CAVERJECT 20 MCG

PATIENT PACKAGE INSERT

IN ACCORDANCE WITH THE PHARMACISTS’

REGULATIONS (PREPARATIONS) - 1986

The dispensing of this medicine requires

a doctor’s prescription

Read this package insert carefully in its entirety

before using this medicine

The format of this leaflet was determined by

the Ministry of Health and its content was

checked and approved

CAVERJECT

CAVERJECT

10 mcg

20 mcg

Solution for injection

(after dissolving the powder)

Composition:

Each vial contains:

Each vial contains:

Alprostadil 10 mcg

Alprostadil 20 mcg

Inactive ingredients:

Lactose, alpha cyclodextrine,

sodium citrate, hydrochloric acid sol., sodium

hydroxide sol., benzyl alcohol, water for injection

Therapeutic group: Prostaglandins.

Therapeutic activity:

The active ingredient of this preparation causes

(rapid) vasodilation. When the

Caverject

injected, it increases blood flow to the genital

area and in this way causes an erection.

When should the preparation not be used?

Do not use this medicine if you are sensitive

to any of its ingredients or to prostaglandins.

Do not use this medicine in case of diseases

that together with the use of this preparation

are likely to cause prolonged erection

(priapism), such as sickle cell anemia, multiple

myeloma, leukemia.

Do not use this medicine in case of penile

implant or when sexual activity is inadvisable

or forbidden.

Do not take this medicine without consulting

a doctor before starting treatment:

If you are suffering, or have suffered in the past,

from impaired function of the blood system (e.g.

coagulation disorder, etc.).

Warnings:

Do not use this medicine frequently, or for a

prolonged period, without consulting a doctor.

If you are sensitive to any type of food or medicine,

inform your doctor before commencing treatment

with this medicine.

Use of this medicine may cause prolonged

erection (priapism) - rare.

Inform your doctor immediately if you experience

an erection that lasts for more than 4 hours or is

painful.

Drug interactions:

If you are taking another drug, including non-

prescription medicines and food supplements,

or if you have just finished treatment with another

medicine, inform the attending doctor, in order

to prevent hazards or lack of efficacy arising from

drug interactions, especially with regard to other

drugs that are intended for the same purpose

and with regard to anticoagulants.

Side effects:

In addition to the desired effect of the medicine,

adverse reactions may occur during the course

of taking this medicine, for example: painful

erection, pain at the injection site, local

hemorrhage. These side effects usually disappear

within a short time following the period of

adaptation to the medicine.

Side effects that require special attention:

Prolonged erection for more than 4 hours (rare):

discontinue treatment and consult a doctor

immediately!

If there is prolonged bleeding or swelling at the

injection site (rare): continue treatment and consult

a doctor.

Signs of absorption of

Caverject

: decrease in

blood pressure, dizziness, arrhythmia (rare):

consult a doctor immediately!

In the event that you experience side effects not

mentioned in this leaflet, or if there is a change

in your general health, consult your doctor

immediately.

Dosage:

Dosage is according to doctor’s instructions only!

This is

after the dose was individualized for

each patient, by injecting Caverject for the first

time at the physician’s clinic and under his

supervision.

The recommended frequency of injections is no

more than one injection a day and no more than

twice a week.

The recommended maximal dosage for injection

is 10-20 micrograms.

Do not exceed the recommended dosage.

Directions for use:

Instructions for the preparation of

Caverject 10-

20 mcg

and for its injection:

A.

Dissolving the powdered medication in the

vial:

Wash your hands thoroughly with soap and

water.

Remove the plastic cap from the powder vial.

Cleanse the rubber stopper of the vial, using

one of the swabs provided (see fig. 1).

(Pay attention: The second swab will be

needed later.) Discard the used swab into

the place designated for trash collection.

Fig. 1: Cleansing the rubber stopper of the vial.

For the blue plastic container:

Take the thick, long needle (labelled 22G1

and gray colored), keeping the needle

covered in its plastic cover. Remove the

rubber shield which is on the syringe and

attach the needle in its place (firmly!).

(see fig. 2).

It is very important to keep the needle sterile.

The needle could become contaminated from

contact with the vial, clothes, fingers, etc.

