Consumer medicine information

APO-Amoxy/Clav 500/125 & APO-Amoxy/Clav 875/125

Amoxicillin; Clavulanic acid

BRAND INFORMATION

Brand name

APO-Amoxy/Clav

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Amoxy/Clav 500/125 & APO-Amoxy/Clav 875/125.

SUMMARY CMI

APO-AMOXY/CLAV 500/125 & APO-AMOXY/CLAV 875/125

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using APO-AMOXY/CLAV?

APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 contain the active ingredients amoxicillin and clavulanic acid and are used for the short term treatment of a wide range of infections caused by bacteria. For more information, see Section 1. Why am I using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125? in the full CMI.

2. What should I know before I use APO-AMOXY/CLAV?

Do not use if you have ever had an allergic reaction to amoxicillin trihydrate, potassium clavulanate, penicillin or similar types of antibiotics (such as cephalosporins), or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use APO-AMOXY/CLAV?

Follow the directions given to you by your doctor and pharmacist. Their directions may differ from the information contained in this leaflet. More instructions can be found in Section 4. How do I use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125? in the full CMI.

5. What should I know while using APO-AMOXY/CLAV?

Things you should do
  • Tell any doctor, dentist or pharmacist you visit that you are using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125
  • Tell your doctor if the symptoms of your infection become worse, or do not improve within a few days of starting APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125
Things you should not do
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours
Driving or using machines
  • Be careful driving or operating machinery until you know how APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 affect you
Drinking alcohol
  • Alcohol should be avoided during and for several days after treatment
Looking after your medicine
  • Protect from moisture and store below 25°C

For more information, see Section 5. What should I know while using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125? in the full CMI.

6. Are there any side effects?

Common side effects include nausea, vomiting, pruritis or urticaria. Serious side effects include itching, rash, dark urine or pale stools, yellowing of the skin or eyes (jaundice), severe stomach cramps, severe watery or bloody diarrhoea, unusual bleeding or bruising or allergic reactions. All medicines can have side effects. If they do occur, they are usually minor and temporary. Do not be alarmed by this list. You may not experience any of them.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

APO-AMOXY/CLAV 500/125 & APO-AMOXY/CLAV 875/125

Active ingredient(s): amoxicillin trihydrate and potassium clavulanate

Consumer Medicine Information (CMI)

This leaflet provides important information about using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125.

Where to find information in this leaflet:

1. Why am I using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125?
2. What should I know before I use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125?
3. What if I am taking other medicines?
4. How do I use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125?
5. What should I know while using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125?
6. Are there any side effects?
7. Product details

1. Why am I using APO-AMOXY/CLAV 500/125 or APO-AMOCY/CLAV 875/125?

APO-AMOXY/CLAV 500/125 and APO-AMOXY/CLAV 875/125 contain the active ingredients amoxicillin and clavulanic acid.

APO-AMOXY/CLAV 500/125 and APO-AMOXY/CLAV 875/125 belong to the penicillin group of antibiotics and work by killing bacteria that cause infections. They will not work against infections caused by viruses such as colds or the flu.

APO-AMOXY/CLAV 500/125 and APO-AMOXY/CLAV 875/125 tablets are 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.

Your doctor may prescribe APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets for another use. If you want more information, ask your doctor.

There is no evidence that APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets are addictive.

2. What should I know before I use APO-AMOXY/CLAV 500/125 or APO-AMOCY/CLAV 875/125?

Warnings

Do not use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 if:

  • you are allergic to amoxicillin trihydrate, potassium clavulanate, penicillin or similar types of antibiotics (such as cephalosporins), or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction may include skin rash, itching, difficulty in breathing and swelling of the face or tongue.
  • you have previously experienced liver problems after taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 or any other medicines.
  • the packaging is torn or shows signs of tampering
  • the expiry date printed on the pack has passed

Always check the ingredients to make sure you can use this medicine.

Do not give this medicine to anyone else; your doctor has prescribed it specifically for you and your condition.

If you are not sure whether you should start taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets, talk to your doctor.

Check with your doctor if you:

  • have ever had an allergic reaction (such as a rash) to antibiotics or other substances in the past.
  • are allergic to foods, dyes, preservatives or any other medicines.
  • have experienced liver problems after taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets or any other medicines.
  • have glandular fever (mononucleosis) or leukemia.
  • have any kidney or liver problems.
  • have to test your urine for sugar (APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets may affect the results of these tests)

The dosage of APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 may need to be changed or you may need to be given an alternative medicine.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor will discuss with you the possible risks and benefits of taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 during pregnancy or while you are breast-feeding.

APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 can pass to your baby from breast milk.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

In particular, tell your doctor or pharmacist if you are taking any of the following:

  • warfarin or other medicines used to prevent blood clots
  • mycophenolate
  • medicines used to treat gout (eg. probenecid or allopurinol).
  • other antibiotics (these may interfere with the actions of APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125).
  • contraceptive pill (as with other antibiotics, you may need to use extra birth control methods (eg. condoms) while taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125).

Some medicines may interfere with APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 and affect how it works.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125.

4. How do I use APO-AMOXY/CLAV 500/125 or APO-AMOCY/CLAV 875/125?

Follow the directions given to you by your doctor and pharmacist. Their directions may differ from the information contained in this leaflet.

Please read the direction label carefully.

If you have any concerns about how to take this medicine, talk to your doctor or pharmacist.

How much to take / use

Swallow the APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablet with a full glass of water or other liquid.

APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets should be taken immediately before or with the first mouthful of food. APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets work best when taken this way. It may also prevent stomach upsets.

However, APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets will still work if they are taken without food.

When to take / use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125

  • Space the doses as evenly as possible throughout the day.
  • If you are taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 tablets twice a day, take a dose about every twelve hours.

How long to take APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 for

Keep taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 until the course is finished or for as long as your doctor tells you.

Do not stop taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 just because you feel better as the infection can return.

Do not stop taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125, or change the dose, without first checking with your doctor.

If you forget to use APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125

APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 should be used regularly at the same time each day.

If your next dose is due within six hours, skip the dose you missed and take your next dose at the normal time. Otherwise, take the missed dose as soon as you remember and then go back to taking your tablets as directed by your doctor.

Do not take a double dose to make up for the dose you missed. Taking more than the prescribed dose can increase the chance of unwanted side-effects.

If you use too much APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125

If you think that you have used too much APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using APO-AMOXY/CLAV 500/125 or APO-AMOCY/CLAV 875/125?

Things you should do

Take APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 exactly as your doctor has prescribed.

Tell your doctor if, for any reason, you have not taken your medicine exactly as directed. Otherwise, your doctor may think that it was not working as it should and change your treatment unnecessarily.

Tell your doctor if the symptoms of your infection become worse, or do not improve within a few days of starting APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125.

Remind any doctor, dentist or pharmacist you visit that you are using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 before starting any other medicines.

Some medicines may affect the way other medicines work.

Things you should not do

  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use to treat any other complaints unless your doctor says to.
  • Do not stop using this medicine until the course is finished or for as long as your doctor tells you.

Things to be careful of

  • If you develop severe diarrhoea either when taking APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 or within several weeks after treatment, tell your doctor as soon as possible.
  • Do not take any medication to stop the diarrhoea (eg. Lomotil® or Imodium®).

Remind any doctor, dentist or pharmacist you visit that you are using APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 affects you.

Generally, these tablets do not cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines, APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 may cause dizziness or tiredness in some people.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol should be avoided during and for several days after treatment with APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125.

Some people who drink alcohol while taking antibiotics similar to APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 have experienced adverse effects.

