Consumer medicine information

Zinnat Suspension

Cefuroxime

BRAND INFORMATION

Brand name

Zinnat Suspension

Active ingredient

Cefuroxime

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Zinnat Suspension.

What is in this leaflet?

Please read this leaflet carefully before you give ZINNAT suspension to your child.

This leaflet answers some common questions about ZINNAT suspension. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the expected benefits of your child taking ZINNAT suspension against the risks this medicine could have for him/her.

If you have any concerns about your child taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine until your child has finished the course of ZINNAT suspension. You may need to read it again.

What is ZINNAT suspension used for?

ZINNAT suspension belongs to a group of medicines called cephalosporin antibiotics.

The active ingredient in ZINNAT suspension (cefuroxime axetil) works by killing bacteria (germs) that cause infections such as infections of the ear, throat and tonsils.

Your doctor may have prescribed ZINNAT suspension for another reason.

ZINNAT suspension is not addictive.

Before your child takes ZINNAT suspension

ZINNAT suspension must not be given if:

  • your child has ever had an allergic reaction to cefuroxime axetil or any of the ingredients listed toward the end of this leaflet. Some of the symptoms of allergic reaction may include skin rash, itchiness, shortness of breath, swelling of the face, lips or tongue.
  • your child has had a serious allergic reaction to penicillins.
  • there may be an increased risk of your child being allergic to ZINNAT suspension if he/she is allergic to penicillins.
  • if you are not sure whether to give ZINNAT suspension to your child, contact your doctor.
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering

Tell your doctor if:

You must tell your doctor if:

  • your child has had an allergic reaction to any antibiotics in the past.
  • your child is allergic to foods, dyes, preservatives or any other medicines. (including cephalosporins or penicillins)
  • your child has had to stop taking other medicine for his/her infection.
  • your child is diabetic.
    ZINNAT suspension contains sugar which the doctor will need to consider when treating your child.
  • your child's urine is tested for sugar.
    ZINNAT suspension may interfere with some urine tests.
  • your child has kidney problems.
  • Your child has ever had any health problems or medical conditions, including: glandular fever, blood disorders such as leukaemia and liver or kidney problems.

Taking other medicines

  • Tell your doctor if your child is taking any other medicines, including medicines you buy without a prescription from the pharmacy, supermarket or health food shop.
  • Some medicines may interfere with ZINNAT. These may include antibiotics and digestion tablets.
  • Your doctor or pharmacist may have information on medicines to be careful with or to avoid while taking ZINNAT.

How to give ZINNAT suspension to your child

How much to give

Give the complete course of ZINNAT suspension as directed by the doctor or pharmacist. Do not stop just because your child feels better, as the medicine may not have killed all the germs and your child may start feeling unwell again.

In infants and children (3 months to 2 years), it may be preferable to adjust dosage according to weight and age. The dose of ZINNAT oral suspension recommended for children with tonsillitis and/or pharyngitis is 10mg/kg twice daily to a maximum of 250mg daily. The dose of ZINNAT oral suspension recommended for children with an ear infection (otitis media) is 15mg/kg twice daily.

Depending on the illness or how you or your child responds to treatment, the starting dose may be changed or more than one course of treatment may be needed.

Follow all directions given to you by your doctor and pharmacist carefully. These directions may differ from the information contained in this leaflet. If you do not understand the instructions on the bottle, ask your doctor or pharmacist for help.

How to give it

Always SHAKE THE BOTTLE before giving ZINNAT. The dose of suspension should then be measured out and swallowed straight away. The suspension can be diluted in cold fruit juice or milk drinks then given immediately. Do not mix ZINNAT suspension with hot liquids.

Before you give the first dose to your child, allow the suspension supplied by your pharmacist to stand for a least one hour.

