Consumer medicine information

Amoxicillin/Clavulanic Acid Viatris 500/125; Amoxicillin/Clavulanic Acid Viatris 875/125

Amoxicillin; Clavulanic acid

BRAND INFORMATION

Brand name

Amoxicillin/Clavulanic Acid Viatris

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amoxicillin/Clavulanic Acid Viatris 500/125; Amoxicillin/Clavulanic Acid Viatris 875/125.

SUMMARY CMI

AMOXICILLIN/CLAVULANIC ACID VIATRIS 500/125 &
AMOXICILLIN/CLAVULANIC ACID VIATRIS 875/125 tablets

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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125?

Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets contains the active ingredients amoxicillin and clavulanic acid. Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets are used for the short term treatment of a wide range of infections.

For more information, see Section 1. Why am I using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125? in the full CMI.

2. What should I know before I use Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets?

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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets?

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

More instructions can be found in Section 4. How do I use Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets? in the full CMI.

5. What should I know while using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets?

Things you should do
  • Take Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets as exactly as your doctor has prescribed.
  • Tell your doctor if, for any reason, you have not taken your medicine exactly as directed.
  • Remind any doctor, dentist or pharmacist you visit that you are using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.
  • Tell your doctor if the symptoms of your infection become worse, or do not improve within a few days of starting Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.
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.
Driving or using machines
  • Be careful before your drive or use any machines or tools until you know how Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets affects you.
Drinking alcohol
  • Alcohol should be avoided during and for several days after treatment with Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.
Looking after your medicine
  • Keep your tablets in the original pack until it is time to take them.
  • Store it in a cool dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets? in the full CMI.

6. Are there any side effects?

The most common side effects of Amoxicillin/Clavulanic Acid Viatris 500/125 and Amoxicillin/Clavulanic Acid Viatris 875/125 tablets are diarrhoea, nausea and vomiting.

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

AMOXICILLIN/CLAVULANIC ACID VIATRIS 500/125 &
AMOXICILLIN/CLAVULANIC ACID VIATRIS 875/125 tablets

Active ingredient(s): amoxicillin (as trihydrate) and clavulanic acid (as potassium clavulanate)

Consumer Medicine Information (CMI)

This leaflet provides important information about using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets. 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.

Where to find information in this leaflet:

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

1. Why am I using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets?

Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets contains two active ingredients. One of these is a penicillin called amoxicillin and the other is clavulanic acid.

Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets belong to the penicillin group of antibiotics. Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets works by killing the bacteria that cause these infections. It will not work against infections caused by viruses such as colds or the flu.

Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets are used for the short term treatment of a wide range of infections in the body caused by bacteria. These infections may affect the chest (bronchitis or pneumonia), bladder (cystitis), sinuses (sinusitis), the ears (otitis media) or the skin.

Your doctor may prescribe Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets for another use. If you want more information, ask your doctor.

There is no evidence that Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets are addictive.

2. What should I know before I use Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets?

Warnings

Do not use Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets or any other medicines.
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or show signs of tampering.

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

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 glandular fever (mononucleosis) or leukaemia.
  • have any kidney or liver problems.
    The dosage of Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets may need to be changed or you may need to be given an alternative medicine.
  • have to test your urine for sugar. Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets may affect the results of these tests.

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 the risks and benefits of taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets during pregnancy or while you are breastfeeding. Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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 to treat gout (e.g. probenecid or allopurinol)
  • other antibiotics. These may interfere with the actions of Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.
  • methotrexate (a medicine used to treat cancer or rheumatic diseases.
  • contraceptive pill. As with other antibiotics, you may need to use extra birth control methods (e.g. condoms) while taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets

Some medicines may interfere with Amoxicillin/Clavulanic Acid Viatris 500/125 and Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.

4. How do I use Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets?

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

  • Swallow the Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets with a full glass of water or other liquid. Amoxicillin/Clavulanic Acid Viatris 875/125 tablets can be broken in half, but should not be chewed.
  • Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets should be taken immediately before or with the first mouthful of food. Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets work best when taken this way. It may also help to prevent stomach upsets. However, Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets will still work if they are taken without food.
  • Space the doses as evenly as possible throughout the day. If you are taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets twice a day, take a dose about every twelve hours.

How long to take it for

  • Keep taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets until the course is finished or for as long as your doctor tells you.
  • Do not stop taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets just because you feel better as the infection can return.
  • Do not stop taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets, or change the dose, without first checking with your doctor.

If you forget to take Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets

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 are not sure what to do, ask your doctor or pharmacist.

If you use too much Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets

If you think that you have used too much Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125, you may need urgent medical attention.

Symptoms of overdose include mild to severe nausea, vomiting, cramps and diarrhoea.

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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125?

Things you should do

  • Take Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.
  • Remind any doctor, dentist or pharmacist you visit that you are using Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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 take this medicine to treat any other complaint unless your doctor says so.

Things to be careful of

If you develop severe diarrhoea either when taking Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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®).

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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, it may cause dizziness or tiredness in some people.

Drinking alcohol

Alcohol should be avoided during and for several days after treatment with Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets. Some people who drink alcohol while taking antibiotics similar to Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets have experienced adverse effects.

Looking after your medicine

Keep your tablets in the original pack until it is time to take them.

Store it in a cool dry place below 25°C 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
Fungal Infection related:
  • white, furry, sore tongue and mouth (oral thrush), abnormal taste
  • soreness or itching of the vagina or vaginal discharge (vaginal thrush)
Gut or Gastrointestinal related:
  • diarrhoea (several loose bowel movements per day), indigestion, pain in the stomach, feeling sick or being sick
  • nausea, vomiting
General disorders:
  • dizziness
  • headache
  • tiredness
Others:
  • tooth discolouration
  • hot flushes
  • unusually active (hyperactive).
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
Gut or Gastrointestinal related:
  • severe stomach cramps
  • severe watery or bloody diarrhoea
Allergy related:
  • itching, rash
Liver related:
  • yellowing of your skin or eyes (jaundice)
  • dark urine or pale stools
Others:
  • 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.
Brain or head related:
  • fits or seizures
Others:
  • aseptic meningitis
  • a red rash commonly seen on both sides of buttocks, upper inner thighs, armpits, neck
Allergic reaction related:
  • 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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets 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.

Remember, you should tell your doctor or pharmacist as soon as possible if any of these, or any other unusual events or problems, occur during or after treatment with Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets.

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.

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

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

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 Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets contains

Active ingredient
(main ingredient)		Amoxicillin/Clavulanic Acid Viatris 500/125 tablets:
amoxicillin 500 mg clavulanic acid 125 mg
Amoxicillin/Clavulanic Acid Viatris 875/125 tablets:
amoxicillin 875 mg clavulanic acid 125 mg
Other ingredients
(inactive ingredients)
  • magnesium stearate
  • purified talc
  • povidone
  • croscarmellose sodium
  • microcrystalline cellulose
  • triethyl citrate
  • ethylcellulose
  • sodium lauryl sulfate
  • cetyl alcohol
  • hypromellose
  • titanium dioxide
Amoxicillin/Clavulanic Acid Viatris 875/125 tablets:
  • silicon dioxide.

Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets do not contain sucrose, lactose, gluten, tartrazine or any other azo dyes.

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

What Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets looks like

Amoxicillin/Clavulanic Acid Viatris 500/125 - Off-white, oval, biconvex, film-coated tablet, scored on both sides.
Blister packs of 10 tablets (AUST R 230395).

Amoxicillin/Clavulanic Acid Viatris 875/125 - White to pale yellow, oblong, biconvex, film-coated tablet, scored on both sides.
Blister packs of 10 tablets (AUST R 230396).

Who distributes Amoxicillin/Clavulanic Acid Viatris 500/125 or Amoxicillin/Clavulanic Acid Viatris 875/125 tablets

Sandoz Pty Ltd
100 Pacific Highway
North Sydney, NSW 2060
Australia

Tel 1800 726 369

This leaflet was revised in June 2024.

® Registered Trade Mark. The trade marks mentioned in this material are the property of their respective owners.

Published by MIMS September 2024

BRAND INFORMATION

Brand name

Amoxicillin/Clavulanic Acid Viatris

Active ingredient

Amoxicillin; Clavulanic acid

Schedule

S4

 

1 Name of Medicine

Amoxicillin trihydrate and potassium clavulanate.

2 Qualitative and Quantitative Composition

Amoxicillin/Clavulanic Acid Viatris 500/125 and Amoxicillin/Clavulanic Acid Viatris 875/125 tablet preparations are combination products containing amoxicillin trihydrate and potassium clavulanate as the active ingredients.
Each tablet contains the following active ingredients (see Table 1):

Excipients with known effect.

Contains sulfites and 24 mg of elemental potassium per tablet.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Amoxicillin/Clavulanic Acid Viatris 500/125 tablets are off-white, oval, biconvex, film-coated and scored on both sides.
Amoxicillin/Clavulanic Acid Viatris 875/125 tablets are white to pale yellow, oblong, biconvex, film-coated and scored on both sides.

4 Clinical Particulars

4.1 Therapeutic Indications

Short-term treatment of bacterial infections at the following sites when caused by amoxicillin/clavulanic acid sensitive, beta-lactamase producing organisms:
Skin and skin structure infections.
Urinary tract infections (complicated and uncomplicated).
Upper respiratory tract infections, such as sinusitis, otitis media and recurrent tonsillitis.
Lower respiratory tract infections, including community acquired pneumonia and acute exacerbations of chronic bronchitis.
Appropriate culture and susceptibility studies should be performed to identify the causative organism(s) and determine its (their) susceptibility to amoxicillin/clavulanic acid tablet preparations. However, when there is reason to believe an infection may involve any of the beta-lactamase producing organisms listed in the microbiological section, therapy may be instituted prior to obtaining the results from bacteriological and susceptible studies. Once these results are known, therapy should be adjusted if appropriate.
The treatment of mixed infections caused by amoxicillin susceptible organisms and beta-lactamase producing organisms susceptible to amoxicillin/clavulanic acid tablet preparations should not require the addition of another antibiotic due to the amoxicillin content of these products.

4.2 Dose and Method of Administration

Amoxicillin/clavulanic acid tablet preparations should be taken immediately before or with the first mouthful of food, to minimise potential gastrointestinal intolerance and to optimise absorption.

Adults.

The usual adult dose is one Amoxicillin/Clavulanic Acid Viatris 500/125 tablet every 12 hours.
For more severe infections, the dose should be one Amoxicillin/Clavulanic Acid Viatris 875/125 tablet every 12 hours.

Note.

Although the proportion of amoxicillin increases with increasing strength of amoxicillin/clavulanic acid tablet preparations, the amount of clavulanic acid remains the same. Therefore, the tablets are not directly substitutable.
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.

Amoxicillin/Clavulanic Acid Viatris 875/125 tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance less than or equal to 30 mL/minute).
Both amoxicillin and clavulanic acid are excreted by the kidneys and the serum half-life increases in patients with renal failure. No adjustment to the initial dose is necessary, but the dosing interval should be extended according to the degree of renal impairment.
The following schedule is proposed for amoxicillin/clavulanic acid tablets preparations:

Mild impairment (creatinine clearance > 30 mL/minute).

No change in dosage.

Moderate impairment (creatinine clearance 10 to 30 mL/minute).

Amoxicillin/Clavulanic Acid Viatris 500/125 - one tablet, 12-hourly only.

Severe impairment (creatinine clearance < 10 mL/minute).

Amoxicillin/Clavulanic Acid Viatris 500/125 - one tablet every 24 hours.
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 are 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. Treatment should usually be continued for 48 to 72 hours beyond the time that the child becomes asymptomatic or evidence of bacterial eradication has been obtained. Treatment should not exceed ten days except for lower respiratory tract infection due to H. influenzae where treatment may be extended up to 14 days.
Children weighing less than 40 kg should not use amoxicillin/clavulanic acid tablet preparations.

4.3 Contraindications

Hypersensitivity to the active substances, penicillin or one or more of the excipients.
History of allergic reactions to beta-lactams, e.g. penicillins, cephalosporins, carbapenems or monobactams.
Previous history of amoxicillin/clavulanic acid associated jaundice or hepatic dysfunction.

4.4 Special Warnings and Precautions for Use

Hypersensitivity reactions.

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.
Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse 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, in atopic individuals 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 amoxicillin/clavulanic acid (see Section 4.8 Adverse Effects (Undesirable Effects)). If an allergic reaction occurs, amoxicillin/clavulanic acid should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline (epinephrine). Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.
Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate (see Section 4.8 Adverse Effects (Undesirable Effects)). DIES is an allergic reaction with the leading symptom of protracted vomiting (1-4 hours after administration of amoxicillin/clavulanate) in the absence of allergic skin or respiratory symptoms. Further symptoms could comprise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia. There have been severe cases including progression to shock.

Pseudomembranous colitis.

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 Cl. difficile should be considered. Fluids, electrolytes and protein replacement therapy 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/clavulanic acid tablet preparations contain 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.
Amoxicillin/clavulanic acid should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxicillin induced skin rashes.
Amoxicillin/clavulanic acid 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/clavulanic acid 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 occurred in patients with serious underlying disease or taking concomitant medications.
Hepatic events subsequent to amoxicillin/clavulanic acid therapy have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. Hepatitis and cholestatic jaundice have also been reported rarely. These events have been noted with other penicillins and cephalosporins.

Use in hepatic impairment.

Amoxicillin/clavulanic acid should be used with care in patients with evidence of hepatic dysfunction. Data is currently insufficient for a dosage recommendation. Dose with caution, and monitor hepatic function at regular intervals.

Use in renal impairment.

In patients with reduced urine output, crystalluria (including acute renal injury) 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. In patients with bladder catheters, a regular check of patency should be maintained (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose).
Amoxicillin/Clavulanic Acid Viatris 875/125 tablets should not be used in patients with moderate to severe renal impairment (creatinine clearance less than or equal to 30 mL/minute).
Amoxicillin/Clavulanic Acid Viatris 500/125 tablets should be used with care in patients with moderate or severe renal impairment. The dosage of Amoxicillin/Clavulanic Acid Viatris 500/125 should be adjusted as recommended in 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, Children.

Effects on laboratory tests.

Oral administration of amoxicillin/clavulanic acid 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 Tes-Tape) be used.
Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with amoxicillin and therefore amoxicillin/clavulanic acid tablet preparations.

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 affect clavulanic acid excretion. Concurrent use with amoxicillin/clavulanic acid 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 hyperuricaemia present in these patients. There are no data with amoxicillin/clavulanic acid and allopurinol administered concurrently.
Concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions.
No information is available about the concurrent use of amoxicillin/clavulanic acid 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/clavulanic acid tablet.
In common with other broad spectrum antibiotics, amoxicillin/clavulanic acid may affect the gut flora, leading to lower estrogen re-absorption and reduced efficacy of 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.
Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

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/clavulanic acid have shown no teratogenic effects. There is limited experience of the use of amoxicillin/clavulanic acid in human pregnancy. In women with pre-term, premature rupture of the foetal membrane (pPROM), prophylactic treatment with amoxicillin/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 doctor.

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/clavulanic acid 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 infant 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/clavulanic acid is given to a breastfeeding woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

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

Clinical trials.

Amoxicillin/clavulanic acid 875 mg/125 mg tablets.

The most frequently reported adverse events related or possibly related to amoxicillin/clavulanic acid 875 mg/125 mg tablets 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 the amoxicillin/clavulanic acid 875 mg/125 mg tablets twice daily regimen, however it should be noted that causality has not necessarily been established for these events. See Table 2.
During clinical trials with amoxicillin/clavulanic acid 500 mg/125 mg tablets, the most frequently reported adverse events related or possibly related to treatment 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 the amoxicillin/clavulanic acid 500 mg/125 mg tablets, however it should be noted that causality has not necessarily been established for these events. See Table 3.

Post marketing.

The following adverse reactions have been reported for ampicillin class antibiotics and may occur with amoxicillin/clavulanic acid tablet preparations:
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; not known: cannot be estimated from the available data.

Infections and infestations.

Common: mucocutaneous candidiasis.
Not known: overgrowth of non-susceptible organism.

Cardiac disorders.

Not known: 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).
Not known: drug-induced enterocolitis syndrome, pancreatitis acute.

Hepatobiliary.

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

Central nervous system.

Uncommon: dizziness, headache.
Very rare: reversible hyperactivity, convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
Not known: aseptic meningitis.

Haemopoietic and lymphatic systems.

Uncommon: thrombocytosis.
Rare: anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, reversible leukopenia (including neutropenia and 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), drug reaction with eosinophilia and systemic symptoms (DRESS), and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) (baboon syndrome) have been reported rarely. Whenever such reactions occur, amoxicillin/clavulanic acid tablets should be discontinued, unless in the opinion of the doctor no alternative treatment is available and continued therapy is considered essential. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillins (see Section 4.4 Special Warnings and Precautions for Use).
Not known: linear lgA disease.

Renal and urinary tract disorders.

Rare: interstitial nephritis.
Not known: crystalluria (including acute renal injury) (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.

4.9 Overdose

Serious and severe clinical symptoms are unlikely to occur after overdosage with amoxicillin/clavulanic acid. 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. Convulsions may occur in patients with impaired renal function or in those receiving high doses.
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).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: combinations of penicillins, including beta-lactamase inhibitors; ATC code: J01CR02.

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 beta-lactamases and the addition of clavulanic acid 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 4-7).

Note.

Resistance can vary from region to region and information on local resistance should be taken into account.
The MIC90 data provided in Table 7 has been collected from the following countries during the time period specified: US: 91-97; UK: not stated; France: 94-95; Belgium: 93-94.
It should be noted that NCCLS breakpoints are reviewed on a regular basis and may be amended according to the data available. The following in vitro data are available, but their clinical significance is unknown. See Table 8.
Proteus vulgaris and Klebsiella species may not be susceptible to amoxicillin/clavulanic acid at concentrations of amoxicillin and clavulanic acid achieved in the plasma. However, at concentrations of amoxicillin and clavulanic acid achievable in the urine the majority of strains are susceptible.
Susceptibility testing.

Diffusion technique.

For Kirby-Bauer method of susceptibility testing, 30 microgram amoxicillin/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/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/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/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.
Recommended amoxicillin/clavulanic acid Susceptibility Ranges1,2. See Tables 9 and 10.

Clinical trials.

Amoxicillin/clavulanic acid 875 mg/125 mg tablets twice daily versus amoxicillin/clavulanic acid 500 mg/125 mg tablets three times daily.

Three pivotal studies in 1,361 patients treated for 7 to 14 days for either lower respiratory tract infections, upper respiratory infections or complicated urinary tract infections compared a regimen of amoxicillin/clavulanic acid 875 mg/125 mg tablets every 12 hours to amoxicillin/clavulanic acid 500 mg/125 mg tablets dosed every 8 hours (584, 170 and 607 patients respectively). 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. The most frequently reported adverse event in two of the studies was diarrhoea; incidence rates were similar for the 875 mg/125 mg tablets every 12 hours and 500 mg/125 mg tablets every 8 hours 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 mg/125 mg 12 hourly dosing versus 2.5% for the 500 mg/125 mg 8 hourly dosing. In the third study the most frequently reported adverse event was headache with an incidence of 5.7% (amoxicillin/clavulanic acid 500 mg/125 mg tablets every 8 hours) versus 8.3% (amoxicillin/clavulanic 875 mg/125 mg tablets every 12 hours).
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 diarrhoea-related withdrawals between the regimens.

Amoxicillin/clavulanic acid 500 mg/125 mg tablets twice daily versus amoxicillin/clavulanic acid 250 mg/125 mg tablets three times daily.

Two pivotal studies in 908 patients treated for between five and ten days for either uncomplicated skin and skin structure infections (SSSI) or acute exacerbation of chronic bronchitis (AECB) compared a regimen of amoxicillin/clavulanic acid 500 mg/125 mg tablets every 12 hours with amoxicillin/clavulanic acid 250 mg/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/clavulanic acid 250 mg/125 mg 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 have been investigated, however these supportive studies were not sufficiently designed to demonstrate the relative efficacy of the twice daily versus three times daily dosage regimens, or compared the proposed regimen with other treatments.

5.2 Pharmacokinetic Properties

Absorption.

Amoxicillin/clavulanic acid tablet preparations 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/clavulanic acid tablet preparations should be administered at the start of a meal. The pharmacokinetics of amoxicillin are not affected by food.
Oral administration at the start of a light meal of amoxicillin/clavulanic acid 875 mg/125 mg tablets every 12 hours was compared with amoxicillin/clavulanic acid 500 mg/125 mg tablets every 8 hours.
The following mean pharmacokinetic parameters (see Tables 11 and 12) were observed for amoxicillin and clavulanic acid following administration of amoxicillin/clavulanic acid 875 mg/125 mg tablets every 12 hours and amoxicillin/clavulanic acid 500 mg/125 mg tablets every 8 hours:
The half-life and Cmax for clavulanate for amoxicillin/clavulanic acid 875 mg/125 mg tablets were not significantly different from amoxicillin/clavulanic acid 500 mg/125 mg tablets. However, the AUC(0-24 hours) was reduced, as would be expected with the lower daily dose of clavulanate, i.e. twice daily dose (125 x 2 mg of clavulanate) versus three times daily dose (125 x 3 mg of clavulanate).
Oral administration of amoxicillin/clavulanic acid 500 mg/125 mg tablets every 12 hours was compared with amoxicillin/clavulanic acid 250 mg/125 mg tablets every 8 hours at the start of a light meal. The following mean pharmacokinetic parameters were observed (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, 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 to 30% and amoxicillin approximately 20%. From animal studies, there is no evidence to suggest either component accumulates in any organ.

Metabolism.

No data available.

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) is present as 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 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 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 carcinogenic or mutagenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Magnesium stearate, purified talc, povidone, croscarmellose sodium, microcrystalline cellulose, triethyl citrate, ethylcellulose, sodium lauryl sulphate, cetyl alcohol, hypromellose and titanium dioxide.
Amoxicillin/clavulanic acid 875/125 mg tablets also contain silicon dioxide.

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 25°C. Protect from moisture.

6.5 Nature and Contents of Container

Container type: aluminium/aluminium blister packs.
Pack size: 10 tablets.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 230395 - Amoxicillin/Clavulanic Acid Viatris 500/125 amoxicillin 500 mg (as trihydrate) and clavulanic acid 125 mg (as potassium) tablet blister pack.
AUST R 230396 - Amoxicillin/Clavulanic Acid Viatris 875/125 amoxicillin 875 mg (as trihydrate) and clavulanic acid 125 mg (as potassium) tablet blister pack.

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

Chemical structure.

Potassium (Z)-(2R, 5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate.

Amoxicillin trihydrate.


Potassium clavulanate.


Amoxicillin trihydrate: C16H19N3O5S.3H2O.
Potassium clavulanate: C8H8KNO5.

Molecular weight.

Amoxicillin trihydrate: 419.4.
Potassium clavulanate: 237.3.
Amoxicillin/clavulanic acid preparations are a combination products containing the semi-synthetic antibiotic amoxicillin (as the trihydrate) and the beta-lactamase inhibitor potassium clavulanate (as the potassium salt of clavulanic acid).
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.
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.

CAS number.

Amoxicillin trihydrate: 61336-70-7.
Potassium clavulanate: 61177-45-5.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes