Consumer medicine information

Augmentin Duo 400 Suspension

Amoxicillin; Clavulanic acid

BRAND INFORMATION

Brand name

Augmentin Duo 400 Suspension

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Augmentin Duo 400 Suspension.

What is in this leaflet?

Please read this leaflet carefully before you give AUGMENTIN DUO 400 SUSPENSION.

This leaflet answers some common questions about AUGMENTIN DUO 400 SUSPENSION. It does not contain all of the available information.

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

All medicines have risks and benefits. Sometimes new risks are found even when a medicine has been used for many years. Your child’s doctor has weighed the expected benefits of your child taking AUGMENTIN DUO 400 SUSPENSION against the risks this medicine could have for your child.

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

Keep this leaflet until your child has finished the course of AUGMENTIN DUO 400 SUSPENSION.

You may need to read it again.

What is AUGMENTIN DUO 400 SUSPENSION used for?

AUGMENTIN DUO 400 SUSPENSION contains two active ingredients. One of these is a penicillin called amoxicillin and the other is clavulanate. AUGMENTIN DUO 400 SUSPENSION belongs to the penicillin group of antibiotics.

AUGMENTIN DUO 400 SUSPENSION is used for the short term treatment of a wide range of infections caused by bacteria. These infections may affect the chest (e.g. bronchitis or pneumonia), bladder (e.g. cystitis), sinuses (e.g. sinusitis), the ears (e.g. otitis media) or the skin.

AUGMENTIN DUO 400 SUSPENSION works by killing the bacteria that cause these infections.

AUGMENTIN DUO 400 SUSPENSION is used for the treatment of the infections listed. However, the doctor may prescribe these medicines for another use. If you want more information ask the doctor.

There is no evidence that AUGMENTIN DUO 400 SUSPENSION is addictive.

Before you give AUGMENTIN DUO 400 SUSPENSION

AUGMENTIN DUO 400 SUSPENSION must not be given if:

  • your child is allergic to penicillin or similar types of antibiotics (such as cephalosporins) or any of the ingredients contained in AUGMENTIN DUO 400 SUSPENSION. If your child has ever had an allergic reaction (such as a rash) when taking an antibiotic you should tell the doctor before any AUGMENTIN DUO 400 SUSPENSION is given.
  • your child has previously experienced liver problems after taking AUGMENTIN DUO 400 SUSPENSION or any other medicines.
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

This medicine is for the person named by the doctor. Do not give this medicine to anyone else.

Before your child starts taking AUGMENTIN DUO 400 SUSPENSION tell the doctor if:

  • your child has ever had an allergic reaction (such as a rash) to any antibiotics in the past.
  • your child is allergic to foods, dyes, preservatives or any other medicines.
  • your child has glandular fever (mononucleosis) or a blood disorder.
  • your child has liver or kidney problems. The dosage of AUGMENTIN DUO 400 SUSPENSION may need to be changed or your child may need to be given an alternative medicine.
  • your child has phenylketonuria.
    AUGMENTIN DUO 400 SUSPENSION contains aspartame.
  • your child’s urine has to be tested for sugar. AUGMENTIN DUO 400 SUSPENSION may affect the results of these tests.
  • your child is taking any other medicines, including medicines you buy without a prescription. In particular, tell the doctor if your child is taking any of the following:
    - probenecid or allopurinol.
    - warfarin or other medicines used to prevent blood clots
    - mycophenolate
    - other antibiotics. These may interfere with the actions of AUGMENTIN DUO 400 SUSPENSION.

Some medicines may affect the way other medicines work. Your child’s doctor or pharmacist will be able to tell you which medicines are safe to take with AUGMENTIN DUO 400 SUSPENSION.

If you have not told the doctor about any of these things, tell them before you give your child any AUGMENTIN DUO 400 SUSPENSION.

How to give AUGMENTIN DUO 400 SUSPENSION to your child

Follow the doctor’s instructions about how and when to give AUGMENTIN DUO 400 SUSPENSION. The doctor will advise how many doses are needed each day, and for how long your child will need to take AUGMENTIN DUO 400 SUSPENSION.