Using a dosing syringe

  1. Shake the bottle
  2. Remove the bottle cap and push the bung firmly into the top of the bottle.
  3. Push the dosing syringe firmly into the top of the bung.
  4. Turn the bottle upside down.
  5. Pull the plunger of the syringe back so that the medicine is drawn from the bottle into the syringe. Pull the plunger back to the point on the scale that corresponds to the dose prescribed for your child.
    Contact your doctor or pharmacist if you are at all confused about how much medicine to draw into the syringe.
  6. Turn the bottle back the right way up and carefully remove the syringe from the bung, holding it by the barrel rather than the plunger.
  7. Gently put the tip of the syringe into the child's mouth, to the inside of the child's cheek.
  8. Slowly and gently push the plunger down to gently squirt the medicine into the inside of your child's cheek. Allow them to swallow it.
    Don't forcefully push down the plunger, or squirt the medicine to the back of your child's mouth or throat, as the child may choke.
  9. Remove the syringe from your child's mouth.
  10. Remove the bung and replace the lid on the bottle.
  11. Rinse the bung and syringe in warm water and leave to dry.
  12. Repeat the above for each dose as instructed by your doctor or pharmacist.

When to give it

ZINNAT suspension works better when taken with food.

How long to give it for

ZINNAT suspension should be given for 5 to 10 days. Your doctor may prescribe a different duration of treatment.

Use in children

ZINNAT suspension should not be given to children younger than 3 months of age unless the doctor says so.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 131126) for advice, if you think your child or anyone else may have taken too much ZINNAT suspension, even if there are no signs of discomfort or poisoning. They may need urgent medical attention.

If you are not sure what to do, contact your doctor or pharmacist.

While you are giving ZINNAT suspension

Things you must do

Tell your doctor if, for any reason, your child has not been given the medicine exactly as directed. Otherwise, your doctor may think that it was not working as it should and change your child's treatment unnecessarily

If your child is about to be started on any new medicines tell the doctor or pharmacist that you he/she is taking ZINNAT suspension.

If your child's symptoms do not improve within a few days, or if they become worse, tell your doctor.

If your child develops itching with swelling or skin rash, or difficulty breathing while taking ZINNAT, do not give more ZINNAT and contact your doctor immediately.

If your child gets severe diarrhoea tell your doctor, pharmacist or nurse immediately. Do this even if it occurs several weeks after ZINNAT has stopped. Diarrhoea may mean that your child has a serious condition affecting the bowel. They may need urgent medical care. Do not give any diarrhoea medicine without first checking with your doctor.

If your child gets a white mouth or tongue while taking or soon after stopping ZINNAT, tell your doctor. Also tell your doctor if your child gets vaginal itching or discharge. This may mean your child has a fungal infection called thrush. Sometimes the use of ZINNAT allows fungi to grow and the above symptoms to occur. ZINNAT does not work against fungi.

If your child's urine has to be tested for sugar while using ZINNAT or if your child has to have any blood tests tell your doctor your child is taking ZINNAT.

If you miss a dose

If it is almost time for your child's next dose, skip the dose you missed and give the next dose when you are meant to. Otherwise, give it as soon as you remember, then go back to giving it as you would normally.

Do not give a double dose to make up for the dose that your child missed.

Things you must not do

Do not give this medicine to anyone else, even if their symptoms seem similar to your child's.

Do not use ZINNAT suspension to treat any other complaints unless the doctor says to.

Do not stop giving ZINNAT because your child is feeling better, unless advised by the doctor. If the full course prescribed by your doctor is not taken, all of the bacteria causing your child's infection may not be killed.

Side effects

Check with your doctor as soon as possible if you think your child is experiencing any side effects or allergic reactions due to being given ZINNAT suspension, even if the problem is not listed below.

Like other medicines, ZINNAT suspension can cause some side-effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

The most commonly reported side-effects are:

  • diarrhoea
  • nausea or vomiting
  • nappy rash
  • stomach pain
  • headache
  • dizziness
  • fungal infections (such as candida)

Tell your doctor immediately if you notice any of the following:

  • skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) erythema multiforme
  • a widespread rash with blisters and skin peeling on much of the body (toxic epidermal necrolysis), particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)
  • if your child gets diarrhoea over a long period, even if it occurs sometime after you have stopped giving ZINNAT.

If any of the following symptoms are experienced stop giving ZINNAT and tell the doctor immediately:

  • severe sickness, diarrhoea or stomach pains
  • bleeding from the rectum
  • yellowing of the skin or eyes.

