CAVERJECT

Main information

  • Trade name:
  • CAVERJECT Pdr+Solv for Soln for Inj 10 Microgram
  • Dosage:
  • 10 Microgram
  • Pharmaceutical form:
  • Pdr+Solv for Soln for Inj
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CAVERJECT Pdr+Solv for Soln for Inj 10 Microgram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0016/046/003
  • Authorization date:
  • 04-04-1997
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0016/046/003

CaseNo:2082960

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PharmaciaLimited

RamsgateRoad,Sandwich,Kent,CT139NJ,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Caverject10microgramsPowderandSolventforSolutionforInjection

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom17/06/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 17/06/2010 CRN 2082960 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Caverject10microgramsPowderandSolventforSolutionforInjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Alprostadil10micrograms.

Whenreconstituted,each1mldeliversadoseof10microgramsofalprostadil.

Excipients:alsoincludesbenzylalcohol7.96mgper1mlofreconstitutedsolution.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Powderandsolventforsolutionforinjection.

Powder:Awhitetooff-whitelyophilizedpowder.

Solvent:Aclear,colourlessliquid.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Caverjectisindicatedforthetreatmentoferectiledysfunctioninadultmalesduetoneurogenic,vasculogenic,

psychogenicormixedaetiology.

Caverjectmaybeausefuladjuncttootherdiagnostictestsinthediagnosisoferectiledysfunction.

4.2Posologyandmethodofadministration

Caverjectisadministeredbydirectintracavernousinjection.A1/2-inch,27to30gaugeneedleisgenerally

recommended.ThedoseofCaverjectshouldbeindividualisedforeachpatientbycarefultitrationundersupervision

byaphysician.

Theintracavernosalinjectionmustbedoneundersterileconditions.Thesiteofinjectionisusuallyalongthe

dorsolateralaspectoftheproximalthirdofthepenis.Visibleveinsshouldbeavoided.Boththesideofthepenisthatis

injectedandthesiteofinjectionshouldbealternated;priortotheinjection,theinjectionsitemustbecleansedwithan

alcoholswab.

ToreconstituteCaverjectusingtheprefilleddiluentsyringe:flipofftheplasticcapfromthevial,anduseoneofthe

swabstowipetherubbercap.Fitthe22gaugeneedletothesyringe.

Injectthe1mlofdiluentintothevial,andshaketodissolvethepowderentirely.Withdrawslightlymorethanthe

requireddoseofCaverjectsolution,removethe22gaugeneedle,andfitthe30gaugeneedle.Adjustvolumetothe

requireddoseforinjection.Followingadministration,anyunusedcontentsofthevialorsyringeshouldbediscarded.

Asanaidtoaetiologicdiagnosis.

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cavernosumandmassagedthroughthepenis.Shouldanensuingerectionpersistformorethanonehourdetumescent

therapy(pleaserefertoSection4.9-Overdose)shouldbeemployedtopreventariskofpriapismpriortothesubject

leavingtheclinic.

Over80%ofsubjectsmaybeexpectedtorespondtoasingle20microgramsdoseofalprostadil.Atthetimeofdischarg

fromtheclinic,theerectionshouldhavesubsidedentirelyandthepenismustbeinacompletelyflaccidstate.

Subjectswithevidenceofneurologicaldysfunction;thesepatientscanbeexpectedtorespondtolowerdosesof

alprostadil.Insubjectswitherectiledysfunctioncausedbyneurologicdisease/traumathedosefordiagnostictestingmu

notexceed10microgramsandaninitialdoseof5microgramsislikelytobeappropriate.Shouldanensuingerection

persistformorethanonehourdetumescenttherapy(pleaserefertoSection4.9-Overdose)shouldbeemployedto

preventariskofpriapismpriortothesubjectleavingtheclinic.Atthetimeofdischargefromtheclinic,theerection

shouldhavesubsidedentirelyandthepenismustbeinacompletelyflaccidstate.

Treatment

Theinitialdoseofalprostadilis2.5micrograms.Theseconddoseshouldbe5microgramsifthereisapartial

response,and7.5microgramsifthereisnoresponse.Subsequentincrementalincreasesof5-10microgramsshould

begivenuntilanoptimaldoseisachieved.Ifthereisnoresponsetotheadministereddose,thenthenexthigherdose

maybegivenwithin1hour.Ifthereisaresponse,thereshouldbeatleasta1-dayintervalbeforethenextdoseis

given.Theusualmaximumrecommendedfrequencyofinjectionisnomorethanoncedailyandnomorethanthree

timesweekly.

Thefirstinjectionsofalprostadilmustbedonebymedicallytrainedpersonnel.Afterpropertrainingandinstruction,

alprostadilmaybeinjectedathome.Ifself-administrationisplanned,thephysicianshouldmakeanassessmentofthe

patient'sskillandcompetencewiththeprocedure.Itisrecommendedthatpatientsareregularlymonitored(e.g.every3

months)particularlyintheinitialstagesofselfinjectiontherapywhendoseadjustmentsmaybeneeded.

Thedosethatisselectedforself-injectiontreatmentshouldprovidethepatientwithanerectionthatissatisfactoryfor

sexualintercourse.Itisrecommendedthatthedoseadministeredproducesadurationoftheerectionnotexceedingone

hour.Ifthedurationislonger,thedoseshouldbereduced.Themajorityofpatientsachieveasatisfactoryresponsewith

dosesintherangeof5to20micrograms.Dosesofgreaterthan60microgramsofalprostadilarenotrecommended.Th

lowesteffectivedoseshouldbeused.

4.3Contraindications

Caverjectshouldnotbeusedinpatientswhohaveaknownhypersensitivitytoanyoftheconstituentsoftheproduct;in

patientswhohaveconditionsthatmightpredisposethemtopriapism,suchassicklecellanaemiaortrait,multiple

myeloma,orleukaemia;orinpatientswithanatomicaldeformationofthepenis,suchasangulation,cavernosal

fibrosis,orPeyronie'sdisease.PatientswithpenileimplantsshouldnotbetreatedwithCaverject.

Caverjectshouldnotbeusedinmenforwhomsexualactivityisinadvisableorcontraindicated.

4.4Specialwarningsandprecautionsforuse

Prolongederectionand/orpriapismmayoccur.Patientsshouldbeinstructedtoreporttoaphysiciananyerection

lastingforaprolongedtimeperiod,suchas4hoursorlonger.Treatmentofpriapismshouldnotbedelayedmorethan

6hours(pleaserefertoSection4.9-Overdose).

Painfulerectionismorelikelytooccurinpatientswithanatomicaldeformationsofthepenis,suchasangulation,

phimosis,cavernosalfibrosis,Peyronie'sdiseaseorplaques.Penilefibrosis,includingangulation,fibroticnodulesand

Peyronie'sdiseasemayoccurfollowingtheintracavernosaladministrationofCaverject.Theoccurrenceoffibrosis

mayincreasewithincreaseddurationofuse.

Regularfollow-upofpatients,withcarefulexaminationofthepenis,isstronglyrecommendedtodetectsignsofpenile

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angulation,cavernosalfibrosis,orPeyronie'sdisease.

Patientsonanticoagulantssuchaswarfarinorheparinmayhaveincreasedpropensityforbleedingafterthe

intracavernousinjection.

Underlyingtreatablemedicalcausesoferectiledysfunctionshouldbediagnosedandtreatedpriortoinitiationof

therapywithCaverject.

Useofintracavernosalalprostadiloffersnoprotectionfromthetransmissionofsexuallytransmitteddiseases.

Individualswhousealprostadilshouldbecounselledabouttheprotectivemeasuresthatarenecessarytoguardagainst

thespreadofsexuallytransmitteddiseases,includingthehumanimmunodeficiencyvirus(HIV).Insomepatients,

injectionofCaverjectcaninduceasmallamountofbleedingatthesiteofinjection.Inpatientsinfectedwithblood-

borndiseases,thiscouldincreasethetransmissionofsuchdiseasestotheirpartner.

ReconstitutedsolutionsofCaverjectareintendedforsingleuseonly,theyshouldbeusedimmediatelyandnotstored.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactosedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noknowninteractions.Caverjectisnotintendedforco-administrationwithanyotheragentforthetreatmentof

erectiledysfunction.

4.6Pregnancyandlactation

Notapplicable.(Highdosesofalprostadil(0.5to2.0mg/kgsubcutaneously)hadanadverseeffectonthereproductive

potentialofmalerats,althoughthiswasnotseenwithlowerdoses(0.05to0.2mg/kg).Alprostadildidnotaffectrat

spermatogenesisatdoses200timesgreaterthantheproposedhumanintrapeniledose.)

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

Cardiacdisorders

Uncommon:Supraventricularextrasystole

Congential,familialandgeneticdisorders

Uncommon:Phimosis

Eyedisorders

Uncommon:Mydriasis

Gastrointestinaldisorders

Common:Nausea;drymouth,abdominalpain

Generaldisordersandadministrationsiteconditions

Common:Haematomaatthesiteoftheinjection;ecchymosisatthesiteofinjection;injectionsiteoedema,flu-like

syndrome

Uncommon:Injectionsitehaemorrhage;injectionsiteinflammation;injectionsiteitching;non-generalisedweakness

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Investigations

Uncommon:Increasedserumcreatinine

Injury,poisoningandproceduralcomplications

Common:Trauma

Infectionsandinfestations

Common:Upperrespiratoryinfection,sinusitis

NotKnown:Yeastinfection

Musculoskeletal,connectivetissueandbonedisorders

Common:Legpain,buttockspain

Uncommon:Legcramps,backpain

Neoplasms,benign,malignantandunspecified(incl.cystsandpolyps)

Common:Skinneoplasm

Nervoussystemdisorders

Common:Headache

Uncommon:Vasovagalreactions;hypaesthesia,numbness,dizziness

Renalandurinarydisorders

Uncommon:Haematuria;impairedurination;urinaryfrequency;urinaryurgency

NotKnown:Urethralbleeding

Reproductivesystemandbreastdisorders

VeryCommon:Penilepain

Common:Penilefibrosis(includingangulation,fibroticnodulesandPeyronie’sdisease),abnormalejaculation,genital

pain,prostaticdisorder,painfulerection;priapism;testicularpain

Uncommon:Balanitis;penilewarmth;pelvicpain;scrotaldisorder(redness,pain,spermatocele);scrotaloedema;

penileoedema,testiculardisorder(warmth,swelling,mass,thickening)

Respiratory,thoracicandmediastinaldisorders

Uncommon:Nasalcongestion,cough

Skinandsubcutaneoustissuedisorders

Uncommon:Rash;diaphoresis;non-applicationsitepruritus,erythema

Vasculardisorders

Common:Hypertension

Uncommon:hypotension;vasodilation;

NotKnown:Venousleak;peripheralvasculardisorder;symptomatichypotension

VeryCommon

1/10(10%)

Common

1/100and <

1/10(1%and<10%)

Uncommon

1/1000and <

1/100(0.1%and<1%)

Rare

1/10,000and <

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4.9Overdose

Thepharmacotoxicsignsofalprostadilaresimilarinallanimalspeciesandincludedepression,softstoolsordiarrhoea

andrapidbreathing.Inanimals,thelowestacuteLD

was12mg/kgwhichis12,000timesgreaterthanthemaximum

recommendedhumandoseof60micrograms.

Inman,prolongederectionand/orpriapismareknowntooccurfollowingintracavernousadministrationofvasoactive

substances,includingalprostadil.Patientsshouldbeinstructedtoreporttoaphysiciananyerectionlastingfora

prolongedtimeperiod,suchas4hoursorlonger.

Thetreatmentofpriapism(prolongederection)shouldnotbedelayedmorethan6hours.Initialtherapyshouldbeby

penileaspiration.Usingaseptictechnique,inserta19-21gaugebutterflyneedleintothecorpuscavernosumand

aspirate20-50mlofblood.Thismaydetumescethepenis.Ifnecessary,theproceduremayberepeatedonthe

oppositesideofthepenisuntilatotalofupto100mlbloodhasbeenaspirated.Ifstillunsuccessful,intracavernous

injectionofalpha-adrenergicmedicationisrecommended.Althoughtheusualcontra-indicationtointrapenile

administrationofavasoconstrictordoesnotapplyinthetreatmentofpriapism,cautionisadvisedwhenthisoptionis

exercised.Bloodpressureandpulseshouldbecontinuouslymonitoredduringtheprocedure.Extremecautionis

requiredinpatientswithcoronaryheartdisease,uncontrolledhypertension,cerebralischaemia,andinsubjectstaking