Please read the direction label carefully. If you have any concerns about how to give AUGMENTIN DUO 400 SUSPENSION, talk to the doctor or pharmacist.

How much to give:

Give AUGMENTIN DUO 400 SUSPENSION as directed by the doctor or pharmacist.

The usual dose of AUGMENTIN DUO 400 SUSPENSION is one dose taken twice a day. The dose may vary depending on your child’s weight.

How to give it:

Shake the suspension well before measuring out the dose in a suitable measure. Make sure the whole dose is swallowed each time.

AUGMENTIN DUO 400 SUSPENSION should be taken immediately before or with the first mouthful of food. AUGMENTIN DUO 400 SUSPENSION works best when taken this way. It may also help to prevent stomach upsets. However, AUGMENTIN DUO 400 SUSPENSION will still work if taken without food.

Space the doses as evenly as possible throughout the day. If your child is taking AUGMENTIN DUO 400 SUSPENSION twice a day, give a dose about every twelve hours.

How long to give it for:

Keep giving AUGMENTIN DUO 400 SUSPENSION until the course is finished or for as long as the doctor advised. Do not stop giving AUGMENTIN DUO 400 SUSPENSION just because your child feels better as the infection can return.

Do not stop giving AUGMENTIN DUO 400 SUSPENSION or change the dose without first checking with the doctor.

If you forget to give it:

Give the missed dose as soon as you remember. Then give the next dose at the time it is normally due. Do not give two doses within six hours of each other.

Do not try to make up for missed doses by giving more than one dose at a time. Giving more than the prescribed dose can increase the chance of unwanted side effects.

What do I do if I give too much? (Overdose)

There are unlikely to be any serious problems following an overdose of AUGMENTIN DUO 400 SUSPENSION.

Immediately telephone the doctor or Poisons Information Centre (telephone 131126) for advice if you think your child or anyone else may have taken too much AUGMENTIN DUO 400 SUSPENSION, even if there are no signs of discomfort or poisoning.

If you are not sure what to do contact your child’s doctor, pharmacist or nearest hospital.

While you are giving AUGMENTIN DUO 400 SUSPENSION

Things you must do:

Tell the doctor if, for any reason, you have not given the medicine exactly as directed.

Otherwise, the doctor may think that it was not working as it should and change your child’s treatment unnecessarily.

Tell the doctor or pharmacist your child is taking AUGMENTIN DUO 400 SUSPENSION before giving any other prescribed medicine. Some medicines may affect the way other medicines work.

If your child develops itching, swelling or a skin rash while taking AUGMENTIN DUO 400 SUSPENSION, do not give any more AUGMENTIN DUO 400 SUSPENSION and tell the doctor immediately.

If your child develops severe diarrhoea either while taking AUGMENTIN DUO 400 SUSPENSION or within several weeks after treatment, tell the doctor as soon as possible. Do not give any medication to stop the diarrhoea (eg Lomotil® or Imodium®).

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 AUGMENTIN DUO 400 SUSPENSION to treat any other complaints unless your child’s doctor says to.

What are the side-effects?

Check with your child’s doctor as soon as possible if you think your child is experiencing any side effects or allergic reactions due to taking AUGMENTIN DUO 400 SUSPENSION, even if the problem is not listed below.

Like other medicines, AUGMENTIN DUO 400 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. Tell the doctor about any effect which is troublesome or ongoing.