If you think your child is having an allergic reaction to ZINNAT suspension, TELL YOUR DOCTOR STRAIGHT AWAY or go to the casualty department at your nearest hospital. Symptoms usually include some or all of the following:

  • wheezing,
  • swelling of the lips/mouth,
  • difficulty in breathing,
  • lumpy rash (hives) or
  • fainting.

This is not a complete list of all possible side-effects. Others may occur in some people and there may be some side-effects not yet known.

Do not be alarmed by this list of possible side-effects. Your child may not experience any of them.

After using ZINNAT suspension

Do not keep the bottle of ZINNAT suspension longer than 10 days after it has been made up and store in the fridge between 2°C and 8°C.

Keep this medicine where children cannot reach it, such as in a locked cupboard.

Keep ZINNAT suspension in a cool, dry place where it stays below 30°C.

Do not leave in a car, on a window sill or in the bathroom.

Return any unused or expired medicine to your pharmacist.

Product description

What ZINNAT suspension looks like

Zinnat granules for oral suspension are presented in bottles and sachets.

Multidose bottles: ZINNAT suspension is provided as white to off-white free-flowing granules forming a white to pale yellow suspension upon reconstitution in water. When reconstituted as directed, it provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension.

Sachets: ZINNAT suspension is provided as dry, white to off-white, tutti-frutti flavoured granule in laminated sachets. When reconstituted as directed, it provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per dose.

Not all presentations are marketed.

Ingredients

Each 5mL of ZINNAT suspension contains either 125mg or 250mg of the active ingredient cefuroxime (as cefuroxime axetil).

ZINNAT 250mg/5mL suspension and granules also contains the following inactive ingredients:

  • povidone
  • stearic acid
  • sucrose
  • tutti frutti 51880 AP0551
  • sucrose
  • stearic acid
  • tutti-frutti 51880 AP0551
  • povidone.

ZINNAT 125mg/5mL suspension and granules contains the following inactive ingredients

  • acesulfame potassium, aspartame
  • xanthan gum
  • povidone
  • stearic acid
  • sucrose
  • tutti frutti 51880 AP0551

Sucrose quantity (g per dose)

125mg/5mL suspension 3.062g

250mg/5mL suspension 2.289g

125mg sachet 3.062g

250mg sachet 6.123g

Supplier

Your ZINNAT suspension is supplied by:

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Australia.

The information provided applies only to: ZINNAT suspension.

ZINNAT cefuroxime (as axetil) 125 mg/5 mL granules for oral suspension bottle: AUST R 178687

ZINNAT cefuroxime (as axetil) 125 mg granules for oral suspension sachet: AUST R 178686

ZINNAT cefuroxime (as axetil) 250 mg/5mL granules for oral suspension bottle; AUST R 81301

ZINNAT cefuroxime (as axetil) 250 mg granules for oral suspension sachet; AUST R 81298

This leaflet was prepared on 11 November 2019.

Published by MIMS January 2020

BRAND INFORMATION

Brand name

Zinnat Suspension

Active ingredient

Cefuroxime

Schedule

S4

 

1 Name of Medicine

Cefuroxime axetil.

2 Qualitative and Quantitative Composition

Zinnat granules for oral suspension contains either 125 mg or 250 mg cefuroxime (as cefuroxime axetil) per 5 mL. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Zinnat granules for oral suspension are presented in bottles and sachets.

Multidose bottles.

Zinnat suspension is provided as white to off-white free-flowing granules forming a white to pale yellow suspension upon reconstitution in water. When reconstituted as directed, it provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension.

Sachets.

Zinnat suspension is provided as dry, white to off-white, tutti-frutti flavoured granule in laminated sachets. When reconstituted as directed, it provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per dose.

4 Clinical Particulars

4.1 Therapeutic Indications

Zinnat suspension is indicated for the treatment of the following mild to moderately severe infections caused by sensitive bacteria in paediatric patients 3 months to 12 years; tonsillitis and pharyngitis, acute bacterial otitis media.
Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefuroxime axetil appears to be as effective as phenoxymethylpenicillin in the eradication of streptococci from the nasopharynx. However, substantial data establishing the efficacy of cefuroxime axetil in the subsequent prevention of rheumatic fever is not available at present.

4.2 Dose and Method of Administration

Zinnat tablets and Zinnat oral suspension are not bioequivalent and are therefore not substitutable on a mg per mg basis (see Section 5.2 Pharmacokinetic Properties).
The usual course of therapy with Zinnat suspension is 7 days (with a range of 5 to 10 days).
Cefuroxime axetil should be taken with a light meal for optimum absorption.
The recommended dose for most infections is 125 mg twice daily. In children aged two years or older with otitis media or where appropriate in children, with more severe infections, the dose is 250 mg twice daily.
There is no clinical experience with the use of Zinnat in infants under the age of 3 months.
In infants and children, it may be preferable to adjust dosage according to weight or age. The dose of Zinnat oral suspension recommended for treatment of tonsillitis and pharyngitis is 10 mg/kg twice daily, to a maximum of 250 mg daily. The dose of Zinnat oral suspension recommended for the treatment of acute bacterial otitis media is 15 mg/kg twice daily, to a maximum of 500 mg daily.
Tables 1 and 2, divided by age group and weight, serve as a guideline for simplified administration from measuring spoons (5 mL) for the 125 mg/5 mL or the 250 mg/5 mL multi-dose suspension, and 125 mg or 250 mg single dose sachets.

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 not be used.
2. Add the total amount of water to the bottle as stated on its label and replace the cap.
3. Invert the bottle and vigorously rock the bottle from side to side so that water rises through the granules.
4. Once the sound of the granules against the bottle disappears, turn the bottle upright and shake vigorously.
5. Refrigerate the reconstituted suspension 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.
Always shake the bottle well before each use.
The reconstituted suspension when refrigerated immediately 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.

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

4.3 Contraindications

Patients with known hypersensitivity to cephalosporin antibiotics or who have experienced a major allergy to penicillin (anaphylaxis, angioneurotic oedema, urticaria).

4.4 Special Warnings and Precautions for Use

Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions have been reported in patients on penicillin/cephalosporin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins/cephalosporins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin/cephalosporin hypersensitivity who have experienced severe reactions when treated with a penicillin/cephalosporins. Past history of a severe allergic reaction to penicillin/cephalosporin is a contraindication to the use of cefuroxime axetil. Before initiating therapy with any penicillin/cephalosporin careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, cefuroxime axetil should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated.
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 other non-susceptible organisms (e.g. Enterococci and Clostridium), which may require interruption of treatment.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including cefuroxime axetil. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Mild cases usually respond to drug discontinuation alone although cholestyramine may help by binding the toxin in the colonic lumen. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
Drugs which delay peristalsis e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.
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.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, cefuroxime should be discontinued immediately and an alternative treatment should be considered.

Use in renal impairment.

There is no information on use of Zinnat suspension in patients with renal impairment however the dosage of cefuroxime tablets in adults should not exceed 500 mg per day and should be repeated after dialysis.

Use in the elderly.

The serum half life of cefuroxime is increased and plasma levels raised in elderly patients with declining renal function. No dosage reduction is necessary in such patients at recommended dosages.

Paediatric use.

No data available.

Effects on laboratory tests.

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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drugs that reduce gastric acidity may result in a lower bioavailability of cefuroxime axetil compared with that of the fasting state and tend to cancel the effect of enhanced absorption after food.
In common with other antibiotics, cefuroxime axetil may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime axetil. However, there is no clinical data on the use of cefuroxime axetil during pregnancy. Therefore it should be administered during pregnancy only if such use is considered essential.
 Cefuroxime is excreted in human milk, and consequently caution should be exercised when cefuroxime axetil is administered to a nursing mother.

4.7 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.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to cefuroxime axetil have been generally mild and transient in nature.

Clinical trial data.

See Table 3.

Post marketing data.

The following adverse reactions to cefuroxime axetil are considered to be drug related and have been reported in clinical trials or post-marketing data. However, the possibility of the occurrence of other adverse reactions, seen with the cephalosporin class of antibiotics, should be borne in mind.

