GlaxoSmithKline (Ireland) Ltd

Zinnat 500mg Film-Coated Tablets

Each tablet contains 500mg cefuroxime as cefuroxime axetil.

Excipients: Contains approximately 0.33 mg parahydroxybenzoates per tablet.

For a full list of excipients see section 6.1

Film-coated tablet.

White to off-white biconvex capsule shaped tablet, plain on one face and the code 'GXEG2' engraved on the reverse.

Zinnat tablets are indicated in the treatment of systemic infections due to Gram-positive and Gram-negative micro-organisms susceptible to this anti-infective in respiratory tract and genito-urinary tract infections.

Skin and soft tissue infections for example, furunculosis, pyoderma and impetigo. Gonorrhoea, acute uncomplicated gonococcal urethritis, and cervicitis.

Treatment of early Lyme disease and subsequent prevention of late Lyme disease in adults and children over 12 years old.

Cefuroxime is also available as the sodium salt (Zinacef) for parenteral 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, Zinnat is effective when used following initial parenteral Zinacef (cefuroxime sodium) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.

Adults (including the elderly):

Lower respiratory tract infections:

Mild to moderate lower respiratory tract infections e.g. bronchitis - the usual dose is 250mg twice daily.

More severe lower respiratory tract infections or if pneumonia is suspected - the usual dose is 500mg twice daily.

Upper respiratory tract infections:

Upper respiratory tract infections - the usual dose is 250mg twice daily.

Urinary tract infections:

For urinary tract infections the usual dose is 125 - 250mg bd.

Gonorrhoea (uncomplicated) - the usual dose is 1g as a single dose.

Lyme disease in adults and children over the age of 12 years - 500mg twice daily for 20 days.

Sequential therapy:

Pneumonia: 1.5g Zinacef tid or bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 7-10 days.

Acute exacerbations of chronic bronchitis: 750 mg Zinacef tds or bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 5-10 days.

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

Children:

Most infections - 125mg (1 x 125mg tablet) twice daily, or 10mg/kg twice daily to a maximum of 250mg daily.

Children aged two years or older with otitis media or where appropriate, with more severe infections - 250mg (1x 250mg tablet) twice daily, or 15mg/kg twice daily to a maximum of 500mg daily.

Renal impairment or on dialysis.

On the basis of experience to date a reduction in dosage is not deemed necessary.

Optimum absorption is achieved if medication is taken after food.

Patients with known hypersensitivity to cephalosporin antibiotics.

Use of cefuroxime should be reserved for serious or severe infections.

Cross-resistance and cross-sensitisation may exist between penicillins and cephalosporins. Cephalosporin antibiotics may in general be given safely to patients, who are hypersensitive to penicillins, although cross-reactions have been reported. Special care is indicated in patients who have experienced an anaphylactic reaction to penicillin.

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

Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics, therefore, it is important to consider its diagnosis in patients who develop serious diarrhoea during or after antibiotic use.

The Jarisch-Herxheimer reaction has been seen following Zinnat treatment of Lyme disease. It results directly from the bactericidal activity of Zinnat on the causative organism of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

Drugs which reduce gastric acidity may result in a lower bioavailability of Zinnat compared with that of the fasting state and tend to cancel the effect of enhanced post-prandial absorption.

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

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

Studies in animals do not suggest an adverse effect in reproductive studies. The drug is excreted in breast milk. There is no experience of use during pregnancy in human beings. Cefuroxime should not be used during pregnancy or lactation in breast feeding women unless considered essential by the physician.

As this medicine may cause dizziness, patients should be warned to be cautious when driving or operating machinery.

Adverse drug reactions to cefuroxime axetil 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 example from placebo-controlled studies) for calculating incidence were not available. In addition the incidence of adverse reactions associated with cefuroxime axetil may vary according to the indication. Data from large clinical studies 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 true frequency. Placebo-controlled trial data were not available. Where incidences have been calculated from clinical trial data, these were based on drug-related (investigator assessed) data.

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

Blood and lymphatic system disorders

Cephalosporins as a class tend to be absorbed onto the surface of red cells membranes and react with antibodies directed against the drug to produce a positive Coombs' test (which can interfere with cross-matching of blood) and very rarely haemolytic anaemia.

Immune system disorders

*Hypersensitivity reactions including

Nervous system disorders

Gastrointestinal disorders

Hepatobiliary disorders

Skin and subcutaneous tissue disorders

See also Immune system disorders

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.

Serum levels of cefuroxime can be reduced by haemodialysis and peritoneal dialysis.

A prodrug of the cephalsoporin, cefuroxime, a bactericide resistant to most B-lactamases, Cefuroxime axetil is well absorbed after oral administration (particularly following a meal) hydrolysed in the intestinal epithelium and blood releasing cefuroxime. Peak serum levels are achieved 2-3 hours post dose and the drug is eliminated without metabolism through the kidney by glomerular filtration and active tubular secretion. Probenecid concurrently administered will delay elimination. About 50% of cefuroxime is protein bound.

Bacteriology:

Cefuroxime is usually active against the following organisms in vitro.

Aerobes Gram-negative:-

− Haemophilus influenzae (including ampicillin-resistant strains)

− Haemophilus parainfluenzae

− Moraxella (Branhamella) catarrhalis

− Neisseria gonorrhoeae (including penicillinase and non-penicillinase producing strains)

− Klebsiella spp.

− Proteus mirabilis

− Providencia spp.

− Proteus rettgeri.

Aerobes Gram-positive:-

− Staphylococcus aureus and Staphylococcus epidermidis (including penicillinase producing strains but excluding methicillin resistant strains)

− Streptococcus pyogenes (and other beta-haemolytic streptococci)

− Streptococcus pneumoniae

− Streptococcus Group B (Streptococcus agalactiae)

Anaerobes:-

− Gram-positive and Gram-negative cocci (including Peptococcus and Peptostreptococcus species)

− Gram-positive bacilli (including Clostridium species)

− Gram-negative bacilli (including Bacteroides and Fusobacterium species)

− Propionibacterium spp.

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 and Staphylococcus epidermidis.

− Legionella spp

− Enterococcus (Streptococcus) faecalis.

Some strains of the following genera are not susceptible to Cefuroxime:-

− Morganella morganii

− Proteus vulgaris

− Enterobacter spp.

− Citrobacter spp.

− Serratia spp.

− Bacteroides fragilis

− Escherichia coli.

Zinnat is well absorbed after oral administration (particularly following a meal) hydrolysed in the intestinal epithelium and blood releasing cefuroxime. Peak serum levels are achieved 2-3 hours post dose and the drug is eliminated without metabolism through the kidney by glomerular filtration and active tubular secretion. Probenecid concurrently administered will delay elimination. About 50% of cefuroxime is protein bound.

No additional data of relevance.

Tablet core:

Microcrystalline cellulose

Croscarmellose sodium type A

Sodium lauril sulfate

Hydrogenated vegetable oil

Silica Colloidal anhydrous

Film coat:

Hypromellose

Propylene glycol

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Titanium dioxide (E171)

Sodium benzoate (E211)

Not applicable

3 years.

Do not store above 30°C.

Zinnat tablets are packed in double aluminium & aluminium/paper foil blisters of 5, 14 and 50 tablets.

Not all pack sizes may be marketed

No special requirements

GlaxoSmithKline (Ireland) Limited

Stonemasons Way,

Rathfarnham,

Dublin 16

PA 1077/15/4

4^th August 1989/17^th April 2009

December 2009