Amoxil Vials 500 mg, powder for solution for injection or infusion

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Amoxicillin sodium
Available from:
GlaxoSmithKline (Ireland) Limited
ATC code:
J01CA; J01CA04
INN (International Name):
Amoxicillin sodium
Dosage:
500 milligram(s)
Pharmaceutical form:
Powder for solution for injection/infusion
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Penicillins with extended spectrum; amoxicillin
Authorization status:
Marketed
Authorization number:
PA1077/033/004
Authorization date:
1977-04-01

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

Implementation Date: March 2019

Text Date: 14/12/2018

Text Issue and Draft No.: Issue6 Draft1

[GSK Logo]

Package leaflet: Information for the user

Amoxil Vials 500 mg

Powder for solution for injection or infusion

amoxicillin

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. See section 4.

What is in this leaflet

What Amoxil is and what it is used for

What you need to know before you take Amoxil

How to take Amoxil

Possible side effects

How to store Amoxil

Contents of the pack and other information

1 What Amoxil is and what it is used for

What Amoxil is

Amoxil is an antibiotic. The active ingredient is amoxicillin. This belongs to a group of medicines called

‘penicillin’.

What Amoxil is used for

Amoxil is used to treat infections caused by bacteria in different parts of the body.

Amoxil Powder for Solution for Injection or Infusion is usually used for urgent treatment of severe infection

or if patients cannot take Amoxil by mouth.

2 What you need to know before you take Amoxil

Do not take Amoxil:

if you are allergic to amoxicillin, penicillin or any of the other ingredients of this medicine (listed in

section 6).

if you have ever had an allergic reaction to any antibiotic. This can include a skin rash or swelling of the

face or throat.

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

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Text Date: 14/12/2018

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Do not take Amoxil if any of the above apply. If you are not sure, talk to your doctor, pharmacist or nurse

before taking Amoxil.

Warnings and Precautions

Talk to your doctor, pharmacist or nurse before taking Amoxil if you:

have glandular fever (fever, sore throat, swollen glands and extreme tiredness)

have kidney problems

are not urinating regularly.

If you are not sure if any of the above apply to you, talk to your doctor, pharmacist or nurse before taking

Amoxil.

Blood and urine tests

If you are having:

Urine tests (glucose) or blood tests for liver function

Oestriol tests (used during pregnancy to check the baby is developing normally)

Tell your doctor, pharmacist or nurse that you are taking Amoxil. This is because Amoxil can affect the

results of these tests.

Other medicines and Amoxil

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

If you are taking allopurinol (used for gout) with Amoxil, it may be more likely that you will have an

allergic skin reaction.

If you are taking probenecid (used for gout), your doctor may decide to adjust your dose of Amoxil.

If you are taking medicines to help stop blood clots (such as warfarin), you may need extra blood tests.

If you are taking other antibiotics (such as tetracycline) Amoxil may be less effective.

If you are taking methotrexate (used for the treatment of cancer and severe psoriasis) Amoxil may cause

an increase in side effects.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor, pharmacist or nurse for advice before taking this medicine.

Driving and using machines

Amoxil can have side effects and the symptoms (such as allergic reactions, dizziness and convulsions) may

make you unfit to drive.

Do not drive or operate machinery unless you are feeling well.

Amoxil Powder for Solution for Injection or Infusion 500 mg contains sodium

Amoxil contains 32 mg (1.37 mmol) of sodium. This should be considered if you are on a sodium controlled

diet.

3 How Amoxil is given

You will never give yourself this medicine. A qualified person, like a doctor or a nurse, will give you this

medicine.

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

Implementation Date: March 2019

Text Date: 14/12/2018

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Amoxil will be given as an injection or an infusion into a vein (intravenously) or muscle

(intramuscularly).

Your doctor will decide how much you need each day and how often the injections should be given.

Make sure you drink plenty of fluids while having Amoxil.

To treat infections

The usual doses are as follows.

Children up to 40 kg

Most infections:

20 mg to 200 mg for every kilogram of body weight in divided doses throughout the

day.

Lyme disease (an infection spread by parasites called ticks):

isolated erythema migrans (early stage –

red or pink circular rash) 25 mg to 50 mg for every kilogram of body weight in divided doses throughout

the day; systemic manifestations (late stage – for more serious symptoms or when the disease spreads

around your body) 100 mg for every kilogram of body weight in divided doses throughout the day.

Intravenous maximum single dose:

50 mg for every kilogram of body weight.

Intramuscular maximum daily dose:

120 mg for every kilogram of body weight as 2 to 6 equally

divided doses.

Adults, elderly patients and children weighing 40 kg or more

Usual daily dosage:

750 mg to 6 g administered in divided doses.

Intravenous maximum daily dose:

12 g per day.

