Consumer medicine information

Cefuroxime SXP

Cefuroxime

BRAND INFORMATION

Brand name

Cefuroxime SXP

Active ingredient

Cefuroxime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cefuroxime SXP.

SUMMARY CMI

CEFUROXIME SXP

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 being given CEFUROXIME SXP?

CEFUROXIME SXP contains the active ingredient cefuroxime sodium. CEFUROXIME SXP is used to prevent infections during surgery.

For more information, see Section 1. Why am I being given CEFUROXIME SXP? in the full CMI.

2. What should I know before I am given CEFUROXIME SXP?

You should not be given CEFUROXIME SXP if you have ever had an allergic reaction to cefuroxime sodium, penicillins, other beta-lactams or any other cephalosporin antibiotics.

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 CEFUROXIME SXP? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with CEFUROXIME SXP 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 am I given CEFUROXIME SXP?

  • CEFUROXIME SXP can be given in two ways: as an injection into a vein or as a drip (intravenous infusion).
  • CEFUROXIME SXP must only be given by a doctor or a nurse.
  • Your doctor will decide on the dose and length of time that you will receive CEFUROXIME SXP.

More instructions can be found in Section 4. How am I given CEFUROXIME SXP? in the full CMI.

5. What should I know while being given CEFUROXIME SXP?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are being given CEFUROXIME SXP.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are being given CEFUROXIME SXP.
  • If you become pregnant while being given this medicine, tell your doctor immediately.
  • If you are about to have any blood tests, tell your doctor that you are being given this medicine.
  • Tell your doctor if you have or have had any kidney conditions.
Driving or using machines
  • CEFUROXIME SXP may cause drowsiness, dizziness or light-headedness in some people. Make sure you know how you react to CEFUROXIME SXP before you drive a car, operate machinery, or do anything else that could be dangerous.
Looking after your medicine
  • CEFUROXIME SXP is stored in a hospital ward or pharmacy in a dry place where the temperature stays below 25°C.

For more information, see Section 5. What should I know while being given CEFUROXIME SXP? in the full CMI.

6. Are there any side effects?

Common side effects include white furry, sore tongue and mouth, sore, itchy vagina with or without discharge, swelling and redness along the vein, swelling, pain or tenderness at the injection site, headache, dizziness, nausea, vomiting, diarrhoea, abdominal pain, tendency to bruise or bleed easily, rash or itchy skin.

Serious side effects include chills or fever, which may be accompanied by shivering, ringing in the ears or hearing loss, low blood pressure, prolonged or severe diarrhoea or stomach cramps, chest pain, seizures, severe skin reactions or allergic reactions. Signs of an allergic reaction such as shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin, limb weakness or numbness, loss of memory, vision, and/or intellect severe headache or migraine, cognitive and behavioral problems, sexual dysfunction, anxiety, depression, or other psychiatric disorders, or altered sensation, tingling, or numbness.

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

CEFUROXIME SXP

Active ingredient(s): cefuroxime sodium

Consumer Medicine Information (CMI)

This leaflet provides important information about using CEFUROXIME SXP. 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 CEFUROXIME SXP.

Where to find information in this leaflet:

1. Why am I being given CEFUROXIME SXP?
2. What should I know before I am given CEFUROXIME SXP?
3. What if I am taking other medicines?
4. How am I given CEFUROXIME SXP?
5. What should I know while be given CEFUROXIME SXP?
6. Are there any side effects?
7. Product details

1. Why am I being given CEFUROXIME SXP?

CEFUROXIME SXP contains the active ingredient cefuroxime sodium. CEFUROXIME SXP is a cephalosporin antibiotic which targets a wide range of common bacteria. This medicine works by killing the bacteria causing an infection or preventing bacterial growth.

CEFUROXIME SXP is used to prevent infections during surgery.

2. What should I know before I am given CEFUROXIME SXP?

Warnings

You should not be given CEFUROXIME SXP if:

  • you are allergic to cefuroxime sodium, penicillins, other beta-lactams or any other cephalosporin antibiotics.
    Some of the symptoms of an allergic reaction may include skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, wheezing or shortness of breath.

Check with your doctor if you:

  • have any have allergies to any other medicines, food, preservative or dyes.
  • have or have had any kidney problems. Extra caution in the elderly or with patients with kidney conditions may be required.
  • take any medicines for any other condition.
  • are having any blood tests, as this medicine may interfere with the results.

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.

There is no experimental evidence of birth defects attributable to CEFUROXIME SXP however; all medicines should be administered with caution.

