Consumer medicine information

Cephazolin Viatris

Cefazolin

BRAND INFORMATION

Brand name

Cephazolin Viatris

Active ingredient

Cefazolin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cephazolin Viatris.

SUMMARY CMI

CEPHAZOLIN VIATRIS

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 CEPHAZOLIN VIATRIS?

CEPHAZOLIN VIATRIS contains the active ingredient cefazolin sodium. CEPHAZOLIN VIATRIS is antibiotic used to treat infections in different parts of the body caused by bacteria.

For more information, see Section 1. Why am I using CEPHAZOLIN VIATRIS? in the full CMI.

2. What should I know before I use CEPHAZOLIN VIATRIS?

Do not use if you have ever had an allergic reaction to cefazolin sodium, or to any other cephalosporins, 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 CEPHAZOLIN VIATRIS? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with CEPHAZOLIN VIATRIS 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 CEPHAZOLIN VIATRIS given?

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

More instructions can be found in Section 4. How is CEPHAZOLIN VIATRIS given? in the full CMI.

5. What should I know while using CEPHAZOLIN VIATRIS?

Things you should do
  • Remind any doctor, nurse, dentist or pharmacist you visit that you are using CEPHAZOLIN VIATRIS.
  • If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.
  • If you get a sore white mouth or tongue or if you get severe diarrhoea, tell your doctor, pharmacist or nurse immediately.
Driving or using machines
  • Be careful driving or operating machinery until you know how CEPHAZOLIN VIATRIS affects you.
  • CEPHAZOLIN VIATRIS may cause dizziness in some people.
Looking after your medicine
  • CEPHAZOLIN VIATRIS will be stored in the pharmacy or on the ward.

For more information, see Section 5. What should I know while using CEPHAZOLIN VIATRIS? in the full CMI.

6. Are there any side effects?

Less serious side effects: oral thrush, vaginal thrush, diarrhoea, nausea or vomiting, or pain, redness and swelling where the injection was given. Serious side effects: severe abdominal cramps or stomach cramps, watery and severe diarrhoea, which may also be bloody, skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty swallowing or breathing, wheezing or shortness of breath, fever, signs of frequent infections such as fever, chills, sore throat and mouth ulcers, bleeding or bruising more easily than normal, seizures, changes in mental function, behaviour or state, and/or muscle jerk.

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

CEPHAZOLIN VIATRIS

Active ingredient: cefazolin sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using CEPHAZOLIN VIATRIS. 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 CEPHAZOLIN VIATRIS.

Where to find information in this leaflet:

1. Why am I using CEPHAZOLIN VIATRIS?
2. What should I know before I use CEPHAZOLIN VIATRIS?
3. What if I am taking other medicines?
4. How is CEPHAZOLIN VIATRIS given?
5. What should I know while using CEPHAZOLIN VIATRIS?
6. Are there any side effects?
7. Product details

1. Why am I using CEPHAZOLIN VIATRIS?

CEPHAZOLIN VIATRIS contains the active ingredient cefazolin sodium. CEPHAZOLIN VIATRIS belongs to a group of antibiotics called cephalosporins. These antibiotics work by killing the bacteria that are causing your infection.

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

Your doctor may have prescribed CEPHAZOLIN VIATRIS for another reason.

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

CEPHAZOLIN VIATRIS is not addictive.

2. What should I know before I use CEPHAZOLIN VIATRIS?

Warnings

Do not use CEPHAZOLIN VIATRIS if:

  • you are allergic to cefazolin sodium, or to any 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 CEPHAZOLIN VIATRIS if you are allergic to penicillin medicines.
  • the packaging is torn or shows signs of tampering.
  • the expiry date on the pack has passed.

If you are not sure whether you should be given CEPHAZOLIN VIATRIS talk to your doctor or nurse.

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 CEPHAZOLIN VIATRIS 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.
  • are pregnant or intend to become pregnant.
  • are breast-feeding or intend to breast-feed.
  • have or have had any medical conditions, including:
    - kidney disease
    - stomach or bowel problems

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

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.

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

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

CEPHAZOLIN VIATRIS passes into breast milk and may affect your baby. Your doctor will discuss the risks and benefits of using CEPHAZOLIN VIATRIS when breast-feeding.

Use in children

CEPHAZOLIN VIATRIS is not recommended for use in premature infants or infants under one month of age. The safety of CEPHAZOLIN VIATRIS 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 CEPHAZOLIN VIATRIS and affect how it works. 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 CEPHAZOLIN VIATRIS 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 CEPHAZOLIN VIATRIS.

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 CEPHAZOLIN VIATRIS.

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

4. How is CEPHAZOLIN VIATRIS given?

CEPHAZOLIN VIATRIS must only be given by a doctor or nurse.

CEPHAZOLIN VIATRIS 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 CEPHAZOLIN VIATRIS. This depends on your condition and whether you are taking any other medicines. For most infections, CEPHAZOLIN VIATRIS is usually given in divided doses throughout the day.

Sometimes only a single dose of CEPHAZOLIN VIATRIS is required for the treatment of certain infections.

If you are given too much CEPHAZOLIN VIATRIS

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

If you are given too much CEPHAZOLIN VIATRIS 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.

5. What should I know while using CEPHAZOLIN VIATRIS?

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 CEPHAZOLIN VIATRIS 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 checking with your doctor.
  • If you get a sore white mouth or tongue while using or soon after stopping CEPHAZOLIN VIATRIS, 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 CEPHAZOLIN VIATRIS allows fungi to grow and the above symptoms to occur. CEPHAZOLIN VIATRIS does not work against fungi.
  • If you become pregnant while you are using CEPHAZOLIN VIATRIS, tell your doctor immediately.
  • If you are about to start taking any new medicine, tell your doctor and pharmacist that you are using CEPHAZOLIN VIATRIS.
  • If you have to test your urine for sugar while you are being given CEPHAZOLIN VIATRIS, make sure your doctor knows which type of test you use.
    CEPHAZOLIN VIATRIS may affect the results of some of these tests.
  • Tell all the doctors, dentists and pharmacists who are treating you that you are using CEPHAZOLIN VIATRIS.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how CEPHAZOLIN VIATRIS affects you.

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

Looking after your medicine

CEPHAZOLIN VIATRIS will be stored in the pharmacy or on the ward.

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

After reconstitution Store at 2 to 8°C. Refrigerate. Do not freeze. (Use within 24 hours after initial reconstitution).

6. Are there any side effects?

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well after you are given CEPHAZOLIN VIATRIS.

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
  • oral thrush – white, furry, sore tongue and mouth
  • vaginal thrush – sore and itchy vagina and/or discharge
  • diarrhoea
  • nausea or vomiting
  • pain, redness and swelling where the injection was given
Speak to your doctor or nurse if you have any of these less serious side effects and they worry you.
These are the more common side effects of CEPHAZOLIN VIATRIS.
These side effects are usually mild.

Serious side effects

Serious side effectsWhat to do
Gastrointestinal related:
  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
Allergic reaction related:
  • skin rash, itching or hives
  • swelling of the face, lips or tongue which may cause difficulty swallowing or breathing
  • wheezing or shortness of breath
Infection related:
  • fever
  • signs of frequent infections such as fever, chills, sore throat and mouth ulcers
Blood related:
  • bleeding or bruising more easily than normal
Neurological related:
  • seizures, changes in mental function, behaviour or state, and/or muscle jerk
Call your doctor or nurse straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
You may need urgent medical attention.
These serious side effects are rare

After finishing CEPHAZOLIN VIATRIS

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

  • 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.

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

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.

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 CEPHAZOLIN VIATRIS contains

Active ingredient
(main ingredient)		cefazolin sodium 2 g per vial
Other ingredients
(inactive ingredients)		nil

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

What CEPHAZOLIN VIATRIS looks like

CEPHAZOLIN VIATRIS is a white to off-white crystalline powder. It is reconstituted before being injected. CEPHAZOLIN VIATRIS is available in packs of 10 vials. (AUST R 154640).

Who distributes CEPHAZOLIN VIATRIS

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in September 2024

CEPHAZOLIN VIATRIS_cmi\Sep24/00

Published by MIMS November 2024

BRAND INFORMATION

Brand name

Cephazolin Viatris

Active ingredient

Cefazolin

Schedule

S4

 

1 Name of Medicine

Cefazolin sodium.

2 Qualitative and Quantitative Composition

Each vial of Cephazolin Viatris 2 g powder for injection contains 2 grams of cefazolin (as sodium) as the active ingredient.

3 Pharmaceutical Form

Cephazolin Viatris 2 g powder for injection is supplied as a white to off white crystalline powder. It is presented in a clear glass vial and must be reconstituted prior to use.

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.
Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to cefazolin.

4.2 Dose and 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, sodium chloride 0.9% injection or lidocaine 0.5% injection according to the dilution table (see Table 1). 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 cefazolin 1 g or 2 g in a minimum of 10 mL of water for injections. Inject solution slowly over three to five minutes. It may be administered directly into a vein or through the tubing for a patient receiving one of the following intravenous solutions: sodium chloride 0.9% injection, glucose 5 or 10% injection, glucose 5% in lactated Ringer's injection, glucose 5% and sodium chloride 0.9% injection (also may be used with glucose 5% and sodium chloride 0.4 or 0.2% injection), lactated Ringer's injection, invert syrup 5 or 10% in water for injections, Ringer's injection, Normosol-M in glucose 5%, Ionosol B with glucose 5%, Plasma-Lyte with glucose 5%.

Intermittent intravenous infusion.

Cefazolin can be administered along with primary intravenous fluid management programs in a volume control set or in a separate, secondary intravenous bottle. Reconstituted cefazolin 1 g or 2 g may be diluted in 50 to 100 mL of water for injections or one of the previously listed parenteral fluids and infused over a period of three to five 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.

