CONFIDENTIAL

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ZINNAT
Cefuroxime axetil

QUALITATIVE AND QUANTITATIVE COMPOSITION

ZINNAT tablets containing either 125 or 250 mg of cefuroxime (as cefuroxime axetil).

PHARMACEUTICAL FORM
Zinnat Tablets 125mg: White, film-coated, capsule-shaped tablets engraved “GXES5” on
one side and plain on the other.

Zinnat Tablets 250mg: White, film-coated, capsule-shaped tablets engraved “GXES7” on

one side and plain on the other.

CLINICAL PARTICULARS
Indications
ZINNAT 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.

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

to ZINNAT will vary with geography and time and local susceptibility data should be
consulted where available (See Pharmacological properties, Pharmacodynamics).

Indications include:

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

– lower respiratory tract infections for example, pneumonia, acute bronchitis, and acute
exacerbations of chronic bronchitis

– 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

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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.

Dosage and Administration

The usual course of therapy is seven days (range 5 to 10 days).

ZINNAT should be taken after food for optimum absorption.

• Adults

Most infections 250 mg twice daily

Urinary tract infections 250 mg twice daily

Mild to moderate lower respiratory tract infections e.g. 250 mg twice daily
bronchitis

More severe lower respiratory tract infections, or if 500 mg twice daily

pneumonia is suspected

Pyelonephritis 250 mg twice daily

Uncomplicated gonorrhoea single dose of 1 g

Sequential therapy

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.

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 125 mg (1 x 125 mg tablet) twice daily

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Children with otitis media or, where 250 mg (1 x 250 mg tablet or 2 x 125 mg
appropriate, with more severe infections tablets) twice daily

ZINNAT tablets should not be crushed or split and are therefore unsuitable for treatment
of patients, such as younger children, who cannot swallow whole tablets.

There is no experience of using ZINNAT in children under the age of 3 months.

• Renal impairment

Cefuroxime is primarily excreted by kidneys. In patients with markedly impaired renal

function it is recommended that the dosage of cefuroxime be reduced to compensate for
its slower excretion (see the table below).

Creatinine Clearance T 1/2 Recommended Dosage

(hours)

≥30 ml/min 1.4 - 2.4 No dose adjustment necessary standard dose

of 125 mg to 500 mg given twice daily

10-29 ml/min 4.6 Standard individual dose given every

24 hours

<10 ml/min 16.8 Standard individual dose given every

48 hours

During haemodialysis 2–4 A single additional standard individual dose

should be given at the end of each dialysis

Contraindications
Patients with known hypersensitivity to cephalosporin antibiotics.

Warnings and Precautions

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

As with other antibiotics, use of ZINNAT 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
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significant diarrhoea occurs or the patient experiences 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.

Please refer to the relevant prescribing information for cefuroxime sodium before
initiating sequential therapy.

Interactions
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, 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 ZINNAT. This antibiotic does not interfere in the alkaline
picrate assay for creatinine.

Pregnancy and Lactation

There is no experimental evidence of embryopathic or teratogenic effects attributable to
ZINNAT 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 ZINNAT is administered to a nursing mother.

Effects on Ability to Drive and Use Machines

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

Adverse Reactions
Adverse drug reactions to ZINNAT 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 ZINNAT 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
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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 to <1/10
uncommon ≥1/1000 to <1/100
rare ≥1/10,000 to <1/1000
very rare <1/10,000

Infections and infestations

Common: Overgrowth of Candida

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 (See Warnings and Precautions)

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

Overdose
Signs and symptoms

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.

Treatment

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

PHARMACOLOGICAL PROPERTIES
Pharmacodynamics
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.

In vitro susceptibility of micro-organisms to Cefuroxime

Where clinical efficacy of cefuroxime axetil has been demonstrated in clinical trials
this is indicated with an asterisk (*).
Commonly Susceptible Species
Gram-Positive Aerobes:
Staphylococcus aureus (methicillin susceptible)*

Coagulase negative staphylococcus (methicillin susceptible)

Streptococcus pyogenes*
Beta-hemolytic streptococci
Gram-Negative Aerobes:
Haemophilus influenzae* including ampicillin resistant strains
Haemophilus parainfluenzae*
Moraxella catarrhalis*
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Neisseria gonorrhoea* including penicillinase and non-penicillinase producing

strains
Gram-Positive Anaerobes:
Peptostreptococcus spp.
Propionibacterium spp.
Spirochetes:
Borrelia burgdorferi*
Organisms for which acquired resistance may be a problem
Gram-Positive Aerobes:
Streptococcus pneumoniae*
Gram-Negative Aerobes:
Citrobacter spp. not including C. freundii
Enterobacter spp. not including E. aerogenes and E. cloacae
Escherichia coli*
Klebsiella spp. including Klebsiella pneumoniae*
Proteus mirabilis
Proteus spp. not including P. penneri and P. vulgaris
Providencia spp.
Gram-Positive Anaerobes:
Clostridium spp. not including C. difficile
Gram-Negative Anaerobes:
Bacteroides spp. not including B. fragilis
Fusobacterium spp.
Inherently resistant organisms
Gram-Positive Aerobes:
Enterococcus spp. including E. faecalis and E. faecium
Listeria monocytogenes
Gram-Negative Aerobes:
Acinetobacter spp.
Burkholderia cepacia
Campylobacter spp.
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Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Morganella morganii
Proteus penneri
Proteus vulgaris
Pseudomonas spp. including Pseudomonas aeruginosa
Serratia spp.
Stenotrophomonas maltophilia
Gram-Positive Anaerobes:
Clostridium difficile
Gram-Negative Anaerobes:
Bacteroides fragilis
Others:
Chlamydia species
Mycoplasma species
Legionella species

Pharmacokinetics
Absorption

After oral administration ZINNAT is slowly 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 shortly after a meal.

Following administration of ZINNAT tablets peak serum levels (2.1 mg/l for a 125 mg
dose, 4.1 mg/l for a 250 mg dose, 7.0 mg/l for a 500 mg dose and 13.6 mg/l for a 1 g
dose) occur approximately 2 to 3 hours after dosing when taken with food.

Distribution

Protein binding has been variously stated as 33 to 50% depending on the methodology
used.

Metabolism

Cefuroxime is not metabolised.

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Elimination

The serum half life is between 1 and 1.5 hours.

Cefuroxime is excreted by glomerular filtration and tubular secretion. Concurrent

administration of probenecid increases the area under the mean serum concentrations
time curve by 50%.

Renal impairment:

Cefuroxime pharmacokinetics have been investigated in patients with various degrees of

renal impairment. Cefuroxime elimination half-life increases with decrease in renal
function which serves as the basis for dosage adjustment recommendations in this group
of patients (See Dosage and Administration). In patients undergoing haemodialysis, at
least 60% of the total amount of cefuroxime present in the body at the start of dialysis
will be removed during a 4-hour dialysis period. Therefore, an additional single dose of
cefuroxime should be administered following the completion of haemodialysis.

Pre-clinical Safety Data

Animal toxicity studies indicated that cefuroxime axetil is of low toxicity with no
significant findings.

PHARMACEUTICAL PARTICULARS
List of Excipients
Microcrystalline cellulose.
Croscarmellose sodium.
Hypromellose
Sodium lauryl sulphate.
Hydrogenated vegetable oil.
Silicon dioxide.
Propylene glycol.
Methylhydroxybenzoate (E218).
Propylhydroxybenzoate (E216).
Titanium dioxide (E171).
Sodium benzoate (E211).

Incompatibilities
None reported.

Shelf Life
The expiry date is indicated on the packaging.
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Special Precautions for Storage

ZINNAT tablets should be stored at temperatures not exceeding 30C.

Nature and Contents of Container

Zinnat Tablets may be packaged into aluminium foil strips or double foil blister packs
and is available in pack sizes of 10 or 50 tablets.

Not all presentations are available in every country.

Instructions for Use/Handling

None.

Manufactured by:
Glaxo Wellcome Operations
Barnard Castle, UK

Version number: v01

Reference: GDS27/IPI07
Date of local revision: 24 April 2018

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©2018 GSK group of companies or its licensor.