Talk to your doctor if you are breastfeeding or intend to breastfeed. CEFUROXIME SXP is passed through breast milk in small amounts.

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 CEFUROXIME SXP and affect how it works. These include:

  • combined oral contraceptives
  • water tablets (diuretics), such as furosemide
  • aminoglycoside-type antibiotics

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking CEFUROXIME SXP.

4. How am I given CEFUROXIME SXP?

How much am I given?

  • Your doctor will decide on the dose and length of time that you will receive CEFUROXIME SXP.
  • CEFUROXIME SXP must only be given by a doctor or a nurse.

How am I given CEFUROXIME SXP?

  • CEFUROXIME SXP can be given in two ways:
    - as an injection into a vein; or
    - as a drip (intravenous infusion)
  • CEFUROXIME SXP is generally given alone although sometimes your doctor may prescribe it in combination with another type of antibiotic called an aminoglycoside or together with an antibacterial agent called metronidazole.

If too much CEFUROXIME SXP is given

As CEFUROXIME SXP is administered by a doctor or nurse, it is unlikely that you will be given too much.

If you think that you have been given too much CEFUROXIME SXP, you may need urgent medical attention.

Symptoms of an overdose may include convulsions.

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 being given CEFUROXIME SXP?

Things you should do

If you are about to started on any new medicine, tell your doctor or pharmacist that you have been given CEFUROXIME SXP.

Tell all the doctors, dentists and pharmacists who are treating you that you have been given this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are using this medicine. It may affect other medicines used during surgery.

If you are about to have any blood tests, tell your doctor that you are using this medicine. It may interfere with the results of some tests.

Tell your doctor if you have or have had any kidney problems.

Call your doctor straight away if you:

  • If you become pregnant while using this medicine, tell your doctor immediately.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how CEFUROXIME SXP affects you.

CEFUROXIME SXP may cause drowsiness, dizziness or light-headedness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Looking after your medicine

CEFUROXIME SXP is stored in a hospital ward or pharmacy in a dry place 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.

Less serious side effects

Less serious side effectsWhat to do
  • white furry, sore tongue and mouth (oral thrush)
  • sore, itchy vagina and/or discharge (vaginal thrush)
  • swelling and redness along the vein
  • drowsiness, dizziness or light-headedness
  • swelling, pain or tenderness at the injection site
  • nausea, vomiting, diarrhoea, abdominal pain
  • tendency to bruise or bleed easily
  • rash or itchy skin
  • headache, dizziness
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
  • chills or fever, which may be accompanied by shivering
  • ringing in the ears or hearing loss
  • low blood pressure
  • prolonged or severe diarrhoea or stomach cramps
  • signs of an allergic reaction such as shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin
  • severe skin reactions
  • chest pain
  • seizure
  • limb weakness or numbness
  • loss of memory, vision, and/or intellect
  • severe headache or migraine
  • behavioural changes
  • sexual dysfunction
  • anxiety, depression, or other psychiatric disorders
  • altered sensation, tingling, or numbness
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 and it is not addictive.

What CEFUROXIME SXP contains

Active ingredient
(main ingredient)		Cefuroxime sodium
Other ingredients
(inactive ingredients)		None

Do not take this medicine if you are allergic to cefuroxime sodium.

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

What CEFUROXIME SXP looks like

CEFUROXIME SXP is supplied in vials which contain 750 mg or 1.5 g of cefuroxime sodium powder for injection or infusion.

CEFUROXIME SXP 750 mg injection is a white or almost white to yellowish powder (AUST R 310373)

CEFUROXIME SXP 1500 mg injection vial is a white or almost white to yellowish powder (AUST R 310375)

Who distributes CEFUROXIME SXP

Southern XP Pty Ltd
Unit 5/118 Church Street
Hawthorn, 3122, Victoria
Australia

Sponsor:
Southern XP IP Pty Ltd
Unit 5/118 Church Street
Hawthorn, 3122, Victoria
Australia

This leaflet was prepared in November 2023.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Cefuroxime SXP

Active ingredient

Cefuroxime

Schedule

S4

 

Notes

Distributed by Southern XP Pty Ltd

1 Name of Medicine

Cefuroxime sodium.

2 Qualitative and Quantitative Composition

Each vial contains 750 mg or 1.5 g cefuroxime as cefuroxime sodium. See Table 1.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection.
White or almost white to yellowish powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Cefuroxime SXP is indicated in adults and children of 40 kg or greater in weight for the prevention of infections associated with certain surgical procedures of the gastrointestinal (including oesophageal), orthopaedic, cardiovascular and gynaecological systems (including caesarean section) (see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).
In the prevention of infections in which it is very likely that anaerobic organisms will be encountered, cefuroxime should be administered with additional appropriate antibacterial agents such as metronidazole.
Consideration should be given to official guidance on the appropriate use of antibacterial agents, as antibiotic prophylaxis is not required in all gastrointestinal, orthopaedic, cardiovascular and gynaecological procedures or surgeries.
For patients with specific cardiac conditions which predispose them to endocarditis who are undergoing abdominal surgery for which surgical antibiotic prophylaxis is indicated, the prophylaxis regimen should additionally include an antibiotic active against enterococci.
For patients undergoing orthopaedic or cardiovascular surgery known to be, or at risk of being, colonised or infected with methicillin-resistant S. aureus (MRSA), add an antibiotic with activity against MRSA, such as vancomycin.
Cefuroxime SXP is not indicated in children < 40 kg in weight.

4.2 Dose and Method of Administration

Dose.

See Table 2.
Renal impairment. Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. Clcr < 20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion.

Dialysis.

Serum levels of cefuroxime are typically reduced when patients are concurrently undergoing haemodialysis or peritoneal dialysis.
Pharmacokinetic data in patients with renal impairment is included in Section 5.2 Pharmacokinetic Properties. This should be taken into consideration with regard to the dosing interval for affected patients.
In patients with creatinine clearance < 20 mL/min, 1.5 g IV every 24 hours is the maximum dose that should be given due to delayed excretion of the drug in renal impairment.
Hepatic impairment. Cefuroxime is primarily eliminated by the kidney. In patients with hepatic dysfunction this is not expected to affect the pharmacokinetics of cefuroxime.

Method of administration.

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.
Cefuroxime should be administered by intravenous injection over a period of 3 to 5 minutes directly into a vein or via a drip tube or infusion over 30 to 60 minutes.

Instructions for constitution.

See Table 3.

Compatibility.

Cefuroxime sodium is compatible with the following infusion fluids. It will retain potency for up to 6 hours at 25°C and 24 hours at 2°C-8°C (in refrigerator) in: 0.18% w/v sodium chloride plus 4% dextrose injection BP; 5% dextrose and 0.9% sodium chloride injection; 5% dextrose and 0.45% sodium chloride injection; 5% dextrose and 0.225% sodium chloride injection; M/6 sodium lactate injection; potassium chloride (10 and 40 mEq/L) in 0.9% sodium chloride injection; dextrose (glucose); sodium chloride; Ringer solution; Ringer's lactate.
Freshly prepared solution for IV administration is yellowish.
Solution can turn darker when standing but change of intensity of colour of diluted solution does not affect safety of administration and effectiveness of medicinal product.

4.3 Contraindications

Hypersensitivity to cefuroxime or to any of the excipients listed in Section 6.1 List of Excipients.
Patients with known hypersensitivity to cephalosporin antibiotics.
History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).

4.4 Special Warnings and Precautions for Use

Identified precautions.

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.
Hypersensitivity reactions. As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. There have been reports of hypersensitivity reaction which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction, see Section 4.8 Adverse Effects (Undesirable Effects)). In case of severe hypersensitivity reactions, treatment with cefuroxime must be discontinued immediately and adequate emergency measures must be initiated.
Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to cefuroxime, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if cefuroxime is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
Cephalosporin antibiotics may, in general, be given safely to patients who are hypersensitive to penicillins, although cross-reactions have been reported. Special care is indicated in patients who have experienced an anaphylactic reaction to penicillin.

Severe cutaneous adverse reactions (SCARS).

