Zinnat Suspension 125mg/5ml

Cefuroxime 125mg/5ml (as 150 mg cefuroxime axetil)

Granules for constitution with water to form a suspension for oral administration.

Cefuroxime axetil is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most β-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms.

It is indicated for the treatment of infections caused by sensitive bacteria.

Indications include: Lower respiratory tract infections for example, acute bronchitis, acute exacerbations of chronic bronchitis and pneumonia.

Upper respiratory tract infections for example, ear, nose, throat infections, such as otitis media, sinusitis, tonsillitis and pharyngitis.

Genito-urinary tract infections for example, pyelonephritis, cystitis and urethritis.

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: Most infections will respond to 250mg b.d. In mild to moderate lower respiratory tract infections e.g. bronchitis 250mg b.d. should be given. For more severe lower respiratory tract infections, or if pneumonia is suspected then 500mg b.d. should be given. For urinary tract infections a dose of 125mg b.d. is usually adequate; in pyelonephritis the recommended dose is 250mg b.d. A single dose of one gram is recommended for the treatment of uncomplicated gonorrhoea.

Lyme disease in adults and children over the age of 12 years: the recommended dose is 500mg b.d. for 20 days.

Sequential therapy:

Pneumonia:

1.5g Zinacef 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 Zinacef bd (iv or im) for 48-72 hours, followed by 500mg 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.

Children: The usual dose is 125mg b.d. (1 x 125mg tablet or 5ml of suspension or 1 x 125mg sachet), or 10mg/kg b.d. to a maximum of 250mg daily. For otitis media, in children less than 2 years of age the usual dosage is 125mg b.d. (1 x 125mg tablet or 5ml of suspension or 1 x 125mg sachet), or 10mg/kg b.d. to a maximum of 250mg daily and in children over 2 years of age, 250mg b.d. (1 x 250mg tablet or 10ml of suspension or 2 x 125mg sachets), or 15mg/kg b.d. to a maximum of 500mg daily. There is no experience in children under 3 months of age.

Zinnat Tablets should not be crushed, therefore in younger children the suspension is more appropriate.

Elderly and Patients with Renal Impairment: No special precautions are necessary in patients with renal impairment or on renal dialysis or in the elderly at dosages up to the normal maximum of 1g per day.

The usual course of therapy is seven days.

Zinnat should be taken after food for optimum absorption.

Hypersensitivity to cephalosporin antibiotics.

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 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-limited consequence of antibiotic treatment of Lyme disease.

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 sodium before initiating sequential therapy.

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

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

In common with other antibiotics, Zinnat 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.

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime axetil but, as with all drugs, it should be administered with caution during early months of pregnancy. Cefuroxime is excreted in human milk, and consequently caution should be exercised when cefuroxime axetil is administered to a nursing mother.

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 following convention has been used for the classification of undesirable effects:- very common (1/10), common (1/100, <1/10), uncommon, (1/1000, <1/100,) rare( 1/10,000,<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 increasesof 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)

Renal and Urinary tract disorders

Very Rare: interstitial nephritis

Overdosage of cephalosporins can cause cerebral irritancy leading to convulsions.

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

Cefuroxime axetil is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most beta-lactamases and is active against a wide range of gram-positive and gram-negative organisms.

Microbiology:

Cefuroxime axetil owes its in vivo bactericidal activity to the parent compound, cefuroxime. Cefuroxime is a well-characterized and effective antibacterial agent which has broad-spectrum bactericidal activity against a wide range of common pathogens, including beta-lactamase-producing strains. Cefuroxime has good stability to bacterial beta-lactamase and consequently, is active against many ampicillin-resistant and amoxicillin-resistant strains. The bactericidal action of cefuroxime results from inhibition of cell-wall synthesis by binding to essential target proteins.

Cefuroxime is usually active against the following organisms in vitro:

Aerobes, Gram-negative: Haemophilus influenzae (including ampicillin-resistant strains); Haemophilus parainfluenzae; Moraxella catarrhalis; Escherichia coli; Klebsiella species; Proteus mirabilis; Proteus inconstans; Providencia species; Proteus rettgeri and Neisseria gonorrhoea (including penicillinase and non-penicillinase-producing strains).

Some strains of Morganella morganii, Enterobacter species and Citrobacter species have been shown by in vitro tests to be resistant to cefuroxime and other beta-lactam antibiotics.

Aerobes, Gram-positive: Staphylococcus aureus (including penicillinase-producing strains but excluding methicillin-resistant strains); Staphylococcus epidermidis, (including penicillinase producing strains but excluding methicillin-resistant strains); Streptococcus pyogenes (and betahaemolytic streptococci), Streptococcus pneumoniae; Streptococcus Group B (Streptococcus agalactiae) and Propionibacterium species.

Certain strains of enterococci, eg. Streptococcus faecalis, are resistant.

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). Most strains of Bacteroides fragilis are resistant.

Other organisms, Borrelia burgdorferi.

Pseudomonas species, Campylobacter species, Acinetobacter calcoaceticus, Listeria monocytogenes, Legionella species and most strains of Serratia and Proteus vulgaris and Clostridium difficile are resistant to many cephalosporins including cefuroxime.

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 cefuroxime levels occur approximately two to three hours after oral dosing. The serum half life is about 1.2 hours. Approximately 50% of serum cefuroxime is protein bound. Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion.

Concurrent administration of probenecid increases the area under the mean serum concentration time curve by 50%. Serum levels of cefuroxime are reduced by dialysis.

No additional data of relevance.

Aspartame

Xanthan gum

Acesulfame potassium

Povidone K30

Stearic Acid

Sucrose

Tutti Frutti Flavour

Purified Water

Sucrose Quantities:

None.

The shelf life of unconstituted Zinnat Suspension from date of manufacture is 24 months stored below 30°C. The reconstituted suspension, when refrigerated between 2 and 8°C can be kept for up to 10 days.

Zinnat Suspension granules should be stored below 30^°C.

Multidose Bottles: The reconstituted suspension must be refrigerated as soon as possible at between 2 and 8°C.

Sachets : Reconstituted suspension should be taken immediately.

Zinnat Suspension 125mg/5ml, granules for oral suspension are supplied in multidose bottles* *of 50, 70, 100, 140 and 200ml (Delete as appropriate) and in 125 and 250mg sachets (heat-sealed laminate of paper/polyethylene/foil/ethylene-methacrylic acid ionomer).

125mg sachets are packed as either 1 duplex sachet in a carton or 7 duplex sachets in a carton (i.e. 2 or 14 doses).

250mg sachets are packed as 7 duplex sachets in a carton (i.e. 14 doses).

*Ph Eur Type III amber glass multiple unit bottles with a closure containing a heat-sealed induction membrane and a re-seal liner.

The bottle should always be shaken vigorously before administration.

The reconstituted suspension in multidose bottles when refrigerated between 2 and 8°C can be kept for up to 10 days.

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

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

Directions for reconstituting suspension in multidose bottles: -

1. Shake the bottle to loosen the granules. Remove the cap and the heat-seal membrane. If the latter is damaged or not present, the product should be returned to the pharmacist.

2. Add the total amount of water to the bottle as stated on its label. Replace the cap.

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

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

5. Refrigerate as soon as possible at between 2 and 8°C.

Directions for reconstituting suspension from sachets: -

1. Empty granules from sachet into a glass.

2. Add a small volume of water.

3. Stir well and drink immediately.

Glaxo Wellcome UK Limited

t/a Glaxo Laboratories

Stockley Park West

Uxbridge

Middlesex UB11 1BT

PL10949/0094

1 July 1993

3 July 2008

POM