GlaxoSmithKline (Ireland) Ltd

Zinnat 125mg/5ml Granules for Oral Suspension

Reconstitution of multidose bottles as directed yields a suspension containing 125mg of cefuroxime (as cefuroxime axetil) in each 5ml.

Each Sachet contains 125mg granules of cefuroxime (as cefuroxime axetil) for single dose administration when reconstituted.

Excipients: Contains approximately 3.062 g of sucrose and 21 mg of aspartame (E951) per dose.

For a full list of excipients, see section 6.1.

Granules for oral suspension

White to off white free flowing granules

For 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 or cellulitis

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

Adults (including the elderly)

LRTI

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

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

URTI

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

UTI

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

Children of 3 months and over:

Most infections - 125mg (5ml of suspension or 1 x 125mg sachet) 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 (10ml of suspension or 2 x 125mg sachet) 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.

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

Use in patients hypersensitive to cephalosporins.

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

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 common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

The sucrose content of Zinnat granules and suspension (see section 6.1 List of Excipients) should be taken into account when treating diabetic patients, and appropriate advice provided.

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

Zinnat Suspension contains aspartame, which is a source of phenylalanine and so should be used with caution in patients with phenylketonuria.

Drugs which reduce gastric acidity may result in a lower bioavailability of cefuroxime axetil compared with that of the fasting state and tend to cancel the effect of enhanced absorption after food.

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.

Cefuroxime should not be used during pregnancy or lactation in breast-feeding women unless considered essential by physician. There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime axetil. Cefuroxime is excreted in human milk.

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

Common: Candida overgrowth

Blood and lymphatic system disorders

Common: *Eosinophilia

Uncommon: *Positive Coombs' test, *thrombocytopenia, *leukopenia (sometimes profound)

Very rare: *Haemolytic anaemia

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

Uncommon: *Skin rashes

Rare: *Urticaria, *pruritus

Very rare: *Drug fever, *serum sickness, *anaphylaxis

Nervous system disorders

Common: *Headache, dizziness

Gastrointestinal disorders

Common: *Gastrointestinal disturbances including *diarrhoea, *nausea, abdominal pain

Uncommon: *Vomiting

Rare: *Pseudomembranous colitis

Hepatobiliary disorders

Common: *Transient increases of hepatic enzyme levels, [ALT (SGPT), AST (SGOT), LDH]

Very rare: *Jaundice (predominantly cholestatic), *hepatitis

Skin and subcutaneous tissue disorders

Very rare: *Erythema multiforme, *Stevens-Johnson syndrome, *toxic epidermal necrolysis (exanthematic necrolysis)

See also Immune system disorders

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by haemodialysis or peritonial 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) and 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.

After oral administration cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolysed in the intestinal mucosa and blood to release cefuroxime into the circulation. Optimum absorption occurs when it is administered after a meal. Peak serum levels (2-3mg/l for a 125mgmg dose, 4-6mg/l for a 250mg dose, 5-8mg/l for a 500mg dose and 9-14mg/l for a 1g dose) occur approximately two to three hours after dosing when taken after food. The rate of absorption of cefuroxime from the suspension compared with the tablets is reduced, leading to later lower peak serum levels and slightly reduced systemic bioavailability (4-17% less). The serum half life is between 1 and 1.5 hours. Protein binding has been variously stated as 33-50% depending on the methodology used. Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion. Concurrent administration of probenecid increases the area under the mean serum concentrations time curve by 50%. Serum levels of cefuroxime are reduced by dialysis.

No information given.

Stearic acid

Sucrose

Tutti Frutti flavour

Povidone K30

Acesulfame potassium

Aspartame (E951)

Xantham gum

The reconstituted suspension or granules should not be mixed with hot liquids.

Unconstituted granules: 2 years.

Reconstituted suspension (multi dose bottles) When refrigerated between 2 and 8°C can be kept for up to 10 days.

The granules from sachets should be taken immediately following reconstitution.

Unconstituted granules: Do not store above 30°C.

Reconstituted suspension (multi dose bottles): Store in a refrigerator at 2^oC to 8^oC.

The reconstituted suspension from sachets should be taken immediately.

Multidose bottles:-

Ph.Eur Type III amber glass bottles with an induction heat seal membrane containing granules for 70ml of suspension for the 125mg/5ml suspension.

Sachets:-

Paper/polyethylene/foil/ethylenemethacrylic acid ionomer laminated sachet, 10 sachets per carton.

Reconstitution with water produces a white to off white fruit flavoured suspension.

Multi dose bottle: Always shake bottle vigorously before taking the medication.

If desired, Zinnat suspension can be further diluted from multidose bottles in cold fruit juices, or milk drinks and should be taken immediately.

Directions for reconstituted suspension in multidose bottles:

1. Shake the bottle to loosen the granules. Remove the cap.

2. Add the total amount of water (27ml) to the bottle as stated on label. Replace the cap.

3. Invert the bottle and rock the bottle vigorously (for about 15 seconds) as shown below.

4. Turn the bottle into an upright position and shake vigorously.

Directions for reconstituting suspension from sachets:-

1) Empty granules from sachet into a glass.

2) Add a small volume of water (approx. 10ml).

3) Stir well and drink immediately.

GlaxoSmithKline (Ireland) Limited,

Stonemasons Way,

Rathfarnham,

Dublin 16.

PA 1077/15/5

16^th January 1991/17^th April 2009.

December 2009.