Fig. 2: Attaching the needle to the syringe.

Remove the needle’s plastic cover and put

it by your side, at hand’s reach.

Keep holding the syringe and the base of the

needle in one hand together. With the other

hand, push the syringe plunger to the 1 ml

mark. (This will get rid of any excess air in

the syringe).

Pierce the needle through the central portion

of the rubber stopper of the vial. With the

syringe positioned above the vial, inject the

water into the vial by pushing on the plunger

until the syringe is emptied (see fig. 3).

Fig. 3: Injecting water from the syringe

into the vial.

Carefully holding the syringe and vial steady

as a unit, gently shake the vial until the

powdered medication dissolves completely.

Do not use if the resulting solution is cloudy

or colored, or if it contains undissolved

particles.

B.

Withdrawing the medication into the syringe

To withdraw the medication, turn the vial

upside down so that the syringe is facing

downwards. Making sure to keep the tip of

the needle below the level of the fluid, slowly

withdraw the plunger out of the syringe until

the amount of solution is the desired one as

recommended by your doctor.

10. If there are air bubbles in the syringe, tap the

syringe gently to expel the air, or inject the

solution back into the vial and slowly withdraw

again (see fig. 4).

Fig. 4: Tapping the syringe to remove air bubbles.

11. Remove the syringe with the needle from the

vial and carefully replace the plastic needle

cover on the needle.

12. Open the package of the short, thin needle

(labelled 27G

and white colored) without

removing the plastic needle cover, and put it

by your side, at hand’s reach.

13. Carefully remove the long needle, covered

in plastic, from the syringe and discard it to

the place designated for trash collection.

14. Holding the syringe in one hand, with the

other hand take the short needle from its

open packet, keeping the plastic needle cover

in place, and attach it to the syringe in the

same way that you attached the long needle.

C.

Self-injecting the medication

For your attention! The first injection of

Caverject

must be done under the supervision

of the attending doctor. The medication is to

be injected into either of two areas of the

penis called the corpora cavernosa (see fig.

5 and 6).

Fig. 5: Cross-section of the penis

showing injection sites.

Fig. 6: Top view of penis showing injection sites.

15. Perform the self-injection procedure while

sitting.

16. Use only the injection areas shown in fig. 5

and 6. Each time you use

Caverject

inject

into a different side of the penis. Even when

injecting into the same area, the actual point

of injection should be changed each time so

that the medicine will be inserted at different

places in the same area.

17. Using the thumb and forefinger, grasp the

head of the penis and stretch the penis until

it is taut so that it will not slip during the

injection. (In uncircumcised men the foreskin

must be retracted to assure proper placement

of the injection).

18. Clean the injection area thoroughly with the

unused alcohol swab. Put the swab by your

side, at hand’s reach.

19. Hold the syringe between thumb and index

finger. (Do no put your thumb on the plunger).

Insert the needle at a 90-degree angle into

the injection site (see fig. 7).

Avoid visible blood vessels.

Fig. 7: Inserting the needle into the injection site.

20. Using your thumb or forefinger press the

plunger towards the bottom of the syringe,

slowly injecting the entire contents of the

syringe (see fig. 8). Avoid any motion during

the injection.

Fig. 8: Injecting the contents of the syringe.

21. Withdraw the needle from your penis.

Continue to apply pressure from both sides

of the penis for about three minutes with the

help of the alcohol swab which you used to

disinfect the injection site. If bleeding occurs,

maintain pressure until the bleeding stops.

22. After using the contents of this pack, gather

all of the materials safely, including needles

in their plastic cover, and insert carefully into

blue plastic

Caverject

container. Remove

the red plastic locking device from the

container. Close the container firmly so that

it snaps shut. To lock the container, push the

red locking device completely into the center

of the lid, where a picture of a lock appears.

The locked container should be discarded.

Avoid poisoning!

This medicine, and all other medicines, must be

stored in a safe place out of the reach of children

and/or infants, to avoid poisoning. If you have

taken an overdose, or if a child has accidentally

swallowed the medicine, proceed immediately

to a hospital emergency room and bring the

package of the medicine with you.

