ZINNAT is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most b(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

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

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

·         ZINNAT should be taken after food for optimum absorption.

·         Adults

USequential therapy

Pneumonia

1.5 g ZINACEF three times a day or twice a day (intravenous (i.v.) or intramuscular ( i.m)) for 48 to 72 hours, followed by ZINNAT (cefuroxime axetil) oral therapy 500 mg twice a day for 7 to10 days.

Acute exacerbations of chronic bronchitis

750 mg ZINACEF three times a day or twice a day (iv or im) for 48 to 72 hours, followed by ZINNAT (cefuroxime axetil) oral therapy 500mg twice a day 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

ZINNAT tablets should not be crushed and are therefore unsuitable for treatment of patients, such as younger children, who cannot swallow tablets. In children ZINNAT oral suspension may be used.

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

·         Renal impairment

Cefuroxime is primarily excreted by the 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).

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 significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.

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.

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.

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.

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. 

ZINNAT is excreted in human milk, and consequently caution should be exercised when ZINNAT 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 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 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, leucopenia (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]

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.

To report any side effect(s):

Kingdom of Saudi Arabia

-National Pharmacovigilance centre (NPC)

·         Fax: +966-11-205-7662

·         Call NPC at +966-11-2038222, Ext: 2317-2356-2353-2354-2334-2340

·         Toll-free: 8002490000

·         E-mail: npc.drug@sfda.gov.sa

·         Website: 17TUwww.sfda.gov.sa/npcU17T

-GlaxoSmithKline - Head Office, Jeddah

·         Tel:  00966(012)6536666

·         Fax: 00966(012)6536660

·         P.O Box 55850, Jeddah 21544, Saudi Arabia.

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.

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.

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.S-S1 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 withfood.

Distribution

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

Metabolism

Cefuroxime is not metabolised.

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.

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

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).

None reported.

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

As registered locally.

None.