CAVERJECT

Main information

  • Trade name:
  • CAVERJECT Pdr+Solv for Soln for Inj 20 Microgram
  • Dosage:
  • 20 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 20 Microgram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0936/009/005
  • Authorization date:
  • 13-03-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Caverject20microgramsPowderandSolventforSolutionforInjection.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Alprostadil20micrograms.

Whenreconstituted,each1mldeliversadoseof20microgramsofalprostadil.

Excipients:each1mlofreconstitutedsolutioncontains7.96mgbenzylalcohol.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Powderandsolventforsolutionforinjection.

Powder:Awhitetooff-whitelyophilisedpowder.

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

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A. Asanaidtoaetiologicdiagnosis.

i)Subjectswithoutevidenceofneurologicaldysfunction;20microgramsalprostadiltobeinjectedintothecorpus

cavernosumandmassagedthroughthepenis.Shouldanensuingerectionpersistformorethanonehourdetumescent

therapy(pleaserefertoSection4.9–Overdose)shouldbeemployedtopreventariskofpriapismpriortothesubject

leavingtheclinic.Over80%ofsubjectsmaybeexpectedtorespondtoasingle20microgramsdoseofalprostadil.At

thetimeofdischargefromtheclinic,theerectionshouldhavesubsidedentirelyandthepenismustbeinacompletely

flaccidstate.

ii)Subjectswithevidenceofneurologicaldysfunction;thesepatientscanbeexpectedtorespondtolowerdosesof

alprostadil.Insubjectswitherectiledysfunctioncausedbyneurologicdisease/traumathedosefordiagnostictesting

mustnotexceed10microgramsandaninitialdoseof5microgramsislikelytobeappropriate.Shouldanensuing

erectionpersistformorethanonehourdetumescenttherapy(pleaserefertoSection4.9-Overdose)shouldbe

employedtopreventariskofpriapismpriortothesubjectleavingtheclinic.Atthetimeofdischargefromtheclinic,

theerectionshouldhavesubsidedentirelyandthepenismustbeinacompletelyflaccidstate.

B. Treatment

Theinitialdoseofalprostadilis2.5micrograms.Theseconddoseshouldbe5microgramsifthereisapartial

response,and7.5microgramsifthereisnoresponse.Subsequentincrementalincreasesof5-10microgramsshould

begivenuntilanoptimaldoseisachieved.Ifthereisnoresponsetotheadministereddose,thenthenexthigherdose

maybegivenwithin1hour.Ifthereisaresponse,thereshouldbeatleasta1-dayintervalbeforethenext

doseisgiven.Theusualmaximumrecommendedfrequencyofinjectionisnomorethanoncedailyandnomorethan

threetimesweekly.

Thefirstinjectionsofalprostadilmustbedonebymedicallytrainedpersonnel.Afterpropertrainingandinstruction,

alprostadilmaybeinjectedathome.Ifself-administrationisplanned,thephysicianshouldmakeanassessmentofthe

patient'sskillandcompetencewiththeprocedure.Itisrecommendedthatpatientsareregularlymonitored(e.g.every3

months)particularlyintheinitialstagesofselfinjectiontherapywhendoseadjustmentsmaybeneeded.

Thedosethatisselectedforself-injectiontreatmentshouldprovidethepatientwithanerectionthatissatisfactoryfor

sexualintercourse.Itisrecommendedthatthedoseadministeredproducesadurationoftheerectionnotexceedingone

hour.Ifthedurationislonger,thedoseshouldbereduced.

Themajorityofpatientsachieveasatisfactoryresponsewithdosesintherangeof5to20micrograms.Dosesof

greaterthan60microgramsofalprostadilarenotrecommended.Thelowesteffectivedoseshouldbeused.

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

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Painfulerectionismorelikelytooccurinpatientswithanatomicaldeformationsofthepenis,suchasangulation,

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

Peyronie’sdiseasemayoccurfollowingtheintracavernosaladministrationofCaverject.Theoccurrenceoffibrosis

mayincreasewithincreaseddurationofuse.Regularfollow-upofpatients,withcarefulexaminationofthepenis,is

stronglyrecommendedtodetectsignsofpenilefibrosisorPeyronie’sdisease.TreatmentwithCaverjectshouldbe

discontinuedinpatientswhodeveloppenileangulation,cavernosalfibrosis,orPeyronie’sdisease.

Patientsonanticoagulantssuchaswarfarinorheparinmayhaveincreasedpropensityforbleedingafterthe

intracavernousinjection.

Underlyingtreatablemedicalcausesoferectiledysfunctionshouldbediagnosedandtreatedpriortoinitiationof

therapywithCaverject.

Useofintracavernosalalprostadiloffersnoprotectionfromthetransmissionofsexuallytransmitteddiseases.

Individualswhousealprostadilshouldbecounselledabouttheprotectivemeasuresthatarenecessarytoguardagainst

thespreadofsexuallytransmitteddiseases,includingthehumanimmunodeficiencyvirus(HIV).Insomepatients,

injectionofCaverjectcaninduceasmallamountofbleedingatthesiteofinjection.Inpatientsinfectedwithblood-

borndiseases,thiscouldincreasethetransmissionofsuchdiseasetotheirpartner.

ReconstitutedsolutionsofCaverjectareintendedforsingleuseonly,theyshouldbeusedimmediatelyandnotstored.

Containsbenzylalcoholwhichmaycausetoxicreactionsandallergicreactions.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noknowninteractions.Caverjectisnotintendedforco-administrationwithanyotheragentforthetreatmentof

erectiledysfunction.

4.6Fertility,pregnancyandlactation

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

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Generaldisordersandadministrationsiteconditions

Common:Haematomaatthesiteoftheinjection;ecchymosisatthesiteofinjection;injectionsiteoedema,flu-like

syndrome

Uncommon:Injectionsitehaemorrhage;injectionsiteinflammation;injectionsiteitching;non-generalisedweakness

NotKnown:Injectionsitesensitivity,injectionsiteswelling;irritation;

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,prostaticdisorderpainfulerection;priapism;testicularpain

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

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

Respiratory,thoracicandmediastinaldisorders

Uncommon:Nasalcongestion,cough

Skinandsubcutaneoustissuedisorders

Uncommon:Rash;diaphoresis;non-applicationsitepruritus,erythema

Vasculardisorders

Common:Hypertension

Uncommon:hypotension;vasodilation;

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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.A200microgram/mlsolutionof

phenylephrineshouldbeprepared,and0.5to1.0mlofthesolutioninjectedevery5to10minutes.Alternatively,a20

microgram/mlsolutionofadrenalineshouldbeused.Ifnecessary,thismaybefollowedbyfurtheraspirationofblood

throughthesamebutterflyneedle.

Themaximumdoseofphenylephrineshouldbe1mg,oradrenaline100micrograms(5mlofthesolution).Asan

alternativemetaraminolmaybeused,butitshouldbenotedthatfatalhypertensivecriseshavebeenreported.Ifthis

stillfailstoresolvethepriapism,urgentsurgicalreferralforfurthermanagement,whichmayincludeashuntprocedure,

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 <

1/1000

(0.01%and<0.1%)

VeryRare

<

1/10,000

(<0.01%)

NotKnown

(cannotbeestimatedfrom

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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

alprostadilismetabolizedinonepassthroughthelungs,primarilybybeta-andomega-oxidation.

Themetabolitesareexcretedprimarilybythekidneyandexcretionisessentiallycompletewithin24hours.Thereisno

evidenceoftissueretentionofalprostadiloritsmetabolitesfollowingintravenousadministration.

5.3Preclinicalsafetydata

Nonestated.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose

SodiumCitrateanhydrous

HydrochloricAcid(pHadjustment)

SodiumHydroxide(pHadjustment)

Solvent

BenzylAlcohol

WaterforInjections

6.2Incompatibilities

Carverjectisnotintendedtobemixedorco-administeredwithanyotherproducts.

6.3Shelflife

LyophilisedPowder:

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ReconstitutedSolution:

Mustbeusedimmediatelyandnotstored.

Solvent:

2years.

6.4Specialprecautionsforstorage

LyophilisedPowder:

Donotstoreabove25 o

Reconstitutedsolution:

Reconstitutedsolutionsareintendedforsingleuseonly,theyshouldbeusedimmediatelyandnotstored.

Solvent:

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

LyophilisedPowder

1x5ml,typeIPh.Eur.,clear,colourless,glassvial,withflurocoatedrubberstopperandanaluminiumoversealwith

flip-offcap.

Solvent:

1x2mltypeIPh.Eur.,clearcolourlessglasssyringe,withbutylrubberplunger.

ThepackagealsoincludesantisepticswabscontainingIsopropylalcoholBP.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forinstructionsregardingreconstitutionoftheproduct,pleaserefertosection4.2.

Afterreconstitutiontheproductisaclearsolution.Donotuseifthesolutionappearscloudyorcontainsparticles.

Caverjectisnotintendedtobemixedorcoadministeredwithanyotherproducts.Thepresenceofbenzylalcoholinthe

reconstitutionvehicledecreasesthedegreeofbindingtopackagesurfaces.Therefore,amoreconsistentproduct

deliveryisproducedwhenBacteriostaticWaterforInjectioncontainingbenzylalcoholisused.

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7MARKETINGAUTHORISATIONHOLDER

PharmaciaIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA0936/009/005

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:13 th

March1995

Dateoflastrenewal:13 th

March2010

10DATEOFREVISIONOFTHETEXT

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