Looking after your medicine

  • Store below 25°C
  • Keep your tablets in the original pack until it is time to take them

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • diarrhoea (several loose bowel movements per day), indigestion, pain in the stomach, feeling sick or being sick
  • nausea, vomiting
  • white, furry, sore tongue and mouth (oral thrush), abnormal taste
  • soreness or itching of the vagina or vaginal discharge (vaginal thrush)
  • headache, dizziness, tiredness, hot flushes
  • tooth discolouration
  • unusually active (hyperactivity)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • itching, rash
  • dark urine or pale stools
  • yellowing of the skin or eyes (jaundice)
  • severe stomach cramps
  • severe watery or bloody diarrhoea
  • unusual bleeding or bruising

Rare events:

  • inflammation of the bowel (colitis)
  • inflammation of the liver (hepatitis)
  • inflammation of the kidney (nephritis)
  • blood disorders
  • crystals in the urine (crystalluria)
Tell your doctor immediately if you notice any of these symptoms during or after taking.
  • fits/seizures
  • aseptic meningitis
  • Allergic reactions:
    - wheezing, hives, severe skin reaction, fainting, swelling of limbs, face, lips, mouth or throat, difficulty swallowing or breathing, joint discomfort or swelling, swollen lymph glands, nausea and vomiting or fever
Stop taking and call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What APO-AMOXY/CLAV 500/125 or APO-AMOXY/CLAV 875/125 contains

Active ingredient
(main ingredient)		amoxicillin 500 mg
clavulanic acid 125 mg
Other ingredients
(inactive ingredients)		magnesium stearate
croscarmellose sodium
talc‐purified
microcrystalline cellulose
The tablet coating on the tablets contains:
titanium dioxide
hypromellose
ethylcellulose
dichloromethane
hydroxypropylcellulose
isopropyl alcohol
propylene glycol
Potential allergensContains 25 mg potassium per tablet

Do not take this medicine if you are allergic to any of these ingredients.

What APO-AMOXY/CLAV 500/125 looks like

APO-AMOXY/CLAV 500/125 tablets come as white, oval shaped, film coated tablet with marking “CA625” on one side (AUST R 255075).

What APO-AMOXY/CLAV 875/125 looks like

APO-AMOXY/CLAV 875/125 tablets come as white elongated capsule shaped film coated tablet (AUST R 255080).

Who distributes APO-AMOXY/CLAV 500/125 and APO-AMOXY/CLAV 875/125

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel St
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

APO-Amoxy/Clav

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals Pty Ltd

1 Name of Medicine

Amoxicillin trihydrate and potassium clavulanate.

2 Qualitative and Quantitative Composition

APO‐Amoxy/Clav 500/125 and APO‐Amoxy/Clav 875/125 tablets (amoxicillin and clavulanic acid tablets) are combination products containing the semisynthetic antibiotic, amoxicillin (as the trihydrate) and the β-lactamase inhibitor, potassium clavulanate (as the potassium salt of clavulanic acid).
Each film coated tablet contains 500 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.
Each film coated tablet contains 875 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO‐Amoxy/Clav 500/125 Tablets.

A white, oval shaped, film coated tablet with marking "CA625" on one side.

APO‐Amoxy/Clav 875/125 Tablets.

A white elongated capsule shaped film coated tablet.

4 Clinical Particulars

4.1 Therapeutic Indications

APO‐Amoxy/Clav 500/125 and APO‐Amoxy/Clav 875/125 tablets are indicated for short term treatment of bacterial infections at the following sites when caused by sensitive organisms (see Section 5.1 Pharmacodynamic Properties, Mechanism of action, Microbiology):
Urinary tract infections (uncomplicated and complicated);
Lower respiratory tract infections, including community acquired pneumonia and acute exacerbations of chronic bronchitis;
Upper respiratory tract infections, such as sinusitis, otitis media and recurrent tonsillitis;
Skin and skin structure infection.
Appropriate culture and susceptibility studies should be performed to identify the causative organism(s) and determine its (their) susceptibility to amoxicillin and clavulanic acid tablets.
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 amoxicillin and clavulanic acid tablets should not require the addition of another antibiotic due to the amoxicillin content of these products.

