV fluids are stable for 24 hours at room temperature and for 96 hours if stored under refrigeration (5°C). However, to minimise the risk of microbial contamination and growth, the preferred practice is to use the reconstituted product as soon as practical after reconstitution and to discard any remaining residue. If storage of the reconstituted solution is necessary, hold at 2 to 8°C for not more than 24 hours.

4.3 Contraindications

Known allergy to the cephalosporin group of antibiotics or previous experience of a major allergy to penicillin (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

Before cefazolin therapy is instituted, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins and penicillin. Cephalosporin C derivatives should be given cautiously in penicillin sensitive patients.
Serious acute hypersensitivity reactions may require adrenaline and other emergency measures.
There is some clinical and laboratory evidence of partial cross allergenicity of the penicillins and the cephalosporins. Patients have been reported to have had severe reactions (including anaphylaxis) to both drugs.
Antibiotics, including cefazolin, should be administered cautiously to any patient who has demonstrated some form of allergy, particularly to drugs. If an allergic reaction to cefazolin occurs, the drug should be discontinued and the patient treated with the usual agents (e.g. adrenaline or other pressor amines, antihistamines or corticosteroids).
Prolonged use of cefazolin may result in the overgrowth of nonsusceptible organisms. Careful clinical observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including cefazolin. 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 Cl. difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
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.
Encephalopathy has been reported with the use of cefazolin in patients with renal failure (see Section 4.8 Adverse Effects (Undesirable Effects)). When cefazolin is administered to patients with low urinary output because of impaired renal function, lower daily dosage is required (see Section 4.2 Dose and Method of Administration).
The intrathecal administration of cefazolin is not an approved route of administration for this antibiotic; in fact, there have been reports of severe CNS toxicity including seizures when cefazolin was administered in this manner.
The intrathecal administration of cefazolin is not an approved route of administration for this antibiotic; in fact there have been reports of tremulousness, headache, agitation, lightheadedness and sensations of seeing flashing lights when cefazolin was administered in this manner for the treatment of infected ventricular shunts.

History of gastrointestinal disease.

Cefazolin, as with all cephalosporins, should be prescribed with caution in individuals with a history of gastrointestinal disease.

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

Use in renal impairment.

When cefazolin is administered to patients with low urinary output because of impaired renal function, lower daily dosage is required (see Section 4.2 Dose and Method of Administration). The dose of cefazolin should be reduced or the dosing interval increased in patients with renal failure.

Use in the elderly.

No data available.

Paediatric use.

Safety for use in premature infants and infants under 1 month of age has not been established.

Effects on laboratory tests.

A false positive reaction for glucose in the urine may occur with Benedict's solution, Fehling's solution or with Clinitest tablets, but not with enzyme based tests, such as Clinistix and Tes-Tape. Positive direct and indirect antiglobulin (Coombs) tests have occurred; these may also occur in neonates whose mothers received cephalosporins before delivery.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Probenecid.

Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels.

Aminoglycoside antibiotics.

Additive nephrotoxicity has been reported following the concomitant administration of cephalosporins and aminoglycoside antibiotics.

Live typhoid vaccine.

Antibiotics which possess bacterial activity against Salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.

Warfarin.

Cefazolin may produce hypoprothrombinemia and may enhance the anticoagulant effect of warfarin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
This category specifies drugs which have been taken only by 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. Cefazolin readily crosses the placental barrier into the cord blood and amniotic fluid.
Studies in animals have not shown evidence of an increased occurrence of foetal damage. Nevertheless, safety of the product for use during pregnancy has not been established.
 Cefazolin is present in very low concentrations in the milk of breastfeeding mothers. Safety for use in lactating women has not been established.

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)

The following reactions have been reported.

Hypersensitivity.

Drug fever, skin rash, vulvar pruritus, eosinophilia, itching and Stevens-Johnson syndrome have occurred.

Haematological.

The most common blood disorder associated with cefazolin has been eosinophilia. Neutropenia, leucopenia, thrombocythaemia, thrombocytopenia and positive direct and indirect Coombs' tests have occurred.

Hepatic and renal.

Isolated transient rise in AST, ALT, serum urea, and alkaline phosphatase levels has been observed without evidence of renal or hepatic impairment.

Gastrointestinal.

Nausea, anorexia, vomiting, diarrhoea and oral candidiasis (oral thrush) have been reported. As with other broad spectrum antibiotics, colitis, including rare instances of pseudomembranous colitis, has been reported in conjunction with therapy with cefazolin (see Section 4.4 Special Warnings and Precautions for Use).

Skin and other subcutaneous tissue disorders.

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.

Other.

Pain at the site of injection after intramuscular administration has occurred, some with induration. Phlebitis at the site of injection has been noted. Other reactions have included genital and anal pruritus, genital candidiasis and vaginitis.
Encephalopathy has been reported with the use of cefazolin in patients with renal failure. The symptoms include tonic-clonic seizures, lethargy, disorientation, memory loss, asterixis and multifocal myoclonus. Toxicity has been attributed to increased cefazolin serum levels and increased permeability of the blood brain barrier caused by uraemia. Therefore when cefazolin sodium is administered to patients with renal failure, lower daily dosage is required (see Section 4.2 Dose and Method of Administration).

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

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

Signs and symptoms.

Toxic signs and symptoms following an overdose of cefazolin may include pain, inflammation and phlebitis at the injection site.
The administration of inappropriately large doses of parenteral cephalosporins may cause dizziness, paraesthesias and headaches. Seizures may occur following overdosage with some cephalosporins, particularly in patients with renal impairment, in whom accumulation is likely to occur.
Laboratory abnormalities may include elevations in creatinine, serum urea, liver enzymes and bilirubin, a positive Coombs' test, thrombocytosis, thrombocytopenia, eosinophilia, leucopenia and prolongation of the prothrombin time.

Treatment.

In managing overdosage, the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics should be considered.
If seizures occur, the drug should be discontinued promptly; anticonvulsant therapy may be administered if clinically indicated. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc.
In cases of severe overdosage, especially in a patient with renal failure, combined haemodialysis and haemoperfusion may be considered if response to more conservative therapy fails. However, no data supporting such therapy are available.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. Cefazolin is active against the following organisms in vitro: Staphylococcus aureus (penicillin sensitive and penicillin resistant); group A beta-haemolytic Streptococci and other strains of Streptococci (many strains of enterococci are resistant); Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella sp., Enterobacter aerogenes, Haemophilus influenzae. Most strains of E. cloacae and indole positive proteus (P. vulgaris, P. morganii, P. rettgeri) are resistant. Methicillin resistant Staphylococci, Serratia, Pseudomonas, Acinetobacter calcoaceticus (formerly mima and herellea sp.) are almost uniformly resistant to cefazolin.

Disc susceptibility tests.

Quantitative methods that require measurements of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure has been recommended for use with discs for testing susceptibility to cephalosporin class antibiotics. Interpretations correlate diameters of the disc test with minimum inhibitory concentration (MIC) values for cefazolin. With this procedure, a report from the laboratory of susceptible indicates that the infecting organism is likely to respond to therapy. A report of resistant indicates that the infecting organism is not likely to respond to therapy. A report of intermediate susceptibility suggests that the organism would 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Table 4 demonstrates the blood levels and duration of cefazolin following intramuscular administration.
Clinical pharmacology studies in patients hospitalised with infections indicate that cefazolin produces mean peak serum levels approximately equivalent to those seen in normal volunteers.
In a study (using normal volunteers) of constant intravenous infusion with dosages of 3.5 mg/kg for one hour (approximately 250 mg) and 1.5 mg/kg for the next two hours (approximately 100 mg) cefazolin produced a steady serum level at the third hour of approximately 28 microgram/mL.
Table 5 shows the average serum concentration after intravenous injection of a single 1 g dose; average half-life was 1.4 hours.

Distribution.

Cefazolin readily crosses an inflamed synovial membrane and the concentration of the antibiotic achieved in the joint space is comparable to levels measured in serum. Cefazolin readily crosses the placental barrier into the cord blood and amniotic fluid. Cefazolin is present in very low concentrations in the milk of breastfeeding mothers.

Metabolism.

Controlled studies on adult normal volunteers receiving 1 g four times daily for ten days, monitoring complete blood count, AST, ALT, bilirubin, alkaline phosphatase, serum urea, creatinine and urinalysis, indicated no clinically significant changes attributed to cefazolin.

Excretion.

Cefazolin is excreted unchanged in the urine. Following intramuscular injection of 500 mg, 56 to 89% of the administered dose was recovered within six hours and 80 to nearly 100% was recovered in 24 hours. Cefazolin achieves peak urine concentrations greater than 1,000 microgram/mL and 4,000 microgram/mL, respectively, following 500 mg and 1 g intramuscular doses. When cefazolin is administered to patients with unobstructed biliary tracts, high concentrations, well over serum levels, occur in the gall bladder tissue and bile. In the presence of obstruction, however, concentration of the antibiotic in bile is considerably lower than the serum level.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Long-term studies in animals to determine the carcinogenic potential of cefazolin have not been performed.

6 Pharmaceutical Particulars

6.1 List of Excipients

Cefazolin-AFT powder for injection contains cefazolin sodium as a single ingredient.

6.2 Incompatibilities

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

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

Powder: Store below 25°C. Protect from light.
Reconstituted solution: Store at 2°C to 8°C. Refrigerate. Do not freeze. (Use within 24 hours after initial reconstitution.) 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. Product is for single use in one patient only. Discard any residue.

6.5 Nature and Contents of Container

This powder for injection is supplied in vials containing cefazolin sodium equivalent to 500 mg and 1 g cefazolin.
Available in packs of 1, 5 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: sodium (6R, 7R)-3-[[5-methyl-1,3,4- thiadiazol-2-yl)sulphanyl]methyl]-8- oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5- thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate.
Molecular formula: C14H13N8NaO4S3.
Molecular weight: 476.5.

CAS number.

27164-46-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes