CAPTOR

Main information

  • Trade name:
  • CAPTOR Tablets 6.25 mg Milligram
  • Dosage:
  • 6.25 mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CAPTOR Tablets 6.25 mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/002/004
  • Authorization date:
  • 01-04-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Captor6.25mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains6.25mgCaptopril.

Forlistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets

White,round,biconvextablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension:

Captorisindicatedforthetreatmentofhypertension.

HeartFailure:

Captorisindicatedforthetreatmentofchronicheartfailurewithreductionofsystolicventricularfunction,in

combinationwithdiureticsandwhenappropriate,digitalisandbeta-blockers.

MyocardialInfarction:

-Short-term(4weeks)treatment:Captorisindicatedinanyclinicallystablepatientswithinthefirst24hoursofan

infarction.

-Longtermpreventionofsymptomaticheartfailure:Captorisindicatedinclinicallystablepatientswithasymptomatic

leftventriculardysfunction(ejectionfraction<40%).

TypeIDiabeticNephropathy:

CaptorisindicatedforthetreatmentofmacroproteinuricdiabeticnephropathyinpatientswithtypeIdiabetes.(See

section5.1,PharmacodynamicProperties).

4.2Posologyandmethodofadministration

Doseshouldbeindividualisedaccordingtopatient’sprofile(seesection4.4,Specialwarningsandprecautionsforuse)

andbloodpressureresponse.Therecommendedmaximumdailydoseis150mg.

Captormaybetakenbefore,duringandaftermeals.

Hypertension:

Therecommendedstartingdoseis25-50mgdailyintwodivideddoses.Thedosemaybeincreasedincrementally,

withintervalsofatleast2weeks,to100-150mg/dayintwodivideddosesasneededtoreachtargetbloodpressure.

Captoprilmaybeusedaloneorwithotherantihypertensiveagents,especiallythiazidediuretics.

Aonce-dailydosingregimenmaybeappropriatewhenconcomitantantihypertensivemedicationsuchasthiazide

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 1

Inpatientswithastronglyactiverenin-angiotensin-aldosteronesystem(hypovolaemia,renovascularhypertension,

cardiacdecompensation)itispreferabletocommencewithasingledoseof6.25mgor12.5mg.Theinaugurationof

thistreatmentshouldpreferablytakeplaceunderclosemedicalsupervision.Thesedoseswillthenbeadministeredata

rateoftwoperday.Thedosagecanbegraduallyincreasedto50mgperdayinoneortwodosesandifnecessaryto

100mgperdayinoneortwodoses.

HeartFailure:

Treatmentwithcaptoprilforheartfailureshouldbeinitiatedunderclosemedicalsupervision.Theusualstartingdoseis

6.25mg-12.5mgBIDorTID.Titrationtothemaintenancedose(75-150mgperday)shouldbecarriedoutbasedon

patient’sresponse,clinicalstatusandtolerability,uptoamaximumof150mgperdayinindividualdoses.Thedose

shouldbeincreasedincrementally,withintervalsofatleast2weekstoevaluatepatientsresponse.

MyocardialInfarction:

Short-termtreatment:Captortreatmentshouldbegininhospitalassoonaspossiblefollowingtheappearanceofthe

signsand/orsymptomsinpatientswithstablehaemodynamics.A6.25mgtestdoseshouldbeadministered,witha

12.5mgdose12hourslater.Fromthefollowingday,captoprilshouldbeadministeredina100mg/daydose,intwo

dailyadministrations,for4weeks,ifwarrantedbytheabsenceofadversehaemodynamicreactions.Attheendofthe4

weeksoftreatment,thepatient’sstateshouldbereassessedbeforeadecisionistakenconcerningtreatmentforthepost-

myocardialinfarctionstage.