  • Tell the doctor if you notice any of the following are troublesome or ongoing:
    - diarrhoea (several loose bowel movements per day), indigestion, pain in the stomach, feeling sick or being sick.
    - soreness of the mouth or tongue, abnormal taste, white or furry tongue (oral thrush).
    - aseptic meningitis, headache, dizziness, tiredness, hot flushes.
    - soreness or itching of the vagina and/or discharge (vaginal thrush).
    - unusually active (hyperactivity)
  • Tell your child’s doctor immediately if you notice any of the following:
    - itching, rash
    - yellowing of the skin or eyes
    - dark urine or pale stools
    - severe diarrhoea
    - unusual bleeding or bruising
  • Stop giving AUGMENTIN DUO 400 SUSPENSION and contact the doctor or take your child to the emergency department of the nearest hospital if any of the following happens:
    - Wheezing, fainting, swelling of the lips/mouth, difficulty in breathing or swallowing, hayfever, lumpy rash (hives), joint discomfort or swelling, swollen lymph glands, nausea and vomiting or fever. These could be symptoms of an allergic reaction or other reaction.
  • Rare events that have been reported with AUGMENTIN DUO 400 SUSPENSION include:
    - inflammation of the bowel (colitis)
    - inflammation of the liver or kidney
    - blood disorders
    - crystals in the urine (crystalluria)

Remember you should tell the doctor or pharmacist as soon as possible if any of these, or any other unusual events or problems which are not mentioned here, occur during or after treatment with AUGMENTIN DUO 400 SUSPENSION.

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.

How do I store AUGMENTIN DUO 400 SUSPENSION?

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

Keep the bottle in the refrigerator where the temperature stays between 2 and 8°C. Heat can destroy AUGMENTIN DUO 400 SUSPENSION.

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

Do not use any suspension left in the bottle 7 days after collecting from the pharmacy. Ask your pharmacist what to do with any doses that are left over.

Product description

What AUGMENTIN DUO 400 SUSPENSION looks like:

AUGMENTIN DUO 400 SUSPENSION is available as an off-white sugar free suspension containing 400 mg of amoxicillin and 57 mg of clavulanate in each 5ml. Augmentin Duo 400 comes in a glass bottle containing powder for preparing 60 mL of suspension.

Other Ingredients:

AUGMENTIN DUO 400 SUSPENSION contains the following inactive ingredients: xanthan gum, aspartame, succinic acid, colloidal anhydrous silica, hypromellose 6, silicon dioxide and a mixed fruit flavour.

AUGMENTIN DUO 400 SUSPENSION does not contain sucrose, lactose, gluten, tartrazine or any other azo dyes.

Supplier:

Your AUGMENTIN DUO 400 SUSPENSION is supplied by:

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

Where to go for further information:

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your child’s doctor or pharmacist is the best person to give you advice on the treatment of your condition.

The information provided applies only to AUGMENTIN DUO 400 SUSPENSION

AUGMENTIN® is a registered trade mark of Aspen Global Incorporated.

AUGMENTIN DUO 400 SUSPENSION AUST R 67352

This leaflet is subject to copyright.

Revised in February 2020

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Augmentin Duo 400 Suspension

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

1 Name of Medicine

Amoxicillin trihydrate and potassium clavulanate.

6.7 Physicochemical Properties

Chemical structure.

Augmentin Duo 400 is a combination product containing the semisynthetic antibiotic, amoxicillin (as the trihydrate) and the β-lactamase inhibitor, potassium clavulanate (as the potassium salt of clavulanic acid).

Amoxicillin trihydrate.

Chemically, amoxicillin is D-(-)- α-amino-p-hydroxybenzylpenicillin. It is susceptible to hydrolysis by β-lactamases.
Amoxicillin trihydrate may be represented structurally as:
(Chemical formula: C16H19N3O5S,3H2O; Molecular weight: 419.4).

CAS number.

CAS-61336-70-7.

Clavulanic acid.

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is an irreversible inhibitor of many β-lactamase enzymes except type 1 (Richmond). It is a β-lactam compound with only weak antibacterial activity. Chemically potassium clavulanate is potassium Z-(2R,5R)-3-(β-hydroxyethylidene) clavam-2-carboxylate, and may be represented structurally as:
(Chemical formula: C8H8KNO5; Molecular weight: 237.3).

CAS number.

CAS-61177-45-5.

2 Qualitative and Quantitative Composition

Amoxicillin trihydrate is a white or almost white, crystalline powder and is slightly soluble in water. A 0.2% solution in water has a pH of 3.5 to 5.5.
Potassium clavulanate is a white or almost white, hygroscopic, crystalline powder and is freely soluble in water. A 1% solution in water has a pH of 5.5 to 8.0.
Augmentin Duo 400 oral suspension also contains xanthan gum, aspartame, succinic acid, colloidal anhydrous silica, hypromellose 6, mixed fruit flavour and silicon dioxide.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Like other penicillins, amoxicillin has a bactericidal effect on sensitive organisms during the stage of active multiplication. However, amoxicillin is susceptible to hydrolysis by β-lactamases and the addition of clavulanic acid in Augmentin Duo 400 extends the antimicrobial spectrum of amoxicillin to include organisms normally resistant to amoxicillin due to beta lactamase production. In vitro studies have demonstrated the susceptibility of most strains of the following organisms. See Tables 3 to 5.
The following in vitro data are available but their clinical significance is unknown. See Table 6.

Susceptibility testing.

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 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.

Clinical trials.

A randomised, single blind study in 868 children aged 2 months to 12 years with acute otitis media compared the efficacy of oral Augmentin suspension 45 mg/kg/day amoxicillin (6.4 mg/kg/day clavulanic acid) administered q12h for 5 days (n = 293) or 10 days (n = 287) with Augmentin 40 mg/kg/day amoxicillin (10 mg/kg/day clavulanic acid) given q8h for 10 days (n = 288). At the end of therapy (days 12 to 14) equivalent per protocol clinical success rates of 78.8% (n = 189) and 86.5% (n = 178), respectively, were demonstrated for the q8h and q12h 10 day treatment groups, compared with a 71.1% (n = 197) success rate for the q12h 5 day treatment group. At 32 to 38 days follow up, equivalent success rates were demonstrated for q8h and q12h 10 day regimens of 64.2% and 63.1%, respectively, compared with a 57.8% success rate for the q12h 5 day treatment group.

5.2 Pharmacokinetic Properties

Absorption.

Amoxicillin is stable in the presence of gastric acid. The two components are rapidly absorbed if administered before or with a meal, but if given after meals, the serum levels of clavulanic acid are significantly reduced. To optimise absorption of clavulanic acid, Augmentin should be administered at the start of a meal. The pharmacokinetics of amoxicillin are not affected by food.
In children aged 2-12 years, oral administration of Augmentin oral suspension (7:1 ratio) every 12 hours (q12h) at a dose of 45 mg/kg/day amoxicillin (6.4 mg/kg/day clavulanic acid) was compared to Augmentin oral suspension (4:1 ratio) every 8 hours (q8h) at a dose of 40 mg/kg/day amoxicillin (10 mg/kg/day clavulanic acid), either immediately prior to the start of a meal or at least three hours after a meal.
In this study, the following mean pharmacokinetic parameters were observed for amoxicillin for Augmentin oral suspension (45 mg/kg/day) taken every 12 hours and Augmentin oral suspension (40 mg/kg/day) taken every 8 hours respectively: peak plasma concentration (Cmax) of 12.0 and 7.33 microgram/mL, area under the plasma concentration time curve between 0 and 24 hours after the first dose (AUC(0-24 hours)) of 35.2 and 18.6 microgram.hour/mL, half-life (t1/2) of 1.22 and 1.02 hours, median time to peak plasma concentration (Tmax) of 1.0 and 2.1 hours and the mean predicted time above the minimum inhibitory concentration (TMIC 24 hours) of 12.3 hours and 14.0 hours.
The following pharmacokinetic parameters were observed for clavulanic acid for Augmentin oral suspension (45 mg/kg/day) taken every 12 hours and Augmentin oral suspension (40 mg/kg/day) taken every 8 hours respectively: Cmax of 5.49 and 2.66 microgram/mL, AUC(0-24 hours) of 13.3 and 5.51 microgram.hour/mL, t1/2 of 0.99 and 0.94 hours and median Tmax of 1.0 and 1.6 hours, and mean predicted TMIC24 hours of 9.80 hours and 9.81 hours.
The clinical efficacy of Augmentin Duo 400 (7:1 ratio) and Augmentin Forte (4:1 ratio) have been shown to be comparable in the approved indications, despite the differences in some pharmacokinetic parameters.

Distribution.

Following oral administration, both amoxicillin and clavulanic acid have been shown to diffuse in significant concentrations into pus, bile, pleural, synovial and peritoneal fluids. Therapeutic concentrations of both compounds have been detected in gall bladder, abdominal tissue, skin fat and muscle tissues. Both penetrate poorly into the CSF when the meninges are normal. Amoxicillin penetrates into the CSF better through inflamed meninges but the maximum concentrations are still much lower than the peak serum levels. There are no data at present on the CSF penetration of clavulanic acid in patients with meningeal inflammation.
Neither amoxicillin nor clavulanic acid is highly protein bound. Clavulanic acid has been variously reported to be bound to human serum in the range of 9-30% and amoxicillin approximately 20% bound. From animal studies, there is no evidence to suggest either component accumulates in any organ.

Excretion.

As with other penicillins, renal excretion is the major route of amoxicillin clearance, while clavulanate clearance is via both renal and nonrenal mechanisms. Approximately seventy percent of the dose of amoxicillin is excreted in urine as amoxicillin. For clavulanic acid, following the administration of 125 mg of radiolabelled potassium clavulanate orally to normal volunteers 68% of the administered radioactivity was recovered in the urine in 24 hours. Of this, 34% (i.e. 23% of the administered dose) represented unchanged clavulanic acid. 2,5-Dihydro-4-(2-hydroxyethyl) -5-oxo-1H-pyrrole-3-carboxylic acid (the major metabolite) and 1-amino-4-hydroxy- butan-2-one accounted for a further 23% and 12% (i.e. 16% and 8%, respectively, of the administered dose). Small amounts of other yet unidentified metabolites were also present. These metabolites were also present in the urine of rat and dog. The extent of urinary excretion of clavulanic acid and its metabolites is lower in rat urine than in dog and human urine.
Concurrent administration of probenecid delays amoxicillin excretion but does not notably delay renal excretion of clavulanic acid.
Similar Augmentin elimination pharmacokinetics occur in adults, children and infants with mature renal function.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of Augmentin was investigated in assays for chromosomal damage (mouse micronucleus test and a dominant lethal test) and gene conversion. All were negative.

Carcinogenicity.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Augmentin.

4 Clinical Particulars

4.1 Therapeutic Indications

Augmentin Duo 400 oral suspension is indicated in the short-term treatment of the following bacterial infections when caused by sensitive organisms:
skin and skin structure infections;
urinary tract infections (complicated and uncomplicated);
upper respiratory tract infections including sinusitis and otitis media;
lower respiratory tract infections including acute exacerbations of chronic bronchitis; and
community acquired pneumonia.
Appropriate culture and susceptibility studies should be performed to identify the causative organism(s) and determine its (their) susceptibility to Augmentin. However, when there is reason to believe an infection may involve any of the β-lactamase producing organisms listed above, therapy may be instituted prior to obtaining the results from bacteriological and susceptibility studies. Once these results are known, therapy should be adjusted if appropriate.
The treatment of mixed infections caused by amoxicillin susceptible organisms and β-lactamase producing organisms susceptible to Augmentin Duo 400, should not require the addition of another antibiotic due to the amoxicillin content of Augmentin Duo 400.

