INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
INTRACEF 250 mg, 750 mg and 1,5 g sterile powder for injection.

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

INTRACEF 250 mg, 750 mg and 1,5 g sterile powder for injection.

COMPOSITION:
Vials containing 250 mg, 750 mg and 1,5 g cefuroxime as cefuroxime sodium.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 - Antimicrobial agents: Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION:
Cefuroxime is a bactericidal semi-synthetic cephalosporin antibiotic which is resistant to most ß-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms. Peak serum levels of cefuroxime are reached 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 produces an elevated peak serum level and restricts the excretion of the antibiotic. There is almost complete recovery of unchanged cefuroxime in the urine within 24 hours of administration the major part being eliminated within the first 6 hours. The tubular excretion component of renal clearance of cefuroxime is of the order of 50%.

INDICATIONS:
Cefuroxime is indicated for the treatment of the following infections when caused by susceptible strains of the designated micro-organisms:
Respiratory tract infections
Ear, nose and throat infections
Urinary tract infections
Bone and joint infections
Soft tissue infections
Obstetrics and gynaecological infections
Gonorrhoea
Prophylaxis against infection in abdominal, cardiac and pulmonary surgery where there is an increased risk of infection.
Bacteriology:
Sensitivity tests should be carried out wherever possible. Cefuroxime is active in vitro against:
Staphylococcus aureus including penicillin-resistant strains but not the rare methicillin-resistant strains
Escherichia coli
Klebsiella spp
Enterobacter spp
Streptococcus pyogenes
Streptococcus viridans
Clostridium spp
Proteus mirabilis
Proteus rettgeri
Proteus vulgaris
Proteus morganii
Neisseria spp - including ß-lactamase producing strains of N. gonorrhoea
Haemophilus influenzae
Bacteroides fragilis
In vitro sensitivity does not necessarily imply in vivo efficacy.

CONTRA-INDICATIONS:
INTRACEF is contra-indicated in patients with a known hyper-sensitivity to cephalosporins.
The safety in pregnancy and lactation has not been established.

WARNINGS:
Before INTRACEF therapy is started, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins or other medicines. Cefuroxime should be given cautiously to penicillin-sensitive patients.

DOSAGE AND DIRECTIONS FOR USE:
General dosage recommendation:
Adults:
The dosage range for adults lies between 1,5 g to 6 g/day. Many infections will respond to 750 mg 3 times daily given by intramuscular or intravenous injection. For more severe infections this dose should be increased to 1,5g 3 times daily intravenously. The frequency of intramuscular or intravenous injection can be increased to 6-hourly if necessary.
Infants and children:
Doses of 30 to 100 mg/kg/day given as 3 to 4 divided doses. A dose of 60 mg/kg/day will be appropriate for most infections.
Other recommendations:
Gonorrhoea:
15 g cefuroxime should be given as a single dose. This may be given as 2 x 750 mg injections into different sites, e.g. into each buttock.
Surgical Infection Prophylaxis:
The usual dose is 1,5 g intravenously with induction of anaesthesia for abdominal and gynaecological operations but this may be supplemented with 2 x 750 mg intramuscular doses 8 and 16 hours later. In cardiac and pulmonary operations, the usual dose is 1,5 g intravenously with induction of anaesthesia continuing with 750 mg intramuscularly 3 times daily for a further 24 to 48 hours.
Dosage in impaired renal function:
Cefuroxime is excreted by the kidneys. Therefore 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 dose until the Glomerular Filtration Rate falls below 20 mL/min. In adults with marked impairment (Glomerular Filtration Rate 10 to 20 mL/min) 750 mg twice daily is recommended and with severe impairment (Glomerular Filtration Rate less than 10 mL/min) 750 mg once daily is adequate. For patients on dialysis, a further 750 mg dose should be given at the end of each dialysis. When continuous peritoneal dialysis is being used, a suitable dosage is usually 750 mg twice daily. In the treatment of beta-haemolytic streptococcal infections a therapeutic dose must be administered for at least 10 days.

ADMINISTRATION
Intramuscular injection:
Add 1 mL sterile water for injections to 250 mg cefuroxime, or 3 mL sterile water for injections to 750 mg cefuroxime. Shake gently to produce an opaque suspension. Suspensions which appear granular must be discarded.
Intravenous injection:
Dissolve cefuroxime in sterile water for injections using at least 2 mL for 250 mg, at least 6 mL for 750 mg or 15 mL for 1,5g. Solutions which appear turbid must be discarded.
Intravenous infusion:
For short intravenous infusion (30 to 60 minutes) 15 g may be dissolved in 50 mL sterile water for injections. These solutions may be given directly into the vein or introduced into the tubing of the administration set if the patient is receiving parenteral fluids. Solutions which appear turbid must be discarded. Solutions of cefuroxime for intramuscular injection and aqueous solutions for direct intravenous injection should be used within 5 hours if kept below 25°C or within 48 hours if refrigerated (2 - 8°C). Some increase in colour from light yellow to amber may occur on storage.
Solutions for short intravenous infusion (1,5g plus 50 mL sterile water for injections) which show less increase in colour, should be used within 24 hours if kept below 25°C or within 72 hours if refrigerated (2 - 8°C).
Cefuroxime is compatible with the more commonly used intravenous fluids. It will retain its potency for up to 24 hours at room temperature (25°C) or seven days under refrigeration in 0,9% m/v Sodium Chloride injection BP, 5% Dextrose injection BP 0,18% m/v Sodium Chloride plus 4% Dextrose injection BP and Compound Sodium Lactate injection BP (Hartmann's solution). The pH of 2,74% m/v Sodium Bicarbonate injection B.P. considerably 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 by infusion the cefuroxime may be introduced into the tube of the administration set. The stability of cefuroxime in 0,9% m/v Sodium Chloride injection BP and in 5%
Dextrose injection is not affected by the presence of hydrocortisone sodium phosphate. Cefuroxime is also compatible with aqueous solution containing up to 1% lignocaine HCl. Darkening of the powder or solution does not affect the potency.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Thrombophlebitis after intravenous injection, gastrointestinal disturbance including diarrhoea, nausea and vomiting and candida intertrigo have been reported.
Hypersensitivity reactions such as skin rashes (maculopapular and urticarial), drug fever reactions resembling serum sickness and anaphylaxis have been reported. There have also been reports of erythema multiforme including the Stevens-Johnson Syndrome, and toxic epidermal necrolysis.
The main changes in haematological parameters seen in some patients have been the unexplained decreased haemoglobin concentration and eosinophilia.
Patients developing eosinophilia should have renal function closely monitored, since hypersensitivity with acute renal failure has previously been documented.
Leucopenia, neutropenia and thrombocytopenia have also been noted.
Patients developing decreased haemoglobin concentration should have their bone marrow response monitored.
A positive Coombs test has been found with patients treated with cefuroxime, which can interfere with the cross-matching of blood. Haemolytic anaemia may occur.
There are sometimes rises in serum liver enzymes or serum bilirubin, particularly in patients with pre-existing liver disease. These have usually returned to normal when therapy has stopped with no ill effect.
There may also be some variation in the results of biochemical tests of renal function, but these do not appear to be of clinical importance. If renal function is already impaired, this should be monitored as a precaution.
Transient pain may be experienced at the site of intramuscular injection, which is more likely to occur with higher doses. However, it is unlikely to be a cause for discontinuation of the treatment.
Precautions:
Care should be taken with patients who have experienced an anaphylactic reaction to penicillin.
Cefuroxime does not interfere with enzyme-based tests for glucosuria. Slight interference with copper reduction methods (Bennedict's, Fehling’s, Clinitest) have been observed. However this should not lead to false-positive results.
It is recommended that either the glucose oxidase or hexokinase methods be used to determine blood/plasma glucose levels in patients treated with cefuroxime.
In the ferricyanide test, cefuroxime may cause false -negative reactions. Some cephalosporins can cause a falsely high reading in the alkaline picrate assay for creatinine, although the degree of elevation is unlikely to be of clinical importance. It is possible that cefuroxime may also interfere with this determination.
Prolonged use may result in the growth of non-susceptible organisms. Patients developing frequent loose stools should be carefully monitored for the possible development of pseudomembranous colitis.
When possible, concomitant use of furosemide and cefuroxime should be avoided. If used together renal function should be monitored closely, since furosemide may enhance the nephrotoxic potential of the cephalosporins.
The combined use of cephalosporins and aminoglycosides seems to increase the risk of nephrotoxicity, and should be undertaken with caution and with close monitoring of renal function.
Cefuroxime should not be administered together with other medicines.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See "Side effects”.
Excessively large doses of all cephalosporins can cause cerebral irritation and may cause convulsions.
Serum levels of cefuroxime are reduced by haemodialysis or peritoneal dialysis.
Treatment is supportive and symptomatic.

IDENTIFICATION:
INTRACEF is a white to faint yellow crystalline powder.

PRESENTATION:
INTRACEF for injection: Clear glass vials containing 250 mg and 750 mg cefuroxime as the sodium salt packed in containers of 10.
Clear glass vials containing 1,5 g cefuroxime as the sodium salt packed individually.
INTRACEF for infusion:
Clear glass vials containing 1,5 g cefuroxime as the sodium salt packed individually.

STORAGE INSTRUCTIONS:
Before reconstitution: Store below 25°C. Protect from light.
Upon storage darkening of the content may occur without affecting the potency.
See "Administration". Keep out of reach of children.

REGISTRATION NUMBER:

INTRACEF 250 mg vials:	30/20.1.1/0483
INTRACEF 750 mg vials:	30/20.1.1/0484
INTRACEF 1,5g vials:	30/20.1.1/0485

NAME AND BUSINESS ADDRESS OF THE APPLICANT:

Pharmacare Limited	Marketed by: Intramed, Division of Pharmacare
7 Fairclough Rd	6 Gibaud Road
PORT ELIZABETH	PORT ELIZABETH
6001	6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
26 July 1996
                        12-749/7-98
                        KOHLER C&P P.E.
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