Chronictreatment:Ifcaptopriltreatmenthasnotbegunduringthefirst24hoursoftheacutemyocardialinfarction

stage,itissuggestedthattreatmentbeinstigatedbetweenthe3 rd

and16 th

daypost-infarctiononcethenecessary

treatmentconditionshavebeenattained(stablehaemodynamicsandmanagementofanyresidualischaemia)Treatment

shouldbestartedinthehospitalunderstrictsurveillance(particularlyofbloodpressure)untilthe75mgdoseis

reached.Theinitialdosemustbelow(seesection4.4,Specialwarningsandprecautionsforuse),particularlyifthe

patientexhibitsnormalorlowbloodpressureattheinitiationoftherapy.Therapyshouldbeinitiatedwithadoseof

6.25mgfollowsby12.5mg3timesdailyfor2daysandthen25mg3timesdailyifwarrantedbytheabsenceof

adversehaemodynamicreactions.Therecommendeddoseforeffectivecardioprotectionduringlong-termtreatmentis

75to150mgdailyintwoorthreedoses.Incasesofsymptomatichypotension,asinheartfailure,thedosageof

diureticsand/orotherconcomitantvasodilatorsmaybereducedinordertoattainthesteadystatedoseofcaptopril.

Wherenecessary,thedoseofcaptoprilshouldbeadjustedinaccordancewiththepatient’sclinicalreactions.Captopril

maybeusedincombinationwithothertreatmentsformyocardialinfarctionsuchasthrombolyticagents,beta-blockers

andacetylsalicylicacid.

TypeIDiabeticnephropathy:

InpatientswithtypeIdiabeticnephropathy,therecommendeddailydoseofcaptroprilis75-100mgindivideddoses.

Ifadditionalloweringofbloodpressureisdesired,additionalantihypertensivemedicationsmaybeadded.

Renalimpairment:

Sincecaptoprilisexcretedprimarilyviathekidneys,dosageshouldbereducedorthedosageintervalshouldbe

increasedinpatientswithimpairedrenalfunction.

Whenconcomitantdiuretictherapyisrequired,aloopdiuretic(e.g.furosemide),ratherthanathiazidediuretic,is

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 2

Inpatientswithimpairedrenalfunction,thefollowingdailydosemayberecommendedtoavoidaccumulationof

captopril.

Elderlypatients:

Aswithotherantihypertensiveagents,considerationshouldbegiventoiniatingtherapywithalowerstartingdose

(6.25mgbid)inelderlypatientswhomayhavereducedrenalfunctionandotherorgandysfunctions(seeaboveand

section4.4,Specialwarningsandprecautionsforuse).

Dosageshouldbetitratedagainstthebloodpressureresponseandkeptaslowaspossibletoachieveadequatecontrol.

Childrenandadolescents:

Theefficacyandsafetyofcaptoprilhavenotbeenfullyestablished.Theuseofcaptoprilinchildrenandadolescents

shouldbeinitiatedunderclosemedicalsupervision.Theinitialdoseofcaptoprilisabout0.3mg/kgbody.Forpatients

requiringspecialprecautions(childrenwithrenaldysfunction,prematureinfants,new-bornsandinfants,becausetheir

renalfunctionisnotthesamewitholderchildrenandadults)thestartingdoseshouldonlybe0.15mgcaptopril/kg

weight.Generally,catoprilisadministeredtochildren3timesaday,butdoseandintervalofdoseshouldbeadapted

individuallyaccordingtopatient’sresponse.

4.3Contraindications

Historyofhypersensitivitytocaptopril,toanyoftheexcipientsoranyotherACEinhibitor.

HistoryofangioedemaassociatedwithpreviousACEinhibitortherapy.

Hereditary/idiopathicangioneuroticoedema.

Secondandthirdtrimesterofpregnancy(seesection4.6,PregnancyandLactation)

Lactation(seesection4.6,PregnancyandLactation)

4.4Specialwarningsandprecautionsforuse

Hypotension:

Rarelyhypotensionisobservedinuncomplicatedhypertensivepatient.Symptomatichypotensionismorelikelyto

occurinhypertensivepatientswhoarevolumeand/orsodiumdepletedbyvigorousdiuretictherapy,dietarysalt

restriction,diarrhoea,vomitingorhaemodialysis.Volumeand/orsodiumdepletionshouldbecorrectedbeforethe

administrationofanACEinhibitorandalowerstartingdoseshouldbeconsidered.

Patientswithheartfailureareatahighriskofhypotensionandalowerstartingdoseisrecommendedwheninitiating

therapywithanACEinhibitor.Cautionshouldbeusedwheneverthedoseofcaptoprilordiureticisincreasedin

patientswithheartfailure.

Aswithanyantihypertensiveagent,excessivebloodpressureloweringinpatientswithischaemiccardiovascularor

cerebrovasculardiseasemayincreasetheriskofmyocardialinfarctionorstroke.

Ifhypotensiondevelops,thepatientshouldbeplacedinasupineposition.Volumerepletionwithintravenousnormal

Creatinineclearance DailyStartingdose Dailymaximumdose

(ml/min/1.73m 2

(mg) (mg)

>40 25-50 150

21-40 25 100

Creatinineclearance DailyStartingdose Dailymaximumdose

(ml/min/1.73m 2

(mg) (mg)

10-20 12.5 75

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 3

Renovascularhypertension:

Thereisanincreasedriskofhypotensionandrenalinsufficiencywhenpatientswithbilateralrenalarterystenosisor

stenosisofthearterytoasinglefunctioningkidneyaretreatedwithACEinhibitors.Lossofrenalfunctionmayoccur

withonlymildchangesinserumcreatinine.Inthesepatients,therapyshouldbeinitiatedunderclosemedical

supervisionwithlowdoses,carefultitrationandmonitoringofrenalfunction.

Renalimpairment:

Incasesofrenalimpairment(creatinineclearance<40ml/min),theinitialdosageofcaptoprilmustbeadjusted

accordingtothepatientscreatineclearance(seesection4.2,Posologyandmethodofadministration)andthenasa

functionofthepatient’sresponsetotreatment.Routinemonitoringofpotassiumandcreatininearepartofnormal

medicalpracticeforthesepatients.

Angioedema:

Angioedemaoftheextremities,face,lips,mucousmembranes,tongue,glottisorlarynxmayoccurinpatientstreated

withACEinhibitorsparticularlyduringthefirstweeksoftreatment.However,inrarecases,severeangioedemamay

developafterlong-termtreatmentwithanACEinhibitor.Treatmentshouldbediscontinuedpromptly.Angioedema

involvingthetongue,glottisorlarynxmaybefatal.Emergencytherapyshouldbeinstituted.Thepatientshouldbe

hospitalizedandobservedforatleast12to24hoursandshouldnotbedischargeduntilcompleteresolutionof

symptomshasoccurred.

Cough:

CoughhasbeenreportedwiththeuseofACEinhibitors.Characteristically,thecoughisnon-productive,persistent

andresolvesafterdiscontinuationoftherapy.

Hepaticfailure:

Rarely,ACEinhibitorshavebeenassociatedwithasyndromethatstartswithcholestaticjaundiceandprogressesto

fulminanthepaticnecrosisand(sometimes)death.Themechanismofthissyndromeisnotunderstood.Patients

receivingACEinhibitorswhodevelopjaundiceormarkedelevationsofhepaticenzymesshoulddiscontinuetheACE

inhibitorandreceiveappropriatemedicalfollowup.

Hyperkalaemia:

ElevationsinserumpotassiumhavebeenobservedinsomepatientstreatedwithACEinhibitors,includingcaptopril.

Patientsatriskforthedevelopmentofhyperkalaemiaincludethosewithrenalinsufficiency,diabetesmellitus,orthose

usingconcomitantpotassium-sparingdiuretics,potassiumsupplementsorpotassium-containingsaltsubstitutes;or

thosepatientstakingotherdrugsassociatedwithincreasesinserumpotassium(e.g.heparin).Ifconcomitantuseofthe

abovementionedagentsisdeemedappropriate,regularmonitoringofserumpotassiumisrecommended.

Lithium:

Thecombinationoflithiumandcaptoprilisnotrecommended(seesection4.5,Interactionwithothermedicinal

productsandotherformsofinteractions)

Aorticandmitralvalvestenos/Obstructivehypertrophiccardiomyopathy:

ACEinhibitorsshouldbeusedwithcautioninpatientswithleftventricularvalvularandoutflowtractobstructionand

avoidedincasesofcardiogenicshockandhaemodynamicallysignificantobstruction.

Neutropenia/Agranulocytosis:

Neutropenia/agranulocytosis,thrombocytopeniaandanaemiahavebeenreportedinpatientsreceivingACEinhibitors,

includingcaptopril.Inpatientswithnormalrenalfunctionandnoothercomplicatingfactors,neutropeniaoccurs

rarely.Captoprilshouldbeusedwithextremecautioninpatientswithcollagenvasculardisease,immunosuppressant

therapy,treatmentwithAllopurinolorprocainamide,oracombinationofthesecomplicatingfactors,especiallyifthere

isapre-existingimpairedrenalfunction.Someofthesepatientsdevelopedseriousinfectionswhichinafewinstances

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 4

Ifcaptoprilisusedinsuchpatients,itisadvisedthatwhitebloodcellcountanddifferentcountsshouldbeperformed

priortotherapy,every2weeksduringthefirst3monthsofcaptopriltherapy,andperiodicallythereafter.During

treatmentallpatientsshouldbeinstructedtoreportanysignofinfection(e.g.sorethroat,fever)whenadifferentwhite

bloodcellcountshouldbeperformed.Captoprilandotherconcomitantmedication(seesection4.5,Interactionswith

othermedicinalproductsandotherformsofinteractions)shouldbedrawnifneutropenia(neutrophilslessthan

1000/mm 3

)isdetectedorsuspected.

Inmostpatientsneutrophilcountsrapidlyreturntonormalupondiscontinuingcaptopril.

Proteinuria:

Proteinuriamayoccurparticularlyinpatientswithexistingrenalfunctionimpairmentoronrelativelyhighdosesof

ACEinhibitors.

Totalurinaryproteinsgreaterthan1gperdaywereseeninabout0.7%ofpatientsreceivingcaptopril.Themajorityof

patientshadevidenceofpriorrenaldiseaseorhadreceivedrelativelyhighdosesofcaptopril(inexcessof150mg/day),

orboth.Nephroticsyndromeoccurredinaboutone-fifthofproteinuricpatients.

Inmostcases,proteinuriasubsidedorclearedwithinsixmonthswhetherornotcaptoprilwascontinued.Parametersof

renalfunction,suchasBUNandcreatinine,wereseldomalteredinthepatientswithproteinuria.

Patientswithpriorrenaldiseaseshouldhaveurinaryproteinestimations(dip-stickonfirstmorningurine)priorto

treatment,andperiodicallythereafter.

Anaphylactoidreactionsduringdesensitisation:

Sustainedlife-threateninganaphylactoidreactionshavebeenrarelyreportedforpatientsundergoingdesensitising

treatmentwithhymenopteravenomwhilereceivinganotherACEinhibitor.Inthesamepatients,thesereactionswere

avoidedwhentheACEinhibitorwastemporarilywithheld,buttheyreappeareduponinadvertentrechallenge.

Therefore,cautionshouldbeusedinpatientstreatedwithACEinhibitorsundergoingsuchdesenitisationprocedures.

Anaphylactoidreactionsduringhigh-fluxdialysis/lipoproteinapheresismembraneexposure:

Anaphylactoidreactionshavebeenreportedinpatientshaemodialysedwithhigh-fluxdialysismembranesor

undergoinglowdensitylipoproteinapheresiswithdextransulphateabsorption.Inthesepatients,considerationshould

begiventousingadifferenttypeofdialysis;membraneoradifferentclassofmedication.

Surgery/Anaesthesia:

Hypotensionmayoccurinpatientsundergoingmajorsurgeryorduringtreatmentwithanaestheticagentsthatare

knowntolowerbloodpressure.Ifhypotensionoccurs,itmaybecorrectedbyvolumeexpansion.

Diabeticpatients:

Theglycaemialevelsshouldbecloselymonitoredinthediabeticpatientspreviouslytreatedwithoralantidiabeticdrugs

orinsulin,namelyduringthefirstmonthoftreatmentwithanACEinhibitor.

Lactose:

Captorcontainslactose,thereforeitshouldnotbeusedincasesofcongenitalgalactosaemia,glucoseandgalactose

malabsorptionorlactasedeficiencysyndromes(raremetabolicdiseases).

Ethnicdifferences:

Aswithotherangiotensinconvertingenzymeinhibitors,captoprilisapparentlylesseffectiveinloweringblood

pressureinblackpeoplethaninnon-blacks,possiblybecauseofahigherprevalenceoflow-reninstatesintheblack

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 5

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Potassiumsparingdiureticsorpotassiumsupplements:

ACEinhibitorsattenuatediureticinducedpotassiumloss.Potassiumsparingdiuretics(e.g.spironolactone,triamterene

oramiloride),potassiumsupplements,orpotassium-containingsaltsubstitutesmayleadtosignificantincreasesin

serumpotassium.Ifconcomitantuseisindicatedbecauseofdemonstratedhypokalemiatheyshouldbeusedwith

cautionandwithfrequentmonitoringofserumpotassium(seesection4.4,Specialwarningsandprecautionsforuse)

Diuretics

(Thiazideorloopdiuretics):Priortreatmentwithhighdosediureticsmayresultinvolumedepletionandariskof

hypotensionwheninitiatingtherapywithcaptopril(seesection4.4,Specialwarningsandprecautionsforuse).The

hypotensiveeffectscanbereducedbydiscontinuationofthediuretic,byincreasingvolumeorsaltintakeorby

initiatingtherapywithalowdoseofcaptopril.However,noclinicallysignificantdruginteractionshavebeenfoundin

specificstudieswithhydrochlorothiazideorfurosemide.

Otherantihypertensiveagents:

Captoprilhasbeensafelyco-administeredwithothercommonlyusedantihypertensiveagents(e.g.beta-blockersand

longactingcalciumchannelblockers).Concomitantuseoftheseagentsmayincreasethehypotensiveeffectsof

captopril.Treatmentwithnitroglycerineandothernitrates,orothervasodilators,shouldbeusedwithcaution.

Treatmentsofacutemyocardialinfarction:

Captoprilmaybeusedconcomitantlywithacetylsalicylicacid(atcardiologicdoses),thrombolytics,beta-blockers

and/ornitratesinpatientswithmyocardialinfarction.

Lithium:

Reversibleincreasesinserumlithiumconcentrationsandtoxicityhavebeenreportedduringconcomitant

administrationoflithiumwithACEinhibitors.Concomitantuseofthiazidediureticsmayincreasetheriskoflithium

toxicityandenhancethealreadyincreasedriskoflithiumtoxicitywithACEinhibitors.Useofcaptoprilwithlithiumis

notrecommended,butifthecombinationprovesnecessary,carefulmonitoringofserumlithiumlevelsshouldbe

performed(seesection4.4,Specialwarningsandprecautionsforuse).

Tricyclicantidepressants/Antipsychotics:

ACEinhibitorsmayenhancethehypotensiveeffectsofcertaintriclyclicantidepressantsandantipsyschotics(see

section4.4,Specialwarningsandprecautionsforuse)Posturalhypotensionmayoccur.

Allopurinol,procainamide,cytostaticorimmuno-suppressiveagents:

ConcomitantadministrationwithACEinhibitorsmayleadtoanincreasedriskforleucopeniaespeciallywhenthelatter

areusedatahigherthancurrentlyrecommendeddoses.

Non-steroidanti-inflammatorymedicinalproducts:

Ithasbeendescribedthatnon-steroidalanti-inflammatorymedicinalproducts(NSAIDs)andACEinhibitorsexertan

additiveeffectontheincreaseinserumpotassiumwhereasrenalfunctionmaydecrease.Theseeffectsareinprinciple,

reversible.Rarely,acuterenalfailuremayoccur,particularlyinpatientswithcompromisedrenalfunctionsuchasthe

elderlyordehydrated.ChronicadministrationofNSAIDsmayreducetheantihypertensiveeffectofanACEinhibitor.

Sympathomimetics:

MayreducetheantihypertensiveeffectsofACEinhibitors;patientsshouldbecarefullymonitored.

Antidiabetics:

PharmacologicalstudieshaveshownthatACEinhibitors,includingcaptopril,canpotentiatethebloodglucose-

reducingeffectsofinsulinandoralantidiabeticssuchassulphonylureaindiabetics.Shouldthisveryrareinteraction

occur,itmaybenecessarytoreducethedoseofantidiabeticduringsimultaneoustreatmentwithACEinhibitors.

ClinicalChemistry:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 6

4.6Pregnancyandlactation

Pregnancy:

Captorisnotrecommendedduringthefirsttrimesterofpregnancy.Whenapregnancyisplannedorconfirmed,the

switchtoanalternativetreatmentshouldbeinitiatedassoonaspossible.ControlledstudieswithACEinhibitorshave

notbeendoneinhumans,butlimitednumberofcasesoffirsttrimesterexposureshavenotshownmalformations.

Captoriscontraindicatedduringthesecondandthirdtrimestersofpregnancy.Prolongedcaptoprilexposureduringthe

secondandthirdtrimesterisknowntoinducetoxicityinfoetuses(decreasedrenalfunction,oligohydramnios,skull

ossificationretardation)andinneonates(neonatalrenalfailure,hypotension,Hyperkalaemia)(seeSection5.3

PreclinicalSafetyData)

Lactation:

Captoriscontraindicatedinthelactationperiod.

4.7Effectsonabilitytodriveandusemachines

Aswithotherantihpertensives,theabilitytodriveandusemachinesmaybereduced,namelyatthestartofthe

treatment,orwhenposologyismodified,andalsowhenusedincombinationwithalcohol,buttheseseffectsdependon

theindividual’ssusceptibility.

4.8Undesirableeffects

Undesirableeffectsreportedforcaptopriland/orACEinhibitorinclude:

Bloodandlymphaticdisorders:

VeryRare:

Neutropenia/agranulocytosis(seesection4.4,Specialwarningsandprecautionsforuse),pancytopeniaparticularlyin

patientswithrenaldysfunction(seesection4.4,Specialwarningsandprecautionsforuse),anemia(includingaplastic

andhaemolytic),thrombocytopenia,lymphadenopathy,eosinophilia,auto-immunediseasesand/orpositiveANA-titres.

Metabolismandnutritiondisorders:

Rare:

Anorexia

VeryRare:

Hyperkalaemia,hypoglycemia(seesection4.4,Specialwarningsandprecautionsforuse)

Psychiatricdisorders:

Common:

Sleepdisorders.

VeryRare:

Confusion,depression.

Nervoussystemdisorders:

Common:

Tasteimpairment,dizziness.

Rare:

Drowsiness,headacheandparaesthesia.

VeryRare:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 7

Eyedisorders:

VeryRare:

Blurredvision.

Cardiacdisorders:

Uncommon:

Tachycardiaortachyarrhythmias,anginapectoris,palpitations.

VeryRare:

Cardiacarrest,cardiogenicshock.

Vasculardisorders:

Uncommon:

Hypotension(seesection4.4SpecialWarningsandPrecautionsforUse),Raynaudsyndrome,flush,pallor.

Respiratory,thoracicandmediastinaldisorders:

Common:

Dry,irritating(nonproductive)cough(seesection4.4SpecialwarningsandprecautionsforUse)anddyspnoea.

VeryRare:

Bronchospasm,rhinitis,allergicalveolitis/eosinophilicpneumonia.

Gastrointestinaldisorders:

Common:

Nausea,vomiting,gastricirritations,abdominalpain,diarrhoea,constipation,drymouth.

Rare:

Stomatitis/aphthousulcerations.

VeryRare:

Glossitis,pepticulcer,pancreatitis.

Hepato-biliarydisorders:

VeryRare:

Impairedhepaticfunctionandcholestasis.(includingjaundice),hepatitisincludingnecrosis,elevatedliverenzymesand

bilirubin.

Skinandsubcutaneoustissuedisorders:

Common:

Prurituswithorwithoutarashandalopecia.

Uncommon:

Angioedema(seesection4.4,Specialwarningsandprecautionsforuse)

VeryRare:

Urticaria,StevensJohnsonsyndrome,erythemamultiform,photosensitivity,erythroderma,pemphigoidreactionsand

exfoliativedermatitis.

Musculoskeletal,connectivetissueandbonedisorders:

Veryrare:

Myalgia,arthralgia.

Renalandurinarydisorders:

Rare:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 8

VeryRare:

Nephroticsyndrome.

Reproductivesystemandbreastdisorders:

VeryRare:

Impotence,gynaecomastia.

Generaldisorders:

Uncommon:

Chestpain,fatigue,malaise

VeryRare:

Fever.

Investigations:

VeryRare:

Proteinuria,eosinophilia,increaseofserumpotassium,decreaseofserumsodium,elevationofBUN,serumcreatinine

andserumbilirubin,decreasesinhaemoglobin,haematocrit,leucocytes,thrombocytes,positiveANA-titre,elevated

ESR.

4.9Overdose

Symptomsofoverdosageareseverehypotension,shock,stupor,bradycardia,electrolytedisturbancesandrenalfailure.

Measurestopreventabsorption(e.g.gastriclavage,administrationofabsorbentsandsodiumsulphatewithin30

minutesafterintake)andhasteneliminationshouldbeappliedifingestionisrecent.Ifhypotensionoccurs,thepatient

shouldbeplacedintheshockpositionandsaltvolumesupplementsshouldbegivenrapidly.Treatmentwith

angiotension-IIshouldbeconsidered.

Bradycardiaorextensivevagalreactionsshouldbetreatedbyadministeringatropine.Theuseofapacemakermaybe

considered.

Captoprilmayberemovedfromcirculationbyhaemodialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:ACEinhibitors,plain,

ATCcode:C09AA01.

Captoprilisahighlyspecific,competitiveinhibitorofangiotensin-Iconvertingenzyme(ACEinhibitors).

ThebeneficialeffectsofACEinhibitorsappeartoresultprimarilyfromthesuppressionoftheplasmarenin-

angiotensin-aldosteronesystem.Reninisanendogenousenzymesynthesizedbythekidneysandreleasedintothe

circulationwhereitconvertsangiotensinogentoangiotensin-Iarelativelyinactivedecapeptide.Angiotensin-Iisthen

convertedbyangiotensinconvertingenzyme,apeptidyl-dipeptidase,toangiotensin-II.Angiotensin-IIisapotent

vasoconstrictorresponsibleforarterialvasoconstrictionandincreasedbloodpressure,aswellasforstimulationofthe

adrenalglandtosecretealdosterone.InhibitionofACEresultsindecreasedplasmaangiotension-IIwhichleadsto

decreasedvasopressoractivityandtoreducealdosteronesecretion.Althoughthelatterdecreaseissmall,small

increasesinserumpotassiumconcentrationsmayoccur,alongwithsodiumandfluidloss.Thecessationofthe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 9

Anotherfunctionoftheconvertingenzymeistodegradethepotentvasodepressivekininpeptidebradykinintoinactive

metabolites.

Therefore,inhibitionofACEresultsinanincreasedactivityofcirculatingandlocalkallikrein-kinin-systemwhich

contributestoperipheralvasodilationbyactivatingtheprostaglandinsystem;itispossiblethatthismechanismis

involvedinthehypotensiveeffectofACEinhibitorsandisresponsibleforcertainadversereactions.

Reductionsofbloodpressureareusuallymaximal60to90minutesafteroraladministrationofindividualdoseof

captopril.Thedurationofeffectisdoserelated.Thereductioninbloodpressuremaybeprogressive,sotoachieve

maximaltherapeuticeffects,severalweeksoftherapymayberequired.Thebloodpressureloweringeffectsof

captoprilandthiazide-typediureticsareadditive.

Inpatientswithhypertension,captoprilcausesareductioninsupineanderectbloodpressure,withoutinducingany

compensatoryincreaseinheartrate,norwaterandsodiumretention.

Inhaemodynamicinvestigations,captoprilcausedamarkedreductioninperipheralarterialresistance.Ingeneralthere

werenoclinicallyrelevantchangesinrenalplasmafloworglomerularfiltrationrate.Inmostpatients,the

antihypertensiveeffectbeganabout15to30minutesafteroraladministrationofcaptopril;thepeakeffectwas

achievedafter60to90minutes.Themaximumreductioninbloodpressureofadefinedcaptoprildosewasgenerally

visibleafterthreetofourweeks.Intherecommendeddailydose,theantihypertensiveeffectpersistsevenduringlong-

termtreatment.Temporarywithdrawalofcaptoprildoesnotcauseanyrapid,excessiveincreaseinbloodpressure

(rebound).Thetreatmentofhypertensionwithcaptoprilleadsalsotoadecreaseinleftventricularhypertrophy.

Haemodynamicinvestigationsinpatientswithheartfailure,showedthatcaptoprilcausedareductioninperipheral

systemicresistanceandariseinvenouscapacity.Thisresultedinareductioninpre-loadandafterloadoftheheart

(reductioninventricularfilingpressure).Inaddition,risesincardiacoutput,workindexandexercisecapacityhave

beenobservedduringtreatmentwithcaptopril.Inalarge,placebo-controlledstudyinpatientswithleftventricular

dysfunction(LVEF<40%)followingmyocardialinfarction,itwasshownthatcaptoril(initiatedbetweenthe3 rd

tothe

dayafterinfarction)prolongedthesurvivaltimeandreducedcardiovascularmortality.Thelatterwasmanifested

asadelayinthedevelopmentofsymptomaticheartfailureandareductioninthenecessityforhospitalizationdueto

heartfailurecomparedtoplacebo.Therewasalsoareductioninre-infarctionandincardiacrevascularisation

proceduresand/orintheneedforadditionalmedicationwithdiureticsand/oranincreaseintheirdosagecomparedto

placebo.

Aretrospectiveanalysisshowedthatcaptoprilreducedrecurrentinfarctsandcardiacrevascularisationprocedures

(neitherweretargetcriteriaofthestudy).

Anotherlarge,placebo-controlledstudyinpatientswithmyocardialinfarctionshowedthatcaptopril(givenwithin24

hoursoftheeventandforadurationofonemonth)significantlyreducedoverallmortalityafter5weekscomparedto

placebo.Thefavourableeffectofcaptoprilontotalmortalitywasstilldetectableevenafteroneyear.Noindicationon

thefirstdayoftreatmentwasfound.

Captoprilcardioprotectioneffectsareobservedregardlessofthepatient’sageorgender,locationoftheinfarctionand

concomitanttreatmentswithprovenefficacyduringthepost-infarctionperiod(thrombolyticagents,beta-blockersand

acetylsalicylicacid).

TypeIdiabeticnephropathy

Inaplacebo-controlled,multicentredoubleblindclinicaltrialininsulin-dependent(TypeI)diabeteswithproteinuria,

withorwithouthypertension(simultaneousadministrationofotherantihypertensivestocontrolbloodpressurewas

allowed),captoprilsignificantlyreduced(by51%)thetimetodoublingofthebaselinecreatinineconcentration

comparedtoplacebo;theincidenceofterminalrenalfailure(dialysis,transplantation)ordeathwasalsosignificantly

lesscommonundercaptoprilthanunderplacebo(51%).Inpatientswithdiabetesandmicroalbuminuria,treatment

withcaptoprilreducedalbuminexcretionwithintwoyears.

Theeffectsoftreatmentwithcaptoprilonthepreservationofrenalfunctionareinadditiontoanybenefitthatmayhave

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 10

5.2Pharmacokineticproperties

Captoprilisanorallyactiveagentthatdoesnotrequirebiotransformationforactivity.Theaverageminimalabsorption

isapproximately75%.Peakplasmaconcentrationarereachedwith60-90minutes.Thepresenceoffoodinthe

gastrointestinaltractreducesabsorptionbyabout30-40%.Approximately25-30%ofthecirculatingdrugisboundto

plasmaproteins.

Theapparenteliminationhalf-lifeofunchangedcaptoprilinbloodisabout2hours.Greaterthan95%oftheabsorbed

doseiseliminatedintheurinewithin24hours;40-50%isunchangeddrugandtheremainderareinactivedisulphide

metabolites(captoprildisulphideandcaptoprilcysteinedisulphide).Impairedrenalfunctioncouldresultindrug

accumulation.Thereforeinpatientswithimpairedrenalfunctionthedoseshouldbereducedand/ordosageinterval

prolonged(seesection4.2,Posologyandmethodofadministration).

Studiesinanimalsindicatethatcaptoprildoesnotcrosstheblood-brainbarriertoanysignificantextent.

5.3Preclinicalsafetydata

Animalstudiesperformedduringorganogenesiswithcaptoprilhavenotalwaysshownanyteratogeniceffectbut

captoprilhasproducedfoetaltoxicityinseveralspecies,includingfoetalmortalityduringlatepregnancy,growth

retardationandpostnatalmortalityintherat.Preclinicaldatarevealnootherspecifichazardforhumansbasedon

conventionalstudiesofsafetypharmacology,repeateddosetoxicology,genotoxicityandcarcinogenicity.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

MicrocrystallineCellulose

MaizeStarch

LactoseMonohydrate

StearicAcid

6.2Incompatibilities

Notapplicable

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C

6.5Natureandcontentsofcontainer

Captor6.25mgtabletsarepackedintostripsofpolypropyleneweldedonaninternallyvarnishedaluminiumsupport.

Thisthermallyweldablefilmpreventsthetabletsfromdirectcontactwiththemetalwhileallowingthestripstoweld

onthesupport.Captor6.25areavailableinsalespacksof30tabletseach.Samplepacksof10tabletswillalsobe

available.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 11

7MARKETINGAUTHORISATIONHOLDER

ROWEXLTD

Bantry

CoCork

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA0711/002/004

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01April1999

Dateoflastrenewal: 01April2004

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 21/08/2008 CRN 2054971 page number: 12