4.2 Dose and Method of Administration

APO‐Amoxy/Clav 500/125 and APO‐Amoxy/Clav 875/125 tablets should be taken immediately before or with the first mouthful of food, to minimise potential gastrointestinal intolerance and to optimise absorption.

Dosage.

Adults. The usual adult dose is one APO‐Amoxy/Clav 500/125 tablet every 12 hours. For more severe infections, the dose should be one APO‐Amoxy/Clav 875/125 tablet every 12 hours.

Note.

Since both APO‐Amoxy/Clav 875/125 and APO‐Amoxy/Clav 500/125 tablets contain the same amount of clavulanic acid (125 mg, as the potassium salt), two APO-Amoxy/Clav 500/125 tablets are not equivalent to one APO‐Amoxy/Clav 875/125 tablet. Therefore, two APO‐Amoxy/Clav 500/125 tablets should not be substituted for one APO-Amoxy/Clav 875/125 tablet for treatment of more severe infections.
Treatment should usually be continued for 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. Treatment should not exceed 14 days without review.
Renal impairment. APO‐Amoxy/Clav 875/125 tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance ≤ 30 mL/min).
Both amoxicillin and clavulanic acid are excreted by the kidneys and the serum half life of each increases in patients with renal failure. *No adjustment to the initial amoxicillin and clavulanic acid tablet dose is necessary, but the dosing interval should be extended according to the degree of renal impairment. See Table 1.
Haemodialysis decreases serum concentrations of both amoxicillin and clavulanic acid and an additional dose should be administered at the end of dialysis.
Hepatic impairment. Data is currently insufficient for a dosage recommendation. Dose with caution, and monitor hepatic function at regular intervals.
Children. Children weighing 40 kg and more should be dosed according to the adult recommendations. It is recommended that amoxicillin and clavulanic acid suspensions be used for children weighing less than 40 kg.

4.3 Contraindications

A history of allergic reaction to β-lactams e.g. penicillins or cephalosporins is a contraindication.
Amoxicillin and clavulanic acid tablets are contraindicated in patients with a previous history of amoxicillin/clavulanic acid-associated jaundice or 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. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction. Presenting symptoms of such reactions can include chest pain occurring in association with an allergic reaction to Augmentin (see Section 4.8 Adverse Effects (Undesirable Effects)). If an allergic reaction occurs, APO‐Amoxy/Clav 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 with 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.

General.

As with any potent drug, periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Since amoxicillin and clavulanic acid tablets contain amoxicillin, an aminopenicillin, these are 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.
Amoxicillin and clavulanic acid tablets should be given with caution to patients with lymphatic leukaemia 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 amoxicillin and clavulanic acid tablets have occurred predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children.

Use in hepatic impairment.

Amoxicillin and clavulanic acid tablets should be used with care in patients with evidence of hepatic dysfunction.

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).
APO‐Amoxy/Clav 875/125 tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance ≤ 30 mL/min).
APO‐Amoxy/Clav 500/125 tablets should be used with care in patients with moderate or severe renal impairment. The dosage of APO‐Amoxy/Clav 500/125 should be adjusted as recommended (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

Oral administration of amoxicillin and clavulanic acid tablets 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 amoxicillin and clavulanic acid tablets.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Probenecid decreases the renal tubular secretion of amoxicillin but does not affect clavulanic acid excretion. Concurrent use with amoxicillin and clavulanic acid tablets 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 amoxicillin and clavulanic acid tablets and allopurinol administered concurrently. No information is available about the concurrent use of amoxicillin and clavulanic acid tablets and alcohol. However, the ingestion of alcohol whilst being treated with some other beta-lactam antibiotics has precipitated a disulfiram (Antabuse) like reaction in some patients. Therefore the ingestion of alcohol should be avoided during and for several days after treatment with amoxicillin and clavulanic acid tablets.
In common with other antibiotics, amoxicillin and clavulanic acid tablets may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. Patients should be warned accordingly.
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 co-administration 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.

Amoxicillin/clavulanic acid at oral doses of up to 1200 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 amoxicillin and clavulanic acid tablets have shown no teratogenic effects. There is limited experience of the use of amoxicillin and clavulanic acid tablets in human pregnancy. In women with preterm, premature rupture of the foetal membrane (pPROM), prophylactic treatment with amoxicillin and clavulanic acid 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 amoxicillin and clavulanic acid tablets 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 obstetrical intervention or resuscitation of the newborn will be necessary.
 Amoxicillin is excreted in the milk; there are no data on the excretion of clavulanic acid in human milk. Therefore, caution should be exercised when amoxicillin and clavulanic acid tablets are administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Amoxicillin and clavulanic acid tablets are generally well tolerated. The majority of events were of a mild and transient nature.

Clinical trials.

During clinical trials, the most frequently reported adverse events related or possibly related to amoxicillin and clavulanic acid 875/125 mg tablet therapy were diarrhoea (14.9%), nausea (7.9%), headache (6.8%), abdominal pain (4.5%), vomiting (3.8%), genital moniliasis (3.6%) and vaginitis (3.4%).
The following adverse events have been observed during clinical trials with amoxicillin and clavulanic acid 875/125 mg tablets, however it should be noted that causality has not necessarily been established for these events (see Table 2):
During clinical trials, the most frequently reported adverse events related or possibly related to amoxicillin and clavulanic acid 500/125 mg tablet therapy were diarrhoea (12.8%), nausea (5.2%), headache (4.8%), abdominal pain (4.5%).
The following adverse events have been observed during clinical trials with amoxicillin and clavulanic acid 500/125 mg tablets, however it should be noted that causality has not necessarily been established for these events (see Table 3):

Postmarketing.

In addition, the following adverse reactions have been reported for ampicillin class antibiotics and may occur with amoxicillin and clavulanic acid 500/125 mg tablets and amoxicillin and clavulanic acid 875/125 mg tablets: 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.

Cardiac disorders.

Very rare: Kounis syndrome (see Section 4.4 Special Warnings and Precautions for Use).

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 putulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported rarely. Whenever such reactions occur, APO‐Amoxy/Clav 500/125 should be discontinued, unless in the opinion of the physician no alternative treatment is available and continued use of APO‐Amoxy/Clav 500/125 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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Serious and severe clinical symptoms are unlikely to occur after overdosage with amoxicillin and clavulanic acid tablets. If encountered, gastrointestinal symptoms and disturbance of the fluid and electrolyte balances 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.
Contact the Poisons Information Centre (telephone 13 11 26) for advice on overdose management.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology. 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 amoxicillin and clavulanic acid tablets extends the antimicrobial spectrum of amoxicillin to include organisms normally resistant to amoxicillin due to β-lactamase production. In vitro studies have demonstrated the susceptibility of most strains of the following organisms (see Tables 4, 5, 6 and 7).
The following in vitro data are available but their clinical significance is unknown (see Table 8).
Susceptibility testing.

Diffusion technique.

For Kirby-Bauer method of susceptibility testing, a 30 microgram amoxicillin and clavulanic acid (20 microgram amoxicillin + 10 microgram clavulanic acid) diffusion disc should be used. With this procedure, a report from the laboratory of "Susceptible" indicates that the infecting organism is likely to respond to amoxicillin and clavulanic acid therapy and a report of "Resistant" indicates that the infecting organism is not likely to respond to therapy. An "Intermediate Susceptibility" report suggests that the infecting organism would be susceptible to amoxicillin and clavulanic acid if the infection is confined to tissues or fluids (e.g. urine) in which high antibiotic levels are attained.

Dilution techniques.