Severe cutaneous adverse reactions including: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with cefuroxime treatment (see Section 4.8 Adverse Effects (Undesirable Effects)).
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cefuroxime should be withdrawn immediately and an alternative treatment considered. If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of cefuroxime, treatment with cefuroxime must not be restarted in this patient at any time.
Concurrent treatment with potent diuretics or aminoglycosides. Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides. Renal impairment has been reported during use of these combinations. Renal function should be monitored in the elderly and those with known pre-existing renal impairment (see Section 4.2 Dose and Method of Administration).
Overgrowth of non-susceptible microorganisms. Use of cefuroxime may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible microorganisms (e.g. enterococci and Clostridium difficile), which may require interruption of treatment (see Section 4.8 Adverse Effects (Undesirable Effects)).
Antibacterial agent-associated pseudomembranous colitis has been reported with use of cefuroxime and may range in severity from mild to life threatening. This diagnosis should be considered in patients with diarrhoea during or subsequent to the administration of cefuroxime (see Section 4.8 Adverse Effects (Undesirable Effects)). Discontinuation of therapy with cefuroxime and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
Intra-abdominal infections. Due to its spectrum of activity, cefuroxime is not suitable for the treatment of infections caused by Gram-negative non-fermenting bacteria (see Section 5.1 Pharmacodynamic Properties).
Interference with diagnostic tests. The development of a positive Coomb's test associated with the use of cefuroxime may interfere with cross matching of blood (see Section 4.8 Adverse Effects (Undesirable Effects)).
Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. However, this should not lead to false-positive results, as may be experienced with some other cephalosporins.
As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime sodium.
Intracameral use and eye disorders. Cefuroxime SXP is not formulated for intracameral use. Individual cases and clusters of serious ocular adverse reactions have been reported following unapproved intracameral use of cefuroxime sodium compounded from vials approved for intravenous/intramuscular administration. These reactions included macular oedema, retinal oedema, retinal detachment, retinal toxicity, visual impairment, visual acuity reduced, vision blurred, corneal opacity and corneal oedema.
Important information about excipients. Cefuroxime SXP powder for solution for injection or infusion contains sodium. This should be considered for patients who are on a controlled sodium diet.
Use in obesity. Antibiotic pharmacokinetics are altered in obese patients, therefore dosage adjustment may be necessary.

Use in renal impairment.

Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. Clcr < 20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion (see Section 5.2 Pharmacokinetic Properties).

Dialysis.

Serum levels of cefuroxime are typically reduced when patients are concurrently undergoing haemodialysis or peritoneal dialysis.
Pharmacokinetic data in patients with renal impairment is included in Section 5.2 Pharmacokinetic Properties. This should be taken into consideration with regard to the dosing interval for affected patients (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

Following IM or IV administration, the absorption, distribution and excretion of cefuroxime in elderly patients are similar to younger patients with equivalent renal function. However, as elderly patients are more likely to have decreased renal function, care should be taken in cefuroxime dose selection, and it may be useful to monitor renal function (see Section 4.2 Dose and Method of Administration).

Paediatric use.

Cefuroxime SXP is not indicated in children < 40 kg, infants and neonates.
Precautions for adults are also applicable to paediatric use.
In children, the serum half-life of 60 to 90 minutes is similar to that observed in adults.

Effects on laboratory tests.

As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime axetil. This antibiotic does not interfere in the alkaline picrate assay for creatinine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Cefuroxime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
Cefuroxime is excreted by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level.

Potential nephrotoxic drugs and loop diuretics.

High-dosage treatments with cephalosporins should be carried out with caution in patients who are taking strong-acting diuretics (such as furosemide) or potential nephrotoxic preparations (such as aminoglycoside antibiotics), since impairment of renal function through such combinations cannot be ruled out.

Other interactions.

Determination of blood/plasma glucose levels (see Section 4.4 Special Warnings and Precautions for Use).
Concomitant use with oral anticoagulants may give rise to increased international normalised ratio (INR).
(Also see Section 4.2 Dose and Method of Administration; Section 6.2 Incompatibilities.)

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data on the effects of cefuroxime sodium on fertility in humans. Reproductive studies in animals have shown no effects on fertility.
(Category B1)
There are limited amounts of data from the use of cefuroxime in pregnant women. Studies in animals have shown no reproductive toxicity (see Section 5.3 Preclinical Safety Data). Cefuroxime SXP should be prescribed to pregnant women only if the benefit outweighs the risk.
Cefuroxime has been shown to cross the placenta and attain therapeutic levels in amniotic fluid and cord blood after intramuscular or intravenous dose to the mother.
Frequent urination, as is the case in many pregnancies, can lead to an increase in the elimination rate of cefuroxime. Combined with a larger volume of distribution, and the likelihood of a consequential decrease in serum concentration, dose adjustment may be required to ensure sufficient antimicrobial coverage is maintained.
 Cefuroxime is excreted in human milk in small quantities. Adverse reactions at therapeutic doses are not expected, although a risk of diarrhoea and fungal infection of the mucous membranes cannot be excluded. The decision whether to use cefuroxime therapy in a breastfeeding woman should take into account the benefits of breastfeeding for the child as well as the benefit of therapy for the woman.

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. However, based on known adverse reactions, cefuroxime is unlikely to have an effect on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

The most common adverse reactions are phlebitis, transient pain at injection site, rash, eosinophilia, neutropenia, transient rise in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver.
The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data for calculating incidence are not available. In addition, the incidence of adverse reactions associated with cefuroxime sodium may vary according to the indication.
Data from clinical trials were used to determine the frequency of very common to rare adverse reactions. The frequencies assigned to all other adverse reactions (i.e. those occurring at < 1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.
Treatment related adverse reactions, all grades, are listed (Table 4) by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilised for the classification of frequency: very common ≥ 1/10; common ≥ 1/100 to < 1/10, uncommon ≥ 1/1,000 to < 1/100; rare ≥ 1/10,000 to < 1/1,000; very rare < 1/10,000 and not known (cannot be estimated from the available data).

Description of selected adverse reactions.

Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coomb's test (which can interfere with cross matching of blood) and very rarely haemolytic anaemia.
Transient rises in serum liver enzymes or bilirubin have been observed which are usually reversible.
Pain at the intramuscular injection site is more likely at higher doses. However it is unlikely to be a cause for discontinuation of treatment.

Paediatric population.

The safety profile for cefuroxime sodium in children is consistent with the profile in adults.

Cephalosporin-class adverse reactions.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see Section 4.2 Dose and Method of Administration). If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Post-marketing experience.

Nervous system disorders.

Seizures, encephalopathy, myoclonus - frequency not known.

Skin and subcutaneous tissue disorders.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (baboon syndrome).

Reporting suspected adverse effects.

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

4.9 Overdose

Overdose can lead to neurological sequelae including encephalopathy, convulsions and coma. Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).
Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antibacterials for systemic use, Second-generation cephalosporins, ATC code: J01DC02.

Mechanism of action.

Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.

Clinical trials.

A large number of randomised, comparative clinical trials involving the use of cefuroxime sodium have been undertaken worldwide and reported in the literature.
Cefuroxime has shown to be as safe and efficacious as other commonly used antimicrobial agents in each of the approved indications.
Cefuroxime has also demonstrated superiority to placebo when used prophylactically prior to surgery.

Mechanism of resistance.

Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms:
hydrolysis by beta-lactamases including (but not limited to) extended-spectrum beta-lactamases (ESBLs), and Amp-C enzymes, that may be induced or stably derepressed in certain aerobic Gram-negative bacterial species;
reduced affinity of penicillin-binding proteins for cefuroxime;
outer membrane impermeability, which restricts access of cefuroxime to penicillin binding proteins in Gram-negative bacteria;
bacterial efflux pumps.
Organisms that have acquired resistance to other injectable cephalosporins are expected to be resistant to cefuroxime. Depending on the mechanism of resistance, organisms with acquired resistance to penicillins may demonstrate reduced susceptibility or resistance to cefuroxime.

Cefuroxime sodium breakpoints.

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows (breakpoints apply to daily IV cefuroxime doses of 0.75 g x 3, unless otherwise specified) (see Table 5).

Microbiological susceptibility.

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is known and the utility of the agent in at least some types of infections is questionable.
Cefuroxime is usually active against the following microorganisms in vitro (see Table 6).

5.2 Pharmacokinetic Properties

Absorption.

Following intravenous (IV) doses of 750 and 1,000 mg, serum concentrations were approximately 44 and 75 microgram/mL, respectively, at 10 minutes.
AUC and Cmax appear to increase linearly with increase in dose over the single dose range of 250 to 1000 mg following IV administration.
Based on a two-compartment model, the AUC for the lower doses nearly doubled as the dose doubled, but this relationship did not hold true for 1 g dose.
There was no evidence of accumulation of cefuroxime in the serum from normal volunteers following repeat intravenous administration of 1,500 mg doses every 8 hours.

Distribution.

Protein binding has been stated as approximately 33%. The average volume of distribution ranges from 9.3 to 15.8 L/1.73 m2 following IV administration over the dosage range of 250 to 1000 mg.
Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in the tonsilla, sinus tissues, bronchial mucosa, bone, pleural fluid, joint fluid, synovial fluid, interstitial space fluid, subcutaneous adipose tissue, bile and sputum. Cefuroxime passes the blood-brain barrier in small amounts when the meninges are inflamed but the drug is not recommended for the treatment of meningitis.

Metabolism.

HPLC analysis of patient urine samples confirmed that at least 95% of the administered dose is excreted as unchanged cefuroxime; cefuroxime is not metabolised.

Excretion.

Cefuroxime is excreted by glomerular filtration and tubular secretion. The serum half-life after either intramuscular or intravenous injection is approximately 65 to 70 minutes. There is an almost complete recovery (greater than 90%) of unchanged cefuroxime in urine within 24 hours of administration. The majority of the cefuroxime is excreted within the first 6 hours. The average renal clearance ranges from 114 to 170 mL/min/1.73 m2 following IV administration over the dosage range of 250 to 1000 mg.

Special patient population.

The pharmacokinetics of cefuroxime sodium are altered in the following patient populations.
Elderly. Following IV administration, the absorption, distribution and excretion of cefuroxime in elderly patients are similar to younger patients with equivalent renal function. However, as elderly patients are more likely to have decreased renal function, care should be taken in cefuroxime dose selection, and it may be useful to monitor renal function (see Section 4.2 Dose and Method of Administration).
Paediatric population. Cefuroxime SXP is not indicated in children < 40 kg, infants and neonates.
In children, the serum half-life of 60 to 90 minutes is similar to that observed in adults.
Renal impairment. Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. Clcr < 20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion (see Section 4.2 Dose and Method of Administration).

Dialysis.

Serum levels of cefuroxime are typically reduced when patients are concurrently undergoing haemodialysis or peritoneal dialysis.
The half-life for patients with GFRs of 20-50 mL/min were calculated to be 1.8 to 3.4 hours and for GFRs < 20 mL/min, 6.1 to 22.5 hours. With dialysis, these values decreased to 3.1 hours in haemodialysis and 5.4 hours in peritoneal dialysis. This should be taken into consideration with regard to the dosing interval for affected patients (see Section 4.2 Dose and Method of Administration).
Hepatic impairment. Since cefuroxime is primarily eliminated by the kidney, hepatic dysfunction is not expected to have an effect on the pharmacokinetics of cefuroxime.
Obesity. Obese patients present a higher volume of distribution, which may result in a consequential decrease in serum and/or tissue concentrations. To ensure clinical effectiveness, tissue concentrations should remain above the minimum inhibitory concentration (MIC), therefore dose adjustment may be required to ensure sufficient antimicrobial coverage is maintained. (See Section 4.4 Special Warnings and Precautions for Use.)

PK/PD relationship.

For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval (%T) that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefuroxime for individual target species (i.e. %T > MIC).

5.3 Preclinical Safety Data

Non-clinical data reveal no specific hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, and toxicity to reproduction and development.
Gamma glutamyl transpeptidase activity in rat urine is inhibited by various cephalosporins, however the level of inhibition is less with cefuroxime. This may have significance in the interference in clinical laboratory tests in humans.

Genotoxicity.

Non-clinical data reveal no specific hazard for humans based on conventional studies of genotoxicity.

Carcinogenicity.

No carcinogenicity studies have been performed; however, there is no evidence to suggest carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

None.

6.2 Incompatibilities

Do not mix in the syringe with aminoglycoside antibiotics.

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.

Reconstituted solution.

Immediate use of the reconstituted solution is recommended.

Chemical and physical stability.

Chemical and physical stability has been demonstrated:
for 5 hours at 25°C and 48 hours at 2-8°C (in refrigerator) for the reconstituted solutions for intramuscular or intravenous injection;
or 6 hours at 25°C and 24 hours at 2-8°C (in refrigerator) for the reconstituted solutions for intravenous infusion.
From a microbiological point of view, the product should be used immediately. If storage is necessary, hold at 2°-8°C for not more than 24 hours.

6.4 Special Precautions for Storage

Store below 25°C, in the original package.
For storage conditions for the reconstituted and diluted medicinal product, see Section 6.3 Shelf Life.

6.5 Nature and Contents of Container

Cefuroxime SXP 750 mg powder for solution for injection or infusion:
Type I clear glass vials with a nominal capacity of 15 mL, sealed with a 20 mm bromobutyl rubber stopper and an aluminium cap.
Packs of 5 and 10 vials.
Cefuroxime SXP 1.5 g powder for solution for injection or infusion:
Type I clear glass vials with a nominal capacity of 15 mL, sealed with a 20 mm bromobutyl rubber stopper and an aluminium cap.
Pack of 1 vial.

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-(carbamoyloxymethyl)-7-[[(2Z)-2-(furan-2-yl)-2-methoxyiminoacetyl] amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate.
Chemical formula: C16H15N4NaO8S.
Molecular weight: 446.366.

CAS number.

56238-63-2.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription only medicine).

Summary Table of Changes