Do not induce vomiting unless explicitly instructed

to do so by a doctor! This medicine has been

prescribed for the treatment of your ailment; in

another patient it may cause harm.

Do not give this medicine to your relatives,

neighbours or acquaintances.

Do not take medicines in the dark! Check the

label and the dose each time you take your

medicine. Wear glasses if you need them.

Storage:

Before reconstitution: Store the preparation at

room temperature (up to 25

The preparation for immediate use after

reconstitution.

Even if kept in their original container and stored

as recommended, medicines may be kept for a

limited period only. Please note the expiry date

of the medicine! In case of doubt, consult the

pharmacist who dispensed the medicine to you.

Do not store different medications in the same

package.

License numbers: 101082.8542, 68132.8275

Manufacturer:

Pfizer NV/SA, Belgium.

License holder:

Pfizer PFE Pharmaceuticals Israel Ltd.,

9 Shenkar St., Herzeliya Pituach 46725.

PrescribingInformation

Caverject    

Alprostadil

Composition

-CAVERJECT  10 µ g

Eachpowdervialcontains:

Alprostadil10 µ g-lactose-sodiumcitrate.WhennecessarypHwasadjustedwithsodium

hydroxideand/orhydrochloricacid.

Eachmlofdiluentcontains:

Benzylalcohol-waterforinjectionq.s.1ml.

-CAVERJECT  20 µ g

Eachpowdervialcontains:

Alprostadil20 µ g-lactose-sodiumcitrate.WhennecessarypHwasadjustedwithsodium

hydroxideand/orhydrochloricacid.

Eachmlofdiluentcontains:

Benzylalcohol-waterforinjectionq.s.1ml.

Forms,waysofadministrationandpackages

Pharmaceuticalformafterreconstitution:injectablesolution.

Wayofadministration:intracavernosal.

Packages:

-Vialwith10 µ galprostadil+pre-filledsyringewith1mlbacteriostaticwaterforinjection+2

needles(22G1½and27G½).

-Vialwith20 µ galprostadil+pre-filledsyringewith1mlbacteriostaticwaterforinjection+2

needles(22G1½and27G½).

Properties

PHARMACODYNAMICS

Alprostadilispresentinvariousmammaliantissuesandfluids.Ithasadiversepharmacologic

profile,amongwhichsomeofitsmoreimportanteffectsarevasodilation,inhibitionofplatelet

aggregation,inhibitionofgastricsecretion,andstimulationofintestinaluterinesmooth

muscle.Thepharmacologiceffectofalprostadilinthetreatmentoferectiledysfunctionis

presumedtobemediatedbyinhibitionofalpha

-adrenergicactivityinpeniletissueandbyits

relaxingeffectoncavernosalsmoothmuscle.

PHARMACOKINETICS

Thepharmacokineticsofintravenouslyadministeredalprostadilhavebeenextensively

studied.Whenadministeredintravenouslytoman,alprostadilisrapidlytransformedto

relativelyinactivemetabolites.Inhealthymen,70%to90%ofalprostadilisextensively

extractedandmetabolizedinasinglepassthroughthelungs,resultinginametabolichalf-life

oflessthanoneminute.Afterintracavernosaladministration,levelsofalprostadilandits

primarymetabolite15-oxo-13,14,-dihydro-PGE

areelevatedinthecavernosa.Nointact

alprostadilisdetectedintheperipheralcirculation,andlevelsofthe15-oxo-13,14,-dihydro-

1 metabolitearenotsignificantlyelevatedintheperipheralcirculationafter

intracavernosaladministration.

Indications

a.Intracavernosalalprostadil(CAVERJECT  )isindicatedforthetreatmentoferectile

dysfunctionduetoneurogenic,vasculogenic,psychogenic,ormixedetiology.

b.Intracavernosalalprostadil(CAVERJECT  )maybeausefuladjuncttootherdiagnostic

tests inthediagnosisoferectiledysfunction.

Dosageandadministration

CAVERJECT  isadministeredbydirectintracavernosalinjection.A½-inch,27-to30-gauge

needleisgenerallyrecommended.

ThedoseofCAVERJECT  shouldbeindividualizedforeachpatientbycarefultitrationunder

supervisionbythephysician.Inclinicalstudies,patientsweretreatedwithCAVERJECT  in

dosesrangingfrom0.2to20micrograms;however,since99%ofpatientsreceiveddosesof

20microgramsorless,dosesofgreaterthan20microgramsarenotrecommended.In

general,thelowestpossibleeffectivedoseshouldalwaysbeemployed.

INITIALTITRATIONINPHYSICIAN’SCLINIC

Thefollowingtitrationscheduleshouldbefollowed,dependingonerectileresponse,untilthe

dosethatproducesanerectionsuitableforintercourseandnotexceedingadurationof60

minutesisreached.Ifthereisnoresponsetotheadministereddose,thenthenexthigher

dosemaybegivenwithin1hour.Ifthereisaresponse,thenthereshouldbeatleasta1-day

intervalbeforethenextdoseisgiven.Thepatientmuststayinthephysician’sclinicuntil

completedetumescenceoccurs.

Neurogenicetiology(spinal

cordinjury) Vasculogenic,

psychogenic,

ormixedetiology

Startingdosetoinject

Seconddosetoinject

Thirddosetoinject

Additionalincrements

increasesuntiloptimal

doseisachieved

1.25mcg

2.5mcg

5.0mcg

5.0mcg 2.5mcg

Partialresponse:5.0mcg

Noresponse:7.5mcg

5.0-10.0mcg

MAINTENANCETHERAPY

ThefirstinjectionsofCAVERJECT  mustbedoneatthephysician’sclinicbymedically

trainedpersonnel.

Self-injectiontherapybythepatientcanbestartedonlyafterthepatientisproperlyinstructed

andwelltrainedintheself-injectiontechnique.Thephysicianshouldmakeacareful

assessmentofthepatient’sskillsandcompetencewiththisprocedure.Theintracavernosal

injectionmustbedoneundersterileconditions.Thesiteofinjectionisusuallyalongthe

dorso-lateralaspectoftheproximalthirdofthepenis.Visibleveinsshouldbeavoided.The

sideofthepenisthatisinjectedandthesiteofinjectionmustbealternated;theinjectionsite

mustbecleansedwithanalcoholswab.

Self-injectiontherapyforuseathomeshouldbeinitiatedatthedosethatwasdeterminedin

thephysician’sclinic.Thedosethatisselectedforself-injectiontreatmentshouldprovidethe

patientwithanerectionthatissatisfactoryforsexualintercourse,andmaintainedforno

longerthan60minutes.Ifthedurationoferectionislongerthan60minutesthedoseshould

bereduced.Carefulandcontinuousfollow-upofthepatientwhileintheself-injectionprogram

mustbeexercised.Thisisespeciallytruefortheinitialself-injections,sinceadjustmentsinthe

CAVERJECT  dosemaybeneeded.Doseadjustment,ifrequired,shouldbemadeonlyafter

consultationwiththephysician,andshouldbeadjustedinaccordancewiththetitration

guidelinesdescribedabove.(Upto57%ofpatientsinoneclinicalstudyrequireddose

adjustment).Whileonself-injectiontreatment,itisrecommendedthatthepatientvisitsthe

prescribingphysician’sclinicevery3months.Atthattime,theefficacyandsafetyofthe

therapyshouldbeassessed,andthedoseofCAVERJECT  shouldbeadjusted,ifneeded.

Therecommendedfrequencyofinjectionisnomorethanoncedailyandnomorethanthree

timesweekly.ThereconstitutedvialofCAVERJECT  isintendedforsingleuseonlyand

shouldbediscardedafteruse.Theusershouldbeinstructedintheproperdisposalofthe

syringe,needle,andvial.

Oncereconstituted,noadditionalmaterialsshouldbeinjectedintothevial.Theproduct

shouldbeinspectedvisuallyforparticulatematteranddiscolorationpriortoadministration.

CAVERJECT  ASANADJUNCTTOTHEDIAGNOSISOFERECTILEDYSFUNCTION

Inthesimplestdiagnostictestforerectiledysfunction(pharmacologictesting),patientsare

monitoredfortheoccurrenceofanerectionafteranintracavernosalinjectionof

CAVERJECT  .ExtensionsofthistestingaretheuseofCAVERJECT  asanadjunctto

laboratoryinvestigations,suchasduplexorDopplerimaging, 133

Xenonwashouttests,

radioisotopepenogram,andpenilearteriography,toallowvisualizationandassessmentof

penilevasculature.Foranyofthesetests,asingledoseofCAVERJECT  thatinducesan

erectionwithfirmrigidityshouldbeused.

DILUTIONANDSELF-INJECTIONPROCEDUREUSINGTHEPRE-FILLEDDILUENT

SYRINGEWITHDETACHEDNEEDLE

Thisguideisnotmeanttosubstitutefortheadviceandcounselofyourdoctor.

1.Washyourhandswithsoapandwater.

2. Removetheplasticcapfromthevial.

3. Wipetherubberstopperofthevial,usingoneoftheswabsprovided(thesecondswabis

neededlater).Discardtheusedswab.

Wipingtherubberstopperofavial(DIAGRAM1)

4.Unwrapthelargerneedle(labelled22G1½),keepingitsplasticneedlecoverinplace.

Joinittothesyringebyslippingthecollaroftheneedleovertheneckofthesyringeand

pushingfirmly.

Joiningtheneedle

tothesyring(DIAGRAM2)

5.Carefullyremovetheneedlecover.

6.Holdingthesyringeandtheneedlepointingupward,pushtheplungertothe1mlmarkon

thesyringe.(Thiswillgetridofanyexcesswaterinthesyringe).

7.Piercetheneedlethroughthecenterportionoftherubberstopperofthevial,andthen

pushdowntheplungertoinjectthewaterintothevial.

Injectingbacteriostaticwaterintothevial(DIAGRAM3)

8.Carefullyholdingthesyringeandvialasaunit,gentlyswirluntilthepowdered

medicationdissolvescompletely.DONOTUSEiftheresultingsolutioniscloudyor

colored,oritcontainsparticles.

WITHDRAWINGTHEMEDICATION

1.Towithdrawthemedication,turnthevialupsidedownwiththesyringeinplace.Making

suretokeepthetipoftheneedlebelowthelevelofthefluid,slowlywithdrawtheplunger

ofthesyringeuntiltheamountofsolutionislevelwiththelinerecommendedbyyour

doctor.

2. Ifthereareairbubblesinthesyringe,tapthesyringegentlytoexpeltheair,orinjectthe

solutionbackintothevialandslowlywithdrawagain.

Tappingthesyringetoremoveairbubbles(DIAGRAM4)

3. Removetheneedlefromthevialandcarefullyreplacetheneedlecoverontheneedle.

4. Openthepackagingofthesmallerneedle(labelled27G½),withoutremovingtheneedle,

andputittooneside.

5. Removethelargeneedleandcapfromthesyringeanddiscard.

6. Holdingthesyringeinonehand,takethesmallerneedlefromitsopenpacket,keeping

theplasticneedlecoverinplace,andjoinittothesyringeinthesamewaythatyouput

onthelargeneedle.

SELF-INJECTINGTHEMEDICATION

DIAGRAMA

Cross-sectionofthepenisshowinginjectionsitesVeins,Arteries,NervesCorpora

Cavernosa(both)

Injectionsites:NeedlecorrectlyenteringoneoftheCorporaCavernosaUrethra

DIAGRAMB

TopviewofpenisshowinginjectionsitesInjectionsites

Themedicationistobeinjectedintoeitheroftwoareasofthepeniscalledthecorpora

cavernosa.

1. Performtheself-injectionprocedurewhilesittinginanuprightorslightlyreclining

position.

2. UseonlytheinjectionareasshownindiagramsAandB.

AlternatetheinjectionsiteseachtimeyouuseCAVERJECT  :chooseonesideforthis

injection,usetheothersidenexttime,andsoon.Withineitherarea,theactualpointof

injectionshouldbechangedeachtime.

3. Grasptheheadofyourpeniswithyourthumbandforefinger.Stretchyourpenistautly

andholditfirmlyagainstyourthighsothatitdoesnotslipduringtheprocedure.In

uncircumcisedmentheforeskinmustberetractedtoassureproperplacementofthe

injection.

4. Cleantheinjectionareathoroughlywiththeunusedalcoholswab.Puttheswabtoone

side.

5. Holdthesyringebetweenyourthumbandindexfinger.Donotputyourthumbonthe

plunger.Withasteady,continuousmotion,inserttheneedleata90-degreeangleinto

theinjectionsiteasdirectedbyyourdoctor.

Avoidvisiblebloodvessels.

Insertingtheneedleintotheinjectionsite(DIAGRAM7)

6. Moveyourthumborforefingertothetopoftheplungerandpressdown.Injecttheentire

contentsofthesyringeinaslow,steadymotion.

Injectingthecontentsofthesyringe(DIAGRAM8)

7. Withdrawtheneedlefromyourpenis.Squeezingbothsidesofthepenis,applypressure

withthealcoholswabtotheinjectionsiteforabout3minutes.Ifbleedingoccurs,

maintainpressureuntilthebleedingstops.

8. Afterusingthecontentsofthispack,disposeofallmaterialssafely.

Yourpharmacistmaybeabletosupplyadisposalboxespeciallyforsyringes.Ifnot,the

plasticCAVERJECT  packmaybeusedasfollows:puttheusedsyringe,needlesand

vialintotheplasticCAVERJECT  container.Thenremovetheredplasticlockingdevice

fromthecontainerandplacetooneside.Closethecontainerfirmlysothatitsnapsshut.

RemovetheperforatedcenterportionoftheCAVERJECT  labeltouncoverakeyway.

Tolockthecontainershut,pushtheredlockingdevicecompletelyintothekeyway.Once

thelockingdeviceisinposition,theCAVERJECT  containerwillbepermanentlyclosed

andcannowbediscardedsafely.Becauseitcontainstheusedsyringe,needlesand

vials,itshouldnotberecycled.

Contra-indications

CAVERJECT  shouldnotbeusedinpatientswhohaveaknownhypersensitivitytothedrug

ortootherprostaglandins,orinpatientswhohaveconditionsthatmightpredisposethemto

priapism,suchassicklecellanemiaortrait,multiplemyeloma,orleukemia,orinpatientswith

anatomicaldeformationofthepenis,suchasangulation,cavernosalfibrosis,orPeyronie’s

disease.PatientswithpenileimplantsshouldnotbetreatedwithCAVERJECT  .

CAVERJECT  shouldnotbeusedinwomenorchildrenandisnotforuseinnewborns.

CAVERJECT  shouldnotbeusedinmenforwhomsexualactivityisinadvisableor

contraindicated.

Adversereactions

Thefollowingadversereactionsinformationwasobtainedfromclinicalstudiessponsoredby

Upjohninvolving1712patientstreatedwithCAVERJECT  .

ThemostfrequentadversereactionafterintracavernosalinjectionofCAVERJECT  ispenile

pain.Instudies,34%ofthepatientsreportedpenilepainduringerectionatleastonce,

however,thiseventwasassociatedwithonly11%oftheadministeredinjections.Inthe

majorityofthecases,burningsensationortensioninthepeniswasratedmildormoderatein

intensity.Threepercentofpatientsdiscontinuedtreatmentbecauseofpenilepain.

Hematomaatthesiteofinjection,whichisrelatedtotheinjectiontechniqueratherthantothe

effectsofalprostadil,occursin3%ofpatients.

Thefrequencyofprolongederection(definedasanerectionthatlastsfor4hours)was2%.

Thefrequencyofpriapism(definedasanerectionthatlasts4hoursorlonger)was0.5%.In

themajorityofcases,spontaneousdetumescenceoccurred.

Thefollowinglocaladversereactionsoccurredin1.0-1.5%ofpatients:injectionsite

ecchymosis,penilerash,penileedema,andpenilefibrosis.Thefollowinglocaladverse

reactionswerereportedbyfewerthan1%ofpatients:balanitis,injectionsitehemorrhage,

injectionsiteinflammation,injectionsiteitching,injectionsiteswelling,urethralbleeding,and

penilewarmth,numbness,yeastinfection,irritation,sensitivity,phimosis,pruritus,erythema,

venousleak,painfulerection,andabnormalejaculation.Intermsofsystemicevents,the

followingwerereportedforfewerthan1%ofpatientsinclinicalstudies,andwerejudgedto

bepossiblyrelatedtoCAVERJECT  use:testicularpain,testicularswelling,scrotal

erythema,painortightness,urinaryfrequency,urinaryurgency,impairedurination,

hypotension,vasodilatation,hypertension,supraventricularextrasystole,peripheralvascular

disorder,dizziness,hypesthesia,buttockweakness,localizedpain(buttockspain,legpain,

genitalpain,abdominalpain),headache,pelvicpain,backpain,flusyndrome,cardiac

arrhythmias,shockandcollapse.