Gastrointestinal.

A small proportion of patients receiving cefuroxime axetil have experienced gastrointestinal disturbances including diarrhoea, nausea, vomiting and abdominal pain. As with other broad-spectrum antibiotics there have been rare reports of pseudomembranous colitis.

Hepatic.

Transient increases of hepatic enzyme levels [ALT (SGPT), AST (SGOT) and LDH]. As with other cephalosporins jaundice (predominantly cholestatic) and hepatitis have been reported very rarely.

CNS.

Headache, dizziness.

Haematological.

Eosinophilia, positive Coomb's test and in very rarely haemolytic anaemia. There have been rare reports of thrombocytopenia and leucopenia (sometimes profound).

Hypersensitivity.

Patients with a history of delayed hypersensitivity to penicillin (but not a cephalosporin) experienced delayed hypersensitivity reaction to cefuroxime axetil in 2.9% cases.
As with other cephalosporins, rare cases of severe hypersensitivity reactions, including Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis (exanthematic necrolysis) and hypersensitivity reactions including skin rashes, urticaria, pruritus, drug fever, serum sickness and very rarely, anaphylaxis have been reported with cefuroxime axetil.

Infections and infestations.

Candida overgrowth has been reported commonly.

Skin and subcutaneous tissue disorders.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by haemodialysis and peritoneal dialysis.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Cefuroxime axetil is a semisynthetic cephalosporin. It is a prodrug which owes its in vivo bactericidal activity to the release of the active compound cefuroxime.
Cefuroxime has bactericidal activity against a wide range of common pathogens, including beta-lactamase producing strains. The bactericidal action of cefuroxime results from inhibition of cell wall synthesis by binding to essential target proteins. Cefuroxime has good stability to bacterial beta-lactamases.

Clinical trials.

Otitis media. Three pivotal, multi-centre, investigator-blind, randomised clinical studies (CAE 331, CAE 331/Howie, CAE 332) evaluated cefuroxime axetil suspension, 30 mg/kg/day in two divided doses for 10 days, in the treatment of otitis media with effusion in 261 paediatric patients aged 3 months to 12 years. The comparator agent was amoxycillin/clavulanate suspension 40 mg/kg/day in three divided doses for 10 days (n = 139). Comparable rates of clinical cure/improvement (82.4% and 79.7% for cefuroxime axetil and amoxycillin/clavulanate respectively) and bacteriological cure (93% and 96% for cefuroxime axetil and amoxycillin/clavulanate respectively) were obtained with the two treatment regimens in the evaluable population.
An open, randomised multi-centre study (CAET95) comparing cefuroxime axetil suspension (250 mg [125 mg if < 2 years old] twice daily) with amoxycillin syrup (250 mg [125 mg if < 2 years old] three times daily) for 10 days in 660 children showed comparable rates of clinical response to both antibiotics (94-95%) in clinically evaluable patients. Bacteriological clearance rates were similar (96.9% for cefuroxime axetil vs 95% for amoxycillin, p > 0.05) in the limited number of patients (approximately 10%) who had positive ear swabs or who underwent tympanocentesis.
An open, randomised, multicentre study (CAEB 4006) to compare the efficacy and safety of a 5-day course of cefuroxime axetil suspension with an 8- or 10-day course of amoxicillin/clavulanate suspension was conducted in 716 children aged between 6 and 36 months suffering from otitis media with effusion. The patients were randomised to receive cefuroxime axetil 30 mg/kg/day in two divided doses for 5 days (n = 252), amoxicillin/clavulanate 40 mg/kg/day in three divided doses for 10 days (n = 255), or amoxicillin/clavulanate 80 mg/kg/day in three divided doses for 8 days (n = 209). In the clinical evaluable population, the proportion of patients with clinical cure at post treatment was 86%, 88% and 88% for each of the groups respectively. Statistical equivalence was demonstrated between the three treatments (95% confidence intervals for cefuroxime axetil treatment vs 10-day and 8-day amoxicillin treatments were -9.0% to 4.8% and -9.5% to 5.1% respectively).
Tonsillopharyngitis. Two, randomised, multi-centre studies (CAE 333, CAE 334) were conducted, in which 509 children aged 2 to 12 years with tonsillopharyngitis and a positive throat culture for Group A streptococci were treated for 10 days with either cefuroxime axetil suspension 20 mg/kg/day in two divided doses or penicillin V syrup 50 mg/kg/day in three divided doses. Clinical efficacy was demonstrated in a higher proportion of cefuroxime axetil-treated patients in both intent-to-treat and evaluable populations (80% vs 71% in ITT population, p = 0.008; 91% vs 83% in evaluable patients, p = 0.013). A bacteriological cure (eradication or presumed eradication of Group A streptococci) or cure with reinfection was achieved in 84% of cefuroxime axetil treated patients compared to 77% treated with penicillin V. Similar overall adverse event rates were reported for both treatments (p = 0.05).
One open-label, multi-centre study (CAET94) was conducted in 633 children, in which seven days of treatment with cefuroxime axetil suspension (62.5 mg twice daily in children < 2 years and 125 mg twice daily in children > 2 years) was compared to seven days of treatment with amoxycillin syrup (125 mg three times daily). Clinical cure or improvement occurred in 95% of evaluable patients treated with cefuroxime axetil compared to 97% treated with amoxycillin. Approximately 30% of patients were bacteriologically evaluable. In this subgroup, similar levels of bacteriological clearance were achieved with the two agents (95% vs 87%, not statistically significant).
An open, randomised, multi-centre study (CAEB 4007) of 406 children with confirmed Group A streptococcal tonsillopharyngitis demonstrated that 5 days of treatment with cefuroxime axetil suspension 20 mg/kg twice daily was equivalent to a 10-day course of treatment in eradication of the pathogen (88% vs 92%, 95% confidence interval -10% to 3%). At 21-28 day follow-up, bacterial eradication was maintained in 85% of patients in the 5-day group and 87% of patients in the 10-day group. Equivalence was also demonstrated for clinical cure rates at post-treatment assessment (96% vs 98%, 95% confidence interval -7% to 2%).
Microbiology. Cefuroxime has been shown to be usually active against the following organisms in vitro and in clinical studies:

Aerobic gram-negative microorganisms.

Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including beta-lactamase-producing strains), Neisseria gonorrhoeae (including beta-lactamase producing strains).

Aerobic gram-positive microoganisms.

Staphylococcus aureus (including penicillinase producing strains but excluding methicillin resistant strains), Streptococcus pyogenes (and other beta-haemolytic streptococci), Streptococcus pneumoniae.
Cefuroxime exhibits in vitro minimum inhibitory concentrations (MICs) of 4.0 microgram/mL or less (systemic susceptible breakpoint) against most (≥ 90%) strains of the following microorganisms; however, the clinical significance of these findings is unknown:

Aerobic gram-positive microorganisms.

Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae.

Aerobic gram-negative microorganisms.

Proteus inconstans, Proteus mirabilis, Providencia rettgeri.

Anaerobic microorganisms.

Peptococcus niger.
The following organisms are not susceptible to cefuroxime: Clostridium difficile; Pseudomonas spp; Campylobacter spp; Acinetobacter calcoaceticus; Morganella morganii; Listeria monocytogenes; Methicillin resistant strains of Staphylococcus aureus and Staphylococcus epidermidis; Legionella spp; Proteus vulgaris; Serratia spp; Bacteroides fragilis; Most strains of Enterococcus faecalis, Citrobacter spp, Enterobacter spp.
See Table 4.
No Australian data is available for Streptococcus pyogenes. However, worldwide, no resistance to cefuroxime or other beta-lactam antibiotics has been reported. Cefuroxime is active against macrolide-resistant strains.
For cefuroxime axetil in common with other cephalosporins, the time that drug concentrations exceed MIC correlates most closely with clinical efficacy. For a given cefuroxime MIC, drug concentrations maintained for 30%-40% of the dosing interval are likely to be effective in patients with community-acquired infections.
In patients with tonsillopharyngitis caused by S. pyogenes with MIC90 0.015 microgram/mL, cefuroxime concentrations t > MIC is likely to be > 10 hours.
In patients with otitis media treated with 15 mg/kg/dose, organisms within the MIC range < 0.06-2 micrograms/mL would be expected to be amenable to treatment, Table 5 shows those derived from fasting subjects. Administration immediately after food would be expected to increase absorption.
In a study of pharmacokinetics in paediatric patients with otitis media, dosed after food at 15 mg/kg, serum concentrations exceeded a MIC of 2 microgram/mL for at least 5 hours (42%) of the dosing interval. (Thoroddsen E. et al. Ped Inf Dis 1997;16:959-962).
Cefuroxime axetil susceptibility relevant to the indications are as follows (see Table 6):
Susceptibility tests. Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of the laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated.
This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Susceptibility to cefuroxime axetil will vary with geography and time and local susceptibility data should be consulted where available.

