Search The Medical Knowledge Base

Drug Details

ZINACEF

• Drug Class Description
  Cephalosporins.
• Generic Name
  Cefuroxime
• Presentation
  Cefuroxime is a white to cream 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.
• Description
  Vials contain either 250mg, 750mg or 1.5g cefuroxime (as sodium).
• Indications
  

  Zinacef is a bactericidal cephalosporin antibiotic which is resistant to most beta-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms. 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 Zinacef 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, (see precautions).

  In situations where mixed aerobic and anaerobic infections are encountered or suspected (e.g. peritonitis, aspiration pneumonia, abscesses in the lung, pelvis and brain), or are likely to occur (e.g. in association with colorectal or gynaecological surgery) it is appropriate to administer Zinacef in combination with metronidazole.

  Most of these infections will respond to an i.v. regimen of Zinacef (750mg) plus metronidazole injection (500mg/100ml) administered eight-hourly. In more severe or well established mixed infections, an i.v. regimen of Zinacef (1.5g) plus metronidazole injection (500mg/100ml) eight-hourly may be indicated. For the prophylaxis of infection in surgery (e.g. colorectal and gynaecological) a single dose of 1.5g Zinacef plus metronidazole injection (500mg/100ml) is appropriate.

  Alternatively this may be followed by two 750mg doses of Zinacef plus metronidazole.

  Indications include:

  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 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.

  Cefuroxime is also available as the axetil ester (Zinnat) for oral administration.

  This permits the use of sequential therapy with the same antibiotic, when a change from parenteral to oral therapy is clinically indicated. Where appropriate Zinacef is effective when used prior to oral therapy with Zinnat (cefuroxime axetil) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.

• Adult Dosage
  

  Intramuscular

  Add 1ml water for injections to 250mg Zinacef or 3ml water for injections to 750mg Zinacef. Shake gently to produce an opaque suspension.

  Intravenous

  Dissolve Zinacef in water for injections using at least 2ml for 250mg, at least 6ml for 750mg or 15ml for 1.5g. For short intravenous infusion (e.g. up to 30 minutes), 1.5g may be dissolved in 50ml water for injections. These solutions may be given directly into the vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluids.

  General Recommendations

  Adults: Many infections will respond to 750mg t.i.d. by im or iv injection. For more severe infections, this dose should be increased to 1.5g t.i.d. iv. The frequency of im or iv injection can be increased to six-hourly if necessary, giving total doses of 3g to 6g daily.

  Where clinically indicated adults with pneumonia and acute exacerbations of chronic bronchitis have been shown to respond to 750mg or 1.5g bd, followed by oral therapy with Zinnat (see Sequential therapy).

  Neonates: Doses of 30 to 100mg/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.

  Elderly: See dosage in adults.

  Other Recommendations

  Gonorrhoea: 1.5g should be given as a single dose. This may be given as 2 x 750mg injections into different sites eg each buttock.

  Meningitis: Zinacef is suitable for sole therapy of bacterial meningitis due to sensitive strains. The following dosages are recommended.

  Neonates: The initial dosage should be 100mg/kg/day iv. A reduction to 50mg/kg/day iv may be made when clinically indicated.

  Adults: 3g iv every eight hours. Data are not yet sufficient to recommend a dose for intrathecal administration.

  Prophylaxis: The usual dose is 1.5g iv with induction of anaethesia for abdominal, pelvic and orthopaedic operations, but may be supplemented with two 750mg im doses eight and sixteen hours later. In cardiac pulmonary oesophageal and vascular operations, the usual dose is 1.5g iv with induction of anaesthesia continuing with 750mg im t.d.s. 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.

  Sequential therapy:

  Pneumonia:

  1.5g bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 7 days.

  Acute exacerbations of chronic bronchitis:

  750mg bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 5-7 days.

  Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.

  Dosage in 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 Zinacef should be reduced to compensate for its slower excretion. However, it is not necessary to reduce the dose until the creatinine clearance falls below 20ml/min. In adults with marked impairment (creatinine clearance 10-20ml/min) 750mg bd is recommended and with severe impairment (creatinine clearance <10ml/min) 750mg once daily is adequate. For patients on haemodialysis a further 750mg dose should be given at the end of each dialysis. When continuous peritoneal dialysis is being used, a suitable dosage is usually 750mg twice daily.

  For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units a suitable dosage is 750mg twice daily. For low-flux haemofiltration follow the dosage recommended under impaired renal function.

  Cefuroxime is also available as the axetil ester (Zinnat) for oral administration. This permits parenteral therapy with cefuroxime to be followed by oral therapy in situations where a change from parenteral to oral is clinically indicated.

• Child Dosage
  

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

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

• Contra Indications
  

  Hypersensitivity to cephalosporin antibiotics

• Special Precautions
  

  Special care is indicated in patients who have experienced an allergic reaction to penicillins or beta-lactams.

  Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide 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. Clinical experience with Zinacef has shown that this is not likely to be a problem at the recommended dose levels.

  There may be some variation on the results of biochemical tests of renal function, but these do not appear to be of clinical importance. As a precaution, renal function should be monitored if this is already impaired.

  Delayed sterilisation of the CSF in patients with Haemophilus influenzae meningitis may result in an adverse outcome such as deafness and /or neurological sequelae. Persistence of positive CSF cultures of H. influenzae at 18-36 hours has been noted in some patients treated with cefuroxime sodium injection and, as with other therapeutic regimens used in the treatment of meningitis, hearing loss has been reported in some children.

  With a sequential therapy regime the timing of change to oral therapy is determined by severity of the infection, clinical status of the patient and susceptibility of the pathogens involved. The change to oral therapy should only be made once there is a clear clinical improvement. If there has been no clinical improvement after 72 hours of parenteral treatment, then the patient's treatment should be reviewed. Please refer to the relevant prescribing information for cefuroxime axetil before initiating sequential therapy.

  As with other antibiotics, prolonged use of cefuroxime may result in the overgrowth of non-susceptible organisms (e.g. Candida, enterococci, Clostridium difficile), which may require interruption of treatment.

• Interactions
  

  In common with other antibiotics, Zinacef may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

  As with other cephalosporin antibiotics in combination with potent diuretics such as furosemide or aminoglycosides, Zinacef may adversely affect renal function.

  Zinacef 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 Zinacef. This antibiotic does not interfere in the alkaline picrate assay for creatinine.

• Adverse Drug Reactions
  

  Adverse drug reactions are very rare (<1/10,000) and are generally mild and transient in nature.

  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 undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/1000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.

  The following convention has been used for the classification of frequency:
  very common 1/10, common 1/100 and <1/10, uncommon 1/1000 and <1/100, rare 1/10,000 and <1/1000, very rare <1/10,000.

  Infections and infestations
  Rare: Candida overgrowth from prolonged use

  Blood and lymphatic system disorders
  Common: Neutropenia, eosinophilia
  Uncommon: Leukopenia, decreased haemoglobin concentration, positive Coomb's test.
  Rare: Thrombocytopenia
  Very Rare: Haemolytic anaemia

  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.

  Immune system disorders/ Hypersensitivity reactions including
  Uncommon: Skin rash, urticaria and pruritus
  Rare: Drug fever
  Very rare: Interstital nephritis, anaphylaxis, cutaneous vasculitis

  See also Skin and subcutaneous tissue disorders and Renal and urinary disorders

  Gastrointestinal disorders
  Uncommon: Gastrointestinal disturbance
  Very rare: Pseudomembranous colitis

  Hepatobiliary disorders
  Common: Transient rise in liver enzymes
  Uncommon: Transient rise in bilirubin

  Transient rises in serum liver enzymes or bilirubin occur, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver.

  Skin and subcutaneous tissue disorders
  Very rare:  Erythema multiforme, toxic epidermal necrolysis and Stevens Johnson Syndrome.

  See also Immune system disorders

  Renal and urinary disorders 
  Very rare:  Elevations in serum creatinine, elevations in blood urea nitrogen and decreased creatinine clearance.

  See also Immune system disorders.

  General disorders and administration site conditions 
  Common: Injection site reactions which may include pain and thrombophlebitis

  Pain at the intramuscular injection site is more likely at higher doses. However it is unlikely to be a cause for discontinuation of treatment.