Intravenous maximum single dose:

2 g by infusion or 1 g by bolus injection.

Intramuscular maximum daily dose:

4 g per day

Intramuscular maximum single dose:

1 g.

Lyme disease (an infection spread by parasites called ticks):

isolated erythema migrans (early stage –

red or pink circular rash) 4 g per day; systemic manifestations (late stage - for more serious symptoms or

when the disease spreads around your body) 6 g per day.

Kidney problems

If you have kidney problems the dose might be lower than the usual dose.

If more Amoxil is given to you than recommended

It is unlikely you will be given too much, but if you think you have been given too much Amoxil, tell your

doctor, pharmacist or nurse immediately. Signs might be an upset stomach (feeling sick, being sick or

diarrhoea) or crystals in the urine, which may be seen as cloudy urine or problems urinating.

If you think you have missed an injection of Amoxil

Speak to your doctor, pharmacist or nurse.

How long will you need to take Amoxil for?

You will not normally be given Amoxil for more than 2 weeks without the doctor reviewing your

treatment.

Thrush (a yeast infection of moist areas of the body which can cause soreness, itching and white discharge)

may develop if Amoxil is used for a long time. If this occurs, tell your doctor, pharmacist or nurse.

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

Implementation Date: March 2019

Text Date: 14/12/2018

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If you are given Amoxil for a long time, your doctor may perform additional tests to check your kidneys, liver

and blood are working normally.

If you have any further questions about how this product is given, ask your doctor, pharmacist or nurse.

4 Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Amoxil and see a doctor straight away, if you notice any of the following serious side effects

– you may need urgent medical treatment:

The following are very rare (may affect up to 1 in 10,000 people)

allergic reactions, the signs may include: skin itching or rash, swelling of the face, lips, tongue, body or

breathing difficulties. These can be serious and occasionally deaths have occurred

rash or pinpoint flat red round spots under the skin surface or bruising of the skin. This is due to

inflammation of blood vessel walls due to an allergic reaction. It can be associated with joint pain

(arthritis) and kidney problems

a delayed allergic reaction can occur usually 7 to 12 days after having Amoxil, some signs include: rashes,

fever, joint pains and enlargement of the lymph nodes especially under the arms

a skin reaction known as ‘erythema multiforme’ where you may develop: itchy reddish purple patches on

the skin especially on the palms of the hands or soles of the feet, ‘hive-like’ raised swollen areas on the

skin, tender areas on the surfaces of the mouth, eyes and genitals. You may have a fever and be very tired

other severe skin reactions can include: changes in skin colour, bumps under the skin, blistering, pustules,

peeling, redness, pain, itching, scaling. These may be associated with fever, headaches and body aches

flu-like symptoms with a rash, fever, swollen glands, and abnormal blood test results (including increased

white blood cells (eosinophilia) and liver enzymes) (Drug Reaction with Eosinophilia and Systemic

Symptoms (DRESS)).

fever, chills, a sore throat or other signs of an infection, or if you bruise easily. These may be signs of a

problem with your blood cells

Jarisch-Herxheimer reaction

which occurs during treatment with Amoxil for Lyme disease and causes

fever, chills, headache, muscle pain and skin rash.

inflammation of the large bowel (colon) with diarrhoea (sometimes containing blood), pain and fever

serious liver side effects may occur. They are mainly associated with people having treatment over a long

period, males and the elderly. You must tell your doctor urgently if you get:

severe diarrhoea with bleeding

blisters, redness or bruising of the skin

darker urine or paler stools

yellowing of the skin or the whites of the eyes (jaundice). See also anaemia below which might

result in jaundice.

These can happen when having the medicine or for up to several weeks after.

If any of the above occurs talk to your doctor or nurse straight away.

Sometimes you may get less severe skin reactions such as:

a mildly itchy rash (round, pink-red patches), ‘hive-like’ swollen areas on forearms, legs, palms, hands or

feet. This is uncommon (may affect up to 1 in 100 people).

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

Implementation Date: March 2019

Text Date: 14/12/2018

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If you have any of these talk to your doctor or nurse as Amoxil will need to be stopped.

The other possible side effects are:

Common

(may affect up to 1 in 10 people)

skin rash

feeling sick (nausea)

diarrhoea.

Uncommon

(may affect up to 1 in 100 people)

being sick (vomiting).

Very rare

(may affect up to 1 in 10,000 people)

thrush (a yeast infection of the vagina, mouth or skin folds), you can get treatment for thrush from your

doctor, pharmacist or nurse

kidney problems

fits (convulsions), seen in patients on high doses or with kidney problems

dizziness

hyperactivity

crystals in the urine, which may be seen as cloudy urine, or difficulty or discomfort in passing urine.

Make sure you drink plenty of fluids to reduce the chance of these symptoms

an excessive breakdown of red blood cells causing a type of anaemia. Signs include: tiredness, headaches,

shortness of breath, dizziness, looking pale and yellowing of the skin and the whites of the eyes

low number of white blood cells

low number of cells involved with blood clotting

the blood may take longer to clot than it normally would. You may notice this if you have a nosebleed or

cut yourself.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not

listed in this leaflet. You can also report side effects directly via HPRA Pharmacovigilance, Earlsfort Terrace,

IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie

; Email:

medsafety@hpra.ie.

By reporting side effects you can help provide more information on the safety of this medicine.

5 How to store Amoxil

Amoxil Powder for Solution for Injection or Infusion is for use in hospital only. The expiry date and storage

instructions stated on the label are for the doctor, pharmacist or nurse’s information. The doctor, pharmacist or

nurse will make up your medicine.

6 Contents of the pack and other information

What Amoxil contains

The active substance in each vial is 500 mg amoxicillin.

Reason for update: TIAin variation to change QP/Batch release site

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Implementation Date: March 2019

Text Date: 14/12/2018

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There are no other ingredients. However, for information about sodium in Amoxil, please see section 2.

The doctor, nurse or pharmacist will make up the injection before use using an appropriate fluid (such as

Water for Injections or an injection/infusion fluid).

What Amoxil looks like and contents of the pack

Amoxil 500 mg powder for solution for injection or infusion is a white to off-white sterile powder filled into a

clear glass 25 ml vial, with a chlorobutyl rubber stopper closure and a tamper evident sealing ring. Available

in packs of 1 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business

Campus, Dublin 24.

Manufacturer: GlaxoSmithKline Trading Services Limited, 12 Riverwalk, Citywest Business Campus, Dublin

24, Ireland

SmithKline Beecham Pharmaceuticals, Worthing, West Sussex BN14 8QH

This medicinal product is authorised in the Member States of the EEA under the following names:

Amoxil 500 mg powder for solution for injection or infusion

France – Clamoxyl

Ireland – Amoxil

United Kingdom – Amoxil

This leaflet was last revised in March 2019.

Trade marks are owned by or licensed to the GSK group of companies.

© 2019 GSK group of companies or its licensor.

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

Implementation Date: March 2019

Text Date: 14/12/2018

Text Issue and Draft No.: Issue6 Draft1

General advice regarding the use of antibiotics

Antibiotics are used to treat infections caused by bacteria. They have no effect against infections

caused by viruses.

Sometimes an infection caused by bacteria does not respond to a course of an antibiotic. One of the

commonest reasons for this to occur is because the bacteria causing the infection are resistant to the

antibiotic that is being taken. This means that they can survive and even multiply despite the

antibiotic.

Bacteria can become resistant to antibiotics for many reasons. Using antibiotics carefully can help

to reduce the chance of bacteria becoming resistant to them.

When your doctor prescribes a course of an antibiotic it is intended to treat only your current

illness. Paying attention to the following advice will help prevent the emergence of resistant

bacteria that could stop the antibiotic working.

It is very important that you take the antibiotic at the right dose, at the right times and for the

right number of days. Read the instructions on the label and if you do not understand

anything ask your doctor or pharmacist to explain.

You should not take an antibiotic unless it has been prescribed specifically for you and you

should use it only to treat the infection for which it was prescribed.

You should not take antibiotics that have been prescribed for other people even if they had

an infection that was similar to yours.

You should not give antibiotics that were prescribed for you to other people.

If you have any antibiotic left over when you have taken the course as directed by your

doctor you should take the remainder to a pharmacy for appropriate disposal.

Reason for update: TIAin variation to change QP/Batch release site

Market: IE

Implementation Date: March 2019

Text Date: 14/12/2018

Text Issue and Draft No.: Issue6 Draft1

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[GSK Logo]

The following information is intended for healthcare professionals only:

Amoxil Vials 500 mg

Powder for solution for injection or infusion

amoxicillin

Please refer to the Summary of Product Characteristics for further information

Intravenous administration

Vial

Diluent (ml)

500 mg

Water for injections is the normal diluent.

A transient pink colouration may or may not develop during reconstitution. Reconstituted solutions are

normally colourless or a pale straw colour. All solutions should be shaken vigorously before injection.

If amoxicillin 500 mg is to be administered by direct injection, it should be administered within 20 minutes of

reconstitution.

Preparation of intravenous infusions and stability:

add without delay the reconstituted solution of 500 mg

(as prepared above) to 50 ml of infusion fluid.

Intravenous amoxicillin may be given in a range of different intravenous fluids. Satisfactory antibiotic

concentrations are retained at 20 °C in the recommended volumes of the following infusion fluids:

Intravenous solution

Stability period at 20 °C

Water for Injection Ph. Eur.

Sodium Chloride BP 0.9% w/v

Compound Sodium Chloride

BPC 1959 (Ringer’s solution)

Compound Sodium Lactate BP

(Ringer-Lactate: Hartmann’s

solution)

30 min

5% Dextrose Injection BP

20 min

0.18% w/v Sodium Chloride plus

4% Dextrose BP

30 min

If reconstituted and maintained at room temperature, infusions should be completed within the times stated.

Intramuscular administration

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Vial

Diluent

500 mg

2.5 ml water for injections

The maximum single dose is 1 g.

All solutions should be shaken vigorously before injection and administered immediately after reconstitution.

Any residual antibiotic solution should be discarded.

For single use only.

This leaflet was last revised in July 2017.

Trade marks are owned by or licensed to the GSK group of companies.

© 2017 GSK group of companies or its licensor.

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Amoxil Vials 500 mg, powder for solution for injection or infusion.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains amoxicillin sodium equivalent to 500 mg amoxicillin

Excipient with known effect

Sodium 32 mg (1.37 mmol) per vial.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for solution for injection or infusion.

Vials containing a white to off-white sterile powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Amoxil is indicated for the treatment of the following infections in adults and children (see sections 4.2, 4.4 and 5.1):

Severe infections of the ear, nose and throat (such as mastoiditis, peritonsillar infections, epiglottitis, and sinusitis

when accompanied by severe systemic signs and symptoms)

Acute exacerbations of chronic bronchitis

Community acquired pneumonia

Acute cystitis

Acute pyelonephritis

Severe dental abscess with spreading cellulitis

Prosthetic joint infections

Lyme disease

Bacterial meningitis

Bacteremia that occurs in association with, or is suspected to be associated with, any of the infections listed

above

Amoxil is also indicated for the treatment and prophylaxis of endocarditis.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology

The dose of Amoxil that is selected to treat an individual infection should take into account:

The expected pathogens and their likely susceptibility to antibacterial agents (see section 4.4)

The severity and the site of the infection

The age, weight and renal function of the patient; as shown below

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The duration of therapy should be determined by the type of infection and the response of the patient, and should

generally be as short as possible. Some infections require longer periods of treatment (see section 4.4 regarding

prolonged therapy).

Adults and children

40 kg

Intramuscular

Maximum daily dosage: 4 g/day.

Maximum single dose: 1 g.

Children < 40 kg

Indication*

Dose*

Severe infections of the ear, nose and throat

(such as mastoiditis peritonsillar infections,

epiglottis and sinusitis when accompanied by

severe systemic signs and symptoms

750 mg to 2 g every 8 hours, or 2 g every 12

hours, maximum of 12 g/day

Acute exacerbations of chronic bronchitis

Community acquired pneumonia

Acute cystitis

Acute pyelonephritis

Severe dental abscess with spreading cellulitis

Prosthetic joint infections

750 mg to 2 g every 8 hours, or 2 g every 12

hours, maximum of 12 g/day

Prophylaxis of endocarditis

2 g single dose 30 to 60 minutes before

procedure.

Treatment of endocarditis

1 g to 2 g every 4 to 6 hours, maximum of 12

g/day

Bacterial meningitis

1 g to 2g every 4 to 6 hours, maximum of 12

g/day

Lyme disease (see section 4.4)

Late stage (systemic involvement): 2 g every 8

hours

Bacteraemia that occurs in association with, or

is suspected to be associated with, any of the

infections listed in section 4.1

1 g to 2 g every 4, 6 or 8 hours, maximum of

12 g/day

*Consideration should be given to the official treatment guidelines for each indication.

Infants and toddlers >3 months and children

< 40 kg

Indication*

Dose*

Severe infections of the ear, nose and throat

(such as mastoiditis peritonsillar infections,

epiglottis and sinusitis when accompanied by

severe systemic signs and symptoms

20 to 200 mg/kg/day given in 2 to 4 equally

divided doses of up to 25 mg/kg or infusions

of up to 50 mg/kg

Community acquired pneumonia

Acute cystitis

Acute pyelonephritis

Severe dental abscess with spreading cellulitis

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Prophylaxis of endocarditis

50 mg/kg single dose 30 to 60 minutes before

procedure

Treatment of endocarditis

200 mg/kg/day in 3 to 4 equally divided does

of up to 25 mg/kg or infusions of up to 50

mg/kg

Bacterial meningitis

100 to 200 mg/kg/day in 3 to 4 equally divided

doses of up to 25 mg/kg or infusions of up to

50 mg/kg

Lyme disease (see section 4.4)

Early stage: 25 to 50 mg/kg/day in three

divided doses for 10 days (range 10 to 21

days)

Late stage (systemic involvement): 50

mg/kg/day in three divided doses

Bacteraemia that occurs in association with, or

is suspected to be associated with, any of the

infections listed in section 4.1

50 to 150 mg/kg/day given in 3 equally

divided doses of up to 25 mg/kg or infusions

of up to 50 mg/kg

*Consideration should be given to the official treatment guidelines for each indication.

Neonates

4kg and infants up to 3 months

Indication*

Dose*

Most infections

Usual daily dose of 20 to 150 mg/kg/day given

in 3 equally divided doses of up to 25 mg/kg or

infusions of up to 50 mg/kg

Treatment of endocarditis

150 mg/kg/day given in 3 equally divided doses

of up to 25 mg/kg or infusions of up to 50

mg/kg

Bacterial meningitis

150 mg/kg/day given in three divided doses

Lyme disease (see section 4.4)

Early stage: 25 to 50 mg/kg/day in three

divided doses for 10 days (range 10 to 21 days)

Late stage (systemic involvement):

50 mg/kg/day in three divided doses

Bacteraemia that occurs in association with, or

is suspected to be associated with, any of the

infections listed in section 4.1

Usual daily dose of 50 to 150 mg/kg/day given

in 3 equally divided doses of up to 25 mg/kg or

infusions of up to 50 mg/kg

*Consideration should be given to the official treatment guidelines for each indication.

Premature Neonates < 4kg

Indication*

Dose*

Most infections

Usual daily dose of 20 to 100 mg/kg/day given

in 2 equally divided doses of up to 25 mg/kg or

infusions of up to 50 mg/kg

Treatment of endocarditis

100 mg/kg/day given in two divided doses

Bacterial meningitis

100 mg/kg/day given in two divided doses

Lyme disease (see section 4.4)

Early stage: 25 to 50 mg/kg/day in two divided

doses for 10 days (range 10 to 21 days)

Late stage (systemic involvement): 50

mg/kg/day in two divided doses

Bacteraemia that occurs in association with, or

is suspected to be associated with, any of the

infections listed in section 4.1

Usual daily dose of 50 to 100 mg/kg/day given

in 2 equally divided doses of up to 25 mg/kg or

infusions of up to 50 mg/kg

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Intramuscular:

Maximum daily dosage: 120 mg/kg/day as 2 to 6 equally divided doses.

Elderly

No adjustment needed; as for adults.

Renal impairment

In patients receiving haemodialysis and peritoneal dialysis

Amoxicillin may be removed from the circulation by haemodialysis.

Method of administration

The standard recommended route of administration is by intravenous injection or intravenous infusion.

Intramuscular

administration should only be considered when the intravenous route is not possible or less appropriate for the patient.

Intravenous

Amoxil may be administered either by slow intravenous injection over a period of 3 to 4 minutes directly into a vein or

via a drip tube or by infusion over 20 to 30 minutes.

Intramuscular

The maximum single dose is 1 g in adults and children

40 kg.

Do not inject more than 60 mg/kg at one time in children < 40 kg.

4.3 Contraindications

*Consideration should be given to the official treatment guidelines for each indication.

Adults and children

40 kg

Children < 40 kg

GFR (ml/min)

Intravenous

Intramuscular

Intravenous

Intramuscular

greater than

30

No adjustment

No adjustment

No adjustment

No adjustment

10 to 30

1g stat, then

500 mg to 1 g

twice day

500 mg every

12 hours

25 mg/kg twice

daily

15 mg/kg every

12 hours

less than 10

1 g stat, then

500 mg/day

500 mg/day given

as a single dose

25 mg/kg/day

given as a single

dose

15 mg/kg/day

given as a single

dose

Haemodialysis

Peritoneal dialysis

Intravenous

Intramuscular

Intravenous

Intramuscular

Adults and

children

40 kg

1 g at the end of

dialysis, then

500 mg every 24

hours

500 mg during

dialysis, 500 mg

at the end, then

500 mg every 24

hours

1 g stat, then

500 mg/day

500 mg/day given

as a single dose

Children <

40 kg

25 mg/kg stat

and 12.5 mg/kg

at the end of the

dialysis, then

25 mg/kg/day

15 mg/kg during

and at the end of

dialysis, then

15 mg/kg every

24 hours

25 mg/kg/day

given as a single

dose

15 mg/kg/day

given as a single

dose

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Hypersensitivity to the active substance, to any of the penicillins or to any of the excipients listed in section 6.1.

History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a

cephalosporin, carbapenem or monobactam).

4.4 Special warnings and precautions for use

Hypersensitivity reactions

Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity

reactions to penicillins, cephalosporins or other beta-lactam agents (see sections 4.3 and 4.8).

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin

therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in

atopic individuals. If an allergic reaction occurs, amoxicillin therapy must be discontinued and appropriate alternative

therapy instituted.

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 (see section 5.1). This particularly applies when considering the treatment of patients with urinary tract

infections and severe infections of the ear, nose and throat.

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).

Renal impairment

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

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 (AGEP, see section 4.8). 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.

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction has been seen following amoxicillin treatment of Lyme disease (see section 4.8). 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.

Overgrowth of non-susceptible microorganisms

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild

to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with

diarrhoea during, or subsequent to, the administration of any antibiotics. Should antibiotic-associated colitis occur,

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amoxicillin should immediately be discontinued, a physician consulted and an appropriate therapy initiated. Anti-

peristaltic medicinal products are contra-indicated in this situation.

Prolonged therapy

Periodic assessment of organ system functions; including renal, hepatic and haematopoietic function is advisable

during prolonged therapy. Elevated liver enzymes and changes in blood counts have been reported (see section 4.8).

Anticoagulants

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring

should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants

may be necessary to maintain the desired level of anticoagulation (see section 4.5 and 4.8).

Crystalluria

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral

therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and

urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular

check of patency should be maintained (see section 4.8 and 4.9).

Interference with diagnostic tests

Elevated serum and urinary levels of amoxicillin are likely to affect certain laboratory tests. Due to the high urinary

concentrations of amoxicillin, false positive readings are common with chemical methods.

It is recommended that when testing for the presence of glucose in urine during amoxicillin treatment, enzymatic

glucose oxidase methods should be used.

The presence of amoxicillin may distort assay results for oestriol in pregnant women.

Important information about excipients

This medicinal product contains 32 mg (1.37 mmol) of sodium per vial. To be taken into consideration by patients on a

controlled sodium diet.

Lidocaine may be used only when administering amoxicillin by the intramuscular route.

4.5 Interaction with other medicinal products and other forms of interaction

Probenecid

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin.

Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin.

Allopurinol

Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin

reactions.

Tetracyclines

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

Oral anticoagulants

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Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction.

However, in the literature there are 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.

Moreover, adjustments in the dose of oral anticoagulants may be necessary (see sections 4.4 and 4.8).

Methotrexate

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Limited data on

the use of amoxicillin during pregnancy in humans do not indicate an increased risk of congenital malformations.

Amoxicillin may be used in pregnancy when the potential benefits outweigh the potential risks associated with

treatment.

Breastfeeding

Amoxicillin is excreted into breast milk in small quantities with the possible risk of sensitisation. Consequently,

diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding

might have to be discontinued. Amoxicillin should only be used during breast-feeding after benefit/risk assessment by

the physician in charge.

Fertility

There are no data on the effects of amoxicillin on fertility in humans. Reproductive studies in animals have shown no

effects on fertility.

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).

4.8 Undesirable effects

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.

The ADRs derived from clinical studies and post-marketing surveillance with amoxicillin, presented by MedDRA

System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (

1/10)

Common (

1/100 to <1/10)

Uncommon (

1/1,000 to <1/100)

Rare (

1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

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Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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

Infections and infestations

Very rare

Mucocutaneous candidiasis

Blood and lymphatic system disorders

Very rare

Reversible leucopenia (including severe

neutropenia or agranulocytosis), reversible

thrombocytopenia and haemolytic anaemia.

Prolongation of bleeding time and prothrombin

time (see section 4.4).

Immune system disorders

Very rare

Severe allergic reactions, including angioneurotic

oedema, anaphylaxis, serum sickness and

hypersensitivity vasculitis (see section 4.4).

Not known

Jarisch-Herxheimer reaction (see section 4.4).

Nervous system disorders

Very rare

Hyperkinesia, dizziness and convulsions (see

section 4.4).

Gastrointestinal disorders

Clinical Trial Data

*Common

Diarrhoea and nausea

*Uncommon

Vomiting

Post-marketing Data

Very rare

Antibiotic associated colitis (including

pseudomembraneous colitis and haemorrhagic

colitis see section 4.4).

Hepatobiliary disorders

Very rare

Hepatitis and cholestatic jaundice. A moderate rise

in AST and/or ALT.

Skin and subcutaneous tissue disorders

Clinical Trial Data

*Common

Skin rash

*Uncommon

Urticaria and pruritus

Post-marketing Data

Very rare

Skin reactions such as erythema multiforme,

Stevens-Johnson syndrome, toxic epidermal

necrolysis, bullous and exfoliative dermatitis,

acute generalised exanthematous pustulosis

(AGEP) (see section 4.4), and drug reaction with

eosinophilia and systemic symptoms (DRESS).

Renal and urinary tract disorders

Very rare:

Interstitial nephritis

Crystalluria (see sections 4.4 and 4.9 Overdose)

* The incidence of these AEs was derived from clinical studies involving a total of approximately

6,000 adult and paediatric patients taking amoxicillin.

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suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1

6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

4.9 Overdose

Symptoms and signs of overdose

Gastrointestinal symptoms (such as nausea, vomiting and diarrhoea) and disturbance of the fluid and electrolyte

balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.

Convulsions may occur in patients with impaired renal function or in those receiving high doses (see sections 4.4 and

4.8).

Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of

large doses. A regular check of patency should be maintained (see section 4.4)

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.

Amoxicillin can be removed from the circulation by haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: penicillins with extended spectrum; ATC code: J01CA04.

Mechanism of action

Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as

penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural

component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is

usually followed by cell lysis and death.

Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum

of activity of amoxicillin alone does not include organisms which produce these enzymes.

Pharmacokinetic/pharmacodynamic relationship

The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy

for amoxicillin.

Mechanisms of resistance

The main mechanisms of resistance to amoxicillin are:

Inactivation by bacterial beta-lactamases.

Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in

Gram-negative bacteria.

Breakpoints

MIC breakpoints for amoxicillin are those of the European Committee on Antimicrobial Susceptibility Testing

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(EUCAST) version 5.0.

The prevalence of resistance may vary geographically and with time for selected species, and local information on

resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when

the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Organism

MIC breakpoint (mg/L)

Susceptible

Resistant >

Enterobacteriaceae

Staphylococcus spp.

Note

Note

Enterococcus spp.

Streptococcus groups A, B, C and G

Note

Note

Streptococcus pneumoniae

Note

Note

Viridans group steprococci

Haemophilus influenzae

Moraxella catarrhalis

Note

Note

Neisseria meningitidis

0.125

Gram positive anaerobes except

Clostridium difficile

Gram negative anaerobes

Helicobacter pylori

0.125

0.125

Pasteurella multocida

Non- species related breakpoints

Wild type Enterobacteriaceae are categorised as susceptible to aminopenicillins. Some

countries prefer to categorise wild type isolates of E. coli and P. mirabilis as intermediate.

When this is the case, use the MIC breakpoint S

0.5 mg/L

Most staphylococci are penicillinase producers, which are resistant to amoxicillin. Methicillin

resistant isolates are, with few exceptions, resistant to all beta-lactam agents.

Susceptibility to amoxicillin can be inferred from ampicillin

The susceptibility of streptococcus groups A, B, C and G to penicillins is inferred from the

benzylpenicillin susceptibility.

Breakpoints relate only to non-meningitis isolates. For isolates categorised as intermediate to

ampicillin avoid oral treatment with amoxicillin. Susceptibility inferred from the MIC of

ampicillin.

Breakpoints are based on intravenous administration. Beta-lactamase positive isolates should

be reported resistant.

Beta lactamase producers should be reported resistant

Susceptibility to amoxicillin can be inferred from benzylpenicillin.

The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish

wild-type isolates from those with reduced susceptibility.

The non-species related breakpoints are based on doses of at least 0.5 g x 3or 4 doses daily

(1.5 to 2 g/day).

In vitro susceptibility of micro-organisms to Amoxicillin

Commonly Susceptible Species

Gram-positive aerobes:

Enterococcus faecalis

Beta-hemolytic streptococci (Groups A, B, C and G)

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Listeria monocytogenes

Species for which acquired resistance may be a problem

Gram-negative aerobes:

Escherichia coli

Haemophilus influenzae

Helicobacter pylori

Proteus mirabilis

Salmonella typhi

Salmonella paratyphi

Pasteurella multocida

Gram-positive aerobes:

Coagulase negative staphylococcus

Staphylococcus aureus

Streptococcus pneumoniae

Viridans group streptococcus

Gram-positive anaerobes:

Clostridium spp.

Gram-negative anaerobes:

Fusobacterium spp.

Other:

Borrelia burgdorferi

Inherently resistant organisms

Gram-positive aerobes:

Enterococcus faecium

Gram-negative aerobes:

Acinetobacter spp.

Enterobacter spp.

Klebsiella spp.

Pseudomonas spp.

Gram-negative anaerobes:

Bacteroides spp. (many strains of Bacteroides fragilis are resistant).

Others:

Chlamydia spp.

Mycoplasma spp.

Legionella spp.

Natural intermediate susceptibility in the absence of acquired mechanism of resistance.

Almost all S.aureus are resistant to amoxilcillin due to production of penicillinase. In

addition, all methicillin-resistant strains are resistant to amoxicillin.

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5.2 Pharmacokinetic properties

The pharmacokinetic results for studies in which amoxicillin was administered to groups of healthy volunteers given as

a bolus intravenous injection are presented below.

Distribution

About 18% of total plasma amoxicillin is bound to protein and the apparent volume of distribution is around 0.3 to

0.4 l/kg.

Following intravenous administration, amoxicillin has been found in gall bladder, abdominal tissue, skin, fat, muscle

tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal

fluid.

From animal studies there is no evidence for significant tissue retention of drug-derived material. Amoxicillin, like

most penicillins, can be detected in breast milk (see section 4.6).

Biotransformation

Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of

the initial dose.

Elimination

The major route of elimination for amoxicillin is via the kidney

Amoxicillin has a mean elimination half-life of approximately one hour and a mean total clearance of approximately

25 l/hour in healthy subjects. Approximately 60 to 70% of the amoxicillin is excreted unchanged in urine during the

first 6 hours after administration of a single 250 mg or 500 dose of amoxicillin. Various studies have found the urinary

excretion to be 50 to 85% for amoxicillin over a 24 hour period.

Concomitant use of probenecid delays amoxicillin excretion (see section 4.5).

Gender

Following oral administration of amoxicillin to healthy males and female subjects, gender has no significant impact on

the pharmacokinetics of amoxicillin.

The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and

adults. For very young children (including preterm newborns) in the first week of life the interval of administration

should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly

patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to

monitor renal function.

Renal impairment

Mean pharmacokinetic parameters

Bolus intravenous injection

Dose

administered

Peak serum

conc (µg/ml)

T 1/2 (h)

(µg.h/ml)

Urinary recovery

(%, 0 to 6 h )

500 mg

32.2

1.07

25.5

66.5

1000 mg

105.4

76.3

77.4

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The total serum clearance of amoxicillin decreases proportionately with decreasing renal function (see section 4.2).

Hepatic impairment

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity,

genotoxicity and toxicity to reproduction and development.

Carcinogenicity studies have not been conducted with amoxicillin.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Amoxil should not be mixed with blood products, other proteinaceous fluids such as protein hydrolysates or with

intravenous lipid emulsions. If prescribed concomitantly with an aminoglycoside, the antibiotics should not be mixed in

the syringe, intravenous fluid container or giving set because of loss of activity of the aminoglycoside under these

conditions.

Amoxil solutions should not be mixed with infusions containing dextran or bicarbonate.

6.3 Shelf life

Powder in vials: 3 years

Reconstituted vials (for intravenous injection or before dilution for infusion): see section 6.6.

From a microbiological point of view, the reconstituted and diluted solution should be used immediately.

6.4 Special precautions for storage

Do not store above 25 °C.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Amoxil 500 mg powder for solution for injection or infusion is packaged in a clear Ph. Eur. Type I or Type III glass 25

ml vial, with a chlorobutyl rubber stopper closure (Ph.Eur. Type I) and a tamper evident sealing ring.

Packs of 1 or 10 vials.

Not all pack sizes may be marketed.

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6.6 Special precautions for disposal and other handling

Intravenous administration

Water for injections is the normal diluent.

A transient

pink colouration may or

may not

develop during reconstitution.

Reconstituted solutions are normally

colourless or a pale straw colour. All solutions should be shaken vigorously before injection.

If amoxicillin 500 mg is to be administered by direct injection, it should be administered within 20 minutes of reconstitution.

Preparation of intravenous infusions and stability: add without delay the reconstituted solution of 500 mg (as

prepared above) to 50 ml of infusion fluid.

Intravenous amoxicillin may be given in a range of different intravenous fluids. Satisfactory antibiotic concentrations

are retained at

20 °C in the recommended volumes of the following infusion fluids:

If reconstituted and maintained at room temperature, infusions should be completed within the times stated.

Intramuscular administration

The maximum single dose is 1 g.

All solutions should be shaken vigorously before injection and administered immediately after reconstitution.

Any residual antibiotic solution should be discarded.

For single use only.

Vial

Diluent (ml)

500 mg

Intravenous solution

Stability period at 20 °C

Water for Injection Ph. Eur.

Sodium Chloride BP 0.9% w/v

Compound Sodium Chloride

BPC 1959 (Ringer’s solution)

Compound Sodium Lactate BP

(Ringer-Lactate: Hartmann’s

solution)

30 min

5% Dextrose Injection BP

20 min

0.18% w/v Sodium Chloride plus

4% Dextrose BP

30 min

Vial

Diluent

500 mg

2.5 ml water for injections

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7 MARKETING AUTHORISATION HOLDER

GlaxoSmithKline (Ireland) Limited

12 Riverwalk,

Citywest Business Campus,

Dublin 24.

8 MARKETING AUTHORISATION NUMBER

PA1077/033/004

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 01 April 1977

Date of last renewal: 01 April 2007

10 DATE OF REVISION OF THE TEXT

April 2018

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