5.2 Pharmacokinetic Properties

Absorption.

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. 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 than the 60% bioavailability seen with tablets). Absorption of cefuroxime axetil suspension is enhanced in the presence of food. Absorption is not decreased by drugs which affect gastrointestinal motility e.g. loperamide, diphenoxylate or castor oil. However, absorption is decreased by concurrent administration of drugs which reduce gastric acidity.

Distribution.

The mean peak serum level of cefuroxime following dosing with a 250 mg tablet in normal healthy adults, after food, was 4.1 mg/L and occurred two to three hours after dosing. Serum levels were significantly higher in the elderly, apparently due to slower excretion.
Unhydrolysed drug has not been detected in the serum but 1-2% of the administered dose is excreted in the urine in a form which indicates that small amounts of the intact ester are absorbed into circulation. The serum half-life of cefuroxime is between 1 and 1.5 hours. Protein binding has been variously stated as 33-50% depending on the methodology used.

Metabolism.

Cefuroxime is not metabolised to any significant extent.

Excretion.

Excretion occurs mainly through the kidney both by glomerular filtration and tubular secretion. Approximately 49% of an administered dose, after food, is recovered in the urine in 24 hours; urinary recovery is significantly reduced if the drug is taken on an empty stomach. After a 250 mg dose urinary concentrations at 0-6 and 6-12 hours were 227 microgram/mL (range 92-515) and 35.3 microgram/mL (range 7.6-102) respectively. See Table 7.
The pharmacokinetic parameters were not significantly affected by patient age or weight. Cmax and AUC∞ increased proportionately with dose in a linear relationship over the dose range 10-20 mg/kg.

5.3 Preclinical Safety Data

Preclinical safety data were either not assessed or not identified as part of the registration of this medicine.

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Zinnat granules for oral suspension also contain:

125 mg granules and 125 mg/5 mL suspension.

Acesulfame potassium, aspartame, povidone, stearic acid, sucrose, tutti frutti 51880 AP0551 and xanthan gum.

250 mg granules and 250 mg/5 mL suspension.

Povidone, stearic acid, sucrose, tutti frutti 51880 AP0551.
See Table 8.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.
The reconstituted suspension must be refrigerated immediately between 2° and 8°C.

6.5 Nature and Contents of Container

Zinnat is supplied in:
Amber glass bottles containing either 50 mL, 70 mL, 100 mL, 140 or 200 mL of 125 mg/5 mL suspension or 50 mL, 70 mL or 100 mL of 250 mg/5 mL suspension.
Sachets containing 10 packs of 125 mg or 250 mg granules.
Not all dose forms/container sizes are being distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Cefuroxime axetil is the 1-(acetyloxy)ethyl ester of cefuroxime. Its chemical name is (RS)-1-hydroxyethyl(6R,7R)-7-[2-(2-furyl)glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo [4.2.0]-oct-2-ene-2-carboxylate, 72)-(Z)-(O-methyoxime), 1-acetate 3-carbamate. Its molecular formula is C20H22N4O10S, and it has a molecular weight of 510.48.
Cefuroxime axetil is in the amorphous form.

Chemical structure.


CAS number.

64544-07-6.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes