Consumer medicine information

Amoxycillin Sandoz Tablets

Amoxicillin

BRAND INFORMATION

Brand name

Amoxycillin Sandoz Tablets

Active ingredient

Amoxicillin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Amoxycillin Sandoz Tablets.

What is in this leaflet

This leaflet answers some common questions about Amoxycillin Sandoz.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Amoxycillin Sandoz against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may need to read it again.

What Amoxycillin Sandoz is used for

The name of your medicine is Amoxycillin Sandoz. It contains the active ingredient amoxicillin trihydrate.

Amoxicillin is an antibiotic used in the treatment of bacterial infections.

Amoxycillin Sandoz belongs to a group of antibiotics called penicillins. These antibiotics work by killing the bacteria that are causing your infection.

Amoxycillin Sandoz is used for the treatment of chest infections.

Amoxycillin Sandoz will not work against infections caused by viruses such as colds or the flu.

Your doctor may have prescribed Amoxycillin Sandoz for another reason. Ask your doctor if you have any questions about why Amoxycillin Sandoz has been prescribed for you.

Amoxycillin Sandoz is available only with a doctor's prescription.

Amoxycillin Sandoz is not addictive.

Before you take Amoxycillin Sandoz

When you must not take it

Do not take Amoxycillin Sandoz if:

  • you have an allergy to amoxicillin, any other penicillins or any of the ingredients listed at the end of this leaflet
  • you have had a serious allergic reaction to any β-lactam antibiotics in the past (e.g. penicillins, cephalosporins carbapenem or monobactam). These are another group of antibiotics similar to penicillins
    You may have an increased chance of being allergic to Amoxycillin Sandoz if you are allergic to cephalosporins.
    Some of the symptoms of an allergic reaction may include wheezing, shortness of breath; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; faintness; skin rash, itching or hives.

Do not take Amoxycillin Sandoz after the expiry date printed on the pack has passed.

Do not take Amoxycillin Sandoz if the packaging is torn or shows signs of tampering or if the medicine shows any signs of deterioration. If the medicine has expired, or is damaged or shows any signs of deterioration, return it to your pharmacist for disposal.

If you are not sure if you should start taking Amoxycillin Sandoz, contact your doctor.

Before you start to take it

Tell your doctor if:

  1. you have had any type of allergic reaction to any penicillin or cephalosporin medicines.
You may have an increased chance of being allergic to Amoxycillin Sandoz if you are allergic to any penicillins or cephalosporins.
  1. you have any allergies to:
  • any other medicines
  • any other substances such as foods, preservatives or dyes
  1. you are pregnant or intend to become pregnant.
Your doctor will discuss the possible risks and benefits of using Amoxycillin Sandoz during pregnancy.
  1. you are breast-feeding or intend to breast-feed.
Amoxycillin Sandoz passes into breast milk. No detrimental effects for the breast-fed infant have been reported after taking amoxicillin. Amoxicillin can be used during breast-feeding. However, breast-feeding must be stopped if gastrointestinal disorders (diarrhoea, candidosis or skin rash) occur in the new born. Your doctor will discuss the risks and benefits of taking Amoxycillin Sandoz when breast-feeding.
  1. you have or have had any medical conditions, including:
  • asthma
  • kidney problems
  • liver problems
  • lymphatic leukaemia
  • glandular fever
  • diabetes
  • seizures history
  • stomach or bowel problems
  • a history of allergic problems, including hay fever.

Taking other medicines

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

Some medicines may interfere with Amoxycillin Sandoz. These include:

  • medicines used to treat gout (e.g. probenecid or allopurinol)
  • digoxin, a medicine used to treat heart failure
  • medicines used to prevent blood clots from the coumarin class (e.g. warfarin)
  • methotrexate, a medicine used to treat arthritis and some types of cancers
  • oral contraceptives (birth control pills)
  • other antibiotics (e.g. tetracycline).

These medicines may be affected by Amoxycillin Sandoz or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Talk to your doctor about the need for an additional method of contraception while taking Amoxycillin Sandoz. Some antibiotics may decrease the effectiveness of some birth control pills.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Amoxycillin Sandoz.

How to take Amoxycillin Sandoz

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

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you the dose of Amoxycillin Sandoz you will need to use each day.

The usual dose for Amoxycillin Sandoz is one tablet twice a day.

How to take it

Take Amoxycillin Sandoz with a glass of water.

