Zinnat

Zinnat

cefuroxime

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GlaxoSmithKline
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Contents
Cefuroxime axetil.
Description
Film-coated tablet: Each tablet contains 125, 250 or 500 mg Cefuroxime (as Cefuroxime axetil).
Granules for oral suspension: Reconstitution of multidose bottles as directed yields a suspension containing 125 mg of cefuroxime (as cefuroxime axetil) in each 5 ml.
ZINNAT Sachets contain 125 mg granules of cefuroxime (as cefuroxime axetil) for single dose administration when reconstituted.
Excipients/Inactive Ingredients: Film-coated tablet: Microcrystalline Cellulose; Croscarmellose Sodium type A; Sodium Lauryl Sulphate; Hydrogenated Vegetable Oil; Colloidal Silicon Dioxide; Hypromellose; Propylene Glycol; Methyl parahydroxybenzoate; Propyl parahydroxybenzoate and Opaspray M-1-7120 J.
Granules for oral suspension: Aspartame, Xanthan gum, Acesulfame potassium, Povidone K30, Stearic acid, Sucrose, Tutti frutti flavour.
Sucrose Quantities: (See Table 1.)


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Action
Pharmacology: Pharmacodynamics: Cefuroxime axetil undergoes hydrolysis by esterase enzymes to the active antibiotic, cefuroxime. Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis.
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. (See Table 2).


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Pharmacokinetics: Absorption: Film-coated tablet: 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.
Oral suspension: After oral administration ZINNAT is absorbed from the gastrointestinal tract and rapidly hydrolysed in the intestinal mucosa and blood to release cefuroxime into the circulation.
Absorption of cefuroxime is enhanced in the presence of food.
The rate of absorption of cefuroxime from the suspension compared with the tablets is reduced, leading to later, lower peak serum levels and reduced systemic bioavailability (4-17% less).
Distribution: Protein binding has been variously stated as 33 to 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 & 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.
Toxicology: Pre-clinical Safety Data: Animal toxicity studies indicated that cefuroxime axetil is of low toxicity with no significant findings.
Indications/Uses
ZINNAT is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most (β) 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 Pharmacology: Pharmacodynamics under Actions).
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.
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/Direction for Use
The usual course of therapy is seven days (range 5 to 10 days).
Film-coated tablet: ZINNAT should be taken after food for optimum absorption.
Adults: (See Table 3).


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Se
quential 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 to 10 days.
Acute exacerbations of chronic bronchitis: 750 mg ZINACEF three times a day or twice a day (i.v. or i.m.) for 48 to 72 hours, followed by ZINNAT (cefuroxime axetil) oral therapy 500 mg 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 aged ≥ 3 months and up to 12 years: (See Table 4.)


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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.
Oral suspension: For optimal absorption, ZINNAT should be taken with food.
Adults: (See Table 5.)


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Children 3 month-12 years: When prescription of a fixed dose is preferred, the recommended dose for most infections is 125 mg twice daily. In children aged two years or older with otitis media or where appropriate, with more severe infections, the dose is 250 mg twice daily, to a maximum of 500 mg daily.
There are no clinical trial data available on the use of ZINNAT in children under the age of 3 months.
In infants and children, it may be preferable to adjust dosage according to weight or age. The dose in infants and children 3 months to 12 years is 10 mg/kg twice daily for most infections, to a maximum of 250 mg daily. In otitis media or more severe infections the recommended dose is 15 mg/kg twice daily to a maximum of 500 mg daily.
The following two tables, divided by age group and weight, serve as a guideline for simplified administration from measuring spoons (5 ml) for the 125 mg/5 ml multi-dose suspension, and 125 mg single dose sachets. (See Tables 6 and 7.)


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To enhance compliance and improve the dosing accuracy in very young children, a dosing syringe can be supplied with a multidose bottle containing 50 ml of suspension. However, dosing in spoonfuls should be considered a more favourable option if the child is able to take the medication from the spoon.
If required, the dosing syringe may also be used in older children (refer to the dosing tables as follows).
The recommended doses for the paediatric dosing syringe are expressed in ml or mg and according to body weight in Tables 8 and 9.


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ZINNAT is also available as the sodium salt (ZINACEF) for parenteral administration. This permits parenteral therapy with ZINNAT to be followed by oral therapy in situations where a change from parenteral to oral treatment is clinically indicated.
Film-coated tablet & oral suspension: 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 Table 10.)


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Overdosage
Signs and symptoms: Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.
Treatment: Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.
Contraindications
Patients with known hypersensitivity to cephalosporin antibiotics.
Film-coated tablet: History of severe hypersensitivity (e.g. anaphylactic reaction) to betalactam antibacterial agent (penicillins, monobactams or carbapenems).
Special 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 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.
Film-coated tablet: 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.
Oral suspension: The sucrose content of Zinnat suspension and granules (see Excipients/Inactive Ingredients under Description) 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.
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.
Use In Pregnancy & 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.
Adverse Reactions
Adverse drug reactions to ZINNAT are generally mild and transient in nature.
The frequency categories assigned to the adverse reactions as follows 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, leukopenia (sometimes profound).
Very rare: Haemolytic anaemia.
Cephalosporins as a class tend to be absorbed onto the surface of red cell 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 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 Immune system disorders as previously mentioned).
Drug Interactions
Drugs which reduce gastric acidity may result in a lower bioavailability of cefuroxime compared with that of the fasting state and tend to cancel the effect of enhanced post-prandial absorption/absorption after food.
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.
Caution For Usage
Oral suspension: Instructions for Use/Handling: Constitution/Administration Instructions: Always shake the bottle vigorously before taking the medication.
The reconstituted suspension when refrigerated between 2 and 8°C can be kept for up to 10 days.
If desired ZINNAT suspension can be further diluted from multidose bottles 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).
4. Turn the bottle into an upright position and shake vigorously.
5. Refrigerate immediately at between 2 and 8°C.
6. If using a dosing syringe, allow the reconstituted suspension to stand for at least one hour before taking the first dose.
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.
Incompatibilities: None.
Storage
Film-coated tablet: Store below 30°C.
Oral suspension: Before reconstitution store below 30°C.
For multidose bottle: the reconstituted suspension must be refrigerated immediately at between 2 and 8°C.
Shelf-Life: Film-coated tablet: 36 months from manufacturing date.
Oral suspension:
24 months from manufacturing date.
The reconstituted suspension when refrigerated between 2 and 8°C can be kept for up to 10 days.
MIMS Class
Cephalosporins
ATC Classification
J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 125 mg (white to off-white, capsule shaped, bi-convex, plain on one side and engraved "GXES5" on the other) x 10's. 250 mg (white to off-white, capsule shaped, bi-convex, plain on one side and engraved "GXES7" on the other) x 10's. 500 mg (white to off-white, capsule shaped, bi-convex, plain on one side and engraved "GXEG2" on the other) x 10's. Granules for oral susp (dry, white to off-white, tutti-frutti flavoured) 125 mg (sachet) x 10's. 125 mg/5 mL (bottle) x 50 mL x 1's.
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