monoamineoxidaseinhibitors.Inthelattercase,facilitiesshouldbeavailabletomanageahypertensivecrisis.A200

microgram/mlsolutionofphenylephrineshouldbeprepared,and0.5to1.0mlofthesolutioninjectedevery5to10

minutes.Alternatively,a20microgram/mlsolutionofadrenalineshouldbeused.Ifnecessary,thismaybefollowed

byfurtheraspirationofbloodthroughthesamebutterflyneedle.Themaximumdoseofphenylephrineshouldbe1mg,

oradrenaline100micrograms(5mlofthesolution).Asanalternativemetaraminolmaybeused,butitshouldbe

notedthatfatalhypertensivecriseshavebeenreported.Ifthisstillfailstoresolvethepriapism,urgentsurgicalreferral

forfurthermanagement,whichmayincludeashuntprocedure,isrequired.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsusedinerectiledysfunction

ATCcode:G04BE01

Alprostadilispresentinvariousmammaliantissuesandfluids.Ithasadiversepharmacologicprofile,amongwhich

someofitsmoreimportanteffectsarevasodilation,inhibitionofplateletaggregation,inhibitionofgastricsecretion,

andstimulationofintestinalanduterinesmoothmuscle.Thepharmacologiceffectofalprostadilinthetreatmentof

erectiledysfunctionispresumedtobemediatedbyinhibitionofalpha1-adrenergicactivityinpeniletissueandbyits

relaxingeffectoncavernosalsmoothmuscle.

5.2Pharmacokineticproperties

Followingintracavernousinjectionof20µgofalprostadil,meanperipherallevelsofalprostadilat30and60minutes

afterinjectionarenotsignificantlygreaterthanbaselinelevelsofendogenousPGE

.Peripherallevelsofthemajor

circulatingmetabolite,15-oxo-13,14-dihydro-PGE

,increasetoreachapeak30minutesafterinjectionandreturnto

pre-doselevelsby60minutesafterinjection.Anyalprostadilenteringthesystemiccirculationfromthecorpus

cavernosumwillberapidlymetabolized.Followingintravenousadministration,approximately80%ofthecirculating

VeryRare

<

1/10,000(<0.01%)

NotKnown

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Themetabolitesareexcretedprimarilybythekidneyandexcretionisessentiallycompletewithin24hours.Thereisno

evidenceoftissueretentionofalprostadiloritsmetabolitesfollowingintravenousadministration.

5.3Preclinicalsafetydata

Nonestated.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Sodiumcitrate

Hydrochloricacid

Sodiumhydroxide

Solvent

Benzylalcohol

Waterforinjections

6.2Incompatibilities

Caverjectisnotintendedtobemixedorco-administeredwithanyotherproducts.

6.3ShelfLife

LyophilisedPowder

2years

ReconstitutedSolution

Mustbeusedimmediatelyandnotstored.

Solvent

2years

6.4Specialprecautionsforstorage

LyophilisedPowder:

Donotstoreabove25°C.

Reconstitutedsolution:

Reconstitutedsolutionsareintendedforsingleuseonly,theyshouldbeusedimmediatelyandnotstored.

Diluent

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6.5Natureandcontentsofcontainer

LyophilisedPowder

1x5ml,TypeIPh.Eur.,clear,colourlessglassvialwithafluorocoatedrubberstopperandanaluminiumoverseal

withflip-offcap.

Solvent

1x2mlTypeIPh.Eur.clear,colourlessglasssyringe,withbutylrubberplungerstopper.

ThepackagealsoincludesantisepticswabscontainingIsopropylalcoholBP.

Forhospitaluseonly,adosetitrationpackcontaining8individualboxesofCaverject10micrograms.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Afterreconstitutiontheproductisaclearsolution.

Thepresenceofbenzylalcoholinthereconstitutionvehicledecreasedthedegreeofbindingtopackagesurfaces.

Therefore,amoreconsistentproductdeliveryisproducedwhenBacteriostaticWaterforInjectioncontainingbenzyl

alcoholisused.

Useimmediatelyafterreconstitution.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaLimited

RamsgateRoad

Sandwich,Kent,CT139NJ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0016/046/003

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:04April1997

Dateoflastauthorisation:04April2007

10DATEOFREVISIONOFTHETEXT

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