Augmentin 500 mg/125 mg film-coated tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
Amoxicillin; Clavulanic acid
Available from:
GlaxoSmithKline (Ireland) Limited
ATC code:
J01CR; J01CR02
INN (International Name):
Amoxicillin; Clavulanic acid
Dosage:
500/125 milligram(s)
Pharmaceutical form:
Film-coated tablet
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
Combinations of penicillins, incl. beta-lactamase inhibitors; amoxicillin and enzyme inhibitor
Authorization status:
Marketed
Authorization number:
PA1077/019/003
Authorization date:
1999-02-19

Package leaflet: Information for the user

Augmentin 500 mg/125 mg film-coated tablets

Amoxicillin/clavulanic acid

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 or pharmacist.

This medicine has been prescribed for you (or for your child) only. Do not pass it on to others. It

may harm them, even if their signs of illness are the same as yours.

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

effects not listed in this leaflet. See section 4.

What is in this leaflet

What Augmentin is and what it is used for

What you need to know before you take Augmentin

How to take Augmentin

Possible side effects

How to store Augmentin

Contents of the pack and other information

1.

What Augmentin is and what it is used for

Augmentin is an antibiotic and works by killing bacteria that cause infections. It contains two different

medicines called amoxicillin and clavulanic acid. Amoxicillin belongs to a group of medicines called

“penicillins” that can sometimes be stopped from working (made inactive). The other active component

(clavulanic acid) stops this from happening.

Augmentin is used in adults and children to treat the following infections:

middle ear and sinus infections

respiratory tract infections

urinary tract infections

skin and soft tissue infections including dental infections

bone and joint infections.

2.

What you need to know before you take Augmentin

Do not take Augmentin:

if you are allergic to amoxicillin, clavulanic acid, penicillin or any of the other ingredients of this

medicine (listed in section 6)

if you have ever had a severe allergic reaction to any other antibiotic. This can include a skin rash

or swelling of the face or throat.

if you have ever had liver problems or jaundice (yellowing of the skin) when taking an antibiotic.

Do not take Augmentin if any of the above apply to you.

If you are not sure, talk to your doctor

or pharmacist before taking Augmentin.

Warnings and precautions

Talk to your doctor or pharmacist before taking Augmentin if you:

have glandular fever

are being treated for liver or kidney problems

are not passing water regularly.

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

Augmentin.

In some cases, your doctor may investigate the type of bacteria that is causing your infection. Depending

on the results, you may be given a different strength of Augmentin or a different medicine.

Conditions you need to look out for

Augmentin can make some existing conditions worse, or cause serious side effects. These include

allergic reactions, convulsions (fits) and inflammation of the large intestine. You must look out for

certain symptoms while you are taking Augmentin, to reduce the risk of any problems. See

Conditions you need to look out for’

Section 4

Blood and urine tests

If you are having blood tests (such as red blood cell status tests or liver function tests) or urine tests (for

glucose), let the doctor or nurse know that you are taking Augmentin. This is because Augmentin can

affect the results of these types of tests.

Other medicines and Augmentin

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

If you are taking allopurinol (used for gout) with Augmentin, 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 Augmentin.

If medicines to help stop blood clots (such as warfarin) are taken with Augmentin then extra blood tests

may be needed.

Augmentin can affect how methotrexate (a medicine used to treat cancer or rheumatic diseases) works.

Augmentin can affect how mycophenolate mofetil (a medicine used to prevent the rejection of

transplanted organs) works.

Pregnancy, breast-feeding and fertility

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

your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Augmentin can have side effects and the symptoms may make you unfit to drive.

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

3.

How to take Augmentin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Adults and children weighing 40 kg and over

The usual dose is:

1 tablet three times a day

Children weighing less than 40 kg

Children aged 6 years or less should preferably be treated with Augmentin oral suspension or sachets.

Ask your doctor or pharmacist for advice when giving Augmentin tablets to children weighing less than

40 kg. The tablets are not suitable for children weighing less than 25 kg.

Patients with kidney and liver problems

If you have kidney problems the dose might be changed. A different strength or a different

medicine may be chosen by your doctor.

If you have liver problems you may have more frequent blood tests to check how your liver is

working.

How to take Augmentin

Take with a meal

Swallow the tablets whole with a glass of water.

Tablets can be broken along the score line to make them easier to swallow. You must take both

pieces of the tablet at the same time.

Space the doses evenly during the day, at least 4 hours apart. Do not take 2 doses in 1 hour.

Do not take Augmentin for more than 2 weeks. If you still feel unwell you should go back to see

the doctor.

If you take more Augmentin than you should

If you take too much Augmentin, signs might include an upset stomach (feeling sick, being sick or

diarrhoea) or convulsions. Talk to your doctor as soon as possible. Take the medicine carton or bottle to

show the doctor.

If you forget to take Augmentin

If you forget to take a dose, take it as soon as you remember. You should not take the next dose too

soon, but wait about 4 hours before taking the next dose. Do not take a double dose to make up for a

forgotten dose.

If you stop taking Augmentin

Keep taking Augmentin until the treatment is finished, even if you feel better. You need every dose to

help fight the infection. If some bacteria survive they can cause the infection to come back.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4.

Possible side effects

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

effects below may happen with this medicine.

Conditions you need to look out for

Allergic reactions:

skin rash

inflammation of blood vessels (

vasculitis

) which may be visible as red or purple raised spots on

the skin, but can affect other parts of the body

fever, joint pain, swollen glands in the neck, armpit or groin

swelling, sometimes of the face or throat (

angioedema

), causing difficulty in breathing

collapse.

Contact a doctor immediately

if you get any of these symptoms.

Stop taking

Augmentin.

Inflammation of large intestine

Inflammation of the large intestine, causing watery diarrhoea usually with blood and mucus, stomach

pain and/or fever.

Contact your doctor as soon as possible

for advice if you get these symptoms.

Very common side effects

These may affect more than 1 in 10 people

diarrhoea (in adults).

Common side effects

These may affect up to 1 in 10 people

thrush (

candida

- a yeast infection of the vagina, mouth or skin folds)

feeling sick (nausea), especially when taking high doses

if affected take Augmentin with a meal

vomiting

diarrhoea (in children).

Uncommon

side effects

These may affect up to 1 in 100 people

skin rash, itching

raised itchy rash (

hives

indigestion

dizziness

headache.

Uncommon side effects that may show up in your blood tests:

increase in some substances (

enzymes

) produced by the liver.

Rare side effects

These may affect up to 1 in 1000 people

skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler

area, with a dark ring around the edge –

erythema multiforme

if you notice any of these symptoms contact a doctor urgently.

Rare side effects that may show up in your blood tests:

low number of cells involved in blood clotting

low number of white blood cells.

Frequency not known

Frequency cannot be estimated from the available data.

Allergic reactions (see above)

Inflammation of the large intestine (see above)

Inflammation of the protective membrane surrounding the brain (

aseptic meningitis

Serious skin reactions:

-

a widespread rash with blisters and peeling skin, particularly around the mouth, nose,

eyes

genitals

Stevens-Johnson

syndrome

more

severe

form,

causing

extensive peeling of the skin (more than 30% of the body surface –

toxic epidermal

necrolysis

-

widespread

skin

rash

with

small

pus-containing

blisters

bullous

exfoliative

dermatitis

-

a red, scaly rash with bumps under the skin and blisters (

exanthemous pustulosis

-

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)

Contact a doctor immediately if you get any of these symptoms.

inflammation of the liver (

hepatitis)

jaundice, caused by increases in the blood of bilirubin (a substance produced in the liver) which

may make your skin and whites of the eyes appear yellow

inflammation of tubes in the kidney

blood takes longer to clot

hyperactivity

convulsions (in people taking high doses of Augmentin or who have kidney problems)

black tongue which looks hairy

Side effects that may show up in your blood or urine tests:

severe reduction in the number of white blood cells

low number of red blood cells (

haemolytic anaemia

crystals in urine.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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 Augmentin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date (EXP) which is stated on the carton. The expiry date

refers to the last day of that month.

Do not store above 25

Tablets supplied in pouches should be used within 30 days of opening the pouch.

Store in the original package to protect from moisture.

Do not use if the tablets are chipped or damaged.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Augmentin contains

The active substances are amoxicillin and clavulanic acid. Each tablet contains amoxicillin

trihydrate equivalent to 500 mg amoxicillin and potassium clavulanate equivalent to 125 mg of

clavulanic acid.

The other ingredients are: Tablet core - magnesium stearate, sodium starch glycolate type A,

colloidal anhydrous silica, microcrystalline cellulose.

Film-coat - titanium dioxide (E171), hypromellose, macrogol (4000, 6000) and silicone oil

(dimeticone).

What Augmentin looks like and contents of the pack

Augmentin 500 mg/125 mg film-coated tablets are white to off-white, oval shaped tablet debossed with

“AC” and a scoreline on one side.

They are packaged in:

blister packs, enclosed in a carton. Each pack contains 4, 10, 12, 14, 16, 20, 24, 30, 100 or 500

tablets;

blister packs inside a pouch, enclosed in a carton. The pouch contains a desiccant sachet. The

desiccant must be kept inside the pouch and must not be eaten. Each pack contains 14, 20 or 21

tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Product Authorisation Holder:

GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24.

Manufacturer:

Glaxo Wellcome Production, Z.I. de la Peyenniere, 53100 Mayenne, France.

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

Austria – Augmentin

Belgium – Augmentin

Bulgaria – Augmentin

Cyprus – Augmentin

Czech Republic –Augmentin

Estonia – Augmentin

Germany - Augmentan

Greece – Augmentin

Hungary – Augmentin Duo

Iceland – Augmentin

Ireland – Augmentin

Latvia – Augmentin

Lithuania – Augmentin

Luxembourg – Augmentin

Malta – Augmentin

Netherlands – Augmentin

Norway - Augmentin

Poland – Augmentin

Portugal – Augmentin

Romania – Augmentin

Slovak Republic – Augmentin

Slovenia – Augmentin

Spain – Augmentine, Clavumox

United Kingdom – Augmentin

This leaflet was last revised in October 2017

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

© 2017 GSK group of companies or its licensor.

[GSK LOGO]

Advice/medical education

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.

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

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

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Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Augmentin500mg/125mgfilm-coatedtablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Eachfilm-coatedtabletcontainsamoxicillintrihydrateequivalentto500 mgamoxicillinandpotassiumclavulanateequivalent

to125 mgofclavulanicacid.

Forthefulllistofexcipients,seesection6.1.

3 PHARMACEUTICAL FORM

Film-coatedtablet.

Whitetooff-white,ovalshapedtabletdebossedwith“AC”andascorelineononeside.

Thescorelineisonlytofacilitatebreakingforeaseofswallowingandnottodivideintoequaldoses.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Augmentinisindicatedforthetreatmentofthefollowinginfectionsinadultsandchildren(seesections4.2,4.4and5.1):

Acutebacterialsinusitis(adequatelydiagnosed)

Acuteotitismedia

Acuteexacerbationsofchronicbronchitis(adequatelydiagnosed)

Communityacquiredpneumonia

Cystitis

Pyelonephritis

Skinandsofttissueinfectionsinparticularcellulitis,animalbites,severedental abscesswithspreading cellulitis.

Boneandjointinfections,inparticularosteomyelitis.

Considerationshouldbegiventoofficialguidanceontheappropriateuseofantibacterialagents.

4.2 Posology and method of administration

Posology

Dosesareexpressedthroughoutintermsofamoxicillin/clavulanicacidcontentexceptwhendosesarestatedintermsofan

individualcomponent.

ThedoseofAugmentinthatisselectedtotreatanindividualinfectionshouldtakeintoaccount:

Theexpectedpathogensandtheirlikelysusceptibilitytoantibacterialagents(seesection4.4)

Theseverityandthesiteoftheinfection

Theage,weightandrenalfunctionofthepatientasshownbelow.

TheuseofalternativepresentationsofAugmentin(e.g.thosethatprovidehigherdosesofamoxicillinand/ordifferentratiosof

amoxicillintoclavulanicacid)shouldbeconsideredasnecessary(seesections4.4and5.1).

For adults and children ≥

40 kg, this formulation of Augmentin provides a total daily dose of 1500 mg amoxicillin/375 mg

clavulanicacid,whenadministeredasrecommendedbelow.Forchildren<40 kg,thisformulationofAugmentinprovidesa

maximum daily dose of 2400 mg amoxicillin/600 mg clavulanic acid, when administered as recommended below. If it is

considered that a higher daily dose of amoxicillin is required, it is recommended that another preparation of Augmentin is

selectedinordertoavoidadministrationofunnecessarilyhighdailydosesofclavulanicacid(seesections4.4and5.1).

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The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require

longer periods of treatment.

Treatment should not be extended beyond 14 days without review (see section 4.4 regarding

prolongedtherapy).

Adults and children ≥ 40 kg

One500 mg/125 mgdosetakenthreetimesaday.

Children < 40 kg

20 mg/5 mg/kg/dayto60 mg/15 mg/kg/daygiveninthreedivideddoses.

ChildrenmaybetreatedwithAugmentintablets,suspensionsorpaediatricsachets.

Asthetabletscannotbedivided,childrenweighinglessthan25kgmustnotbetreatedwithAugmentintablets

The table below presents the received dose (mg/kg body weight) in children weighing 25 kg to 40 kg upon administering a

single500mg/125mgtablet.

Bodyweight[kg]

Singledose

recommended

[mg/kgbody

weight](see

above)

Amoxicillin[mg/kgbodyweight]persingledose(1film-coatedtablet)

12.5

14.3

16.7

20.0

6.67-20

Clavulanicacid[mg/kgbodyweight]persingledose(1film-coatedtablet)

1.67-5

Children aged 6 years and below or weighing less than 25 kg

should preferably be treated with Augmentin suspension or

paediatricsachets.

NoclinicaldataareavailableondosesofAugmentin4:1formulationshigherthan40 mg/10 mg/kgperdayinchildrenunder2

years.

Elderly

Nodoseadjustmentisconsiderednecessary.

Renal impairment

Doseadjustmentsarebasedonthemaximumrecommendedlevelofamoxicillin.

Noadjustmentindoseisrequiredinpatientswithcreatinineclearance(CrCl)greaterthan30ml/min.

Adults and children ≥ 40 kg

CrCl:10-30 ml/min

500 mg/125 mgtwicedaily

CrCl<10 ml/min

500 mg/125 mgoncedaily

Haemodialysis

500 mg/125 mgevery24hours,plus500 mg/125 mgduringdialysis,toberepeatedattheendofdialysis

(asserumconcentrationsofbothamoxicillinandclavulanicacidaredecreased)

Children < 40 kg

CrCl:10-30 ml/min

15 mg/3.75 mg/kgtwicedaily(maximum500 mg/125 mgtwicedaily).

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CrCl<10 ml/min

15 mg/3.75 mg/kgasasingledailydose(maximum500 mg/125 mg).

Haemodialysis

15 mg/3.75 mg/kgperdayoncedaily.

Priortohaemodialysis15 mg/3.75 mg/kg. Inordertorestorecirculatingdruglevels,15 mg/3.75 mgper

kgshouldbeadministeredafterhaemodialysis.

Hepatic impairment

Dosewithcautionandmonitorhepaticfunctionatregularintervals(seesections4.3and4.4).

Method of administration

Augmentinisfororaluse.

Augmentinshouldbeadministeredwithamealtominimisepotentialgastrointestinalintolerance.

TherapycanbestartedparenterallyaccordingtheSmPCoftheIVformulationandcontinuedwithanoralpreparation.

4.3 Contraindications

Hypersensitivitytotheactivesubstances,toanyofthepenicillinsortoanyoftheexcipientslistedinsection6.1.

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

carbapenemormonobactam).

Historyofjaundice/hepaticimpairmentduetoamoxicillin/clavulanicacid(seesection4.8).

4.4 Special warnings and precautions for use

Beforeinitiatingtherapywithamoxicillin/clavulanicacid,carefulenquiryshouldbemadeconcerningprevioushypersensitivity

reactionstopenicillins,cephalosporinsorotherbeta-lactamagents(seesections4.3and4.8).

Seriousandoccasionallyfatalhypersensitivityreactions(includinganaphylactoidandseverecutaneousadversereactions)have

beenreportedinpatientsonpenicillintherapy.Thesereactionsaremorelikelytooccurinindividualswithahistoryofpenicillin

hypersensitivityandinatopicindividuals.Ifanallergicreactionoccurs,amoxicillin/clavulanicacidtherapymustbediscontinued

andappropriatealternativetherapyinstituted.

Inthecasethataninfectionisproventobeduetoanamoxicillin-susceptibleorganisms(s)thenconsiderationshouldbegiven

toswitchingfromamoxicillin/clavulanicacidtoamoxicillininaccordancewithofficialguidance.

ThispresentationofAugmentinisnotsuitableforusewhenthereisahighriskthatthepresumptivepathogenshavereduced

susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by

clavulanicacid. Thispresentationshouldnotbeusedtotreatpenicillin-resistantS. pneumoniae.

Convulsionsmayoccurinpatientswithimpairedrenalfunctionorinthosereceivinghighdoses(seesection4.8).

Amoxicillin/clavulanicacidshouldbeavoidedifinfectiousmononucleosisissuspectedsincetheoccurrenceofamorbilliform

rashhasbeenassociatedwiththisconditionfollowingtheuseofamoxicillin.

Concomitantuseofallopurinolduringtreatmentwithamoxicillincanincreasethelikelihoodofallergicskinreactions.

Prolongedusemayoccasionallyresultinovergrowthofnon-susceptibleorganisms.

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 Augmentin discontinuation and

contra-indicatesanysubsequentadministrationofamoxicillin.

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Amoxicillin/clavulanicacidshouldbeusedwithcautioninpatientswithevidenceofhepaticimpairment(seesections4.2,4.3

and4.8).

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged

treatment.Theseeventshavebeenveryrarelyreportedinchildren.Inallpopulations,signsandsymptomsusuallyoccurduring

orshortlyaftertreatmentbutinsomecasesmaynotbecomeapparentuntilseveralweeksaftertreatmenthasceased.These

are usually reversible. Hepatic events may be severe and, in extremely rare circumstances, deaths have been reported. These

havealmostalwaysoccurredinpatientswithseriousunderlyingdiseaseortakingconcomitantmedicationsknowntohavethe

potentialforhepaticeffects(seesection4.8).

Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin 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

presentwithdiarrhoeaduringorsubsequenttotheadministrationofanyantibiotics.Shouldantibiotic-associatedcolitisoccur,

amoxicillin/clavulanicacidshouldimmediatelybediscontinued,aphysicianbeconsultedandanappropriatetherapyinitiated.

Anti-peristalticmedicinalproductsarecontra-indicatedinthissituation.

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

prolongedtherapy.

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid. Appropriate

monitoring should be undertaken when anticoagulants are prescribed concomitantly.

Adjustments in the dose of oral

anticoagulantsmaybenecessarytomaintainthedesiredlevelofanticoagulation(seesections4.5and4.8).

Inpatientswithrenalimpairment,thedoseshouldbeadjustedaccordingtothedegreeofimpairment(seesection4.2).

Inpatientswithreducedurineoutput,crystalluriahasbeenobservedveryrarely,predominantlywithparenteraltherapy.During

theadministrationofhighdosesofamoxicillin,itisadvisabletomaintainadequatefluidintakeandurinaryoutputinorderto

reduce the possibility of amoxicillin crystalluria.

In patients with bladder catheters, a regular check of patency should be

maintained(seesection4.9).

During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of

glucoseinurinebecausefalsepositiveresultsmayoccurwithnon-enzymaticmethods.

The presence of clavulanic acid in Augmentin may cause a non-specific binding of IgG and albumin by red cell membranes

leadingtoafalsepositiveCoombstest.

TherehavebeenreportsofpositivetestresultsusingtheBio-RadLaboratoriesPlatelia

Aspergillus

EIAtestinpatientsreceiving

amoxicillin/clavulanic

acid

who

were

subsequently

found

to

be

free

of

Aspergillus

infection.

Cross-reactions

with

non-Aspergillus polysaccharidesandpolyfuranoseswithBio-RadLaboratoriesPlatelia

Aspergillus

EIAtesthavebeenreported.

Therefore,positivetestresultsinpatientsreceivingamoxicillin/clavulanicacidshouldbeinterpretedcautiouslyandconfirmed

byotherdiagnosticmethods.

4.5 Interaction with other medicinal products and other forms of interactions

Beforeinitiatingtherapywithamoxicillin/clavulanicacid,carefulenquiryshouldbemadeconcerningprevioushypersensitivity

reactionstopenicillins,cephalosporinsorotherbeta-lactamagents(seesections4.3and4.8).

Seriousandoccasionallyfatalhypersensitivityreactions(includinganaphylactoidandseverecutaneousadversereactions)have

beenreportedinpatientsonpenicillintherapy.Thesereactionsaremorelikelytooccurinindividualswithahistoryofpenicillin

hypersensitivityandinatopicindividuals.Ifanallergicreactionoccurs,amoxicillin/clavulanicacidtherapymustbediscontinued

andappropriatealternativetherapyinstituted.

Inthecasethataninfectionisproventobeduetoanamoxicillin-susceptibleorganisms(s)thenconsiderationshouldbegiven

toswitchingfromamoxicillin/clavulanicacidtoamoxicillininaccordancewithofficialguidance.

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ThispresentationofAugmentinisnotsuitableforusewhenthereisahighriskthatthepresumptivepathogenshavereduced

susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by

clavulanicacid. Thispresentationshouldnotbeusedtotreatpenicillin-resistantS. pneumoniae.

Convulsionsmayoccurinpatientswithimpairedrenalfunctionorinthosereceivinghighdoses(seesection4.8).

Amoxicillin/clavulanicacidshouldbeavoidedifinfectiousmononucleosisissuspectedsincetheoccurrenceofamorbilliform

rashhasbeenassociatedwiththisconditionfollowingtheuseofamoxicillin.

Concomitantuseofallopurinolduringtreatmentwithamoxicillincanincreasethelikelihoodofallergicskinreactions.

Prolongedusemayoccasionallyresultinovergrowthofnon-susceptibleorganisms.

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 Augmentin discontinuation and

contra-indicatesanysubsequentadministrationofamoxicillin.

Amoxicillin/clavulanicacidshouldbeusedwithcautioninpatientswithevidenceofhepaticimpairment(seesections4.2,4.3

and4.8).

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged

treatment.Theseeventshavebeenveryrarelyreportedinchildren.Inallpopulations,signsandsymptomsusuallyoccurduring

orshortlyaftertreatmentbutinsomecasesmaynotbecomeapparentuntilseveralweeksaftertreatmenthasceased.These

are usually reversible. Hepatic events may be severe and, in extremely rare circumstances, deaths have been reported. These

havealmostalwaysoccurredinpatientswithseriousunderlyingdiseaseortakingconcomitantmedicationsknowntohavethe

potentialforhepaticeffects(seesection4.8).

Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin 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

presentwithdiarrhoeaduringorsubsequenttotheadministrationofanyantibiotics.Shouldantibiotic-associatedcolitisoccur,

amoxicillin/clavulanicacidshouldimmediatelybediscontinued,aphysicianbeconsultedandanappropriatetherapyinitiated.

Anti-peristalticmedicinalproductsarecontra-indicatedinthissituation.

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

prolongedtherapy.

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid. Appropriate

monitoring should be undertaken when anticoagulants are prescribed concomitantly.

Adjustments in the dose of oral

anticoagulantsmaybenecessarytomaintainthedesiredlevelofanticoagulation(seesections4.5and4.8).

Inpatientswithrenalimpairment,thedoseshouldbeadjustedaccordingtothedegreeofimpairment(seesection4.2).

Inpatientswithreducedurineoutput,crystalluriahasbeenobservedveryrarely,predominantlywithparenteraltherapy.During

theadministrationofhighdosesofamoxicillin,itisadvisabletomaintainadequatefluidintakeandurinaryoutputinorderto

reduce the possibility of amoxicillin crystalluria.

In patients with bladder catheters, a regular check of patency should be

maintained(seesection4.9).

During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of

glucoseinurinebecausefalsepositiveresultsmayoccurwithnon-enzymaticmethods.

The presence of clavulanic acid in Augmentin may cause a non-specific binding of IgG and albumin by red cell membranes

leadingtoafalsepositiveCoombstest.

TherehavebeenreportsofpositivetestresultsusingtheBio-RadLaboratoriesPlatelia

Aspergillus

EIAtestinpatientsreceiving

amoxicillin/clavulanic

acid

who

were

subsequently

found

to

be

free

of

Aspergillus

infection.

Cross-reactions

with

non-Aspergillus polysaccharidesandpolyfuranoseswithBio-RadLaboratoriesPlatelia

Aspergillus

EIAtesthavebeenreported.

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Therefore,positivetestresultsinpatientsreceivingamoxicillin/clavulanicacidshouldbeinterpretedcautiouslyandconfirmed

byotherdiagnosticmethods.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development,

parturitionorpostnataldevelopment(seesection5.3).Limiteddataontheuseofamoxicillin/clavulanicacidduringpregnancy

inhumansdonotindicateanincreasedriskofcongenitalmalformations.Inasinglestudyinwomenwithpreterm,premature

ruptureofthefoetalmembraneitwasreportedthatprophylactictreatmentwithamoxicillin/clavulanicacidmaybeassociated

with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered

essentialbythephysician.

Breastfeeding

Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant).

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.

The

possibility

of

sensitisation

should

be

taken

into

account.

Amoxicillin/clavulanicacidshouldonlybeusedduringbreast-feedingafterbenefit/riskassessmentbythephysicianincharge.

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.allergicreactions,dizziness,convulsions),whichmayinfluencetheabilitytodriveandusemachines(seesection4.8).

4.8 Undesirable effects

Themostcommonlyreportedadversedrugreactions(ADRs)arediarrhoea,nauseaandvomiting.

The ADRs derived from clinical studies and post-marketing surveillance with Augmentin, sorted by MedDRA System Organ

Classarelistedbelow.

Thefollowingterminologieshavebeenusedinordertoclassifytheoccurrenceofundesirableeffects.

Verycommon(≥1/10)

Common(≥1/100to<1/10)

Uncommon(≥1/1,000to<1/100)

Rare(≥1/10,000to<1/1,000)

Veryrare(<1/10,000)

Notknown(cannotbeestimatedfromtheavailabledata)

Infections and infestations

Mucocutaneouscandidosis

Common

Overgrowthofnon-susceptibleorganisms

Notknown

Blood and lymphatic system disorders

Reversibleleucopenia(includingneutropenia)

Rare

Thrombocytopenia

Rare

Reversibleagranulocytosis

Notknown

Haemolyticanaemia

Notknown

Prolongationofbleedingtimeand

prothrombintime

Notknown

Immune system disorders

Angioneuroticoedema

Notknown

Anaphylaxis

Notknown

Serumsickness-likesyndrome

Notknown

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Hypersensitivityvasculitis

Notknown

Nervous system disorders

Dizziness

Uncommon

Headache

Uncommon

Reversiblehyperactivity

Notknown

Convulsions

Notknown

Asepticmeningitis

Notknown

Gastrointestinal disorders

Diarrhoea

Verycommon

Nausea

Common

Vomiting

Common

Indigestion

Uncommon

Antibiotic-associatedcolitis

Notknown

Blackhairytongue

Notknown

Hepatobiliary disorders

RisesinASTand/orALT

Uncommon

Hepatitis

Notknown

Cholestaticjaundice

Notknown

Skin and subcutaneous tissue disorders

Skinrash

Uncommon

Pruritus

Uncommon

Urticaria

Uncommon

Erythemamultiforme

Rare

Stevens-Johnsonsyndrome

Notknown

Toxicepidermalnecrolysis

Notknown

Bullousexfoliative-dermatitis

Notknown

Acutegeneralisedexanthemouspustulosis(AGEP)

Notknown

Drugreactionwitheosinophiliaand

systemicsymptoms(DRESS)

Notknown

Renal and urinary disorders

Interstitialnephritis

Notknown

Crystalluria

Notknown

Seesection4.4

Seesection4.4

Nauseaismoreoftenassociatedwithhigheroraldoses. If

gastrointestinalreactionsareevident,theymaybereducedby

takingamoxicillin/clavulanicacidwithameal.

4

Includingpseudomembranouscolitisandhaemorrhagiccolitis

(seesection4.4)

AmoderateriseinASTand/orALThasbeennotedinpatients

treatedwithbeta-lactamclassantibiotics,butthesignificanceof

thesefindingsisunknown.

6

Theseeventshavebeennotedwithotherpenicillinsand

cephalosporins(seesection4.4).

Ifanyhypersensitivitydermatitisreactionoccurs,treatment

shouldbediscontinued(seesection4.4).

Seesection4.9

Seesection4.4

Seesections4.3and4.4

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 suspected

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Page8of13

adversereactionsviaHPRAPharmacovigilance,EarlsfortTerrace,IRL-Dublin2;Tel:+35316764971; Fax:+35316762517.

Website:www.hpra.ie;E-mail:medsafety@hpra.ie.

4.9 Overdose

Symptoms and signs of overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in

somecasesleadingtorenalfailure,hasbeenobserved(seesection4.4).

Convulsionsmayoccurinpatientswithimpairedrenalfunctionorinthosereceivinghighdoses.

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

doses.Aregularcheckofpatencyshouldbemaintained(seesection4.4).

Treatment of intoxication

Gastrointestinalsymptomsmaybetreatedsymptomatically,withattentiontothewater/electrolytebalance.

Amoxicillin/clavulanicacidcanberemovedfromthecirculationbyhaemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeuticgroup:Combinationsofpenicillins,incl.beta-lactamaseinhibitors;ATCcode:J01CR02.

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

componentofthebacterialcellwall.Inhibitionofpeptidoglycansynthesisleadstoweakeningofthecellwall,whichisusually

followedbycelllysisanddeath.

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

activityofamoxicillinalonedoesnotincludeorganismswhichproducetheseenzymes.

Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby

preventinginactivationofamoxicillin.Clavulanicacidalonedoesnotexertaclinicallyusefulantibacterialeffect.

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

Thetwomainmechanismsofresistancetoamoxicillin/clavulanicacidare:

Inactivationbythosebacterialbeta-lactamasesthatarenotthemselvesinhibitedbyclavulanicacid,includingclass

B,CandD.

AlterationofPBPs,whichreducetheaffinityoftheantibacterialagentforthetarget.

Impermeabilityofbacteriaoreffluxpumpmechanismsmaycauseorcontributetobacterialresistance,particularlyin

Gram-negativebacteria.

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Breakpoints

MICbreakpointsforamoxicillin/clavulanicacidarethoseoftheEuropeanCommitteeonAntimicrobialSusceptibilityTesting

(EUCAST)

Organism

SusceptibilityBreakpoints

(microgram/ml)

Susceptible

Intermediate

Resistant

Haemophilus influenzae

1

≤1

>1

Moraxella catarrhalis

1

≤1

>1

Staphylococcus aureus

2

≤2

>2

Coagulase-negativestaphylococci

2

≤0.25

>0.25

Enterococcus

1

≤4

>8

Streptococcus A, B, C, G

5

≤0.25

>0.25

Streptococcus pneumoniae

3

≤0.5

>2

Enterobacteriaceae

1,4

>8

Gram-negativeAnaerobes

1

≤4

>8

Gram-positiveAnaerobes

1

≤4

>8

Non-speciesrelatedbreakpoints

1

≤2

>8

Thereportedvaluesareforamoxicillinconcentrations. Forsusceptibility

testingpurposes,theconcentrationofclavulanicacidisfixedat2 mg/l.

Thereportedvaluesareoxacillinconcentrations.

Breakpointvaluesinthetablearebasedonampicillinbreakpoints.

TheresistantbreakpointofR>8 mg/lensuresthatallisolateswith

resistancemechanismsarereportedresistant.

Breakpointvaluesinthetablearebasedonbenzylpenicillinbreakpoints.

Theprevalenceofresistancemayvarygeographicallyandwithtimeforselectedspecies,andlocalinformationonresistanceis

desirable,particularlywhentreatingsevereinfections.Asnecessary,expertadviceshouldbesoughtwhenthelocalprevalence

ofresistanceissuchthattheutilityoftheagentinatleastsometypesofinfectionsisquestionable.

Commonly susceptible species

Aerobic Gram-positive micro-organisms

Enterococcus faecalis

Gardnerella vaginalis

Staphylococcus aureus (methicillin-susceptible)£

Coagulase-negativestaphylococci(methicillin-susceptible)

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenesandotherbeta-haemolyticstreptococci

Streptococcus viridans group

Aerobic Gram-negative micro-organisms

Capnocytophaga spp.

Eikenella corrodens

Haemophilus influenzae

Moraxella catarrhalis

Pasteurella multocida

Anaerobic micro-organisms

Bacteroides fragilis

Fusobacterium nucleatum

Prevotellaspp.

Species for which acquired resistance may be a problem

Aerobic Gram-positive micro-organisms

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Enterococcus faecium $

Aerobic Gram-negative micro-organisms

Escherichia coli

Klebsiella oxytoca

Klebsiella pneumoniae

Proteus mirabilis

Proteus vulgaris

Inherently resistant organisms

Aerobic Gram-negative micro-organisms

Acinetobacter sp.

Citrobacter freundii

Enterobactersp.

Legionella pneumophila

Morganella morganii

Providencia spp.

Pseudomonas sp.

Serratia sp.

Stenotrophomonas maltophilia

Other micro-organisms

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetti

Mycoplasma pneumoniae

$Naturalintermediatesusceptibilityintheabsenceofacquiredmechanismofresistance.

£Allmethicillin-resistantstaphylococciareresistanttoamoxicillin/clavulanicacid

Streptococcus pneumoniaethatareresistanttopenicillinshouldnotbetreatedwiththispresentationofamoxicillin/clavulanic

acid(seesections4.2and4.4).

2

StrainswithdecreasedsusceptibilityhavebeenreportedinsomecountriesintheEUwithafrequencyhigherthan10%.

5.2 Pharmacokinetic properties

Absorption

Amoxicillinandclavulanicacid,arefullydissociatedinaqueoussolutionatphysiologicalpH.Bothcomponentsarerapidlyand

wellabsorbedbytheoralrouteofadministration.Followingoraladministration,amoxicillinandclavulanicacidare

approximately70%bioavailable.Theplasmaprofilesofbothcomponentsaresimilarandthetimetopeakplasma

concentration(T

)ineachcaseisapproximatelyonehour.

Thepharmacokineticresultsforastudy,inwhichamoxicillin/clavulanicacid(500 mg/125 mgtabletsthreetimesdaily)was

administeredinthefastingstatetogroupsofhealthyvolunteersarepresentedbelow.

Mean(±SD)pharmacokineticparameters

Activesubstance(s)

administered

Dose

max

AUC

(0-24h)

T1/2

(mg)

(microgram/ml)

(microgram.h/ml)

Amoxicillin

AMX/CA

500/125 mg

7.19

±2.26

(1.0-2.5)

53.5

±8.87

1.15

±0.20

Clavulanicacid

AMX/CA

500 mg/125 mg

2.40

±0.83

(1.0-2.0)

15.72

±3.86

0.98

±0.12

AMX–amoxicillin,CA–clavulanicacid

*Median(range)

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Amoxicillinandclavulanicacidserumconcentrationsachievedwithamoxicillin/clavulanicacidaresimilartothoseproducedby

theoraladministrationofequivalentdosesofamoxicillinorclavulanicacidalone.

Distribution

About25%oftotalplasmaclavulanicacidand18%oftotalplasmaamoxicillinisboundtoprotein.Theapparentvolumeof

distributionisaround0.3-0.4l/kgforamoxicillinandaround0.2l/kgforclavulanicacid.

Followingintravenousadministration,bothamoxicillinandclavulanicacidhavebeenfoundingallbladder,abdominaltissue,

skin,fat,muscletissues,synovialandperitonealfluids,bileandpus.Amoxicillindoesnotadequatelydistributeintothe

cerebrospinalfluid.

Fromanimalstudiesthereisnoevidenceforsignificanttissueretentionofdrug-derivedmaterialforeithercomponent.

Amoxicillin,likemostpenicillins,canbedetectedinbreastmilk.Tracequantitiesofclavulanicacidcanalsobedetectedin

breastmilk(seesection4.6).

Bothamoxicillinandclavulanicacidhavebeenshowntocrosstheplacentalbarrier(seesection4.6).

Biotransformation

Amoxicillinispartlyexcretedintheurineastheinactivepenicilloicacidinquantitiesequivalenttoupto10to25%oftheinitial

dose.Clavulanicacidisextensivelymetabolizedinmanandeliminatedinurineandfaeces,andascarbondioxideinexpiredair.

Elimination

Themajorrouteofeliminationforamoxicillinisviathekidney,whereasforclavulanicaciditisbybothrenalandnon-renal

mechanisms.

Amoxicillin/clavulanicacidhasameaneliminationhalf-lifeofapproximatelyonehourandameantotalclearanceof

approximately25 l/hinhealthysubjects.Approximately60to70%oftheamoxicillinandapproximately40to65%ofthe

clavulanicacidareexcretedunchangedinurineduringthefirst6hafteradministrationofsingleAugmentin250 mg/125 mgor

500 mg/125 mgtablets.Variousstudieshavefoundtheurinaryexcretiontobe50-85%foramoxicillinandbetween27-60%for

clavulanicacidovera24hourperiod.Inthecaseofclavulanicacid,thelargestamountofdrugisexcretedduringthefirst2

hoursafteradministration.

Concomitantuseofprobeneciddelaysamoxicillinexcretionbutdoesnotdelayrenalexcretionofclavulanicacid(seesection

4.5).

Theeliminationhalf-lifeofamoxicillinissimilarforchildrenagedaround3monthsto2yearsandolderchildrenandadults.For

veryyoungchildren(includingpretermnewborns)inthefirstweekoflifetheintervalofadministrationshouldnotexceedtwice

dailyadministrationduetoimmaturityoftherenalpathwayofelimination.Becauseelderlypatientsaremorelikelytohave

decreasedrenalfunction,careshouldbetakenindoseselection,anditmaybeusefultomonitorrenalfunction.

Gender

Followingoraladministrationofamoxicillin/clavulanicacidtohealthymalesandfemalesubjects,genderhasnosignificant

impactonthepharmacokineticsofeitheramoxicillinorclavulanicacid.

Renal impairment

Thetotalserumclearanceofamoxicillin/clavulanicaciddecreasesproportionatelywithdecreasingrenalfunction.The

reductionindrugclearanceismorepronouncedforamoxicillinthanforclavulanicacid,asahigherproportionofamoxicillinis

excretedvia therenalroute.Dosesinrenalimpairmentmustthereforepreventundueaccumulationofamoxicillinwhile

maintainingadequatelevelsofclavulanicacid(seesection4.2).

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Hepatic impairment

Hepaticallyimpairedpatientsshouldbedosedwithcautionandhepaticfunctionmonitoredatregularintervals.

5.3 Preclinical safety data

Non-clinicaldatarevealnospecialhazardforhumansbasedonstudiesofsafetypharmacology,genotoxicityandtoxicityto

reproduction.

Repeatdosetoxicitystudiesperformedindogswithamoxicillin/clavulanicaciddemonstrategastricirritancyandvomiting,and

discolouredtongue.

Carcinogenicitystudieshavenotbeenconductedwithamoxicillin/clavulanicacid.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core

Magnesiumstearate

Sodiumstarchglycolate,TypeA

Colloidalanhydroussilica

Microcrystallinecellulose

Tablet film-coat

Titaniumdioxide(E171)

Hypromellose

Macrogol(4000,6000)

Dimeticone

6.2 Incompatibilities

Notapplicable.

6.3 Shelf life

2yearsincoldformedaluminiumblisters(CFB)anddesiccatedpouchpacks(DPP).

Tabletsindesiccatedpouchpacksshouldbeusedwithin30daysofopening.

6.4 Special precautions for storage

Storeintheoriginalpackagetoprotectfrommoisture.

Donotstoreabove25°C.

6.5 Nature and contents of container

PVC/Aluminium/Polyamidelaminatewithaluminiumliddingfoilreferredtoasacoldformedaluminiumblister(CFB)

containing4,10,12,14,16,20,24,30,100or500tablets.

AluminiumPVC/PVdCblisterenclosedwithinanaluminiumlaminatepouchcontainingadesiccantsachet,referredtoasa

desiccatedpouchpack(DPP)containing14,20or21tablets.

Notallpacksizesmaybemarketed

6.6 Special precautions for disposal and other handling

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Anyunusedmedicinalproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7 MARKETING AUTHORISATION HOLDER

GlaxoSmithKline(Ireland)Limited

12Riverwalk

CitywestBusinessCampus

Dublin24

Ireland

8 MARKETING AUTHORISATION NUMBER

PA1077/019/003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Dateoffirstauthorisation:19February1999Dateoflastrenewal:19October2014

10 DATE OF REVISION OF THE TEXT

March2018

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