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. Alternatively, fill up the Cephazolin Viatris 2 g infusion bottle with 50 to 100 mL of the listed intravenous solution. The choice of saline or glucose solution and the volume to be employed are dictated by fluid and electrolyte management.

Dosage.

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 1 g every 12 hours may be used.
In moderate or severe infections, the usual adult dosage is cefazolin 1 g every six to eight hours. Cefazolin has been administered in dosages of 6 g/day in serious infections such as endocarditis.
In patients with renal impairment, cefazolin is not readily excreted. After a loading dose of 500 mg, the recommendations in Table 2 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.
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.
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 3).
Cephazolin Viatris contains no antimicrobial preservative. It is for single use in one patient only. Discard any residue. To reduce microbiological hazard, use as soon as practicable after initial reconstitution. If storage is necessary, store at 2 degrees to 8 degrees Celsius 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).
Lidocaine should not be used as a diluent for intramuscular injection in patients who are hypersensitive to lidocaine.

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 (epinephrine) 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 (epinephrine) or other pressor amines, antihistamines or corticosteroids).
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.
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.
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.
Tremulousness, headache, agitation, lightheadedness, sensation of seeing flashing lights have been reported after patients receiving cefazolin intraventricularly for the treatment of infected ventricular shunts. Cefazolin is not to be used via this route for the treatment of shunt infections.

History of gastrointestinal disease.

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

Use in renal impairment.

As with other beta-lactam antibiotics, seizures may occur if inappropriately high doses are administered to patients with impaired renal function. 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).
Encephalopathy has been reported with the use of cefazolin in patients with renal failure. The symptoms have included 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. The dose of cefazolin should be reduced or the dosing interval increased in patients with renal failure.

Neurotoxicity.

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

Use in 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 or Fehling's solution or with Clinitest tablets, but not with Tes-Tape.
Several cases of positive direct and indirect antiglobulin (Coombs') tests have been reported following cefazolin therapy. These may also occur in neonates whose mothers received cefazolin prior to 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.

Coadministration of aminoglycoside antibiotics with cephalosporins could produce additive nephrotoxic effects. Use of these agents should be avoided in patients with prior renal insufficiency. If coadministration of these two antibiotic classes is necessary, patients should be monitored for evidence of nephrotoxicity.

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.

Patients receiving oral anticoagulant therapy with warfarin should be closely monitored using the prothrombin time ratio or international normalised ratio (INR) during concurrent therapy with cefazolin. Adjustment of the warfarin dosage to maintain the desired anticoagulant effect may be necessary. An alternative would be to use a cephalosporin which does not possess hypoprothrombinaemic properties.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
Safety of this product for use during pregnancy has not been established in human clinical trials. Studies in animals are inadequate or lacking, but available data show no evidence of an increased occurrence of fetal damage. Studies of cord blood show prompt transfer of cefazolin across the placenta. Drug levels in cord blood were approximately one-quarter to one-third maternal drug levels.
 Cefazolin is present in very low concentrations in the milk of breastfeeding mothers. Caution should be exercised when cefazolin is administered to a breastfeeding mother.

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).

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.

Post-marketing experience.

Nervous system disorders.

Seizures, encephalopathy, myoclonus - frequency not known.

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 www.tga.gov.au/reporting-problems.

4.9 Overdose

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.
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.

Semisynthetic cephalosporin for parenteral administration.

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.

Susceptibility tests.

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

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

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.
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. 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. 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.

5.3 Preclinical Safety Data

Genotoxicity.

Mutagenicity studies have not been performed.

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

The product contains no excipients or preservatives.

6.2 Incompatibilities

Cephazolin Viatris must not be reconstituted with other products except those mentioned in Section 4.2 Dose and Method of Administration.

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 for injection.

Store below 25°C. Protect from light and moisture.

Reconstituted solution.

Store at 2°C to 8°C. Refrigerate. Do not freeze. Use within 24 hours after initial reconstitution.

6.5 Nature and Contents of Container

Cephazolin Viatris 2 g powder for injection is presented in a type III clear glass vial sealed with a polytetrafluoroethylene (PTFE) membrane-coated chlorobutyl rubber stopper and aluminium flip-off cap. Each carton contains 1 or 10 vials.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 154640 - Cephazolin Viatris cefazolin 2 g powder for solution for injection vial.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Chemical name: sodium (6R, 7R)-3-[(5-methyl- 1,3,4-thiadiazol-2- yl)thiomethyl]-8-oxo- 7-[2-(1H-tetrazol-1-yl)acetamido]- 5-thia-1-azabicyclo[4.2.0]oct- 2-ene-2-carboxylate.
Structural formula:
Molecular formula: C14H13N8NaO4S3. Molecular weight: 476.5.

CAS number.

27164-46-1.
Cefazolin sodium is a white to off white crystalline powder with a solubility in water of greater than or equal to 100 mg/mL.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes