“Ceruxim” is a bactericidal cephalosporin antibiotic that is resistant to the majority of b-lactamases, and is active against a wide range of gram positive and gram negative organisms. Indicated for use in infections before the organism has been identified or when the infection is caused by sensitive bacteria. Effective for post operative infection prophylaxis. It is usually effective as monotherapy, but when appropriate may be used in combination with an aminoglycoside antibiotic or metronidazole.

Administration in combination with metronidazole is appropriate where mixed aerobic and anaerobic infections are found or suspected, such as peritonitis, aspiration pneumonia and abscesses of lung, pelvis or brain, or are likely to occur, such as in association with gynaecological or colorectal surgery.

Indications include:

Bone and joint infections: such as septic arthritis, osteomyelitis.

Gonorrhoea: especially when penicillin is not suitable.

Obstetric and gynaecological infections: pelvic inflammatory diseases.

Prophylaxis: where there is an increased risk of infection, such as abdominal, cardiac, oesophageal, orthopaedic, pelvic, pulmonary or vascular surgery.

Respiratory tract infections: such as acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess and post operative chest infections.

Soft tissue infections: such as cellulitis, erysipelas, peritonitis and infected wounds.

Urinary tract infections: such as asymptomatic bacteriuria, cystitis and acute and chronic pyelonephritis.

Other infections: including septicaemia and meningitis.

 “Ceruxim” 1.5g is administered by intravenous injection, or by slow intravenous infusion.

Preparation for i.v. administration: Add 15 ml of water for injections into the 1.5g vial. Shake well so as to obtain a clear solution. After reconstitution the solutions are stable for 24 hours when stored in a refrigerator, although it is recommended to use only freshly prepared solutions. For slow intravenous infusion the 1.5 g vial may be further diluted into 50 ml of a suitable infusion fluid such as:

·      10% dextrose injection

·      5% dextrose injection

·      0.9% sodium chloride

·      Ringer’s solution

·      Lactated Ringers solution

The final solution can be administered intravenously over a period of 30 minutes. According to Good Clinical Practice it is recommended to use only freshly prepared solutions, although the solutions are stable for 24 hours when stored in a refrigerator.

General dosage:

Adults: The majority of infections respond to 750mg three times a day by intramuscular or intravenous injection. In severe infections the dose should be increased to 1.5g three times a day by the intravenous route. The frequency of dose can be increased to intramuscular or intravenous injections every six hours. The total daily dose range is 3g to 6g.

Children and Infants: A dose of 60mg per kilogram bodyweight per day is appropriate for most infections. Dose range is 30mg to 100mg per kg bodyweight per day, given in three or four divided doses.

Neonates: From 30mg to 100mg/kg/day, in two or three divided doses. The serum half life of cefuroxime can be three to five times longer than in adults in the first few weeks of life.

Other recommendations:

Meningitis: “Ceruxim” is suitable for sole therapy of bacterial meningitis due to susceptible organisms.

Adults: 3g intravenously every eight hours.

Children and Infants: 200 to 240mg/kg/day, intravenously in three or four divided doses. After three days, or when clinical improvement occurs, dose may be reduced to 100mg/kg/day.

Neonates: 100mg/kg/day intravenously. After three days, or when clinical improvement occurs, dose may be reduced to 50mg/kg/day.

Gonorrhoea: 1.5g as a single dose, or as two 750mg injections at different sites, such as both buttocks.

Prophylaxis: 1.5g intravenously with anaesthesia induction. In orthopaedic, pelvic and abdominal procedures may be followed with a further 750mg at eight and sixteen hours later. In vascular, cardiac, oesophageal and pulmonary procedures this may be further supplemented  with 750mg intramuscularly three times a day for a further 24 or 48 hours.

In total joint replacement, 1.5g may be mixed dry with every pack of cement polymer before addition of liquid monomer.

Elderly: dosage as for adults.

Renal impairment: Cefuroxime is excreted by the kidneys. Dosage must be reduced in patients with impaired renal function, creatinine clearance <20ml/minute. Recommended doses are as follows:

To Report any side effect:

Hypersensitivity reactions

As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. 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.

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.

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.

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). 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.

Interference with diagnostic tests

The development of a positive Coombs Test associated with the use of cefuroxime may interfere with cross matching of blood.

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.

Important information about excipients

Ceruxim powder for solution for injection and infusion contains sodium. This should be considered for patients who are on a controlled sodium diet.

Probenecid administered concurrently administered prolongs the excretion and elevates peak serum level of cefuroxime.

Slight interference with Fehling’s and Benedict’s test may occur,  it should not cause false positive results.

There is no interference with enzyme based tests for glycosuria, or with creatinine measured by the alkaline picrate method.

It is recommended that determination of blood/plasma glucose levels be done using glucose oxidase or hexokinase methods.

Pregnancy category B.

No embryopathic or teratogenic effects were revealed in animal studies. As with all drugs, cefuroxime should be used with caution during pregnancy.

Cefuroxime is excreted in human milk. Caution should be exercised in administering to a nursing mother.

Cefuroxime is not known to affect ability to drive or operate machinery.

Adverse effects are generally transient, infrequent and mild, and cefuroxime is well tolerated.

Gastro-intestinal: nausea, diarrhoea and very rarely, pseudomembranous colitis, which occurs with most broad spectrum antibiotics.

Haematological: decrease in haemaglobin concentration, eosinophilia, leucopenia and neutropenia have been noted. Positive Coomb’s test has been reported. Rare reports, as with other cephalosporins, of thrombocytopenia.

Hepatic: particularly in patients with pre-existing liver disease, observations of transient rise in serum bilirubin or liver enzymes.

Hypersensitivity reactions: these include maculopapular and urticarial skin rashes, fever and, very rarely, anaphylaxis. As with all antibiotics, prolonged usage may lead to overgrowth of non-susceptible organisms, such as Candida sp.

Renal: may be variation in results of biochemical tests or renal function. These do not appear to be clinically significant.

Other: thrombophlebitis may occur occasionally at intravenous injection site. Transient pain may occur at intramuscular injection site.

Can lead to cerebral irritation and seizures. If seizures occur, the drug should be discontinued and anti-convulsant and supportive therapy administered as appropriate. Haemodialysis or peritoneal dialysis will reduce serum concentrations of cefuroxime.

Cefuroxime sodium is a broad spectrum, semi-synthetic cephalosporin antibiotic. It is bactericidal, acting by inhibition of cell wall synthesis, and is resistant to most b-lactamases.

It is active against the following organisms:

Gram negative bacteria: Bordatella pertussis, Enterobacter sp., Escherichia coli, Haemophilus influenzae, Klebsiella sp., including K. pneumoniae, Morganella morganii, previously P. morganii,  Neisseria sp., including N. gonorrhoeae, Proteus mirabilis,  Proteus rettgeri, Proteus vulgaris, Salmonella sp., including Salmonella typhi and Salmonella typhimurium, and Shigella sp.

Gram positive bacteria: Staphylococcus aureus, including penicillin resistant strains, Staphylococcus epidermidis and certain strains of streptococci, such as Streptococcus pyogenes and Streptococcus mitis, viridans group.

Anaerobic bacteria: Bacteroides fragilis, Clostridium sp.

Resistant strains: Acinetobacter calcoaceticus, Campylobacter sp., Clostridium difficile, Legionella sp., Pseudomonas sp. And methicillin resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. Some strains of Bacteroides fragilis, Citrobacter sp., Enterobacter sp., Morganella morganii, Proteus vulgaris, Serratia sp., Streptococcus faecalis.

Cefuroxime and aminoglycoside antibiotics in combination, in vitro, have been shown to be at least additive, and occasional evidence of synergistic activity.

Following either intravenous or intramuscular administration, the serum half life is about 70 minutes. Peak serum level, following intramuscular administration, happens at about 45 minutes.

Levels of cefuroxime, above minimum inhibitory levels for common pathogens, can be found in aqueous humour, bone and synovial fluid. Cefuroxime passes the blood/brain barrier if the meninges are inflamed.

Excretion of cefuroxime is about 50% by glomerular filtration and 50% renal tubules. Almost complete recovery of unchanged cefuroxime in the urine is achieved within 24 hours, the majority being excreted within 6 hours.

No experimental evidence of embryopathic or teratogenic effects due to cefuroxime.

None.

Do not mix in the syringe with aminoglycoside antibiotics.

Store below 30°C, keep in the original package in order to protect from light.

For storage conditions of the reconstituted and diluted medicinal product, see section 6.3

Ceruxim 1.5g powder for solution for injection or infusion: Type I clear glass vials having a nominal capacity of 15ml that are sealed with a 20mm bromobutyl rubber stopper and an aluminium cap.

Boxes of 1, 10, 50 or 100 vials

See “Dosage and Administration”