When to take it

In order for Amoxycillin Sandoz to be most effective, it should be taken at the same times each day. Your doctor or pharmacist can advise you on a dosing schedule if you are unsure.

Amoxycillin Sandoz can be taken with or without food.

How long to take it

Continue taking Amoxycillin Sandoz until you finish the tablets or for as long as your doctor recommends.

Keep taking this medicine for the full course of treatment, even if you begin to feel better after a few days. If you do not complete the full course prescribed by your doctor, the infection may not clear completely or your symptoms may return.

Check with your doctor if you are not sure how long you should be taking Amoxycillin Sandoz.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed.

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

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much Amoxycillin Sandoz. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Amoxycillin Sandoz, you may experience symptoms such as diarrhoea, nausea, vomiting or stomach cramps.

While you are taking Amoxycillin Sandoz

Things you must do

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

If you develop itching, swelling, a skin rash or difficulty in breathing while you are taking Amoxycillin Sandoz, do not take any more Amoxycillin Sandoz and tell your doctor immediately.

If you get severe diarrhoea, tell your doctor or pharmacist immediately. Do this even if it occurs several weeks after Amoxycillin Sandoz has been stopped. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any diarrhoea medicine without first checking with your doctor.

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

If you become pregnant while taking Amoxycillin Sandoz, tell your doctor immediately.

If you have to test your urine for sugar while you are using Amoxycillin Sandoz, make sure your doctor knows which type of test you use. Amoxycillin Sandoz may affect the results of some of these tests.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Amoxycillin Sandoz.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Amoxycillin Sandoz.

Things you must not do

Do not stop taking your medicine because you are feeling better, unless advised by your doctor.

If you do not complete the full course prescribed by your doctor, all of the bacteria causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear completely or it may return.

Do not give Amoxycillin Sandoz to anyone else, even if they have the same condition as you.

Do not use Amoxycillin Sandoz to treat any other complaints, unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how Amoxycillin Sandoz affects you. Amoxycillin Sandoz may cause tiredness or dizziness in some people. Make sure you know how you react to Amoxycillin Sandoz before you drive a car, operate machinery or do anything else that may be dangerous if you are affected.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Amoxycillin Sandoz.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects. The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.

Ask your doctor or pharmacist to answer any questions you may have.

While you are taking Amoxycillin Sandoz

Tell your doctor if you notice any of the following and they worry you:

  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina or discharge
  • mild diarrhoea
  • feeling sick (nausea), vomiting
  • soreness of the mouth or tongue
  • discoloration of the teeth (especially with the suspension). Usually the discoloration can be removed by teeth brushing
  • headache, tiredness.

These side effects are usually mild.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • signs of anaemia such as looking pale, short of breath when exercising, dizziness
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • bruising or bleeding more easily than normal
  • dark coloured urine or blood in the urine
  • passing more or less urine than is normal for you
  • yellowing of the skin or eyes
  • convulsions
  • aching or swollen joints.

These are serious side effects. You may need urgent medical attention. Serious side effects are rare.

If any of the following happen, stop taking Amoxycillin Sandoz and tell your doctor immediately, or go to Accident and Emergency at the nearest hospital:

  • any skin rash, itching or hives or blistering or peeling of the skin
  • wheezing, shortness of breath or difficulty breathing
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • severe abdominal cramps or stomach cramps
  • excessive abnormal muscle movements
  • watery and severe diarrhoea, which may also be bloody.

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

After finishing it

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • fever, in combination with one or both of the above.

You may have a serious condition affecting your bowel, and you may need urgent medical attention. These are rare but serious side effects.

Do not take any diarrhoea medicine without first checking with your doctor.

Other side effects not listed in this leaflet may also occur in some patients. Tell your doctor if you notice anything that is making you feel unwell.

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

After using Amoxycillin Sandoz

Storage

  • Keep your Amoxycillin Sandoz in its original container, in a safe place out of the reach of children.
  • Store Amoxycillin Sandoz tablets in a cool dry place, away from sunlight, where the temperature stays below 25°C.
  • Do not store your medicine in the bathroom or near a sink. Heat and dampness can destroy some medicines.
  • Do not leave your medication in a car or on a window sill.

Disposal

If your doctor tells you to stop taking Amoxycillin Sandoz, or the medicine has passed its expiry date, ask your pharmacist what to do with any medicine left over.

Product description

What it looks like

Amoxycillin Sandoz are white to cream-coloured, oval, biconvex tablets scored on both sides and supplied in blister packs of 2 or 14 tablets in a cardboard carton.

Ingredients

Amoxycillin Sandoz tablets contain 1000 mg amoxicillin (as amoxicillin trihydrate) as the active ingredient.

The tablets also contain the following inactive ingredients:

  • magnesium stearate
  • cellulose - microcrystalline
  • povidone
  • sodium starch glycollate
  • titanium dioxide
  • talc - purified
  • hypromellose.

Supplier

Sandoz Pty Ltd
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

This leaflet was revised in May 2023.

Australian register number
1000mg Tablets: AUST R 98758 (Blisters)

® Registered Trademark

Published by MIMS July 2023

BRAND INFORMATION

Brand name

Amoxycillin Sandoz Tablets

Active ingredient

Amoxicillin

Schedule

S4

 

1 Name of Medicine

Amoxicillin trihydrate.

2 Qualitative and Quantitative Composition

Each Amoxycillin Sandoz 1000 mg tablet contains 1000 mg amoxicillin as the trihydrate.
Amoxicillin trihydrate is a white or almost white, crystalline powder.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Amoxycillin Sandoz tablets are oval, biconvex, white to cream-coloured, scored on both sides.

4 Clinical Particulars

4.1 Therapeutic Indications

Amoxycillin Sandoz is indicated in the treatment of acute exacerbation of chronic bronchitis.

Notes.

Therapy should be guided by bacteriologic studies including sensitivity tests and by clinical response. Amoxicillin alone or in combination with another antibiotic may be used in an emergency where the causative agent has yet to be identified.
Amoxycillin Sandoz 1000 mg tablets have not been shown to be bioequivalent to the 500 mg and 250 mg capsule formulations given in equivalent doses. Therefore, Amoxycillin Sandoz 1000 mg tablets and other forms of amoxicillin are not considered interchangeable.
Infections caused by pathogens with established penicillin G susceptibility should preferentially be treated with penicillin G.

4.2 Dose and Method of Administration

Dosage.

Adults.

1000 mg twice daily.
Treatment should be continued for a minimum of 48 to 72 hours beyond the time when patients become asymptomatic or evidence of bacterial eradication has been obtained.
Bacteriological and clinical appraisals may have to be continued for several months following cessation of treatment.

Method of administration.

Amoxycillin Sandoz may be taken without regard to food.

Dosage adjustment.

Renal impairment.

In renal impairment, the excretion of the antibiotic will be delayed, and depending on the degree of impairment, it may be necessary to reduce the total daily dose.

4.3 Contraindications

Amoxicillin is a penicillin and should not be given to patients with a history of hypersensitivity to β-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenem or monobactam). Known and suspected hypersensitivity to penicillins. Potential cross allergy to other beta-lactams such as cephalosporins should be taken into account.
Known hypersensitivity to the active substance, to any of the penicillins or to any of the excipients.
Antibiotics have no place in trivial infections.

4.4 Special Warnings and Precautions for Use

Hypersensitivity reactions.

Serious, and occasionally fatal, hypersensitivity reactions (including anaphylaxis, anaphylactoid, and severe cutaneous reactions) have been reported in patients receiving beta-lactam antibiotics. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction (see Section 4.8 Adverse Effects (Undesirable Effects)). These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. Before commencing therapy with any penicillin careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, appropriate therapy should be instituted and amoxicillin therapy discontinued. Patients should be told about the potential occurrence of allergic reactions and instructed to report them.
Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airways management, including intubation, should be administered as necessary.
Special caution should be exercised in patients with allergic diatheses or bronchial asthma and hay fever.
Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin (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) 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.

Skin reactions.

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AEGP). This reaction requires amoxicillin discontinuation and contra-indicates any subsequent administration.
Amoxicillin 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.

Lymphatic leukaemia.

Amoxicillin should be given with caution to patients with lymphatic leukaemia as they are susceptible to amoxicillin induced skin rashes.

Non-susceptible microorganisms.

Amoxicillin is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with amoxicillin. This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.
Amoxicillin, an aminopenicillin, 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.

Overgrowth of non-susceptible microorganisms.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents and may range in severity from mild diarrhoea to fatal colitis. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil), may prolong and/or worsen the condition and should not be used.

Convulsions.

Convulsions may occur in patients with impaired renal function or in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders (see Section 4.8 Adverse Effects (Undesirable Effects)).

Anticoagulants.

Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin 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.

Prolonged therapy.

As with any potent drug, periodic assessment of renal, hepatic and haematopoietic function should be made during prolonged therapy. The possibility of superinfection with mycotic or bacterial pathogens should be kept in mind. If superinfection occurs (usually involving Aerobacter, Pseudomonas or Candida) discontinue the drug and/or institute appropriate therapy.
Elevated liver enzymes and changes in blood counts have been reported.

Jarisch-Herxheimer reaction.

The Jarisch-Herxheimer reaction has been seen following amoxicillin treatment of Lyme disease. It results directly from the bactericidal activity of amoxicillin on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

Crystalluria.

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. 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). At high doses, adequate fluid intake and urinary output must be maintained to minimise the possibility of amoxicillin crystalluria.

Urinary tract infections.

Following single dose therapy of acute lower urinary tract infections, the urine should be cultured. A positive culture may be evidence of a complicated or upper urinary tract infection and call for longer or larger course of therapy.

Use in renal impairment.

Dosage should be adjusted in patients with renal impairments (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use, Convulsions).

Use in the elderly.

No data available.

Paediatric use.

Precaution should be taken in premature children and during neonatal period: renal, hepatic and haematological functions should be monitored.

Effects on laboratory tests.

Oral administration of amoxicillin will result in high urine concentrations of amoxicillin. Since high urine concentrations of amoxicillin 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 enzyme-based 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.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Allopurinol.

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. Similar reactions can be expected with amoxicillin.

Digoxin.

An increase in the absorption of digoxin is possible on concurrent administration with amoxicillin. A dose adjustment of digoxin may be necessary.

Anticoagulants.

Concomitant administration of amoxicillin and anticoagulants from the coumarin class, may prolong the bleeding time. A dose adjustment of anticoagulants may be necessary (see Section 4.4 Special Warnings and Precautions for Use). If coadministration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin.
A large number of cases showing an increase of oral anticoagulant activity has been reported in patients receiving antibiotics. The infectious and inflammatory context, age and the general status of the patient appear as risk factors. In these circumstances, it is difficult to know the part of the responsibility between the infectious disease and its treatment in the occurrence of INR disorders. However, some classes of antibiotics are more involved, notably fluoroquinolones, macrolides, cyclines, cotrimoxazole and some cephalosporins.
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.

Methotrexate.

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity. Serum methotrexate levels should be closely monitored in patients who receive amoxicillin and methotrexate simultaneously (see Section 4.4 Special Warnings and Precautions for Use). Amoxicillin decreases the renal clearance of methotrexate, probably by competition at the common tubular secretion system.

Tetracyclines.

Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin.

Probenecid.

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin may result in increased and prolonged blood levels of amoxicillin. Oral administration of amoxicillin 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 enzyme based glucose oxidase reactions (such as Clinistix or Testape) be used.
Caution is recommended when amoxicillin is given concomitantly with:

Oral hormonal contraceptives.

In common with other antibiotics, amoxicillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. Administration of amoxicillin can transiently decrease the plasma level of oestrogens and progesterone, and may reduce the efficacy of oral contraceptives. It is therefore recommended to take supplemental non-hormonal contraceptive measures.

Other forms of interactions.

Forced diuresis leads to a reduction in blood concentrations by increased elimination of amoxicillin.
Amoxicillin may decrease the amount of urinary estriol in pregnant women.
At high concentrations, amoxicillin may diminish the results of serum glycemia levels.
Amoxicillin may interfere with protein testing when colorimetric methods are used.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data on the effects of amoxicillin on fertility in humans. Reproductive studies in animals have shown no effects on fertility.
(Category A)
Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
Animal studies with amoxicillin have shown no teratogenic effects. The product has been in extensive clinical use since 1972 and its suitability in human pregnancy has been well documented in clinical studies.
Amoxicillin may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

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 and duration of contractions. However, it is not known whether the use of amoxicillin 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.
 Ampicillin class antibiotics are excreted in breast milk; therefore, caution should be exercised when amoxicillin is administered to a nursing woman. So far no detrimental effects for the breast-fed infant have been reported after taking amoxicillin. Amoxicillin can be used during breast-feeding. However, breast-feeding must be stopped if gastrointestinal disorders (diarrhoea, candidosis or skin rash) occur in the newborn.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Amoxicillin 1000 mg tablets twice daily and amoxicillin 500 mg capsules three times daily for ten days were compared in a study of 395 adult patients with acute exacerbations of chronic bronchitis. There were no significant differences on the incidence or severity of adverse events between the treatment groups.
The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.
The incidence of adverse events reported at a frequency of > 1%, and possibly or probably drug related, is shown in Table 1.
As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins. The following adverse reactions have been reported as associated with the use of amoxicillin.

Cardiac disorders.

Kounis syndrome: not known.

Gastrointestinal.

Nausea, vomiting, diarrhoea. Intestinal candidiasis and antibiotic associated colitis (including pseudomembranous colitis and haemorrhagic colitis), superficial discoloration of the teeth (especially with the suspension) have been reported rarely (see Section 4.4 Special Warnings and Precautions for Use). Usually the discoloration can be removed by teeth brushing. If severe and persistent diarrhoea occurs, the very rare possibility of pseudomembranous colitis should be considered. The administration of anti-peristaltic drug is contraindicated. Black hairy tongue and haemorrhagic colitis have been reported very rarely.
Drug-induced enterocolitis syndrome: not known (see Section 4.4 Special Warnings and Precautions for Use).

Hypersensitivity.

Erythematous maculopapular rash, pruritus and urticaria have been reported occasionally. Rarely, skin reactions such as erythema multiforme exudativum, acute generalised exanthematous pustulosis (AGEP), Lyell's syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, Jarisch-Herxheimer reaction and bullous, exfoliative dermatitis and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. As with other antibiotics, severe allergic reactions including angioneurotic oedema, anaphylaxis, serum sickness, hypersensitivity vasculitis and interstitial nephritis (crystalluria) have been reported rarely.
Whenever such reactions occur, amoxicillin should be discontinued.

Note.

Urticaria, other skin rashes and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids.
Anaphylaxis is the most serious reaction experienced (see Section 4.4 Special Warnings and Precautions for Use).

Hepatic.

A moderate rise in AST and/or ALT has occasionally been noted, but the significance of this finding is unknown. As with other beta-lactam antibiotics, hepatitis and cholestatic jaundice have been reported rarely.

Renal.

Crystalluria has been reported rarely.

Haemic and lymphatic systems.

Reactions such as anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia and leucopenia (including severe neutropenia or agranulocytosis) have been reported during therapy with other penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Prolongation of bleeding time and prothrombin time have also been reported rarely.

Renal and urinary tract disorders.

Interstitial nephritis, crystalluria (including acute renal injury) have been reported very rarely (see Section 4.9 Overdose).

Skin and subcutaneous tissue disorders.

Linear IgA disease: not known.

Central nervous system effects.

CNS effects have been seen rarely. They include hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses. Aseptic meningitis has also been reported.

Infections and infestations.

Mucocutaneous candidiasis have been reported very rarely.

Miscellaneous.

Superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.
As the blood-brain barrier becomes more permeable in meningitis, toxic symptoms may be precipitated by lower levels of amoxicillin in patients with meningitis.

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

Signs of overdosage of amoxicillin would predominantly be gastrointestinal related. The symptoms may include abdominal or stomach cramps and pain, severe nausea, vomiting or diarrhoea. Treatment of penicillin overdosage should be symptomatic and supportive. Haemodialysis may aid in the removal of penicillins from the blood.
See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects).
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology. Amoxicillin trihydrate is a broad-spectrum penicillin similar to ampicillin in its bactericidal action. It is believed to act through the inhibition of biosynthesis of cell wall mucopeptide. It is active against both Gram-positive and Gram-negative microorganisms. Amoxicillin is active in vitro against beta-lactamase negative strains of Proteus mirabilis, and Haemophilus influenza. In vitro studies have also demonstrated activity against most strains of alpha- and beta-haemolytic Streptococci, Streptococcus pneumoniae, and beta-lactamase negative strains of Staphylococci, Neisseria gonorrhoeae, Neisseria meningitidis and Enterococcus faecalis. However, some of the organisms are sensitive to amoxicillin only at concentrations achieved in the urine. Strains of gonococci, which are relatively resistant to benzylpenicillin, may also be resistant to amoxicillin. Amoxicillin is not effective against penicillinase producing bacteria, particularly resistant Staphylococci which now have a high prevalence. All strains of Pseudomonas, Klebsiella, Enterobacter, indole positive Proteus, Serratia marcescens, Citrobacter, penicillinase producing N. gonorrhoeae and penicillinase producing H. influenzae are also resistant. Escherichia coli isolates are becoming increasingly resistant to amoxicillin in vitro due to the presence of penicillinase-producing strains. See Table 2.
Disc susceptibility testing.

Dilution or diffusion techniques.

Either quantitative (MIC) or breakpoint should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy may be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

Amoxycillin Sandoz (1000 mg tablets bid) and amoxicillin (500 mg capsules tds) were compared in a multi-centre, double-blind, randomised study of 395 adult patients with acute exacerbations of chronic bronchitis. Patients were treated for 10 days and were assessed during therapy (days 3-5), after the end of therapy (days 12-15) and at follow-up (days 28-35).
The statistical analysis for each clinical efficacy parameter during therapy (pooling moderate/ severe severity and mucopurulent/ purulent sputum appearance) is shown in Table 3.
The primary endpoint of this study was the clinical success at the end of therapy. For clinically evaluable patients, the clinical success rate at the end of therapy was 156/175 (89.1%) in the Amoxycillin Sandoz 1000 mg bid group and 150/162 (92.6%) in the amoxicillin 500 mg tds group. The results (p-value = 0.27; CI 95% = -0.96%, 2.7%) confirm the equivalence in clinical efficacy between the two treatment groups. Bacteriological success was a secondary endpoint in this study. A total of 219 patients were eligible for assessment of bacteriological success at the end of treatment. Bacteriological success was achieved for 85/109 (78%) of patients given Amoxycillin Sandoz and 83/110 (75.5%) of patients given amoxicillin 500 mg tds.
Assessment at follow-up yielded a clinical recurrence rate of 13.4% in the bid group and 13.7% in the tds group. No statistically significant differences between the two treatment groups.

5.2 Pharmacokinetic Properties

Absorption.

Amoxicillin is stable in the presence of gastric acid and is rapidly and well absorbed after oral administration, even in the presence of food. Peak serum levels are reached within 1 to two hours after ingestion.
Efficacy of β-lactam antibiotic is related to the time in which the concentration of antibiotic at the site of infection exceeds the minimal inhibitory concentration (MIC) of that antibiotic for the pathogen. Analysis of pharmacokinetic data from a single dose study of the amoxicillin 500 mg capsule and a single dose study of the amoxicillin 1 g film-coated tablet showed that the mean amoxicillin plasma concentrations were above the (MIC) for similar proportions of the dose interval for the MIC levels of 0.5, 1.0 and 2.0 microgram/mL. The time above the MIC for other MIC levels and the time above MIC at steady state were not assessed for either formulation and/or dose regimen of amoxicillin.
Data to establish the bioequivalence of the 1 x 1000 mg tablet with 2 x 500 mg capsules have not been submitted and, as such, the products should not be directly substituted.

Distribution.

Amoxicillin readily distributes in most body tissues and fluids with the exception of brain and spinal fluid except when the meninges are inflamed. Amoxicillin has been shown to diffuse into sputum and saliva.
Amoxicillin is only 17% protein bound in serum.

Metabolism.

No data available.

Excretion.

Amoxicillin is excreted mainly via the urine where it exists in a high concentration. Concentrations in the bile vary and are dependent upon normal biliary function. Amoxicillin is eliminated with a half-life of 61.3 minutes with normal renal function and up to 16-20 hours in the absence of renal function. Amoxicillin is excreted in the urine as unchanged drug and as penicilloic acid. Approximately 75% of a 1 g dose is excreted in the urine within six hours with normal renal function. However, there is a proportional difference in the amount excreted following different doses, due to lack of linearity in the rate of absorption with higher doses. Elimination of amoxicillin can be delayed by concurrent administration of probenecid.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Magnesium stearate, povidone, sodium starch glycollate, cellulose-microcrystalline, titanium dioxide, talc-purified and hypromellose.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5.

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

Amoxycillin Sandoz are packed in blisters of 2 or 14 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

The chemical name of amoxicillin trihydrate is (2S,5R,6R)-6-[(R)-2-amino-2-(4-hydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid trihydrate. Its molecular formula is C16H19N3O5S.3H2O (Molecular Weight: 419.4) and its structural formula is:

CAS number.

61336-70-7.
It is slightly soluble in water and in ethanol (96%), practically insoluble in chloroform, in ether and in fatty oils.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes