Cefuroxime sodium for injection 250mg, cefuroxime sodium for injection 750mg and cefuroxime sodium for injection 1.5g.

Each vial contains, as the active ingredient, cefuroxime sodium for injection equivalent to 250mg, 750mg or 1.5g of cefuroxime.

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

Cefuroxime sodium for injection is indicated for the treatment of infections caused by susceptible strains of the designated micro-organisms, 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 postoperative 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 (eg, 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.

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 750mg 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 3g to 6g.

Infants and children: Doses of 30 to 100mg/kg/day given in three or four divided doses. A dose of 60mg/kg/day will be appropriate for most infections.

Neonates: Doses of 30 to 100mg/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

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

Meningitis

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

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

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

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

Prophylaxis

The usual dose is 1.5g intravenously with induction of anaesthesia. For orthopaedic, pelvic and abdominal operations this may be followed with two 750mg doses 8 and 16 hours later. For vascular, cardiac, oesophageal and pulmonary operations this may be supplemented with 750mg intramuscularly three times a day for a further 24 to 48 hours.

In total joint replacement, 1.5g 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 20ml/min, as follows:

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

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.

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.

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 oxidase methods are used for determination of blood/plasma glucose levels.

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.

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

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, eg, Candida.

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

Gastro-intestinal 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.

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.

Cefuroxime is a cephalosporin antibiotic, ATC code J01DA06 (Cephalosporins and Related Substances). All cephalosporins (β-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 β-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 organisms and intermediately susceptible from resistant organisms are used.

Table 1:Susceptibility Breakpoints

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

Cross-Reactivity Between Cefuroxime and Other Antibiotics

Cross-resistance between cefuroxime and several other β-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 Staphylococcus 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:

• Production of β-lactamases which are able to hydrolyse cefuroxime efficiently (eg, several of the extended-spectrum and chromosomally-mediated β-lactamases).

• Reduced affinity of penicillin-binding proteins for cefuroxime (eg, penicillin-resistant Streptococcus pneumoniae).

• Cell wall impermeability.

• Efflux pumps.

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.

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

Each vial contains only the active ingredient, cefuroxime sodium.

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

Before reconstitution: 36 months.

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.

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.

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 and 10 vials. Not all pack sizes may be marketed.

Intramuscular injection: Add 1ml of water for injections to 250mg or 3ml of water for injections to 750mg. Shake gently to produce a suspension.

Intravenous administration: Dissolve cefuroxime in water for injections using at least 2ml for 250mg, at least 6ml for 750mg and at least 15ml for 1.5g. For short intravenous infusion, 1.5g may be dissolved in 50ml 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 20mEq potassium chloride

0.9% sodium chloride injection

M/6 sodium lactate injection

Ringer's injection

Lactated Ringer's injection

Heparin (10 and 50 units/ml) in 0.9% sodium chloride injection

10mEq 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.

Flynn Pharma Ltd

Alton House

4 Herbert Street

Dublin 2

Ireland

Cefuroxime sodium for injection 250mg: PL 13621/0017

Cefuroxime sodium for injection 750mg: PL 13621/0018

Cefuroxime sodium for injection 1.5g: PL 13621/0019

Date of first authorisation: 1^st June 2005

January 2009

POM

1.5g x 1, 20ml vial

250mg x 1, 10ml vial

750mg x 1, 10ml vial