Broth or agar dilution methods may be used to determine the minimal inhibitory concentration (MIC) value susceptibility of bacterial isolates to amoxicillin and clavulanic acid. Tubes should be inoculated to contain 104 to 105 organisms/mL or plates "spotted" with 103 to 104 organisms.
The recommended dilution method employs a constant amoxicillin/clavulanic acid ratio of 2 to 1 in all tubes with increasing concentrations of amoxicillin. MICs are reported in terms of amoxicillin concentration in the presence of clavulanic acid at constant 2 parts amoxicillin to 1 part clavulanic acid. See Tables 9 and 10.

Clinical trials.

Amoxicillin and clavulanic acid (875/125 mg) tablets vs amoxicillin and clavulanic acid (500/125 mg) tablets.

Three pivotal studies in 1,361 patients treated for between 7 and 14 days for either lower respiratory tract infections, upper respiratory infections or complicated urinary tract infections compared a regimen of amoxicillin and clavulanic acid (875/125 mg) tablets every 12 hours (q12h) to amoxicillin and clavulanic acid (500/125 mg) tablets dosed every 8 hours (q8h) (584, 170 and 607 patients, respectively). Comparable efficacy was demonstrated between the q12h and q8h dosing regimens. There was no significant difference in the percentage of adverse events in each group. The most frequently reported adverse event in two of the studies was diarrhoea; incidence rates were similar for the 875/125 mg q12h and 500/125 mg q8h dosing regimens (14.9% and 14.3%, respectively). However, there was a statistically significant difference (p < 0.05) in rates of severe diarrhoea or withdrawals with diarrhoea between the regimens: 1.0% for 875/125 mg q12h dosing versus 2.5% for the 500/125 mg q8h dosing. In the third study the most frequently reported adverse event was headache with an incidence of 5.7% (amoxicillin and clavulanic acid (500/125 mg) tablets q8h) vs 8.3% (amoxicillin and clavulanic acid (875/125 mg) tablets q12h).
As noted previously although there was no significant difference in the percentage of adverse events in each group there was a statistically significant difference in rates of severe diarrhoea or withdrawals with diarrhoea between the regimens.

Amoxicillin and clavulanic acid (500/125 mg) tablets vs amoxicillin and clavulanic acid (250/125 mg) tablets.

Two pivotal studies in 908 patients treated for between 5 and 10 days for either uncomplicated Skin and Skin Structure Infections or Acute Exacerbation of Chronic Bronchitis compared a regimen of amoxicillin and clavulanic acid (500/125 mg) tablets every 12 hours with amoxicillin and clavulanic acid (250/125 mg) tablets every 8 hours. Comparable efficacy was demonstrated between the 12 hourly and 8 hourly dosing regimens.
There was no significant difference in the percentage of adverse events in each group, with the most frequently reported adverse event in the two studies being diarrhoea.
The clinical efficacy of amoxicillin and clavulanic acid tablets given in a twice daily versus three times daily regimen have been shown to be comparable in AECB and SSSI, despite the differences in some pharmacokinetic parameters.
Given the similar TMIC and the demonstration of equivalence between AECB and SSSI it would be reasonable to extrapolate to the remaining indications. Clinical safety and efficacy in other indications were investigated, however these supportive studies were not sufficiently designed to demonstrate the relative efficacy of the two amoxicillin and clavulanic acid tablets regimens, or compared the proposed regimen with other treatments.

5.2 Pharmacokinetic Properties

Absorption.

Amoxicillin and clavulanic acid tablets are stable in the presence of gastric acid. Their 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, amoxicillin and clavulanic acid tablets should be administered at the start of a meal. The pharmacokinetics of amoxicillin are not affected by food.
Oral administration of amoxicillin and clavulanic acid (875 mg/125 mg) tablets every 12 hours was compared with amoxicillin and clavulanic acid (500 mg/125 mg) tablets every 8 hours at the start of a light meal. The following mean pharmacokinetic parameters were observed for amoxicillin for amoxicillin and clavulanic acid (875/125 mg) tablets taken every 12 hours and amoxicillin and clavulanic acid (500 mg/125 mg) tablets taken every 8 hours. See Tables 11 and 12.
The t1/2 and Cmax for clavulanate for amoxicillin and clavulanic acid (875/125 mg) tablets were not significantly different from amoxicillin and clavulanic acid (500/125 mg) tablets. However, the AUC(0-24 hours) was reduced, as would be expected with the lower daily dose of clavulanate i.e. 250 mg in amoxicillin and clavulanic acid (875/125 mg) tablets vs 375 mg in amoxicillin and clavulanic acid (500/125 mg) tablets.
Oral administration of amoxicillin and clavulanic acid (500 mg/125 mg) tablets every 12 hours was compared with amoxicillin and clavulanic acid (250 mg/125 mg) every 8 hours at the start of a light meal.
The following mean pharmacokinetic parameters were observed for amoxicillin for amoxicillin and clavulanic acid (500/125 mg) tablets taken every 12 hours and amoxicillin and clavulanic acid (250 mg/125 mg) taken every 8 hours. See Tables 13 and 14.

Distribution.

Following oral administration, both amoxicillin and clavulanic acid have been shown to diffuse in significant concentrations into pus, bile, and pleural, synovial and peritoneal fluids. Both penetrate poorly into the cerebrospinal fluid (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.

Metabolism.

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.

Excretion.

As with other penicillins, renal excretion is the major route of amoxicillin clearance, while clavulanate elimination is via both renal and non-renal mechanisms. Approximately 70% 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.
Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of amoxicillin/clavulanic acid was investigated in assays for chromosomal damage (mouse micronuclucleus test and a dominant lethal test) and gene conversion. All were negative.

Carcinogenicity.

Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

APO‐Amoxy/Clav 500/125 tablets also contain the inactive ingredients: magnesium stearate, croscarmellose sodium, purified talc and microcrystalline cellulose. The tablet coating contains titanium dioxide, hypromellose, ethyl cellulose, hyprolose and propylene glycol.
APO‐Amoxy/Clav 875/125 tablets also contain the inactive ingredients: magnesium stearate, croscarmellose sodium, purified talc and microcrystalline cellulose. The tablet coating contains titanium dioxide, hypromellose, ethyl cellulose, hyprolose and propylene glycol.

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

APO‐Amoxy/Clav 500/125 and APO‐Amoxy/Clav 875/125 tablets should be stored below 25°C and protected from moisture.

6.5 Nature and Contents of Container

APO‐Amoxy/Clav 500/125 Tablets.

Available as PVC-Al blister packs of 2, 10 and 60.

APO‐Amoxy/Clav 875/125 Tablets.

Available as PVC/Al blister packs of 2, 10 and 60.
Not all pack 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 it to your local pharmacy.

6.7 Physicochemical Properties

Amoxicillin trihydrate.

Amoxicillin trihydrate is white to almost white, crystalline powder, slightly soluble in water and in alcohol, practically insoluble in ether and in fatty oils. It dissolves in dilute acids and dilute solutions of alkali hydroxides. It has a pKa of 2.8 and 7.2, with a partition coefficient of -2.69.

Chemical structure.

Chemically, amoxicillin trihydrate is (2S,5R,6R)-6-[[(2R)-2-Amino-2-(4-hydroxyphenyl)acetyl] amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate. It is susceptible to hydrolysis by β-lactamases. Amoxicillin trihydrate may be represented structurally as:
Molecular formula: C16H19N3O5S.3H2O.
Molecular weight: 419.4.

CAS number.

61336-70-7.

Clavulanic acid.

Potassium clavulanate is white to almost white, crystalline powder, hygroscopic, freely soluble in water, slightly soluble in alcohol, and very slightly soluble in acetone. The pKa is 2.7, with a partition coefficient of -1.38.

Chemical structure.

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 (2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate, and may be represented structurally as:
Molecular formula: C8H8KNO5.
Molecular weight: 237.3.

CAS number.

61177-45-5.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes