Zinacef

Cefuroxime sodium.

Each 750 mg vial contains 42 mg sodium (1.8 mEq).
Vials containing 750 mg, or 1.5 g 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.
Excipients/Inactive Ingredients: None.

Pharmacology: Pharmacodynamics: Cefuroxime is a well characterised and effective antibacterial agent which has bactericidal activity against a wide range of common pathogens, including β-lactamase producing strains. Cefuroxime has good stability to bacterial β-lactamase, and consequently is active against many ampicillin-resistant or amoxycillin-resistant strains.
The bactericidal action of cefuroxime results from inhibition of cell wall synthesis by binding to essential target proteins.
The prevalence of acquired resistance is geographically and time dependent and for select species may be very high. Local information on resistance is desirable, particularly when treating severe infections. (See Table 1.)

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Pharmacokinetics: Peak levels of cefuroxime are achieved within 30 to 45 minutes after i.m. administration.
Protein binding has been variously stated as 33-50% depending on the methodology used.
Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in bone, synovial fluid and aqueous humour. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion.
The serum half-life after either i.m. or i.v. injection is approximately 70 minutes.
In the first weeks of life the serum half-life of cefuroxime can be 3 to 5 times that in the adult.
Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level. There is an almost complete recovery (85 to 90%) of unchanged cefuroxime in urine within 24 hours of administration. The major part is excreted in the first 6 hours.
Serum levels of cefuroxime are reduced by dialysis.
Toxicology: Pre-clinical Safety Data: No additional data of relevance.

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. Susceptibility to ZINACEF will vary with geography and time and local susceptibility data should be consulted where available (see Pharmacology: Pharmacodynamics under Actions).
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, pharyngitis and otitis media; urinary tract infections for example, acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria; soft-tissue infections for example, cellulitis, erysipelas 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, meningitis and peritonitis; prophylaxis against infection in abdominal, pelvic, orthopaedic, cardiac, pulmonary, oesophageal and vascular surgery where there is increased risk from infection.
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), especially for prophylaxis in colonic or gynaecological surgery.
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.

ZINACEF Injection for intravenous (i.v.) and/or intramuscular (i.m.) administration.
ZINACEF 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.
No more than 750 mg should be injected at one intramuscular site.
GENERAL DOSING RECOMMENDATIONS: Adults: Many infections will respond to 750 mg three times daily by i.m. or i.v. injection. For more severe infections, the dose should be increased to 1.5 g three times daily given i.v. The frequency of administration may be increased to 6-hourly if necessary, giving total daily doses of 3 to 6 g. Where clinically indicated, some infections respond to 750 mg or 1.5 g twice daily (i.v. or i.m.) followed by oral therapy with ZINNAT.
Infants and Children: 30 to 100 mg/kg/day given as 3 or 4 divided doses. A dose of 60 mg/kg/day is appropriate for most infections.
Neonates: 30 to 100 mg/kg/day given as 2 or 3 divided doses (see Pharmacology: Pharmacokinetics under Actions).
GONORRHOEA: Adults: 1.5 g as a single dose (as 2 x 750 mg injections given i.m. with different sites, e.g. each buttock).
MENINGITIS: ZINACEF is suitable for sole therapy of bacterial meningitis due to sensitive strains.
Adults: 3 g given i.v. every 8 hours.
Infants and Children: 150 to 250 mg/kg/day given i.v. in 3 or 4 divided doses.
Neonates: The dosage should be 100 mg/kg/day given i.v.
PROPHYLAXIS: The usual dose is 1.5 g given i.v. with induction of anaesthesia for abdominal, pelvic and orthopaedic operations. This may be supplemented with two 750 mg i.m. doses 8 and 16 hours later.
In cardiac, pulmonary, oesophageal and vascular operations, the usual dose is 1.5 g given i.v. with induction of anaesthesia, continuing with 750 mg given i.m. three times daily for a further 24 to 48 hours.
In total joint replacement, 1.5 g ZINACEF powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.
SEQUENTIAL THERAPY: Adults: Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.
Pneumonia: 1.5 g ZINACEF twice daily (given i.v. or i.m.) for 48 to 72 hours, followed by 500 mg twice daily ZINNAT (cefuroxime axetil) oral therapy for 7 to 10 days.
Acute exacerbations of chronic bronchitis: 750 mg ZINACEF twice daily (given i.v. or i.m.) for 48 to 72 hours, followed by 500 mg twice daily ZINNAT (cefuroxime axetil) oral therapy for 5 to 10 days.
RENAL IMPAIRMENT: 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.
It is not necessary to reduce the standard dose (750 mg to 1.5 g 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 i.v. or i.m. at the end of each dialysis. In addition to parenteral use, ZINACEF can be incorporated into the peritoneal dialysis fluid (usually 250 mg for every 2 litres of dialysis fluid).
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 previously.

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.

Hypersensitivity to cephalosporin antibiotics.

Special care is indicated in patients who have experienced an allergic reaction to penicillins or other 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 (see Dosage & Administration).
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 ZINACEF. Persistence of positive cerebral spinal fluid (CSF) cultures of Haemophilus influenzae at 18 - 36 hours has also been noted with ZINACEF injection, as well as with other antibiotic therapies; however, the clinical relevance of this is unknown.
As with other antibiotics, use of ZINACEF may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of other non-susceptible organisms (e.g. enterococci and Clostridium difficile), which may require interruption of treatment.
Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experience abdominal cramps, treatment should be discontinued immediately and the patient investigated further.
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. If there is no clinical improvement within 72 hours, then the parenteral course of treatment must be continued.
Refer to the relevant prescribing information for ZINNAT before initiating sequential therapy.
Effects on Ability to Drive and Use Machines: None reported.

There is no experimental evidence of embryopathic or teratogenic effects attributable to ZINACEF, but, as with all drugs, 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 ZINACEF is administered to a nursing mother.

The most common adverse reactions are neutropenia, eosinophilia, transient rise in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver and injection site reactions.
The frequency categories assigned to the adverse reactions as follows are estimates, as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with ZINACEF may vary according to the indication.
Data from clinical trials were used to determine the frequency of very common to rare adverse reactions. The frequencies assigned to all other adverse reactions (i.e. those occurring at <1/10,000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.
Treatment related adverse reactions, all grades, are listed as follows by MedDRA body system class, frequency and grade of severity. The following convention has been used for the classification of frequency: very common ≥1/10; common ≥1/100 to <1/10; uncommon ≥1/1,000 to <1/100; rare ≥1/10,000 to <1/1,000; very rare <1/10,000 and not known (cannot be estimated from the available data). (See Table 2.)

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Paediatric population: The safety profile for cefuroxime sodium in children is consistent with the profile in adults.

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

Instructions for Use/Handling: Intramuscular: Add 3 ml Water for Injections to 750 mg ZINACEF. Shake gently to produce an opaque suspension.
Intravenous: Dissolve ZINACEF in Water for Injections using at least 6 ml for 750 mg, or 15 ml for 1.5 g.
Intravenous infusion: Dissolve 1.5 g of ZINACEF in 15 ml of Water for Injections. Add the reconstituted solution of ZINACEF to 50 to 100 ml of a compatible infusion fluid (see Compatibility as follows). 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.
Compatibility: 1.5 g ZINACEF constituted with 15 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.
1.5 g ZINACEF is compatible with azlocillin 1 g (in 15 ml) or 5 g (in 50 ml) for up to 24 hours at 4°C or 6 hours below 25°C.
ZINACEF (5 mg/ml) in 5% w/v or 10% w/v xylitol injection may be stored for up to 24 hours at 25°C.
ZINACEF is compatible with aqueous solutions containing up to 1% lidoocaine hydrochloride.
ZINACEF is compatible with the more commonly used i.v. 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 0.45% 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; Compound Sodium Lactate Injection BP (Hartmann's Solution).
The stability of ZINACEF in Sodium Chloride Injection BP 0.9% w/v and in 5% Dextrose Injection is not affected by the presence of hydrocortisone sodium phosphate.
ZINACEF has also been found compatible for 24 hours at room temperature when admixed in i.v. 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.
Incompatibilities: ZINACEF should not be mixed in the syringe with aminoglycoside antibiotics.
The pH of 2.74% w/v Sodium Bicarbonate Injection BP considerably affects the colour of the solution and therefore this solution is not recommended for the dilution of ZINACEF. However, if required, for patients receiving Sodium Bicarbonate Injection by infusion ZINACEF may be introduced into the tube of the giving set.

Store below 30°C. Protect from light.
Some increase in the colour of prepared solutions and suspensions of ZINACEF may occur on storage.
Shelf-Life: Wet Shelf Life: Suspensions of ZINACEF for intramuscular injection and aqueous solutions for direct intravenous injection should be used immediately after reconstitution.

Cephalosporins

J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.

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