CANDESARTAN TEVA PHARMA 32 Milligram Tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

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Active ingredient:
CANDESARTAN CILEXETIL
Available from:
Teva Pharma B.V.
INN (International Name):
CANDESARTAN CILEXETIL
Dosage:
32 Milligram
Pharmaceutical form:
Tablets
Prescription type:
Product subject to prescription which may be renewed (B)
Authorization status:
Withdrawn
Authorization number:
PA0749/171/004
Authorization date:
2014-06-26

Amends: Approval: Senior Artwork Co-ordinato r

Subject to Reg. Agency approval Approved by Reg. Dept. for print

Signed Signed

27226

Candesartan T eva Pharma

4/8/16/32mg T abs All TEI (BLU)

V2 27-2-13

12-03-14 TB

Leafl et Cutter Guide

PMS Process Black PMS Green Indesign CS6 Last amend:

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Supplier Instructions Artwork, text and content must NOT be altered. The only exceptions to this are: bleeds,

. If you have any diffi culties

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Body: Univers 55 Roman/

CANDESARTAN

TEVA PHARMA

4 mg, 8 mg, 16 mg &

32 mg TABLETS

candesartan cilexetil

PACKAGE LEAFLET: INFORMATION

FOR THE USER

Read all of this leafletcarefully

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 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.

WHAT IS IN THIS LEAFLET:

1. What Candesartan Teva Pharma

is and what it is used for

2. What you need to know before

you take Candesartan Teva

Pharma

3. How to take Candesartan Teva

Pharma

4. Possible side effects

5. How to store Candesartan Teva

Pharma

6. Contents of the pack and other

information

WHAT CANDESARTAN TEVA

PHARMA IS AND WHAT IT IS

USED FOR

The name of your medicine is

Candesartan Teva Pharma. The

active ingredient is Candesartan

cilexetil. This belongs to a group

of medicines called angiotensin II

receptor antagonists. It works by

making your blood vessels relax

and widen. This helps to lower your

blood pressure. It also makes it

easier for your heart to pump blood

to all parts of your body.

This medicine is used for:

Treating high blood pressure

(hypertension) in adult patients.

Treating adult heart failure

patients with reduced heart

muscle function in addition to

Angiotensin Converting Enzyme

(ACE) inhibitors or when ACE

inhibitors cannot be used

(ACE inhibitors are a group of

medicines used to treat heart

failure).

WHAT YOU NEED TO

KNOW BEFORE YOU TAKE

CANDESARTAN TEVA

PHARMA

Do NOT take Candesartan Teva

Pharma

if you are allergic to candesartan

cilexetil or any of the other

ingredients of Candesartan Teva

Pharma (see section 6).

if you are more than 3 months

pregnant (it is also better to avoid

Candesartan Teva Pharma in

early pregnancy – see pregnancy

section).

if you have severe liver disease or

biliary obstruction (a problem with

the drainage of the bile from the

gall bladder).

If you are not sure if any of these

apply to you, talk to your doctor or

pharmacist before taking

CandesartanTevaPharma.

Warnings and precautions

Talk to your doctor or pharmacist

before taking Candesartan Teva

Pharma:

if you have heart, liver or kidney

problems, or are on dialysis.

if you have recently had a kidney

transplant.

if you are vomiting, have recently

had severe vomiting, or have

diarrhoea.

if you have a disease of the

adrenal gland called Conn’s

syndrome (also called primary

hyperaldosteronism).

if you have low blood pressure.

if you have ever had a stroke.

you must tell your doctor if you

think you are (or might become)

pregnant.

Candesartan Teva Pharma is not

recommended in early pregnancy,

and must not be taken if you are

more than 3 months pregnant, as

it may cause serious harm to your

baby if used at that stage (see

pregnancy section).

Your doctor may want to see you

more often and do some tests if you

have any of these conditions.

If you are going to have an

operation, tell your doctor or dentist

that you are taking Candesartan

Teva Pharma. This is because

Candesartan Teva Pharma, when

combined with some anaesthetics,

may cause a drop in blood pressure.

Use in children

There is no experience with the use

of Candesartan Teva Pharma in

children (below the age of 18 years).

Therefore Candesartan Teva Pharma

Other medicines and Candesartan

Teva Pharma

Tell your doctor or pharmacist if

you are using, have recently used

or might use any other medicines,

including medicines obtained

without a prescription.

Candesartan Teva Pharma can affect

the way some other medicines work

and some medicines can have an

effect on Candesartan Teva Pharma.

If you are using certain medicines,

your doctor may need to do blood

tests from time to time.

In particular, tell your doctor if

you are using any of the following

medicines:

Other medicines to help lower

your blood pressure, including

beta-blockers, diazoxide and

ACE inhibitors such as enalapril,

captopril, lisinopril or ramipril.

Non-steroidal anti-inflammatory

drugs (NSAIDs) such as ibuprofen,

naproxen, diclofenac, celecoxib

or etoricoxib (medicines to relieve

pain and inflammation).

Acetylsalicylic acid (if you are

taking more than 3 g each day)

(medicine to relieve pain and

inflammation).

Potassium supplements or salt

substitutes containing potassium

(medicines that increase the

amount of potassium in your

blood).

Heparin (a medicine for thinning

the blood).

Water tablets (diuretics).

Lithium (a medicine for mental

health problems).

Candesartan Teva Pharma with

food, drink and alcohol

You can take Candesartan Teva

Pharma with or without food.

When you are prescribed

Candesartan Teva Pharma, discuss

with your doctor before drinking

alcohol. Alcohol may make you

feel faint or dizzy.

Pregnancy and breast-feeding

Pregnancy

You must tell your doctor if you think

you are (or might become)pregnant.

Your doctor will normally advise

you to stop taking Candesartan

Teva Pharma before you become

pregnant or as soon as you know

you are pregnant and will advise

you to take another medicine instead

of Candesartan Teva Pharma.

Candesartan Teva Pharma is not

recommended in early pregnancy,

and must not be taken when more

than 3 months pregnant, as it may

cause serious harm to your baby

if used after the third month of

pregnancy.

Breast-feeding

Tell your doctor if you are breast-

feeding or about to start breast-

feeding. Candesartan Teva Pharma is

not recommended for mothers who

are breast-feeding, and your doctor

may choose another treatment

for you if you wish to breast-feed,

especially if your baby is newborn,

or was born prematurely.

Driving and using machines

Some people may feel tired or dizzy

when taking Candesartan Teva

Pharma. If this happens to you,

do not drive or use any tools or

machines.

Candesartan Teva Pharma contains

lactose

Candesartan Teva Pharma contains

lactosewhich is a type of sugar. If

you have been told by your doctor

that you have an intolerance to some

sugars, contact your doctor before

taking this medicine.

HOW TO TAKE

CANDESARTAN TEVA

PHARMA

Always take Candesartan Teva

Pharma exactly as your doctor has

told you. You should check with your

doctor or pharmacist if you are not

sure. It is important to keep taking

Candesartan Teva Pharma every

day.

You can take Candesartan Teva

Pharma with or without food.

Swallow the tablet with a drink of

water.

Try to take the tablet at the same

time each day. This will help you to

remember to take it.

High blood pressure:

The usual dose of Candesartan

Teva Pharma is 8 mg once a day.

Your doctor may increase this

dose to 16 mg once a day and

further up to 32 mg once a day

depending on blood pressure

response.

In some patients, such as those

with liver problems, kidney

problems or those who recently

have lost body fluids,e.g.,

through vomiting or diarrhoea or

by using water tablets, the doctor

may prescribe a lower starting

dose.

Some black patients may have a

reduced response to this type of

medicine, when given as the only

treatment, and these patients may

need a higher dose.

Heart failure:

The usual starting dose of

Candesartan Teva Pharma is 4 mg

once a day. Your doctor may

increase your dose by doubling

the dose at intervals of at least 2

weeks up to 32 mg once a day.

Candesartan Teva Pharma can

be taken together with other

medicines for heart failure, and

your doctor will decide which

treatment is suitable for you.

If you take more Candesartan Teva

Pharma than you should

If you take more Candesartan

Teva Pharma than prescribed by

your doctor, contact a doctor or

pharmacist immediately for advice.

If you forget to take Candesartan

Teva Pharma

Do not take a double dose to make

up for a forgotten tablet. Just take

the next dose as normal.

If you stop taking Candesartan Teva

Pharma

If you stop taking Candesartan

Teva Pharma, your blood pressure

may increase again. Therefore do

not stop taking Candesartan Teva

Pharma without first talking to your

doctor.

If you have any further questions

on the use of this product, ask your

doctor or pharmacist.

POSSIBLE SIDE EFFECTS

Like all medicines, Candesartan

Teva Pharma can cause side effects,

although not everybody gets them.

It is important that you are aware of

what these side effects may be.

Stop taking Candesartan Teva

Pharma and seek medical help

immediately if you have any of the

following allergic reactions:

difficulties in breathing, with or

without swelling of the face, lips,

tongue and/or throat.

swelling of the face, lips, tongue

and/or throat, which may cause

difficulties in swallowing.

severe itching of the skin (with

raised lumps).

Candesartan Teva Pharma may

cause a reduction in number of

white blood cells. Your resistance

to infection may be decreased

and you may notice tiredness, an

infection or a fever. If this happens

contact your doctor. Your doctor may

occasionally do blood tests to check

whether Candesartan Teva Pharma

has had an effect on your blood

(agranulocytosis).

Other possible side effects include:

Common (affects 1 to 10 users in 100)

Feeling dizzy/spinning sensation.

Headache.

Respiratory infection.

Low blood pressure. This may

make you feel faint or dizzy.

Changes in blood test results:

- An increased amount of

potassium in your blood,

especially if you already have

kidney problems or heart failure.

If this is severe you may notice

tiredness, weakness, irregular

heart beat or pins and needles.

Effects on how your kidneys work,

especially if you already have

kidney problems or heart failure.

In very rare cases, kidney failure

may occur.

Very rare (affects less than 1 user in

10,000)

Swelling of the face, lips, tongue

and/or throat.

A reduction in your red or white

blood cells. You may notice

tiredness, an infection or a fever.

Skin rash, lumpy rash (hives).

Itching.

Back pain, pain in joints and

muscles.

Changes in how your liver is

working, including inflammation

of the liver (hepatitis). You may

notice tiredness, yellowing of your

skin and the whites of your eyes

and flu like symptoms.

Nausea.

Changes in blood test results:

- A reduced amount of sodium in

your blood. If this is severe then

you may notice weakness, lack

of energy, or muscle cramps.

If you get any side effects, talk to

your doctor or pharmacist. This

includes any side effects not listed in

this leaflet.

HOW TO STORE

CANDESARTAN TEVA

PHARMA

Keep this medicine out of the

sight and reach of children.

Do not use Candesartan Teva

Pharma after the expiry date

which is stated on the carton after

{EXP}. The expiry date refers to

the last day of that month.

Do not store above 25 °C

(4 mg, 8 mg).

This medicinal product does

not require any special storage

conditions. (16 mg, 32 mg).

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

CONTENTS OF THE PACK

AND OTHER INFORMATION

What Candesartan Teva Pharma

contains

The active substance is candesartan

cilexetil.

Each Candesartan Teva Pharma 4 mg

Tablet contains 4 mg candesartan

cilexetil.

Each Candesartan Teva Pharma 8 mg

Tablet contains 8 mg candesartan

cilexetil.

Each Candesartan Teva Pharma

16 mg Tablet contains 16 mg

candesartan cilexetil.

Each Candesartan Teva Pharma

32 mg Tablet contains 32 mg

candesartan cilexetil.

The other ingredients are

docusate sodium, sodium

laurilsulphate, carmellose calcium,

pregelatinised maize starch,

hydroxypropylcellulose, lactose

monohydrate, magnesium stearate

(E572), iron oxide red (E172) (16 mg

and 32 mg tablets only).

What Candesartan Teva Pharma

looks like and contents of the pack

Candesartan Teva Pharma 4 mg is

supplied in the following pack sizes:

Blister packages with 7, [10, 14, 15,

20, 28, 30, 50, 50x1 unit dose, 56,

60, 84, 90, 98, 100] white, round

biconvex tablets, marked CC on one

face and 04 on the other face and

scored on both faces.

Candesartan Teva Pharma 8 mg is

supplied in the following pack sizes:

Blister packages with 7, [10, 14, 15,

20, 28, 30, 50, 50x1 unit dose, 56,

60, 84, 90, 98, 100] white, round

biconvex tablets, marked CC on one

face and 08 on the other face and are

scored on both faces.

Candesartan Teva Pharma 16 mg is

supplied in the following pack sizes:

Blister packages with 7, [10, 14, 15,

20, 28, 30, 50, 50x1 unit dose, 56,

60, 84, 90, 98, 100] light red, round

biconvex tablets, marked CC on one

face and 16 on the other face and are

scored on both faces.

Candesartan Teva Pharma 32 mg is

supplied in the following pack sizes:

Blister packages with 7, [10, 14, 15,

20, 28, 30, 50, 50x1 unit dose, 56,

60, 84, 90, 98, 100] light red, elliptic

biconvex tablets, marked CC and 32

on the same face and are scored on

both faces.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and

Manufacturer

Marketing Authorisation Holder:

Teva Pharma B.V.

Computerweg 10

3542 DR Utrecht

The Netherlands

Manufacturer(s) (responsible for

batch release):

Bluepharma Indústria

Farmacêutica, S.A.

S. Martinho do Bispo, 3045-016

Coimbra

Portugal

Cemelog-BRS Ltd.

Vasút u. 13, 2040 Budaörs

Hungary

TEVA Pharmaceutical Works Private

Limited Company

Pallagi út 13, 4042 Debrecen

Hungary

Teva Pharma B.V.

Swensweg 5, 2031 GA, Haarlem

The Netherlands

Pharmachemie B.V.

Swensweg 5, 2031 GA Haarlem

The Netherlands

This medicinal product is authorised

in the Member States of the EEA

under the following names:

Bulgaria: ACRUX 8 mg,

16 mg and 32 mg

tablets

Estonia: Candesartan Teva

4 mg, 8 mg,

16 mg and 32 mg

tabletid

Hungary: Candesartan-Teva

4 mg, 8 mg,

16 mg and 32 mg

tabletta

Ireland: Candesartan Teva

Pharma 4 mg,

8 mg, 16 mg and

32 mg Tablets

Lithuania: Candesartan Teva

4 mg, 8 mg,

16 mg and 32 mg

tablet ė s

Latvia: Candesartan Teva

4 mg, 8 mg,

16 mg and 32 mg

tablet ė s

Romania: HIPOSTYN

4 mg, 8 mg,

16 mg and 32 mg

comprimate

The Netherlands:Candesartan

cilexetil 4 mg,

8 mg, 16 mg

and 32 mg Teva,

tabletten

This leaflet was last revised in

November 2013.

H27226 211266.02-IE

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CandesartanTevaPharma32mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains32mgcandesartancilexetil.

Excipientwithknowneffect:

363.5mglactosemonohydrate/tablet.

Forthefulllistofexcipient,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

CandesartanTevaPharma32mgtabletsarelightred,ellipticbiconvextablets,markedCCand32onthesamefaceand

arescoredonbothfaces.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CandesartanTevaPharmaisindicatedforthe:

Treatmentofessentialhypertensioninadults.

Treatmentofadultpatientswithheartfailureandimpairedleftventricularsystolicfunction(leftventricular

ejectionfraction 40%)asadd-ontherapytoAngiotensinConvertingEnzyme(ACE)inhibitorsorwhenACE

inhibitorsarenottolerated(seesection5.1).

4.2Posologyandmethodofadministration

PosologyinHypertension

TherecommendedinitialdoseandusualmaintenancedoseofCandesartanTevaPharmais8mgoncedaily.Mostof

theantihypertensiveeffectisattainedwithin4weeks.Insomepatientswhosebloodpressureisnotadequately

controlled,thedosecanbeincreasedto16mgoncedailyandtoamaximumof32mgoncedaily.Therapyshouldbe

adjustedaccordingtobloodpressureresponse.CandesartanTevaPharmamayalsobeadministeredwithother

antihypertensiveagents.Additionofhydrochlorothiazidehasbeenshowntohaveanadditiveantihypertensiveeffect

withvariousdosesofCandesartanTevaPharma.

Elderlypopulation

Noinitialdoseadjustmentisnecessaryinelderlypatients.

Patientswithintravascularvolumedepletion

Aninitialdoseof4mgmaybeconsideredinpatientsatriskforhypotension,suchaspatientswithpossiblevolume

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Patientswithrenalimpairment

Thestartingdoseis4mginpatientswithrenalimpairment,includingpatientsonhaemodialysis.Thedoseshouldbe

titratedaccordingtoresponse.Thereislimitedexperienceinpatientswithverysevereorendstagerenalimpairment

creatinine <15ml/min)(seesection4.4).

Patientswithhepaticimpairment

Aninitialdoseof4mgoncedailyisrecommendedinpatientswithmildtomoderatehepaticimpairment.Thedose

maybeadjustedaccordingtoresponse.CandesartanTevaPharmaiscontraindicatedinpatientswithseverehepatic

impairmentand/orcholestasis(seesections4.3and5.2).

Blackpatients

Theantihypertensiveeffectofcandesartanislesspronouncedinblackpatientsthaninnon-blackpatients.

Consequently,uptitrationofCandesartanTevaPharmaandconcomitanttherapymaybemorefrequentlyneededfor

bloodpressurecontrolinblackpatientsthaninnon-blackpatients(seesection5.1).

PosologyinHeartFailure

TheusualrecommendedinitialdoseofCandesartanTevaPharmais4mgoncedaily.Up-titrationtothetargetdoseof

32mgoncedaily(maximumdose)orthehighesttolerateddoseisdonebydoublingthedoseatintervalsofatleast2

weeks(seesection4.4).Evaluationofpatientswithheartfailureshouldalwayscompriseassessmentofrenalfunction

includingmonitoringofserumcreatinineandpotassium.CandesartanTevaPharmacanbeadministeredwithother

heartfailuretreatment,includingACEinhibitors,beta-blockers,diureticsanddigitalisoracombinationofthese

medicinalproducts.ThecombinationofanACEinhibitor,apotassium-sparingdiuretic(e.g.spironolactone)and

CandesartanTevaPharmaisnotrecommendedandshouldbeconsideredonlyaftercarefulevaluationofthepotential

benefitsandrisks(seesections4.4,4.8and5.1).

Specialpatientpopulations

Noinitialdoseadjustmentisnecessaryforelderlypatientsorinpatientswithintravascularvolumedepletionorrenal

impairmentormildtomoderatehepaticimpairment.

PaediatricPopulation

ThesafetyandefficacyofCandesartanTevaPharmainchildrenagedbetweenbirthand18yearshavenotbeen

establishedinthetreatmentofhypertensionandheartfailure.Nodataareavailable.

Methodofadministration

Oraluse.

CandesartanTevaPharmashouldbetakenoncedailywithorwithoutfood.

Thebioavailabilityofcandesartanisnotaffectedbyfood.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipientslistedinsection6.1.

Secondandthirdtrimestersofpregnancy(seesections4.4and4.6).

Severehepaticimpairmentand/orcholestasis.

4.4Specialwarningsandprecautionsforuse

Renalimpairment

Aswithotheragentsinhibitingtherenin-angiotensin-aldosteronesystem,changesinrenalfunctionmaybeanticipated

insusceptiblepatientstreatedwithCandesartanTevaPharma.

WhenCandesartanTevaPharmaisusedinhypertensivepatientswithrenalimpairment,periodicmonitoringofserum

potassiumandcreatininelevelsisrecommended.Thereislimitedexperienceinpatientswithverysevereorend-stage

renalimpairment(Cl

creatinine <15ml/min).InthesepatientsCandesartanTevaPharmashouldbecarefullytitratedwith

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Evaluationofpatientswithheartfailureshouldincludeperiodicassessmentsofrenalfunction,especiallyinelderly

patients75yearsorolder,andpatientswithimpairedrenalfunction.DuringdosetitrationofCandesartanTevaPharma,

monitoringofserumcreatinineandpotassiumisrecommended.Clinicaltrialsinheartfailuredidnotincludepatients

withserumcreatinine>265µmol/l(>3mg/dl).

ConcomitanttherapywithanACEinhibitorinheartfailure

Theriskofadversereactions,especiallyrenalfunctionimpairmentandhyperkalaemia,mayincreasewhenCandesartan

TevaPharmaisusedincombinationwithanACEinhibitor(seesection4.8).Patientswithsuchtreatmentshouldbe

monitoredregularlyandcarefully.

Haemodialysis

DuringdialysisthebloodpressuremaybeparticularlysensitivetoAT

-receptorblockadeasaresultofreducedplasma

volumeandactivationoftherenin-angiotensin-aldosteronesystem.Therefore,CandesartanTevaPharmashouldbe

carefullytitratedwiththoroughmonitoringofbloodpressureinpatientsonhaemodialysis.

Renalarterystenosis

Othermedicinalproductsthataffecttherenin-angiotensin-aldosteronesystem,includingangiotensinIIreceptor

antagonists(AIIRAs),mayincreasebloodureaandserumcreatinineinpatientswithbilateralrenalarterystenosisor

stenosisofthearterytoasolitarykidney.

Kidneytransplantation

ThereisnoexperienceregardingtheadministrationofCandesartanTevaPharmainpatientswitharecentkidney

transplantation.

Hypotension

HypotensionmayoccurduringtreatmentwithCandesartanTevaPharmainheartfailurepatients.Itmayalsooccurin

hypertensivepatientswithintravascularvolumedepletionsuchasthosereceivinghighdosediuretics.Cautionshould

beobservedwheninitiatingtherapyandcorrectionofhypovolemiashouldbeattempted.

Anaesthesiaandsurgery

HypotensionmayoccurduringanaesthesiaandsurgeryinpatientstreatedwithangiotensinIIantagonistsdueto

blockadeoftherenin-angiotensinsystem.Veryrarely,hypotensionmaybeseveresuchthatitmaywarranttheuseof

intravenousfluidsand/orvasopressors.

Aorticandmitralvalvestenosis(obstructivehypertrophiccardiomyopathy)

Aswithothervasodilators,specialcautionisindicatedinpatientssufferingfromhaemodynamicallyrelevantaorticor

mitralvalvestenosis,orobstructivehypertrophiccardiomyopathy.

Primaryhyperaldosteronism

Patientswithprimaryhyperaldosteronismwillnotgenerallyrespondtoantihypertensivemedicinalproductsacting

throughinhibitionoftherenin-angiotensin-aldosteronesystem.Therefore,theuseofCandesartanTevaPharmaisnot

recommendedinthispopulation.

Hyperkalaemia

ConcomitantuseofCandesartanTevaPharmawithpotassium-sparingdiuretics,potassiumsupplements,salt

substitutescontainingpotassium,orothermedicinalproductsthatmayincreasepotassiumlevels(e.g.heparin)may

leadtoincreasesinserumpotassiuminhypertensivepatients.Monitoringofpotassiumshouldbeundertakenas

appropriate.

InheartfailurepatientstreatedwithCandesartanTevaPharmahyperkalaemiamayoccur.Periodicmonitoringofserum

potassiumisrecommended.ThecombinationofanACEinhibitor,apotassium-sparingdiuretic(e.g.spironolactone)

andCandesartanTevaPharmaisnotrecommendedandshouldbeconsideredonlyaftercarefulevaluationofthe

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General

Inpatientswhosevasculartoneandrenalfunctiondependpredominantlyontheactivityoftherenin-angiotensin-

aldosteronesystem(e.g.patientswithseverecongestiveheartfailureorunderlyingrenaldisease,includingrenalartery

stenosis),treatmentwithothermedicinalproductsthataffectthissystemhasbeenassociatedwithacutehypotension,

azotaemia,oliguriaor,rarely,acuterenalfailure.ThepossibilityofsimilareffectscannotbeexcludedwithAIIRAs.As

withanyantihypertensiveagent,excessivebloodpressuredecreaseinpatientswithischaemiccardiopathyorischaemic

cerebrovasculardiseasecouldresultinamyocardialinfarctionorstroke.

Theantihypertensiveeffectofcandesartanmaybeenhancedbyothermedicinalproductswithbloodpressurelowering

properties,whetherprescribedasanantihypertensiveorprescribedforotherindications.

CandesartanTevaPharmacontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

Pregnancy

AIIRAsshouldnotbeinitiatedduringpregnancy.UnlesscontinuedAIIRAtherapyisconsideredessential,patients

planningpregnancyshouldbechangedtoalternativeantihypertensivetreatmentswhichhaveanestablishedsafety

profileforuseinpregnancy.Whenpregnancyisdiagnosed,treatmentwithAIIRAsshouldbestoppedimmediately,

and,ifappropriate,alternativetherapyshouldbestarted(seesections4.3and4.6).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Compoundswhichhavebeeninvestigatedinclinicalpharmacokineticstudiesincludehydrochlorothiazide,warfarin,

digoxin,oralcontraceptives(i.e.ethinylestradiol/levonorgestrel),glibenclamide,nifedipineandenalapril.Noclinically

significantpharmacokineticinteractionswiththesemedicinalproductshavebeenidentified.

Concomitantuseofpotassium-sparingdiuretics,potassiumsupplements,saltsubstitutescontainingpotassium,orother

medicinalproducts(e.g.heparin)mayincreasepotassiumlevels.Monitoringofpotassiumshouldbeundertakenas

appropriate(seesection4.4).

Reversibleincreasesinserumlithiumconcentrationsandtoxicityhavebeenreportedduringconcomitant

administrationoflithiumwithACEinhibitors.AsimilareffectmayoccurwithAIIRAs.Useofcandesartanwith

lithiumisnotrecommended.Ifthecombinationprovesnecessary,carefulmonitoringofserumlithiumlevelsis

recommended.

WhenAIIRAsareadministeredsimultaneouslywithnon-steroidalanti-inflammatorydrugs(NSAIDs)(i.e.selective

COX-2inhibitors,acetylsalicylicacid(>3g/day)andnon-selectiveNSAIDs),attenuationoftheantihypertensive

effectmayoccur.

AswithACEinhibitors,concomitantuseofAIIRAsandNSAIDsmayleadtoanincreasedriskofworseningofrenal

function,includingpossibleacuterenalfailure,andanincreaseinserumpotassium,especiallyinpatientswithpoor

pre-existingrenalfunction.Thecombinationshouldbeadministeredwithcaution,especiallyintheelderly.Patients

shouldbeadequatelyhydratedandconsiderationshouldbegiventomonitoringrenalfunctionafterinitiationof

concomitanttherapy,andperiodicallythereafter.

4.6Fertility,pregnancyandlactation

Pregnancy

TheuseofAIIRAsisnotrecommendedduringthefirsttrimesterofpregnancy(seesection4.4).TheuseofAIIRAs

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EpidemiologicalevidenceregardingtheriskofteratogenicityfollowingexposuretoACEinhibitorsduringthefirst

trimesterofpregnancyhasnotbeenconclusive;howeverasmallincreaseinriskcannotbeexcluded.Whilstthereisno

controlledepidemiologicaldataontheriskwithAIIRAs,similarrisksmayexistforthisclassofdrugs.Unless

continuedAIIRAtherapyisconsideredessential,patientsplanningpregnancyshouldbechangedtoalternativeanti-

hypertensivetreatmentswhichhaveanestablishedsafetyprofileforuseinpregnancy.Whenpregnancyisdiagnosed,

treatmentwithAIIRAsshouldbestoppedimmediatelyand,ifappropriate,alternativetherapyshouldbestarted.

ExposuretoAIIRAtherapyduringthesecondandthirdtrimestersisknowntoinducehumanfetotoxicity(decreased

renalfunction,oligohydramnios,skullossificationretardation)andneonataltoxicity(renalfailure,hypotension,

hyperkalaemia)(seesection5.3).ShouldexposuretoAIIRAshaveoccurredfromthesecondtrimesterofpregnancy,

ultrasoundcheckofrenalfunctionandskullisrecommended.InfantswhosemothershavetakenAIIRAsshouldbe

closelyobservedforhypotension(seesections4.3and4.4).

Lactation

BecausenoinformationisavailableregardingtheuseofCandesartanTevaPharmaduringbreastfeeding,Candesartan

TevaPharmaisnotrecommendedandalternativetreatmentswithbetterestablishedsafetyprofilesduringbreast-

feedingarepreferable,especiallywhilenursinganewbornorpreterminfant.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsofcandesartanontheabilitytodriveandusemachineshavebeenperformed.However,it

shouldbetakenintoaccountthatoccasionallydizzinessorwearinessmayoccurduringtreatmentwithCandesartan

TevaPharma.

4.8Undesirableeffects

TreatmentofHypertension

Incontrolledclinicalstudiesadversereactionsweremildandtransient.Theoverallincidenceofadverseeventsshowed

noassociationwithdoseorage.Withdrawalsfromtreatmentduetoadverseeventsweresimilarwithcandesartan

cilexetil(3.1%)andplacebo(3.2%).

Inapooledanalysisofclinicaltrialdataofhypertensivepatients,adversereactionswithcandesartancilexetilwere

definedbasedonanincidenceofadverseeventswithcandesartancilexetilatleast1%higherthantheincidenceseen

withplacebo.Bythisdefinition,themostcommonlyreportedadversereactionsweredizziness/vertigo,headacheand

respiratoryinfection.

Thetablebelowpresentsadversereactionsfromclinicaltrialsandpost-marketingexperience.

Thefrequenciesusedinthetablesthroughoutsection4.8are:verycommon( 1/10),common( 1/100to<1/10),

uncommon(1/1,000to<1/100),rare(1/10,000to<1/1,000)andveryrare(<1/10,000).

SystemOrganClass Frequency UndesirableEffect

Infectionsandinfestations Common Respiratoryinfection

Bloodandlymphaticsystem

disorders Veryrare Leukopenia,neutropenia

andagranulocytosis

Metabolismandnutritiondisorders Veryrare Hyperkalaemia,

hyponatraemia

Nervoussystemdisorders Common Dizziness/vertigo,

headache

Gastrointestinaldisorders Veryrare Nausea

Hepato-biliarydisorders Veryrare Increasedliverenzymes,

abnormalhepaticfunction

orhepatitis

Skinandsubcutaneoustissue

disorders Veryrare Angioedema,rash,

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Laboratoryfindings

Ingeneral,therewerenoclinicallyimportantinfluencesofCandesartanTevaPharmaonroutinelaboratoryvariables.

Asforotherinhibitorsoftherenin-angiotensin-aldosteronesystem,smalldecreasesinhaemoglobinhavebeenseen.No

routinemonitoringoflaboratoryvariablesisusuallynecessaryforpatientsreceivingCandesartanTevaPharma.

However,inpatientswithrenalimpairment,periodicmonitoringofserumpotassiumandcreatininelevelsis

recommended.

TreatmentofHeartFailure

TheadverseexperienceprofileofCandesartanTevaPharmainheartfailurepatientswasconsistentwiththe

pharmacologyofthedrugandthehealthstatusofthepatients.IntheCHARMclinicalprogramme,comparing

Candesartanindosesupto32mg(n=3,803)toplacebo(n=3,796),21.0%ofthecandesartancilexetilgroupand16.1%

oftheplacebogroupdiscontinuedtreatmentbecauseofadverseevents.Themostcommonlyreportedadversereactions

werehyperkalaemia,hypotensionandrenalimpairment.Theseeventsweremorecommoninpatientsover70yearsof

age,diabetics,orsubjectswhoreceivedothermedicinalproductswhichaffecttherenin-angiotensin-aldosterone

system,inparticularanACEinhibitorand/orspironolactone.

Thetablebelowpresentsadversereactionsfromclinicaltrialsandpost-marketingexperience.

Laboratoryfindings

HyperkalaemiaandrenalimpairmentarecommoninpatientstreatedwithCandesartanTevaPharmafortheindication

Musculoskeletalandconnective

tissuedisorders Veryrare Backpain,arthralgia,

myalgia

Renalandurinarydisorders Veryrare Renalimpairment,

includingrenalfailurein

susceptiblepatients(see

section4.4)

SystemOrganClass Frequency UndesirableEffect

Bloodandlymphaticsystem

disorders Veryrare Leukopenia,neutropenia

andagranulocytosis

Metabolismandnutritiondisorders Common Hyperkalaemia

Veryrare Hyponatraemia

Nervoussystemdisorders Veryrare Dizziness,headache

Vasculardisorders Common Hypotension

Gastrointestinaldisorders Veryrare Nausea

Hepato-biliarydisorders Veryrare Increasedliverenzymes,

abnormalhepaticfunction

orhepatitis

Skinandsubcutaneoustissue

disorders Veryrare Angioedema,rash,

urticaria,pruritus

Musculoskeletalandconnective

tissuedisorders Veryrare Backpain,arthralgia,

myalgia

Renalandurinarydisorders Common Renalimpairment,

includingrenalfailurein

susceptiblepatients(see

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4.9Overdose

Symptoms

Basedonpharmacologicalconsiderations,themainmanifestationofanoverdoseislikelytobesymptomatic

hypotensionanddizziness.Inindividualcasereportsofoverdose(ofupto672mgcandesartancilexetil)patient

recoverywasuneventful.

Management

Ifsymptomatichypotensionshouldoccur,symptomatictreatmentshouldbeinstitutedandvitalsignsmonitored.The

patientshouldbeplacedsupinewiththelegselevated.Ifthisisnotsufficient,plasmavolumeshouldbeincreasedby

infusionof,forexample,isotonicsalinesolution.Sympathomimeticmedicinalproductsmaybeadministeredifthe

above-mentionedmeasuresarenotsufficient.Candesartanisnotremovedbyhaemodialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:AngiotensinIIantagonists,plain,ATCcodeC09CA06.

AngiotensinIIistheprimaryvasoactivehormoneoftherenin-angiotensinaldosteronesystemandplaysaroleinthe

pathophysiologyofhypertension,heartfailureandothercardiovasculardisorders.Italsohasaroleinthepathogenesis

ofendorganhypertrophyanddamage.ThemajorphysiologicaleffectsofangiotensinII,suchasvasoconstriction,

aldosteronestimulation,regulationofsaltandwaterhomeostasisandstimulationofcellgrowth,aremediatedviathe

type1(AT

)receptor.

Candesartancilexetilisaprodrugsuitablefororaluse.Itisrapidlyconvertedtotheactivesubstance,candesartan,by

esterhydrolysisduringabsorptionfromthegastrointestinaltract.CandesartanisanAIIRA,selectiveforAT

receptors,

withtightbindingtoandslowdissociationfromthereceptor.Ithasnoagonistactivity.

CandesartandoesnotinhibitACE,whichconvertsangiotensinItoangiotensinIIanddegradesbradykinin.Thereisno

effectonACEandnopotentiationofbradykininorsubstanceP.Incontrolledclinicaltrialscomparingcandesartan

withACEinhibitors,theincidenceofcoughwaslowerinpatientsreceivingcandesartancilexetil.Candesartandoesnot

bindtoorblockotherhormonereceptorsorionchannelsknowntobeimportantincardiovascularregulation.The

antagonismoftheangiotensinII(AT

)receptorsresultsindoserelatedincreasesinplasmareninlevels,angiotensinI

andangiotensinIIlevels,andadecreaseinplasmaaldosteroneconcentration.

Hypertension

Inhypertension,candesartancausesadose-dependent,long-lastingreductioninarterialbloodpressure.The

antihypertensiveactionisduetodecreasedsystemicperipheralresistance,withoutreflexincreaseinheartrate.Thereis

noindicationofseriousorexaggeratedfirstdosehypotensionorreboundeffectaftercessationoftreatment.

Afteradministrationofasingledoseofcandesartancilexetil,onsetofantihypertensiveeffectgenerallyoccurswithin2

hours.Withcontinuoustreatment,mostofthereductioninbloodpressurewithanydoseisgenerallyattainedwithin

fourweeksandissustainedduringlong-termtreatment.Accordingtoameta-analysis,theaverageadditionaleffectofa

doseincreasefrom16mgto32mgoncedailywassmall.Takingintoaccounttheinter-individualvariability,amore

thanaverageeffectcanbeexpectedinsomepatients.Candesartancilexetiloncedailyprovideseffectiveandsmooth

bloodpressurereductionover24hours,withlittledifferencebetweenmaximumandtrougheffectsduringthedosing

interval.Theantihypertensiveeffectandtolerabilityofcandesartanandlosartanwerecomparedintworandomised,

double-blindstudiesinatotalof1,268patientswithmildtomoderatehypertension.Thetroughbloodpressure

reduction(systolic/diastolic)was13.1/10.5mmHgwithcandesartancilexetil32mgoncedailyand10.0/8.7mmHg

withlosartanpotassium100mgoncedaily(differenceinbloodpressurereduction3.1/1.8mmHg,p<0.0001/p<0.0001).

Whencandesartancilexetilisusedtogetherwithhydrochlorothiazide,thereductioninbloodpressureisadditive.An

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Medicinalproductsthatblocktherenin-angiotensin-aldosteronesystemhavelesspronouncedantihypertensiveeffectin

blackpatients(usuallyalow-reninpopulation)thaninnon-blackpatients.Thisisalsothecaseforcandesartan.Inan

openlabelclinicalexperiencetrialin5,156patientswithdiastolichypertension,thebloodpressurereductionduring

candesartantreatmentwassignificantlylessinblackthannon-blackpatients(14.4/10.3mmHgvs19.0/12.7mmHg,

p<0.0001/p<0.0001).

Candesartanincreasesrenalbloodflowandeitherhasnoeffecton,orincreasesglomerularfiltrationratewhilerenal

vascularresistanceandfiltrationfractionarereduced.Ina3-monthclinicalstudyinhypertensivepatientswithtype2

diabetesmellitusandmicroalbuminuria,antihypertensivetreatmentwithcandesartancilexetilreducedurinaryalbumin

excretion(albumin/creatinineratio,mean30%,95%CI15 -42%).Thereiscurrentlynodataontheeffectof

candesartanontheprogressiontodiabeticnephropathy.

Theeffectsofcandesartancilexetil8-16mg(meandose12mg),oncedaily,oncardiovascularmorbidityandmortality

wereevaluatedinarandomisedclinicaltrialwith4,937elderlypatients(aged70-89years;21%aged80orabove)with

mildtomoderatehypertensionfollowedforameanof3.7years(StudyonCOgnitionandPrognosisintheElderly).

Patientsreceivedcandesartancilexetilorplacebowithotherantihypertensivetreatmentaddedasneeded.Theblood

pressurewasreducedfrom166/90to145/80mmHginthecandesartangroup,andfrom167/90to149/82mmHginthe

controlgroup.Therewasnostatisticallysignificantdifferenceintheprimaryendpoint,majorcardiovascularevents

(cardiovascularmortality,non-fatalstrokeandnon-fatalmyocardialinfarction).Therewere26.7eventsper1000

patient-yearsinthecandesartangroupversus30.0eventsper1000patient-yearsinthecontrolgroup(relativerisk0.89,

95%CI0.75to1.06,p=0.19).

HeartFailure

Treatmentwithcandesartancilexetilreducesmortality,reduceshospitalisationduetoheartfailureandimproves

symptomsinpatientswithleftventricularsystolicdysfunctionasshownintheCandesartaninHeartfailure–

AssessmentofReductioninMortalityandmorbidity(CHARM)programme.

Thisplacebocontrolled,double-blindstudyprogrammeinchronicheartfailure(CHF)patientswithNYHAfunctional

classIItoIVconsistedofthreeseparatestudies:CHARM-Alternative(n=2,028)inpatientswithLVEF 40%not

treatedwithanACEinhibitorbecauseofintolerance(mainlyduetocough,72%),CHARM-Added(n=2,548)in

patientswithLVEF 40%andtreatedwithanACEinhibitor,andCHARM-Preserved(n=3,023)inpatientswith

LVEF>40%.PatientsonoptimalCHFtherapyatbaselinewererandomisedtoplaceboorcandesartancilexetil(titrated

from4mgor8mgoncedailyto32mgoncedailyorthehighesttolerateddose,meandose24mg)andfollowedfora

medianof37.7months.After6monthsoftreatment63%ofthepatientsstilltakingcandesartancilexetil(89%)wereat

thetargetdoseof32mg.

InCHARM-Alternative,thecompositeendpointofcardiovascularmortalityorfirstCHFhospitalisationwas

significantlyreducedwithcandesartanincomparisonwithplacebo,hazardratio(HR)0.77(95%CI:0.67to0.89,p<

0.001).Thiscorrespondstoarelativeriskreductionof23%.Ofcandesartanpatients33.0%(95%CI:30.1to36.0)and

ofplacebopatients40.0%(95%CI:37.0to43.1)experiencedthisendpoint,absolutedifference7.0%(95%CI:11.2to

2.8).Fourteenpatientsneededtobetreatedforthedurationofthestudytopreventonepatientfromdyingofa

cardiovasculareventorbeinghospitalisedfortreatmentofheartfailure.Thecompositeendpointofall-causemortality

orfirstCHFhospitalisationwasalsosignificantlyreducedwithcandesartan,HR0.80(95%CI:0.70to0.92,p=0.001).

Ofcandesartanpatients36.6%(95%CI:33.7to39.7)andofplacebopatients42.7%(95%CI:39.6to45.8)experienced

thisendpoint,absolutedifference6.0%(95%CI:10.3to1.8).Boththemortalityandmorbidity(CHFhospitalisation)

componentsofthesecompositeendpointscontributedtothefavourableeffectsofcandesartan.Treatmentwith

candesartancilexetilresultedinimprovedNYHAfunctionalclass(p=0.008).

InCHARM-Added,thecompositeendpointofcardiovascularmortalityorfirstCHFhospitalisationwassignificantly

reducedwithcandesartanincomparisonwithplacebo,HR0.85(95%CI:0.75to0.96,p=0.011).Thiscorrespondstoa

relativeriskreductionof15%.Ofcandesartanpatients37.9%(95%CI:35.2to40.6)andofplacebopatients42.3%

(95%CI:39.6to45.1)experiencedthisendpoint,absolutedifference4.4%(95%CI:8.2to0.6).Twenty-threepatients

neededtobetreatedforthedurationofthestudytopreventonepatientfromdyingofacardiovasculareventorbeing

hospitalisedfortreatmentofheartfailure.Thecompositeendpointofall-causemortalityorfirstCHFhospitalisation

wasalsosignificantlyreducedwithcandesartan,HR0.87(95%CI:0.78to0.98,p=0.021).Ofcandesartanpatients

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difference3.9%(95%CI:7.8to0.1).Boththemortalityandmorbiditycomponentsofthesecompositeendpoints

contributedtothefavourableeffectsofcandesartan.TreatmentwithcandesartancilexetilresultedinimprovedNYHA

functionalclass(p=0.020).

InCHARM-Preserved,nostatisticallysignificantreductionwasachievedinthecompositeendpointofcardiovascular

mortalityorfirstCHFhospitalisation,HR0.89(95%CI:0.77to1.03,p=0.118).

All-causemortalitywasnotstatisticallysignificantwhenexaminedseparatelyineachofthethreeCHARMstudies.

However,all-causemortalitywasalsoassessedinpooledpopulations,CHARM-AlternativeandCHARM-Added,HR

0.88(95%CI:0.79to0.98,p=0.018)andallthreestudies,HR0.91(95%CI:0.83to1.00,p=0.055).

Thebeneficialeffectsofcandesartanwereconsistentirrespectiveofage,genderandconcomitantmedication.

Candesartanwaseffectivealsoinpatientstakingbothbeta-blockersandACEinhibitorsatthesametime,andthe

benefitwasobtainedwhetherornotpatientsweretakingACEinhibitorsatthetargetdoserecommendedbytreatment

guidelines.

InpatientswithCHFanddepressedleftventricularsystolicfunction(leftventricularejectionfraction,LVEF 40%),

candesartandecreasessystemicvascularresistanceandpulmonarycapillarywedgepressure,increasesplasmarenin

activityandangiotensinIIconcentration,anddecreasesaldosteronelevels.

5.2Pharmacokineticproperties

Absorptionanddistribution

Followingoraladministration,candesartancilexetilisconvertedtotheactivesubstancecandesartan.Theabsolute

bioavailabilityofcandesartanisapproximately40%afteranoralsolutionofcandesartancilexetil.Therelative

bioavailabilityofthetabletformulationcomparedwiththesameoralsolutionisapproximately34%withverylittle

variability.Theestimatedabsolutebioavailabilityofthetabletistherefore14%.Themeanpeakserumconcentration

)isreached3-4hoursfollowingtabletintake.Thecandesartanserumconcentrationsincreaselinearlywith

increasingdosesinthetherapeuticdoserange.Nogenderrelateddifferencesinthepharmacokineticsofcandesartan

havebeenobserved.Theareaundertheserumconcentrationversustimecurve(AUC)ofcandesartanisnot

significantlyaffectedbyfood.Candesartanishighlyboundtoplasmaprotein(morethan99%).Theapparentvolume

ofdistributionofcandesartanis0.1l/kg.

Thebioavailabilityofcandesartanisnotaffectedbyfood.

Biotransformationandelimination

Candesartanismainlyeliminatedunchangedviaurineandbileandonlytoaminorextenteliminatedbyhepatic

metabolism(CYP2C9).AvailableinteractionstudiesindicatenoeffectonCYP2C9andCYP3A4.Basedoninvitro

data,nointeractionwouldbeexpectedtooccurinvivowithdrugswhosemetabolismisdependentuponcytochrome

P450isoenzymesCYP1A2,CYP2A6,CYP2C9,CYP2C19,CYP2D6,CYP2E1orCYP3A4.Theterminalhalf-lifeof

candesartanisapproximately9hours.Thereisnoaccumulationfollowingmultipledoses.

Totalplasmaclearanceofcandesartanisabout0.37ml/min/kg,witharenalclearanceofabout0.19ml/min/kg.The

renaleliminationofcandesartanisbothbyglomerularfiltrationandactivetubularsecretion.Followinganoraldoseof

C-labelledcandesartancilexetil,approximately26%ofthedoseisexcretedintheurineascandesartanand7%asan

inactivemetabolitewhileapproximately56%ofthedoseisrecoveredinthefaecesascandesartanand10%asthe

inactivemetabolite.

Pharmacokineticsinspecialpopulations

Intheelderly(over65years)C

andAUCofcandesartanareincreasedbyapproximately50%and80%,

respectivelyincomparisontoyoungsubjects.However,thebloodpressureresponseandtheincidenceofadverse

eventsaresimilarafteragivendoseofCandesartanTevaPharmainyoungandelderlypatients(seesection4.2).

InpatientswithmildtomoderaterenalimpairmentC

andAUCofcandesartanincreasedduringrepeateddosingby

approximately50%and70%,respectively,butt

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Thecorrespondingchangesinpatientswithsevererenalimpairmentwereapproximately50%and110%,respectively.

Theterminalt

ofcandesartanwasapproximatelydoubledinpatientswithsevererenalimpairment.TheAUCof

candesartaninpatientsundergoinghaemodialysiswassimilartothatinpatientswithsevererenalimpairment.

Intwostudies,bothincludingpatientswithmildtomoderatehepaticimpairment,therewasanincreaseinthemean

AUCofcandesartanofapproximately20%inonestudyand80%intheotherstudy(seesection4.2).Thereisno

experienceinpatientswithseverehepaticimpairment.

5.3Preclinicalsafetydata

Therewasnoevidenceofabnormalsystemicortargetorgantoxicityatclinicallyrelevantdoses.Inpreclinicalsafety

studiescandesartanhadeffectsonthekidneysandonredcellparametersathighdosesinmice,rats,dogsand

monkeys.Candesartancausedareductionofredbloodcellparameters(erythrocytes,haemoglobin,haematocrit).

Effectsonthekidneys(suchasinterstitialnephritis,tubulardistension,basophilictubules;increasedplasma

concentrationsofureaandcreatinine)wereinducedbycandesartanwhichcouldbesecondarytothehypotensiveeffect

leadingtoalterationsofrenalperfusion.Furthermore,candesartaninducedhyperplasia/hypertrophyofthe

juxtaglomerularcells.Thesechangeswereconsideredtobecausedbythepharmacologicalactionofcandesartan.For

therapeuticdosesofcandesartaninhumans,thehyperplasia/hypertrophyoftherenaljuxtaglomerularcellsdoesnot

seemtohaveanyrelevance.

Foetotoxicityhasbeenobservedinlatepregnancy(seesection4.6).

Datafrominvitroandinvivomutagenicitytestingindicatesthatcandesartanwillnotexertmutagenicorclastogenic

activitiesunderconditionsofclinicaluse.Therewasnoevidenceofcarcinogenicity.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Docusatesodium

Sodiumlaurilsulphate

Carmellosecalcium

Pregelatinisedmaizestarch

Hydroxypropylcellulose

Lactosemonohydrate

Magnesiumstearate(E572)

Ironoxidered(E172)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

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Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

Netherlands

8MARKETINGAUTHORISATIONNUMBER

PA0749/171/004

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:22 nd

June2012

Dateoflastrenewal:31 st

December2012

10DATEOFREVISIONOFTHETEXT

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