INFORMATION FOR HEALTH PROFESSIONALS
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Rubber capped vials with flip-off plastic cover containing 250 mg, 750 mg or 1500 mg cefuroxime as cefuroxime sodium.
Cefuroxime is a white to faintly-yellow powder to which appropriate amounts of water are added to prepare an off-white suspension for intramuscular use or a yellowish solution for intravenous administration. Variations in the intensity of this colour do not indicate any change in either the efficacy or safety of the product.
CEFUROXIME is a well characterised and effective β-lactamic antibacterial agent which has bactericidal activity against a wide range of common pathogens, including β-lactamase producing strains. It is indicated for the treatment of infections before the infecting organism has been identified or when caused by sensitive bacteria. In addition, it is an effective prophylactic against post-operative infection in a variety of operations. Usually CEFUROXIME will be effective alone, but when appropriate it may be used in combination with an aminoglycoside antibiotic, or in conjunction with metronidazole (orally or by suppository or injection), especially for prophylaxis in colonic or gynaecological surgery (see Pharmaceutical Precautions).
The bactericidal action of cefuroxime results from inhibition of the cell wall synthesis by binding to essential target proteins.
Cefuroxime has good stability to bacterial β-lactamase, and consequently is active against many ampicillin-resistant or amoxycillin-resistant strains.
Cefuroxime is usually active against the following organisms in vitro:
Aerobes Gram-positive: Staphylococcus aureus and Staphylococcus epidermidis(including penicillinase producing strains but excluding methicillin resistant strains), Streptococcus pyogenes (and other β-haemolytic streptococci), Streptococcus pneumoniae, Streptococcus Group B (Streptococcus agalactiae), Streptococcus mitis (Viridans group), and Bordetella pertussis.
Aerobes Gram-negative: Escherichia coli, Klebsiella spp, Providencia spp, Proteus mirabilis, Proteus rettgeri, Haemophilus influenzae (including ampicillin-resistant strains), Moraxella (Branhamella) catarrhalis, Neisseria gonorrhaeae (including penicillinase and non-penicillinase producing strains), Neisseria meningitidis, and Salmonella spp.
Anaerobes: Gram-positive and Gram-negative cocci (including Peptococcus and Peptostreptococcus species), Gram-positive bacilli (including most Clostridium species) and Gram-negative bacilli (including Bacteroides and Fusobacterium species), Propionibacterium species.
Other organisms: Borrelia burgdorferi.
The following organisms are not susceptible to Cefuroxime: Clostridium difficile, Pseudomonas spp, Campylobacter spp, Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin resistant strains of staphylococcus aureus, methicillin resistant strains of staphylococcus epidermidis, and Legionella spp.
Some strains of the following genera are not susceptible to Cefuroxime: Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp, Citrobacter spp, Serratia spp, and Bacteroides fragilis.
In vitro the activities of CEFUROXIME and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.
Peak levels of cefuroxime are achieved within 30 to 45 minutes after intramuscular administration. The serum half-life after either intramuscular or intravenous injection is approximately 70 minutes. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level. Protein binding has been variously stated as 33-50% depending on the methodology used. There is almost complete recovery (85-90%) of unchanged cefuroxime in urine within 24 hours of administration. The major part is excreted in the first six hours. Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion. Serum levels of cefuroxime are reduced by dialysis. Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in bone, synovial fluid and aqueous humor. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
CEFUROXIME is indicated in the treatment of the following infections caused by susceptible microorganisms:
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, pharyngitis and otitis media.
Urinary Tract Infections: for example, acute and chronic pyelonephritis, cystitis and symptomatic 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 diseases. Gonorrhoea, particularly when 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.
Adults: Many infections will respond to 750 mg t.d.s. by IM or IV injection. For more severe infections, this dose should be increased to six-hourly if necessary, giving total doses of 3 g to 6 g daily.
Infants and Children: Doses of 30 to 100 mg/kg/day given as two or three 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 as 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: 1500 mg should be given as a single dose. This may be given as 2 x 750 mg injections (intramuscularly) into different sites, e.g. each buttock.
Meningitis: CEFUROXIME is suitable for sole therapy of bacterial meningitis due to sensitive strains. The following doses are recommended.
Prophylaxis: The usual dose is 1500 mg IV with induction of anaesthesia for abdominal, pelvic and orthopaedic operations, but may be supplemented with two 750 mg IM doses 8 and 16 hours later. In cardiac, pulmonary, oesophageal and vascular operations, the usual dose is 1500 mg IV with induction of anaesthesia continuing with 750 mg IM t.d.s. for a further 24 to 48 hours.
In total joint replacement: 1500 mg cefuroxime powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.
Dosage and Impaired Renal Function: Cefuroxime is excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function it is recommended that the dosage of CEFUROXIME should be reduced to compensate for its slower excretion. However, it is not necessary to reduce the standard dose (750 mg-1500 mg three times daily) until the creatinine clearance falls to 20 ml/min or below. In adults with marked impairment (creatinine clearance 10 to 20 ml/min) 750 mg twice daily is recommended and with severe impairment (creatinine clearance ( 10 ml/min) 750 mg once daily is adequate. For patients on haemodialysis a further 750 mg dose should be given IV or IM at the end of each dialysis. In addition to parenteral use, Cefuroxime can be incorporated into the peritoneal dialysis fluid usually 250 mg for every 2 litres of dialysis fluid given IV.
Dosage in continuous arteriovenous haemodialysis (CAVHD) or haemofiltration (CAVH): For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units a suitable dosage is 750 mg twice daily. For low-flux haemofiltration follow the dosage recommended under Dosage in Impaired Renal Function.
Intramuscular: Add 1 ml water for injection to 250 mg CEFUROXIME or 3 ml water for injections to 750 mg CEFUROXIME. Shake gently to obtain a solution for the 250 mg strength and opaque suspension for 750 mg strength. Inject into a large muscle mass.
Intravenous: Dissolve CEFUROXIME in water for injections using at least 2 ml for 250 mg, at least 6 ml for 750 mg, or 16 ml for 1500 mg. For short intravenous infusion (eg. up to 30 minutes), 1500 mg may be dissolved in 40-100 ml water for injections. These solutions may be given directly into the vein or introduced into the tubing or the giving set if the patient is receiving parenteral fluids.
CEFUROXIME is compatible with the more commonly used intravenous fluids ( see Warning and Precautions ).
CEFUROXIME is contraindicated in patients with hypersensitivity to cephalosporin antibiotics.
This product should not ordinarily be given to those known to be allergic to penicillin or to cephalosporins especially if they have experienced an allergic or urticarial reaction.
There is no experimental evidence of embryopathic or teratogenic effects attributable to CEFUROXIME but, as with all medicines, it should be administered with caution during the early months of pregnancy. Cefuroxime is excreted in human milk, and consequently caution should be exercised when CEFUROXIME is administered to a nursing mother.
CEFUROXIME does not interfere in enzyme based tests for glycosuria. 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.
It is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving CEFUROXIME. This antibiotic does not interfere in the alkaline picrate assay for creatinine.
Adverse reactions to CEFUROXIME have occurred relatively infrequently and have been generally mild and transient in nature. Hypersensitivity reactions have been rarely reported; these included skin rashes, urticaria, pruritus, interstitial nephritis, medicine fever and very rarely anaphylaxis. As with other cephalosporins, there have been rare reports of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (exanthematic necrolysis).
As with other antibiotics, prolonged use may result in the overgrowth of non-susceptible organism, e.g. Candida. Gastrointestinal disturbance, including, very rarely, symptoms of pseudomembranous colitis during or after treatment.
As with other therapeutic regimens used in the treatment of meningitis, mild-to-moderate hearing loss has been reported in a few paediatric patients treated with cefuroxime sodium. Persistence of positive CSF culture of Haemophilus infuenzae at 18-36 hours has also been noted with cefuroxime sodium injection, as well as with other antibiotic therapies. The correlation between delayed CSF sterilisation and subsequent hearing impairment has not been fully established and the clinical relevance is unknown.
The principal changes in haematological parameters seen in some patients have been decreased haemoglobin concentration and eosinophilia, leukopenia and neutropenia. A positive Coombs' test has been found in some patients treated with cefuroxime - this phenomenon can interfere with the cross matching of blood. Although there are sometimes transient rises in serum liver enzymes or serum bilirubin, particularly in patients with pre-existing liver disease, there is no evidence of harm to the liver.
Elevations in serum creatinine and/or blood urea nitrogen and a decreased creatinine clearance have been observed ( see Warnings and Precautions ).
Transient pain may be experienced at the site of intramuscular injection. This is more likely to occur with higher doses. However, it is unlikely to be a cause for discontinuation of treatment.
Occasionally thrombophlebitis may follow intravenous injection.
In vitro the activities of CEFUROXIME and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.
Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as frusemide or aminoglycosides, as renal impairment has been reported with these combinations. Renal function should be monitored in these patients, the elderly and those with pre-existing renal impairment ( see Dosage and Administration ). CEFUROXIME does not interfere in the alkaline picrate assay for creatinine.
Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.
CEFUROXIME has a shelf-life of 2 years stored below 25°C and protected from light.
CEFUROXIME should not be mixed in the syringe with aminoglycoside antibiotics.
Suspensions of CEFUROXIME for intramuscular injection and aqueous solutions for direct intravenous injection retain their potency for five hours if kept below 25°C and for 48 hours if refrigerated.
More dilute solutions, i.e. 1500 mg plus 50 ml water for injections, retain satisfactory potency for 24 hours if kept below 25°C and for 72 hours if refrigerated.
Some increase in the colour of prepared solutions and suspensions of CEFUROXIME may occur on storage.
1500 mg CEFUROXIME constituted with 16 ml water for injections may be added to metronidazole injection (500 mg/100 ml) and both retain their activity for up to 24 hours below 25°C. 1500 mg CEFUROXIME is compatible with azlocillin 1 g (in 15 ml) or 5g (in 50 ml) for up to 24 hours at 4°C or 6 hours below 25°C.
CEFUROXIME (5 mg/ml) in 5% w/v or 10% w/v Xylitol injection may be stored for up to 24 hours at 25°C.
CEFUROXIME is compatible with the more commonly used intravenous infusion fluids. It will retain potency for up to 24 hours at room temperature in: Sodium Chloride Injection BP 0.9% w/v, 5% Dextrose Injection BP, 0.18% w/v Sodium Chloride plus 4% Dextrose Injection BP, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.225% Sodium Chloride Injection, 10% Dextrose Injection, 10% Invert Sugar in Water for Injection, Ringer's Injection USP, Lactated Ringer's Injection USP, M/6 Sodium Lactate Injection, and Compound Sodium Lactate Injection BP (Hartmann's solution).
The pH of 2.74% w/v Sodium Bicarbonate Injection BP considerable affects the colour of the solution and therefore this solution is not recommended for the dilution of CEFUROXIME. However, if required, for patients receiving Sodium Bicarbonate Injection by infusion the CEFUROXIME may be introduced into the tube of the giving set.
The stability of CEFUROXIME in Sodium Chloride Injection BP 0.9% w/v and in 5% Dextrose Injection is not affected by the presence of hydrocortisone sodium phosphate.
CEFUROXIME has also been found compatible for 24 hours at room temperature when admixed in intravenous infusion with: Heparin (10 and 50 units/ml) in 0.9% Sodium Chloride Injection; Potassium Chloride (10 and 40 mEqL) in 0.9% Sodium Chloride Injection.
Prescription Medicine
Clear glass vials containing 250 mg, 750 mg or 1500 mg cefuroxime as the sodium salt.
Cefuroxime is [6R-[6α,7β(Z)]]-3-[[(Aminocarbonyl)oxy]methyl]-7-[[2-furanyl(methoxyimino) acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. It has a molecular formula and weight of C16H16N4O8S and 424.39 respectively.
Douglas Pharmaceuticals Ltd
PO Box 45-027
Auckland 8
Ph: (09) 835-0660
Fax: (09) 835-0690
6 October 1999