Hemodynamicchanges,manifestedasdecreasesinbloodpressureandincreasesinpulse

rate,wereobservedduringclinicalstudies,principallyatdosesabove20microgramsand

above30microgramsofCAVERJECT  ,respectively,andappearedtobedose-dependent.

Onlythreepatients(0.2%)discontinuedthetreatmentbecauseofsymptomatichypotension.

CAVERJECT  hadnoclinicallyimportanteffectonserumorurinelaboratorytests.

Specialprecautions

a.Priapism(erectionlastingover4hours)isknowntooccurfollowingintracavernosal

administrationofvasoactivesubstances,includingCAVERJECT  .Thepatientshouldbe

instructedtoimmediatelyreporttohisphysiciananyerectionthatpersistsforlongerthan4

hours.Treatmentofpriapismshouldbeaccordingtoestablishedmedicalpractice.

b.Painfulerectionismorelikelytooccurinpatientswithanatomicaldeformationsofthe

penis,suchasangulation,phimosis,cavernosalfibrosis,Peyronie’sdiseaseorplaques.

TreatmentwithCAVERJECT  shouldbediscontinuedinpatientswhodeveloppenile

angulation,cavernosalfibrosis,orPeyronie’sdisease.

c.Patientsonanticoagulantssuchaswarfarinorheparinmayhaveincreasedpropensityfor

bleedingafterintracavernosalinjection.

d.Underlyingtreatablemedicalcausesoferectiledysfunctionshouldbediagnosedpriorto

initiationoftherapywithCAVERJECT  .

e.UseofCAVERJECT  offersnoprotectionfromthetransmissionofsexuallytransmitted

diseases.IndividualswhouseCAVERJECT  shouldbecounselledabouttheprotective

measuresthatarenecessarytoguardagainstthespreadofsexuallytransmitteddiseases,

includingthehumanimmunodeficiencyvirus(HIV).

Incompatibilities

CAVERJECT  isnotintendedtobemixedorcoadministeredwithanyotherproducts.

Thepresenceofbenzylalcoholinthereconstitutionvehicledecreasesthedegreeofbinding

topackagesurfaces.Therefore,amoreconsistentproduct/deliveryisproducedwhen

bacteriostaticwaterforinjectioncontainingbenzylalcoholisused.

Interactions

Noknowninteractions.CAVERJECT  isnotintendedforcoadministrationwithanyother

agentforthetreatmentoferectiledysfunction.

Pregnancyandlactation

Notapplicable.

Abilitytodriveandtooperatemachinery

Notapplicable.

Overdosage

Inman,prolongederectionand/orpriapismareknowntooccurfollowingintracavernosal

administrationofvasoactivesubstances,includingalprostadil.Thetreatmentofpriapismmay

includedifferentapproachessuchasaspiration,intracavernosalinjectionofsympathomimetic

aminesorsurgery.Patientsshouldbeinstructedtoreporttoaphysiciananyerectionlasting

foraprolongedtimeperiod,suchas4hoursorlonger.

Storage

Storeatroomtemperatuebelow25 o

C.

Forimmediateuseafterreeconstitution.

Theexpirydate(month/year)ismentionedonthepackageafter“EXP.”(EXP.+expirydate).

Dispensing

Onmedicalprescriptiononly.

Manufacturer:PfizerManufacturingBelgiumNV/SA.

LicneseHolder:PfizerPharmaceuticalsIsraelLtd.,9ShenkarSt.,HerzliaPituach46725.

TheformatofthisinsertwasdeterminedbytheMinistryofHealthanditscontentwas

checkedandapprovedinMay2011.