4.3 Contraindications

A history of allergic reaction to β-lactams, e.g. penicillins or cephalosporins is a contraindication.
Augmentin is contraindicated in patients with a previous history of Augmentin-associated jaundice/hepatic dysfunction.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Before initiating therapy with amoxicillin-clavulanate, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. 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 hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, Augmentin 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.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin. 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). Mild cases usually respond to drug discontinuation alone. However in moderate to severe cases appropriate therapy with a suitable oral antibiotic 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.
As with any potent drug, periodic assessment of organ system functions, including renal, hepatic and hematopoietic function is advisable during prolonged therapy.
Since Augmentin Duo 400 contains amoxicillin, an aminopenicillin, it is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis, in the presence of which there is a high incidence of rash if amoxicillin is used.
Augmentin should be given with caution to patients with lymphatic leukemia since they are especially susceptible to amoxicillin induced skin rashes.
Amoxicillin-clavulanate should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin-clavulanate and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted.
Cholestatic hepatitis, which may be severe but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent until several weeks after treatment has ceased. In most cases resolution has occurred with time. However, in extremely rare circumstances, deaths have been reported. These have almost always been cases associated with serious underlying disease or concomitant medications. Hepatic events subsequent to Augmentin have occurred predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. Augmentin Duo 400 should be used with care in patients with evidence of hepatic dysfunction.
Augmentin Duo 400 contains aspartame, and should be used with caution in patients with phenylketonuria.

Use in renal impairment.

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria (see Section 4.9 Overdose).

Use in the elderly.

No data available.

Paediatric use.

In children with renal impairment, dosage should be adjusted according to degree of impairment using the alternative Augmentin (4:1 ratio) 125 mg/31.25 mg or 250 mg/62.5 mg formulations. Augmentin Duo 400 formulation is not recommended for use in children with renal impairment.

Effects on laboratory tests.

Oral administration of Augmentin Duo 400 will result in high urine concentrations of amoxicillin. Since high urine concentrations of ampicillin may result in false positive reactions when testing for the presence of glucose in urine using Clinitest, Benedict's solution or Fehling's solution, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix or TesTape) be used.
Following administration of ampicillin to pregnant women a transient decrease in plasma concentration of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone and oestradiol has been noted. This effect may also occur with amoxicillin and therefore Augmentin Duo 400.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin but does not notably affect clavulanic acid excretion. Concurrent use with Augmentin Duo 400 may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with Augmentin Duo 400 and allopurinol administered concurrently.
In common with other antibiotics, Augmentin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
In the literature there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If coadministration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Augmentin at oral doses of up to 1,200 mg/kg/day had no effect on fertility and reproductive performance in rats dosed with a 2:1 ratio formulation of amoxicillin and clavulanate.
(Category B1)
Animal studies with orally and parenterally administered Augmentin have shown no teratogenic effects. There is limited experience of the use of Augmentin in human pregnancy. In women with preterm, premature rupture of the foetal membrane (pPROM), prophylactic treatment with Augmentin may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the physician.

Use in labour and delivery.

Oral ampicillin class antibiotics are generally poorly absorbed during labour. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions and duration of contractions. However, it is not known whether the use of Augmentin in humans during labour or delivery has immediate or delayed adverse effects on the foetus, prolongs the duration of labour or increases the likelihood that forceps delivery or other obstetric intervention or resuscitation of the newborn will be necessary.
Amoxicillin is excreted in milk. There are no data on the excretion of clavulanic acid in human or animal milk. Therefore, caution should be exercised when Augmentin is administered to a nursing woman.

4.8 Adverse Effects (Undesirable Effects)

Augmentin is generally well tolerated. The majority of events were of a mild and transient nature.

Clinical trials.

The following adverse events reported in a pivotal clinical trial with Augmentin Duo 400 (45/6.4 mg/kg/day q12h for 10 days) and are compared to Augmentin Forte (40/10 mg/kg/day q8h for 10 days) in Table 2.

Post marketing.

In addition, the following adverse reactions have been reported for ampicillin class antibiotics and may occur with Augmentin Duo 400. Very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1,000 and < 1/100; rare: ≥ 1/10,000 and < 1/1,000; very rare: < 1/10,000.

Infections and infestations.

Common: mucocutaneous candidiasis.

Gastrointestinal disorders.

Very common: diarrhoea.
Common: nausea, vomiting.
Uncommon: indigestion.
Rare: gastritis, stomatitis, glossitis, black 'hairy' tongue, enterocolitis. Antibiotic associated colitis (including pseudomembranous colitis and haemorrhagic colitis), see Section 4.4 Special Warnings and Precautions for Use.

Hepatobiliary.

Uncommon: moderate rise in AST and/or ALT.
Rare: hepatitis, cholestatic jaundice which may be severe but is usually reversible.

Nervous system disorders.

Uncommon: dizziness, headache.
Very rare: reversible hyperactivity, aseptic meningitis, convulsions. Convulsions may occur in patients with impaired renal function or those receiving high doses.

Haematopoietic and lymphatic systems.

Uncommon: thrombocytosis.
Rare: anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, reversible leukopenia (including neutropenia or agranulocytosis) these are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena, prolongation of bleeding time and prothrombin time.

Hypersensitivity and skin.

Common: skin rashes, pruritus, urticaria.
Rare: angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, erythema multiforme, Stevens-Johnson syndrome, hypersensitivity, vasculitis, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported rarely. Whenever such reactions occur, Augmentin Duo 400 should be discontinued, unless in the opinion of the physician no alternative treatment is available and continued use of Augmentin Duo 400 is considered essential. Serious and occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillins (see Section 4.4 Special Warnings and Precautions for Use).

Renal and urinary disorders.

Rare: interstitial nephritis.
Very rare: crystalluria (see Section 4.9 Overdose).

Miscellaneous.

Rare: superficial tooth discolouration which can usually be removed by brushing.

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.

4.2 Dose and Method of Administration

Augmentin Duo 400 should be taken immediately before or with the first mouthful of food, to minimise potential gastrointestinal intolerance and to optimise absorption.

Children aged 2 months up to 12 years.

For moderate to severe infections the dose should be 45 mg/kg/day, based on the amoxicillin component, (or 6.4 mg/kg/day clavulanic acid) in two divided doses every 12 hours.
The children's dosage is intended for individuals whose weight will not cause dosage to be calculated greater than that recommended for adults. Children weighing 40 kg and more should be dosed according to the adult recommendations for other Augmentin preparations.
There are no clinical data available for Augmentin Duo 400 in infants with immature renal function. The use of Augmentin Duo 400 in this group cannot be recommended.

Dosage adjustment in hepatic impairment.

Data is currently insufficient for a dosage recommendation. Dose with caution and monitor hepatic function at regular intervals.

Dosage in normal renal function.

Augmentin Duo 400 is not recommended for use in children with renal impairment or in haemodialysis. In children with renal impairment, dosage should be adjusted according to degree of impairment using the alternative Augmentin (4:1 ratio) 125 mg/31.25 mg or 250 mg/62.5 mg formulations.

Direction for reconstituting the oral suspension.

Prepare the oral suspension at time of dispensing as follows. Tap bottle until all the powder flows freely. Add approximately ½ of the total amount of water for reconstitution (see Table 1) and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.
Shake oral suspension well before using. Reconstituted syrup must be stored under refrigeration (2-8°C) and discarded after 7 days.

4.7 Effects on Ability to Drive and Use Machines

Adverse effects on the ability to drive or operate machinery have not been observed.

4.9 Overdose

Problems of overdosage with Augmentin Duo 400 are unlikely to occur. If encountered, gastrointestinal symptoms and disturbance of the fluid and electrolyte balance may be evident. They may be treated symptomatically, with attention to the water/electrolyte balance.
Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see Section 4.4 Special Warnings and Precautions for Use).
Amoxicillin may be removed from the circulation by haemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

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 dry powder below 25°C. Under these conditions the shelf life is 18 months.
Store reconstituted suspension at 2-8°C in a refrigerator. Under these conditions the shelf life is 7 days.

6.5 Nature and Contents of Container

Augmentin Duo 400 Oral Suspension: Each 5 mL of reconstituted off-white mixed fruit flavoured suspension contains 400 mg amoxicillin and 57 mg clavulanic acid as the potassium salt. It is presented in 107 mL bottles containing off-white dry powder for reconstitution in water to form an oral suspension.

Note.

Augmentin Duo 400 oral suspension contains aspartame 12.5 mg per 5 mL. Each 125 mg of potassium clavulanate is equivalent to 0.63 mmol of potassium.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes