Package leaflet:

Information for the user

Cefuroxime Sodium for Injection 750mg & 1.5g

The name of your medicine is Cefuroxime Sodium for Injection 750mg & 1.5g, which will be referred to as Cefuroxime Injection throughout this document.

Read all of this leaflet carefully before you start taking this medicine.

■    Keep this leaflet. You may need to read it again.

■    If you have any further questions, ask your doctor or pharmacist.

■    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

■    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Cefuroxime Injection is and what it is used for

2.    Before you are given Cefuroxime Injection

3.    How you are given Cefuroxime Injection

4.    Possible side effects

5.    How to store Cefuroxime Injection

6.    Further information

1    What Cefuroxime Injection is and what it is used for

Cefuroxime Injection contains the active ingredient cefuroxime sodium, which is an antibiotic.

Cefuroxime Injection is used to treat infections caused by bacteria that can be killed by cefuroxime, in the following infections:

■    Lungs and airways e.g. bronchitis, pneumonia

■    Ear, nose and throat e.g. tonsillitis, pharyingitis, sinusitis

■    Urinary tract e.g. kidney and bladder

■    Soft tissue e.g. skin, cellulitis

■    Bone and joint

■    Pelvic inflamatory disease (e.g. infection of the female reproductive system)

■    Gonorrhoea (a sexually transmitted disease), particularly if penicillin is unsuitable

■    Other infections including blood poisoning (septicaemia) and meningitis.

Cefuroxime Injection can also be used to prevent infection during surgery where there is an increased risk of infection.

2    Before you are f»iven Cefuroxime Injection

Do not take Cefuroxime Injection if

■    you are allergic (hypersensitive) to cefuroxime or any cephlosporin (other similar antibiotics). An allergic reaction may include rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue.

Take special care with Cefuroxime Injection if you

■    have had a severe allergic reaction to penicillin in the past

Taking other medicines

Please tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines, including medicines obtained without a prescription. This is especially important of the following, as they may interact with your Cefuroxime Injection:

■    probenecid (a treatment for gout)

■    strong diuretics (water tablets used to treat high blood pressure or fluid retention)

■    aminoglycosides (another type of antibiotic e.g. tobramycin, gentamicin).

It may still be all right for you to be given Cefuroxime Injection and your doctor will be able to decide what is suitable for you.

Interference with laboratory tests

Tell your doctor if you are having blood or urine tests. Cefuroxime Injection may interfere with these tests.

Pregnancy and breast-feeding

You should tell your doctor if you are pregnant or breast-feeding. Ask your doctor or pharmacist before taking any medicine.

Driving and using machines

Cefuroxime Injection should not affect your ability to drive or use machines.

3 How you are given Cefuroxime Injection

Cefuroxime Injection will be given to you by a doctor or nurse.

Dosage

The dose depends on the infection to be treated and the condition of the patient. For adults:

The usual dose is 750mg three times daily by injection into a muscle (intramuscular) or into a vein (intravenous injection).

For more severe infections this dose should be increased to 1.5g three times daily intravenously.

The dose may be increased by giving the injection four times daily giving a total daily doses of 3g to 6g.

For infants and children:

The usual total daily dose is 30 to 100mg/kg (body weight) given in three or four doses. A total daily dose of 60mg/kg is effective for most infections. For newborn babies:

The usual total daily dose is 30 to 100mg/kg per day given in two or three doses.

Gonorrhoea 1.5g as a single dose.

Meningitis For adults:

3g intravenously every eight hours.

Adults: Many infections will respond to 750 mg three times daily by intramuscular or intravenous injection. For more severe infections this dose should be increased to 1,5g three times daily intravenously. The frequency of dosage may be increased to six-hourly injections intramuscular or intravenous, giving total daily doses of 3 g to 6 g.

Infants and children: Doses of 30 to 100 mg/kg/day given in three or four divided doses.

A dose of 60 mg/kg/day will be appropriate for most infections.

Neonates: Doses of 30 to 100 mg/kg/day given in two or three divided doses. In the first weeks of life the serum half-life of cefuroxime can be three to five times that in adults.

Gonorrhoea

1.5 g should be given as a single dose or as two 750 mg injections into different sites, e.g. each buttock. Meningitis

Cefuroxime therapy is suitable for sole therapy of bacterial meningitis due to sensitive strains.

Infants and children: 200 to 240 mg/kg/day intravenously in three or four divided doses. This dosage may be reduced to 100 mg/kg/day after three days or when clinical improvement occurs.

Neonates: The initial dosage should be 100 mg/kg/day intravenously.

This dosage may be reduced to 50 mg/kg/day after three days or when clinical improvement occurs. Adults: 3 g intravenously every eight hours. No data is currently available to recommend a dose for intrathecal administration.

Prophylaxis

The usual dose is 1.5 g intravenously with induction of anaesthesia. For orthopaedic, pelvic and abdominal operations this may be followed with two 750 mg doses 8 and 16 hours later.

For vascular, cardiac, oesophageal and pulmonary operations this may be supplemented with 750 mg intramuscularly three times a day for a further 24 to 48 hours.

In total joint replacement, 1.5 g cefuroxime powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.

Dosage in Impaired Renal Function

As cefuroxime is excreted by the kidneys, the dosage should be reduced to allow for slower excretion in patients with impaired renal function, once creatinine clearance falls below 20 ml/min, as follows.

4.3    Contra-indications

Contra-indicated in patients hypersensitive to the cephalosporin group of antibiotics.

4.4    Special Warnings and Special Precautions for Use

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 patien-ts who have experienced an anaphylactic reaction to penicillin.

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving potent diuretics or aminoglycosides as these combinations are suspected of adversely affecting renal function. Clinical experience has shown that this is not likely to be a problem at the recommended dose levels.

4.5    Interaction with other Medicinal Products and other Forms of Interaction

Concurrent administration of probenecid prolongs the excretion of cefuroxime and produces an elevated peak serum level.

Concurrent administration of potent diuretics, aminoglycosides may adversely affect renal function, (see section 4.4)

Interference with Laboratory Tests

Slight interference may occur with the copper reduction methods (Fehling's, Benedict's) but this should not lead to false-positive results. Cefuroxime does not interfere with the enzyme based tests for glycosuria, or with the alkaline picrate method for creatinine. It is recommended that either the hexokinase or glucose oxidasemethods are used for determination of blood/plasma glucose levels.

4.6    Pregnancy and Lactation

Studies in animals revealed no evidence of embryopathic or teratogenic effects due to cefuroxime, but, as with all drugs, it should be used with caution during pregnancy. Since cefuroxime is excreted in human milk, caution should be exercised when administering this antibiotic to a nursing mother.

4.7    Effects on the Ability to Drive and Use Machines Cefuroxime is not known to affect the ability to drive or use machines.

4.8    Undesirable Effects

Hypersensitivity reactions: including skin rashes (maculopapular and urticarial) interstitial nephritis, drug fever and very rarely anaphylaxis. As with any antibiotic, prolonged use may lead to overgrowth of non-susceptible organisms, e.g. Candida.

As with other cephalosporins, there have been rare reports of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Gastrointestinal disturbance: including, very rarely, pseudomembranous colitis, which has been reported with most broad spectrum antibiotics.

Haematological: a decrease in haemoglobin concentration, eosinophilia, leucopenia and neutropenia have been observed. Positive Coombs' tests have been reported. As with other cephalosporins, thrombocytopenia has been reported rarely.

Hepatic: Transient rises in liver enzymes or serum bilirubin have been observed particularly in patients with pre-existing liver disease, but there is no evidence of hepatic involvement.

Renal: There may be some variation in the results of biochemical tests of renal function, but these results do not appear to be of clinical significance.

Other:Transient pain may be experienced at the site of intramuscular injection. Occasionally thrombophlebitis may occur at the site of intravenous injection. A burning sensation may be observed after intravenous injection. Mild to moderate hearing loss has been reported in some children treated for meningitis.

Dizziness and headache has been reported in patients receiving cefuroxime.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/vellowcard

4.9 Overdose

Overdosage of cephalosporins can lead to cerebral irritation and seizures. With seizures the drug should be discontinued and appropriate anticonvulsive and supportive therapy administered. Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Cefuroxime is a cephalosporin antibiotic, ATC code J01DA06 Cephalosporins and related substances. All cephalosporins ((3-lactam antibiotics) inhibit cell wall production and are selective inhibitors of peptidoglycan synthesis. The initial step in drug action consists of binding of the drug to cell receptors, called Penicillin-Binding Proteins. After a (3-lactam antibiotic has bound to these receptors,

the transpeptidation reaction is inhibited and peptidogiycan synthesis is blocked. Bacterial lysis is

the end result

Susceptibility

The following MIC breakpoints separating susceptible from intermediately susceptible organism and intermediately susceptible from resistant organism are used.

Table 1: Susceptibility breakpoints

NCCLS: National Committee for Clinical Laboratory Standards DIN: Deutches Institut fur Normung BSAC: British Society for Antimicrobial Chemotherapy S: Susceptible, I: Intermediately susceptible, R: Resistant

The prevalence of resistance may vary geographically and with time for selected species and local information is desirable, particularly when treating several infections. This information gives only an approximate guidance on probabilities whether organisms will be susceptible to cefuroxime or not.

Table 2: Range of bacterial resistance to cefuroxime in Europe.

CATEGORY    RANGE OF RESISTANCE IN EUROPE

SUSCEPTIBLE GRAM + VE AEROBES

Stoph. oureus (methicillin-susceptible strains)

Stoph. epidermidis (methicillin-susceptible strains)

Streptococcus pneumoniae Streptococcus pyogenes Streptococcus viridans GRAM-VE AEROBES Escherichia coli Haemophilus influenzae

Klebsiella spp.    6-21%

Moraxella catarrhalis Neisseria spp.

Proteus mirabilis    0-17%

Providencia spp. including Providencia rettgeri    0-75%

Providencia rettgeri only ANAEROBES Clostridium perfringens INTERMEDIATE GRAM-VE AEROBES Bordetella pertussis

Citrobacter    21-52%

Enterobacter spp.    36-83%

ANAEROBES Bacteroides fragilis INSUSCEPTIBLE GRAM + VE AEROBES Enterococcus faecalis

Staph, aureus (methicillin-resistant strains)

Staph, epidermidis (methicillin-resistant strains)

GRAM-VE AEROBES Acinetobacter spp.

Campylobacter spp.

Legionella spp.

Pseudomonas spp.

Serratia spp.

Morganella morganii    70-94%

Proteus vulgaris    75-100%

ANAEROBES Clostridium difficile

Cross-reactivity between cefuroxime and other antibiotics

Cross-resistance between cefuroxime and several other (3-lactam antibiotics including amoxicillin, methicillin, penicillin and ampicillin and some cephalosporins has been recorded. Amoxicillin-sensitive Haemophilus influenzae are more likely to be susceptible to cefuroxime than amoxicillin-resistant Haemophilus influenzae. Similarly, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermidis are usually Cefuroxime-susceptible, while methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis are resistant to cefuroxime.

Resistance of Staphylococcus aureus and Streptococcus pneumoniae to penicillin can result in an increase in the cefuroxime MIC50 and MIC90 values for these organisms. In addition, resistance of Escherichia coli and Haemophilus influenzae to ampicillin may result in an increase of the cefuroxime MIC50 values for these organisms.

Mechanisms of resistance to cefuroxime

Known mechanisms of resistance in targeted pathogens are the following:

1)    Production of (3-lactamases which are able to hydrolyse cefuroxime efficiently (e.g. several of the extended-spectrum and chromosomally-mediated (3-lactamases).

2)    Reduced affinity of Penicillin- Binding Proteins for cefuroxime (e.g. Penicillin-resistant Streptococcus pneumoniae).

3)    Cell wall impermeability.

4)    Efflux pumps.

5.2    Pharmacokinetic Properties

The serum half-life after either intramuscular or intravenous administration is approximately 70 minutes. After intramuscular injection the peak serum level occurs after about 45 minutes. The antibiotic can be found in bone, synovial fluid and aqueous humour above the minimum inhibitory levels for common pathogens. The blood-brain barrier can be passed by cefuroxime when the meninges are inflamed.

Cefuroxime is excreted approximately 50% by glomerular filtration and 50% through the renal tubules. Cefuroxime is almost completely recovered unchanged in the urine within 24 hours, most being excreted within six hours.

5.3    Predinical Safety Data

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime.

6 Pharmaceutical Particulars

6.1    List of Excipients

Each vial contains only the active ingredient cefuroxime sodium.

6.2    Incompatibilities

Cefuroxime should not be mixed in the syringe with aminoglycoside antibiotics.

6.3    She If-Life

Before reconstitution: 3 years.

In keeping with good pharmaceutical practice, freshly constituted suspensions or solutions should be used immediately. If this is not practicable then solution may be stored at 2°C - 8°C (in a refrigerator) for up to 24 hours.

6.4    Special Precautions for Storage

Protect from light. Before reconstitution do not store above 25°C. After reconstitution the product may be stored at 2°C - 8°C (in a refrigerator) for up to 24 hours.

6.5    Nature and Contents of Container

Type III flint glass vial stoppered with halobutyl closures and sealed with aluminium seals that may be combined with a polypropylene cap.

Pack sizes of 1 (all presentations), 10 (750 mg and 1.5 g) and 50 (750 mg only) vials.

Not all pack sizes may be marketed.

For infants and children:

The usual total daily dose is 200 -240mg/kg (body weight) given in three or four doses. This dose may be reduced after three days or when your child's health improves.

For newborn babies:

The usual total daily dose is 100mg/kg (body weight) given in three or four doses. This dose may be reduced after three days or when your child's health improves.

To prevent infections (prophylaxis)

The usual dose is 1.5g given intravenously at the same time as you have your anaesthetic. Your doctor may give you more Cefuroxime Injection if they think it appropriate.

The dose of drug you are given will be reduced if you have severe kidney problems e.g. you are on dialysis.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4 Possible side effects

Like all medicines, Cefuroxime Injection can cause side effects, although not everybody gets them.

All medicines can cause allergic reactions, although serious allergic reactions are very rare.

Serious side effects

The following side effects are serious.

You should stop taking this medicine and contact your doctor immediately if you experience them:

■    serious peeling or blistering of the skin

■    severe diarrhoea with blood or mucus. Tell your doctor immediately if you get any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body).

The following side effects have also been reported

With prolonged use, there may be:

■    thrush (Candida)

■    itchy red wheals (urticaria)

■    rash (alone)

■    fever

■    diarrhoea

■    changes in blood counts, which may show up as bruising or a very tired feeling. You will need a blood test to confirm this.

■    damage to your liver or kidneys which can only be detected by a blood and / or urine test

■    jaundice (yellow skin and eyes)

■    temporary pain at the injection site

■    swelling of the vein where your drip goes in

■    burning sensation in your arm where the drip goes in

■    mild to moderate hearing loss in some children treated for meningitis

■    dizziness

■    headache.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/vellowcard By reporting side effects you can help provide more information on the safety of this medicine.

5    How to store Cefuroxime Injection

Your doctor or pharmacist will know how to store Cefuroxime Injection.

It should be kept out of the sight and reach of children.

Before it is made up, it should be stored below 25°C and protected from light. After it is made up Cefuroxime Injection may be stored at 2°C-8°C (in a refrigerator) for up to 24 hours.

Medicines should not be disposed of via wastewater or household waste.

Ask your doctor how to dispose of medicines no longer required. These measures will help to protect the environment.

6    Further information

What Cefuroxime Injection contains

The active substance is cefuroxime sodium. There are no other ingredients.

What Cefuroxime Injection looks like and contents of the pack

Cefuroxime Injection is contained in glass vials with rubber stoppers.

Pack sizes of 1 and 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Flynn Pharma Ltd

Alton House, 4 Herbert Street

Dublin 2, Ireland.

Manufacturer:

Facta Farmaceutici,

Nucleo Industriale S. Atto,

S. Nicolo a Tordino, 64020 Teramo, Italy

This leaflet was last revised in

June 2014.

FLYNN

PHARMA

LTD

Artwork for:	Flynn Pharma Limited
Product name:	Cefuroxime Sodium for Injection
Size:
PL/PA no:	PL 13621/0018, 0019
Type:	Leaflet
Artwork dimensions:	140mm x 700mm
Profile supplied:	Yes
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Date of revision:	1 August 2014
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Information for the Health Care Professional

CEFUROXIME SODIUM FOR INJECTION

1    Name of the Medicinal Product

Cefuroxime Sodium for Injection 750 mg and Cefuroxime Sodium for Injection 1.5 g.

2    Qualitative and Quantitative Composition

Each vial contains, as the active ingredient, cefuroxime sodium for injection equivalent to 750 mg or 1.5 g of cefuroxime.

3    Pharmaceutical Form

Vials containing an off-white to slightly yellow sterile powder for solution for injection or infusion.

4    Clinical Particulars

4.1    Therapeutic Indications

Cefuroxime Sodium for Injection is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms, or before the infecting organism has been identified, in the diseases listed below.

Respiratory tract infections, for example, acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess and post operative chest infections.

Ear, nose and throat infections, for example, sinusitis, tonsillitis and pharyngitis.

Urinary tract infections, for example, acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria.

Soft tissue infections, for example, cellulitis, erysipelas, peritonitis and wound infections.

Bone and joint infections, for example, osteomyelitis and septic arthritis. Obstetric and gynaecological infections, pelvic inflammatory disease. Gonorrhoea, particularly if penicillin is unsuitable.

Other infections, including septicaemia and meningitis.

Prophylaxis against infection in abdominal, pelvic, orthopaedic, cardiac, pulmonary, oesophageal and vascular surgery where there is increased risk from infection.

Consideration should be given to official local guidance (e.g. national recommendations) on the appropriate use of antibacterial agents. Susceptibility of the causative organism to the treatment should be tested (if possible), although therapy may be initiated before the results are available.

4.2    Posology and Method of Administration

Usually cefuroxime is effective when administered alone, but when appropriate it may be used in combination with metronidazole or an aminoglycoside.

General Dosage

Adults: Many infections will respond to 750 mg three times daily by intramuscular or intravenous injection. For more severe infections this dose should be increased to 1.5g three times daily intravenously. The frequency of dosage may be increased to six-hourly injections intramuscular or intravenous, giving total daily doses of 3 g to 6 g. Infants and children: Doses of 30 to 100 mg/kg/day given in three or four divided doses.

A dose of 60 mg/kg/day will be appropriate for most infections. Neonates: Doses of 30 to 100 mg/kg/day given in two or three divided doses. In the first weeks of life the serum half-life of cefuroxime can be three to five times that in adults.

Gonorrhoea

1.5 g should be given as a single dose or as two 750 mg injections into different sites, e.g. each buttock.

Meningitis

Cefuroxime therapy is suitable for sole therapy of bacterial meningitis due to sensitive strains.

Infants and children: 200 to 240 mg/kg/day intravenously in three or four divided doses. This dosage may be reduced to 100 mg/kg/day after three days or when clinical improvement occurs.

Neonates: The initial dosage should be 100 mg/kg/day intravenously. This dosage may be reduced to 50 mg/kg/day after three days or when clinical improvement occurs.

Adults: 3 g intravenously every eight hours. No data is currently available to recommend a dose for intrathecal administration.

Prophylaxis

The usual dose is 1.5 g intravenously with induction of anaesthesia. For orthopaedic, pelvic and abdominal operations this may be followed with two 750 mg doses 8 and 16 hours later.

For vascular, cardiac, oesophageal and pulmonary operations this may be supplemented with 750 mg intramuscularly three times a day for a further 24 to 48 hours.

In total joint replacement, 1.5 g cefuroxime powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.

Dosage in Impaired Renal Function

As cefuroxime is excreted by the kidneys, the dosage should be reduced to allow for slower excretion in patients with impaired renal function, once creatinine clearance falls below 20 ml/min, as follows.

4.3    Contra-indications

Contra-indicated in patients hypersensitive to the cephalosporin group of antibiotics.

4.4    Special Warnings and Special Precautions for Use

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 patien-ts who have experienced an anaphylactic reaction to penicillin.

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving potent diuretics or aminoglycosides as these combinations are suspected of adversely affecting renal function.

Clinical experience has shown that this is not likely to be a problem at the recommended dose levels.

4.5    Interaction with other Medicinal Products and other Forms of Interaction

Concurrent administration of probenecid prolongs the excretion of cefuroxime and produces an elevated peak serum level.

Concurrent administration of potent diuretics, aminoglycosides may adversely affect renal function, (see section 4. 4)

Interference with Laboratory Tests

Slight interference may occur with the copper reduction methods (Fehling’s, Benedict’s) but this should not lead to false-positive results. Cefuroxime does not interfere with the enzyme based tests for glycosuria, or with the alkaline picrate method for creatinine. It is recommended that either the hexokinase or glucose oxidasemethods are used for determination of blood/plasma glucose levels.

4.6    Pregnancy and Lactation

Studies in animals revealed no evidence of embryopathic or teratogenic effects due to cefuroxime, but, as with all drugs, it should be used with caution during pregnancy. Since cefuroxime is excreted in human milk, caution should be exercised when administering this antibiotic to a nursing mother.

4.7    Effects on the Ability to Drive and Use Machines

Cefuroxime is not known to affect the ability to drive or use machines.

4.8    Undesirable Effects

Hypersensitivity reactions: including skin rashes (maculopapular and urticarial) interstitial nephritis, drug fever and very rarely anaphylaxis. As with any antibiotic, prolonged use may lead to overgrowth of non-susceptible organisms, e.g. Candida.

As with other cephalosporins, there have been rare reports of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. Gastrointestinal disturbance: including, very rarely, pseudomembranous colitis, which has been reported with most broad spectrum antibiotics. Haematological: a decrease in haemoglobin concentration, eosinophilia, leucopenia and neutropenia have been observed. Positive Coombs’ tests have been reported. As with other cephalosporins, thrombocytopenia has been reported rarely.

Hepatic: Transient rises in liver enzymes or serum bilirubin have been observed particularly in patients with pre-existing liver disease, but there is no evidence of hepatic involvement.

Renal:There may be some variation in the results of biochemical tests of renal function, but these results do not appear to be of clinical significance. Other: Transient pain may be experienced at the site of intramuscular injection. Occasionally thrombophlebitis may occur at the site of intravenous injection. A burning sensation may be observed after intravenous injection. Mild to moderate hearing loss has been reported in some children treated for meningitis.

Dizziness and headache has been reported in patients receiving cefuroxime.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Flealthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9    Overdose

Overdosage of cephalosporins can lead to cerebral irritation and seizures. With seizures the drug should be discontinued and appropriate anticonvulsive and supportive therapy administered. Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Cefuroxime is a cephalosporin antibiotic, ATC code J01DA06 Cephalosporins and related substances. All cephalosporins (p-lactam antibiotics) inhibit cell wall production and are selective inhibitors of peptidoglycan synthesis. The initial step in drug action consists of binding of the drug to cell receptors, called Penicillin-Binding Proteins.

After a p-lactam antibiotic has bound to these receptors, the transpeptidation reaction is inhibited and peptidoglycan synthesis is blocked. Bacterial lysis is the end result.

Susceptibility

The following MIC breakpoints separating susceptible from intermediately susceptible organism and intermediately susceptible from resistant organism are used.

Marked impairment (creatinine clearance 10 to 20 ml/min)	750 mg twice daily
Severe impairment (creatinine clearance of less than 10 ml/min) ’	750 mg once daily
Continuous peritoneal dialysis	750 mg twice daily
Renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units	750 mg twice daily
Low-flux haemofiltration	as for impaired renal function

* For patients on haemodialysis, a further 750 mg should be given at the end of each dialysis session.

package leaflet: Information for the user

Cefuroxime Sodium for Injection 750mg & 1.5g

The name of your medicine is Cefuroxime Sodium for Injection 750mg & 1,5g, which will be referred to as Cefuroxime Injection throughout this document.

Read all of this leaflet carefully before you start taking this medicine.

■    Keep this leaflet. You may need to read it again.

■    If you have any further questions, ask your doctor or pharmacist.

■    This medicine has been prescribed for you. Do not pass it on to others.

It may harm them, even if their symptoms are the same as yours.

■    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Cefuroxime Injection is and what it is used for

2.    Before you are given Cefuroxime Injection

3.    How you are given Cefuroxime Injection

4.    Possible side effects

5.    How to store Cefuroxime Injection

6.    Further information

1 What Cefuroxime Injection is and what it is used for

Cefuroxime Injection contains the active ingredient cefuroxime sodium, which is an antibiotic.

Cefuroxime Injection is used to treat infections caused by bacteria that can be killed by cefuroxime, in the following infections:

■    Lungs and airways e.g. bronchitis, pneumonia

■    Ear, nose and throat e.g. tonsillitis, pharyingitis, sinusitis

■    Urinary tract e.g. kidney and bladder

■    Soft tissue e.g. skin, cellulitis

■    Bone and joint

■    Pelvic inflamatory disease (e.g. infection of the female reproductive system)

■    Gonorrhoea (a sexually transmitted disease), particularly if penicillin is unsuitable

■    Other infections including blood poisoning (septicaemia) and meningitis.

Cefuroxime Injection can also be used to prevent infection during surgery where there is an increased risk of infection.

2 Before you are given Cefuroxime Injection Do not take Cefuroxime Injection if

■    you are allergic (hypersensitive) to cefuroxime or any cephlosporin (other similar antibiotics). An allergic reaction may include rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue.

Take special care with Cefuroxime Injection if you

■    have had a severe allergic reaction to penicillin in the past

Taking other medicines

Please tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines, including medicines obtained without a prescription. This is especially important of the following, as they may interact with your Cefuroxime Injection:

■    probenecid (a treatment for gout)

■    strong diuretics (water tablets used to treat high blood pressure or fluid retention)

aminoglycosides (another type of antibiotic e.g. tobramycin, gentamicin).

It may still be all right for you to be given Cefuroxime Injection and your doctor will be able to decide what is suitable for you.

Interference with laboratory tests

Tell your doctor if you are having blood or urine tests. Cefuroxime Injection may interfere with these tests.

Pregnancy and breast-feeding

You should tell your doctor if you are pregnant or breast-feeding. Ask your doctor or pharmacist before taking any medicine.

Driving and using machines

Cefuroxime Injection should not affect your ability to drive or use machines.

NCCLS: National Committee for Clinical Laboratory Standards

DIN: Deutches Institutfur Normung

BSAC: British Society for Antimicrobial Chemotherapy

S: Susceptible, I: Intermediately susceptible, R: Resistant The prevalence of resistance may vary geographically and with time for selected species and local information is desirable, particularly when treating several infections. This information gives only an approximate guidance on probabilities whether organisms will be susceptible to cefuroxime or not.

Table 2: Range of bacterial resistance to cefuroxime in Europe.

CATEGORY    RANGE OF

RESISTANCE IN EUROPE

SUSCEPTIBLE

GRAM + VE AEROBES

Staph.aureus (methicillin-susceptible strains)

Staph.epidermidis (methicillin-susceptible strains) 0-46%

Providencia rettgerionly ANAEROBES Clostridium perfringens INTERMEDIATE GRAM - VE AEROBES Bordetella pertussis

Citrobacter    21 -52%

Enterobacterspp.    36-83%

ANAEROBES

Bacteroides fragilis

INSUSCEPTIBLE

GRAM + VE AEROBES

Enterococcus faecalis

Staph. Aureus (methicillin-resistant strains)

Staph, epidermidis (methicillin-resistant strains)

GRAM - VE AEROBES Acinetobacterspp.

Campylobacterspp.

Legionellaspp.

Pseudomonasspp.

Serratiaspp.

Morganella morganii    70-94%

Proteus vulgaris    75-100%

ANAEROBES

Clostridium difficile

Cross-reactivity between cefuroxime and other antibiotics Cross-resistance between cefuroxime and several other 6-lactam antibiotics including amoxicillin, methicillin, penicillin and ampicillin and some cephalosporins has been recorded. Amoxicillin-sensitive Haemophilus influenzae are more likely to be susceptible to cefuroxime than amoxicillin-resistant Haemophilus influenzae. Similarly, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermidis are usually Cefuroxime-susceptible, while methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis are resistant to cefuroxime.

Resistance of Staphylococcus aureus and Streptococcus pneumoniae to penicillin can result in an increase in the cefuroxime MIC50 and MIC90 values for these organisms. In addition, resistance of Escherichia coli and Haemophilus influenzaeto ampicillin may result in an increase of the cefuroxime MIC50 values for these organisms.

Mechanisms of resistance to cefuroxime

Known mechanisms of resistance in targeted pathogens are the following:

1)    Production of 6-lactamases which are able to hydrolyse cefuroxime efficiently (e.g. several of the extended-spectrum and chromosomally -mediated 6-lactamases).

2)    Reduced affinity of Penicillin- Binding Proteins for cefuroxime (e.g. Penicillin-resistant Streptococcus pneumoniae).

3)    Cell wall impermeability.

4)    Efflux pumps.

5.2    Pharmacokinetic Properties

The serum half-life after either intramuscular or intravenous administration is approximately 70 minutes. After intramuscular injection the peak serum level occurs after about 45 minutes.

The antibiotic can be found in bone, synovial fluid and aqueous humour above the minimum inhibitory levels for common pathogens. The blood-brain barrier can be passed by cefuroxime when the meninges are inflamed.

Cefuroxime is excreted approximately 50% by glomerular filtration and 50% through the renal tubules. Cefuroxime is almost completely recovered unchanged in the urine within 24 hours, most being excreted within six hours.

5.3    Preclinical Safety Data

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime.

6    Pharmaceutical Particulars

6.1    List of Excipients

Each vial contains only the active ingredient cefuroxime sodium.

6.2    Incompatibilities

Cefuroxime should not be mixed in the syringe with aminoglycoside antibiotics.

6.3    Shelf-Life

Before reconstitution: 3 years.

In keeping with good pharmaceutical practice, freshly constituted suspensions or solutions should be used immediately. If this is not practicable then solution may be stored at 2°C - 8°C (in a refrigerator) for up to 24 hours.

6.4    Special Precautions for Storage

Protect from light. Before reconstitution do not store above 25°C. After reconstitution the product may be stored at 2°C - 8°C (in a refrigerator) for up to 24 hours.

6.5    Nature and Contents of Container

Type III flint glass vial stoppered with halobutyl closures and sealed with aluminium seals that may be combinedwith a polypropylene cap.

Pack sizes of 1 (all presentations), 10 (750 mg and 1.5 g) and 50 (750 mg only) vials. Not all pack sizes may be marketed.

6.6    Instructions for Use / Handling

Intramuscular injection: Add 3 ml of Water for Injections to 750 mg. Shake gently to produce a suspension.

Intravenous administration: Dissolve cefuroxime in Water for Injections using at least 6 ml for 750 mg and at least 15 ml for 1.5 g. For short intravenous infusion 1.5 g may be dissolved in 50 ml of Water for Injections.

Reconstituted solutions may be diluted with:

5% or 10% Dextrose

5% Dextrose containing 0.2%, 0.225%, 0.45% or 0.9% Sodium Chloride Injection

5% Dextrose containing 20 mEq Potassium Chloride 0.9% Sodium Chloride Injection Ringer’s Injection Lactated Ringer’s Injection

Heparin (10 and 50 units/ml) in 0.9% Sodium Chloride Injection 10 mEq Potassium Chloride in 0.9% Sodium Chloride Injection These solutions may be given directly into a vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluids.

7    Marketing Authorisation Holder

Flynn Pharma Limited, Alton House, 4 Herbert Street, Dublin 2, Ireland.

8    Marketing Authorisation Numbers

Cefuroxime Sodium for Injection 750 mg PL 13621/0018 Cefuroxime Sodium for Injection 1.5g PL 13621/0019

9    Date of First Authorisation/Renewal of Authorisation Date of last renewal of authorisation: 19 Feb 2002

10    Date of (Partial) Revision of the Text July 2014

L15GBCEFU07502

3 How you are given Cefuroxime Injection

Cefuroxime Injection will be given to you by a doctor or nurse.

Dosage

The dose depends on the infection to be treated and the condition of the patient.

For adults:

The usual dose is 750mg three times daily by injection into a muscle (intramuscular) or into a vein (intravenous injection). For more severe infections this dose should be increased to 1,5g three times daily intravenously. The dose may be increased by giving the injection four times daily giving a total daily doses of 3g to 6g.

For infants and children:

The usual total daily dose is 30 to 100mg/kg (body weight) given in three or four doses. A total daily dose of 60mg/kg is effective for most infections.

For newborn babies:

The usual total daily dose is 30 to 100mg/kg per day given in two or three doses.

Gonorrhoea

1.5g as a single dose.

Meningitis For adults:

3g intravenously every eight hours.

For infants and children:

The usual total daily dose is 200 - 240mg/kg (body weight) given in three or four doses. This dose may be reduced after three days or when your child’s health improves.

For newborn babies:

The usual total daily dose is 100mg/kg (body weight) given in three or four doses. This dose may be reduced after three days or when your child’s health improves.

To prevent infections (prophylaxis)

The usual dose is 1,5g given intravenously at the same time as you have your anaesthetic. Your doctor may give you more Cefuroxime Injection if they think it appropriate. The dose of drug you are given will be reduced if you have severe kidney problems e.g. you are on dialysis.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4 Possible side effects

Like all medicines, Cefuroxime Injection can cause side effects, although not everybody gets them.

All medicines can cause allergic reactions, although serious allergic reactions are very rare.

Serious side effects

The following side effects are serious. You should stop taking this medicine and contact your doctor immediately if you experience them:

■    serious peeling or blistering of the skin

■    severe diarrhoea with blood or mucus.

Tell your doctor immediately if you get any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body).

The following side effects have also been reported

With prolonged use, there may be:

■    thrush (Candida)

■    itchy red wheals (urticaria)

■    rash (alone)

■    fever

■    diarrhoea

■    changes in blood counts, which may show up as bruising or a very tired feeling. You will need a blood test to confirm this.

■    damage to your liver or kidneys which can only be detected by a blood and / or urine test

■    jaundice (yellow skin and eyes)

■    temporary pain at the injection site

■    swelling of the vein where your drip goes in

■    burning sensation in your arm where the drip goes in

■    mild to moderate hearing loss in some children treated for meningitis

■    dizziness

■    headache.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.goy.uk/yellowcard By reporting side effects you can help provide more information on the safety of this medicine.

5    How to store Cefuroxime Injection

Your doctor or pharmacist will know howto store Cefuroxime Injection.

It should be kept out of the sight and reach of children.

Before it is made up, it should be stored below 25°C and protected from light. After it is made up Cefuroxime Injection may be stored at 2°C-8°C (in a refrigerator) for up to 24 hours.

Medicines should not be disposed of via wastewater or household waste. Ask your doctor how to dispose of medicines no longer required. These measures will help to protect the environment.

6    Further information

What Cefuroxime Injection contains

The active substance is cefuroxime sodium.

There are no other ingredients.

What Cefuroxime Injection looks like and contents of the pack

Cefuroxime Injection is contained in glass vials with rubber stoppers.

Pack sizes of 1 and 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Flynn Pharma Ltd

Alton House, 4 Herbert Street

Dublin 2, Ireland.

Manufacturer:

Facta Farmaceutici,

Nucleo Industriale S. Atto,

S. Nicolo a Tordino 64020 Teramo, Italy

This leaflet was last revised in June 2014.

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