Zinnat Tablets 125mg

Each tablet contains 125mg cefuroxime (as cefuroxime axetil).

White, film-coated, capsule-shaped tablet plain on one side and engraved with 'GXES5' on the other.

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

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.

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

Gonorrhoea acute uncomplicated gonococcal urethritis, and cervicitis.

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.

Route of administration: oral

Dosage in adults

Most infections will respond to 250mg bd. In mild to moderate lower respiratory tract infections e.g. bronchitis 250mg bd should be given. For more severe lower respiratory tract infections, or if pneumonia is suspected then 500mg bd should be given. For urinary tract infections a dose of 125mg bd is usually adequate; in pyelonephritis the recommended dose is 250mg bd. 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 bd 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 bd 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.

Dosage in children

The usual dose is 125mg bd or 10mg/kg bd to a maximum of 250mg daily. For otitis media, in children less than 2 years of age the usual dosage is 125mg bd or 10mg/kg bd to a maximum of 250mg daily and in children over 2 years of age, 250mg bd or 15mg/kg bd 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 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.

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.

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

A positive Coomb's test has been reported during treatment with cephalosporins. This phenomenon can interfere with cross matching of blood.

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 frequency:

very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <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)

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 epidermis, (including penicillinase - producing strains but excluding methicillin-resistant strains); Streptococcus pyogenes (and other betahaemolytic streptococci); Streptococcus pneumonia 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 gastro-intestinal 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%.

No additional data of relevance.

Microcrystalline cellulose

Croscarmellose sodium, Type A

Sodium lauryl sulphate

Hydrogenated vegetable oil

Silica Colloidal Anhydrous

Methylhydroxypropyl cellulose

Propylene glycol

Methyl parahydroxybenzoate

Propyl parahydroxybenzoate

Opaspray white M-1-7120J

A positive Coombs' test has been reported during treatment with cephalosporins - this phenomenon can interfere with cross-matching of blood.

36 months in aluminium foil strips or blister packs.

24 months in HDPE bottles (not marketed in the UK)

Cefuroxime axetil tablets in foil strips or blisters should be stored below 30°C.

Cefuroxime axetil tablets in HDPE bottles should be stored below 25°C (not marketed in the UK)

Aluminium foil blister pack with an aluminium lid.

Pack size: 2, 4, 14 and 50

(2 and 4 not marketed in the UK)

Aluminium foil strips coated with surlyn polymer.

Pack size: 14 and 50

(not marketed in the UK)

White opaque, high density polyethylene bottles fitted with a clic-loc child resistant closure containing a pulp board wad to which is wax-bonded a 'lectraseal' membrane.

Pack size: 14 and 60

(not marketed in the UK)

None stated.

Glaxo Wellcome UK Limited trading as GlaxoSmithKline UK

Stockley Park West

Uxbridge

Middlesex

UB11 1BT

PL 10949/0095

15 October 1998

3 July 2008

POM