CATHATE 0.625 Milligram Coated Tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
ESTROGENS CONJUGATED
Available from:
Pfizer Healthcare Ireland
INN (International Name):
ESTROGENS CONJUGATED
Dosage:
0.625 Milligram
Pharmaceutical form:
Coated Tablets
Prescription type:
Product subject to prescription which may not be renewed (A)
Authorization status:
Transfer Pending
Authorization number:
PA0822/091/001
Authorization date:
0000-00-00

PACKAGELEAFLET:INFORMATION FOR THEUSER

Cathate0.625mgCoatedTablets

(conjugatedestrogens)

Readallofthis leafletcarefullybefore youstarttakingthis medicinebecause itcontains important

informationforyou.

Keep this leaflet. You mayneedto read itagain.

Ifyou haveanyfurtherquestions, askyourdoctororpharmacist.

Thismedicinehasbeen prescribed foryouonly. Donotpassiton to others. Itmayharmthem,

even iftheirsignsofillnessare thesame as yours.

Ifyou getanysideeffects, talkto yourdoctororpharmacist. Thisincludesanypossibleside

effectsnotlisted in thisleaflet.

Whatisinthis leaflet:

1.WHATCATHATEISANDWHATITISUSED FOR

2.WHATYOU NEED TO KNOWBEFOREYOU TAKECATHATE

3.HOWTO TAKECATHATE

4.POSSIBLE SIDE EFFECTS

5.HOWTO STORECATHATE

6.CONTENTSOFTHEPACKAND OTHERINFORMATION

1.WHATCATHATEISAND WHATITISUSEDFOR

Cathate is a Hormone ReplacementTherapy(HRT).Itcontainsthefemale hormoneestrogen. Cathateis

used to treatsomeofthesymptomsand conditionsassociated withthemenopause.

Cathateisusuallyprescribed forwomen who havehad theirwombremoved(hysterectomy).However

women who havenothad thisoperation can stilltakeCathateand theirdoctormayprescribeasecondtype

oftabletcontaininganotherhormonecalledaprogestogentobetaken12-14dayspermonthaswellasthe

Cathate tablets.

Cathate is used for:

Reliefofsymptoms occuring after menopause

Duringthemenopause, theamountoftheestrogen produced byawoman’sbodydrops. Thiscan cause

symptoms such as hotface, neckand chest("hotflushes"). Cathate alleviates these symptoms after

menopause. You willonlybeprescribed Cathateifyoursymptomsseriouslyhinderyourdailylife.

Preventionofosteoporosis

Afterthemenopausesomewomen maybeatriskofdevelopingfragilebones(osteoporosis). You should

discussallavailabletreatmentoptionswith yourdoctor.

Ifyou are atan increased riskof fractures dueto osteoporosis and othermedicines are notsuitablefor

you, you can useCathateto preventosteoporosisaftermenopause.

2.WHATYOU NEEDTOKNOWBEFOREYOU TAKECATHATE

Medicalhistory andregularcheck-ups

Theuse of HRTcarries risks whichneedtobeconsideredwhendecidingwhethertostart takingit,or

whetherto carryon takingit.

Theexperience in treatingwomen with apremature menopause (dueto ovarian failure or surgery)is

limited. Ifyou have a premature menopause therisks of usingHRTmaybedifferent. Please talkto your

doctor.

Beforeyoustart(orrestart)HRT,yourdoctorwillaskaboutyourown and yourfamily’smedicalhistory.

Yourdoctormaydecidetoperformaphysicalexamination. Thismayincludeanexaminationofyour

breastsand/oran internalexamination, ifnecessary.

Onceyouhavestartedon Cathateyou should seeyourdoctorforregularcheck-ups(atleastonce a year).

Atthese check-ups, discusswith yourdoctorthebenefitsand risksofcontinuingwith Cathate.

Go for regularbreastscreening, as recommended byyourdoctor.

2.1 Do nottakeCathate

ifanyofthefollowingappliesto you. Ifyou arenotsureaboutanyofthepointsbelow,talkto yourdoctor

before takingCathate.

Donottake Cathate:

Ifyou haveorhaveeverhadbreastcancer, orifyou aresuspected ofhavingit.

Ifyou havecancerwhichissensitivetoestrogens,suchascancerofthewomblining

(endometrium)orifyou aresuspected ofhavingit.

Ifyou haveanyunexplained vaginalbleeding.

Ifyou haveexcessivethickeningofthewomb lining(endometrialhyperplasia)thatisnotbeing

treated.

Ifyouhave or have everhadabloodclotina vein(thrombosis),suchas inthelegs (deepvein

thrombosis)orthelungs(pulmonaryembolism).

Ifyou haveabloodclotting disorder(suchasprotein C, protein Sorantithrombin deficiency).

Ifyouhave or recentlyhave hada disease causedbybloodclotsinthearteries,suchasaheart

attack, strokeorangina.

Ifyouhave or have everhadaliver diseaseand yourliverfunction testshavenotreturned to

normal.

Ifyou areallergic(hypersensitive)toconjugatedestrogensoranyoftheotheringredientsof

Cathatetablets(listed in Section 6).

Ifyou havearareblood problemcalled “porphyria”which ispassed down in families(inherited).

Ifyou knoworsuspectyou arepregnant, oryou arebreast-feeding.

IfanyoftheaboveconditionsappearforthefirsttimewhiletakingCathate, stop takingitatonceand

consultyourdoctorimmediately.

Warning and precautions

Tellyourdoctorifyou haveeverhad anyofthefollowingproblems, beforeyou startthetreatment, as

thesemayreturn orbecomeworseduringtreatmentwith Cathate. Ifso, you should seeyourdoctormore

often forcheck-ups:

fibroidsinsideyourwomb

growth ofwomb liningoutsideyourwomb (endometriosis)orahistoryofexcessivegrowth of

thewomb lining(endometrialhyperplasia)

increased riskof developingblood clots (see section2.3 Bloodclotsina vein(thrombosis)for

more detail)

increased riskof gettinga estrogen-sensitive cancer(such as havinga mother, sisteror

grandmotherwho has had breastcancer)

high blood pressure

aliverdisorder, such asabenign livertumour

diabetes

gallbladderdisease or gallstones

migraineor severe headaches

adiseaseof theimmunesystemthataffects manyorgansofthebody(systemiclupus

erythematosus, SLE)

epilepsy

asthma

a disease affectingtheeardrumand hearing(otosclerosis)

averyhigh leveloffatin yourblood (triglycerides)

fluid retention dueto cardiacorkidneyproblems

hypocalcaemia (lowcalciumlevels)

thyroid deficiency

Stoptaking Cathateandseea doctorimmediately

Ifyou noticeanyofthefollowingwhen takingHRT:

anyoftheconditionsmentioned in the“Do nottakeCathate” section

yellowingofyourskinorthe whites ofyoureyes (jaundice).These maybe signs ofa liverdisease

a large rise inyourbloodpressure (symptoms maybe headache,tiredness,dizziness)

migraine-like headaches whichhappenforthe firsttime

ifyou becomepregnant

havean allergicreaction, signsofwhich includearash, itching, shortnessofbreath,difficultyin

breathinganda swollenface

ifyou noticesignsofablood clot, such as:

opainfulswellingand rednessofthelegs

osudden chestpain

odifficultyin breathing

Formoreinformation,see section2.3BloodClotsina vein(thrombosis).

Note: Cathateisnotacontraceptive. Ifitislessthan 12 monthssinceyourlastmenstrualperiod oryou

areunder50 yearsold, you maystillneed to useadditionalcontraception to preventpregnancy. Speakto

yourdoctorforadvice.

2.2 HRTandcancer

Excessive thickeningoftheliningofthewomb(endometrialhyperplasia)andcanceroftheliningof

the womb(endometrialcancer)

Takingestrogen-onlyHRTwillincrease theriskof excessive thickeningof theliningof thewomb

(endometrialhyperplasia)and cancerofthewomb lining(endometrialcancer).

Takingaprogestogen in addition to theestrogen foratleast12 daysofeach 28 daycycleprotectsyou

fromthisextrarisk. So yourdoctorwillprescribeaprogestogen separatelyifyou stillhaveyourwomb.

Ifyou havehad yourwomb removed (ahysterectomy), discusswith yourdoctorwhetheryou can safely

takethisproductwithoutaprogestogen.

In women who stillhaveawomb and who arenottakingHRT, onaverage,5in1000willbediagnosed

with endometrialcancerbetween theagesof50 and 65.

Forwomen aged 50 to 65 who stillhaveawomb and who takeestrogen-onlyHRT, between 10 and 60

women in 1000 willbediagnosed with endometrialcancer(i.e. between 5 and 55 extracases), depending

on thedoseand forhowlongitistaken.

Cathate containsa higherdose of estrogensthan otherestrogen-onlyHRTproducts. Theriskof

endometriumcancerwhen usingCathatetogetherwith aprogestogen isnotknown.

Ifyoustillhaveyourwomb, yourdoctor mayprescribea progestogen as wellas estrogen. Ifso, these

maybeprescribed separately, oras a combined HRTproduct.

Ifyouhavehadyourwombremoved(a hysterectomy), yourdoctorwilldiscusswith you whetheryou

can safelytake estrogen withouta progestogen.

Ifyou’vehadyour wombremovedbecause ofendometriosis, anyendometriumleftin yourbodymay

beatrisk. So yourdoctormayprescribeHRTthatincludes a progestogen as wellas an estrogen.

Yourproduct, Cathate, isan estrogen-onlyproduct.

Irregular bleeding

Youmayhave irregularbleedingordropsofblood (spotting)duringthefirst3-6 monthsoftakingCathate.

Howeverifthe irregularbleeding:

carrieson formorethan thefirst6 months

startsafteryou havebeen takingCathateformorethan 6 months

carries on afteryou have stopped takingCathate

see your doctorassoonaspossible.

BreastCancer

Womenwho havebreastcancer, orhavehadbreastcancer inthe past, shouldnot take HRT.

Evidence suggests thattakingcombined estrogen-progestogen and possiblyalso estrogen-onlyHRT

increases theriskof breastcancer. Theextra riskdependson howlongyou take HRT. Theadditionalrisk

becomes clearwithin afewyears. However, itreturnsto normalwithin afewyears (atmost5) after

stoppingtreatment.

Forwomen who havehad theirwomb removed and who areusingestrogen-onlyHRTfor5 years, little

or no increase in breastcancerriskis shown.

Yourriskof breastcanceris also higher:

ifyou have a close relative (mother, sisteror grandmother)who has had breastcancer

ifyou are seriouslyoverweight.

Compare

Women aged 50 to 79who arenottakingHRT,on average,9 to 17in 1000willbediagnosed with breast

cancerovera 5-yearperiod. Forwomen aged 50 to 79 who aretakingestrogen-progestogen HRTover5

years, therewill be13 to 23cases in 1000 users (i.e. an extra 4 to 6 cases).

Regularly checkyour breasts. See your doctorifyounoticeany changessuchas:

dimplingoftheskin

changesin thenipple

anylumpsyou can see or feel.

OvarianCancer

Ovarian cancer(cancerof theovaries)is rare, butitis serious. Itcan bedifficultto diagnose, because

thereareoften no obvioussignsof thedisease.

Aslightlyincreased riskof ovarian cancerhas been reported in women takingHRTfor atleast5 to 10

years. Women aged 50 to 69 who arenottakingHRT, on averageabout2 women in 1000 willbe

diagnosed with ovarian cancerovera 5-yearperiod. Forwomen who havebeen takingHRTfor5 years,

there willbebetween 2 and 3 cases per1000 users (i.e. up to 1 extra case).

2.3Effects ofHRTon yourheartandcirculation

Bloodclotsin a vein (thrombosis)

Theriskofbloodclotsin theveins(also calleddeep vein thrombosis, orDVT), isabout1.3 to 3-times

higherin HRTusersthan in non-users, especiallyduringthefirstyearof takingit.

Blood clotscan beserious, and ifonetravelsto thelungs, itcan causechestpain, breathlessness, fainting

oreven death. Thiscondition iscalledpulmonaryembolism, orPE.

DVTand PEare examples of a condition calledvenousthromboembolism, orVTE.

You aremorelikelyto getablood clotin yourveinsasyou getolderand ifanyofthefollowingapplies

to you. Informyourdoctorifanyofthesesituationsappliesto you:

you are unable to walkfor a longtime because of major surgery, injuryor illness (see also

section 3, Ifyou need to havesurgery)

you are seriouslyoverweight(BMI>30 kg/m 2 )

you haveanyblood clottingproblemthatneedslong-termtreatmentwith amedicineused to

preventblood clots

ifanyofyourcloserelativeshaseverhad ablood clotin theleg, lungoranotherorgan

you haveanyblood clottingproblemthatneedstreatmentwith amedicineused to preventblood

clots

you have systemic lupuserythematosus(SLE)

you have cancer

you arepregnantorhaverecentlyhad ababy.

For signsof a blood clot, see “Stop takingCathate and see a doctor immediately”.

Compare

Lookingatwomen in their50swho arenottakingHRT, on average, overa 5-yearperiod, 4 to 7in 1000

would beexpected to getablood clotin avein.

Forwomen in their50swho havebeentakingestrogen-progestogen HRTforover5 years, therewill be9

to 12 cases in 1000 users (i.e. an extra 5 cases).

Forwomen in their50swho havehad theirwomb removed and havebeen takingestrogen-onlyHRTfor

over5 years, there willbe5 to 8 cases in 1000 users (i.e. 1 extra case).

HeartDisease (heartattack)

HRTis not recommendedforwomenwho haveheartdisease, orhavehadheartdisease recently.If

you haveeverhad heartdisease, talkto yourdoctorto seeifyou should betakingHRT.

There is no evidence that HRTwillpreventa heartattack.

Women overtheage of 60 who use estrogen-progestogen HRTare slightlymore likelyto develop heart

disease than those nottakinganyHRT.

Forwomen who havehad theirwomb removed and aretakingestrogen-onlytherapythere is no increased

riskofdevelopingaheartdisease.

Ifyouget:

apain in yourchestthatspreadsto yourarmorneck

Seea doctorassoonaspossibleanddo nottakeany moreHRTuntilyourdoctorsays

you can. Thispain could beasign ofheartdisease.

Stroke

Theriskofgettingstrokeisabout1.5 timeshigherin HRTusersthan in non-users. Thenumberofextra

cases of stroke dueto use of HRTwillincrease with age.

Otherthings thatcan increase theriskof stroke include:

gettingolder

high blood pressure

smoking

drinkingtoo much alcohol

an irregularheartbeat.

Ifyouareworriedaboutany ofthesethings,orifyouhavehada strokein thepast, talkto your

doctorto seeifyou should takeHRT.

Compare

Lookingatwomen in their50swho arenottakingHRT, on average, 8 in 1000 would beexpected to have

a stroke overa 5-yearperiod. Forwomen in their50swho aretakingHRT, therewillbe11 casesin 1000

users, over5 years (i.e. an extra 3 cases).

Ifyouget:

unexplained migraine-typeheadaches, with orwithoutdisturbed vision

Seea doctorassoonaspossibleanddo nottakeany moreHRTuntilyourdoctorsays

you can. These headaches maybean earlywarningsign ofa stroke.

2.4Otherconditions

HRTwillnotpreventmemoryloss. There is some evidence of a higherriskofmemorylossin women

who startusingHRTaftertheageof65. Speakto yourdoctorforadvice.

Women with pre-existinghypertriglyceridaemia(high levelsoffatin theblood)mayexperience large

increases oftheirplasma triglycerides,whichcanleadtoinflammationofthe pancreas (pancreatitis). Ifyou

havethiscondition yourdoctorwillmonitoryou closely.

Other medicinesand Cathate

Tellyourdoctor or pharmacistifyou are taking, have recentlytaken ormighttake anyothermedicines.

Somemedicines mayinterfere withtheeffectof Cathate.This mightleadtoirregularbleeding.This

appliesto thefollowingmedicines:

Medicines forepilepsy(such asphenobarbital, phenytoin,

carbamazepine)

Medicines fortuberculosis(such asrifampicin, rifabutin)

Medicines forHIVinfection(such asnevirapine, efavirenz, ritonavir, nelfinavir)

Ketoconazole(mostcommonlyused inthetreatmentoffungalinfections)

Erythromycin (mostcommonlyused in thetreatmentand prevention ofinfections)

Cimetidine(mostcommonlyused to reducestomach acidityin ulcers)

HerbalremediescontainingSt. John’swort(Hypericumperforatum)

Metyrapone(mostcommonlyused in thetreatmentofCushing’ssyndrome)

Laboratory tests

Ifyou need ablood test, tellyourdoctororthelaboratorystaffthatyou aretakingCathate, because this

medicinecan affecttheresults of some tests.

Pregnancy,breast-feedingandfertility

Cathateisforusein postmenopausalwomen only.You shouldstop takingCathateand tellyourdoctor

immediatelyifyou knoworsuspectyou arepregnant, orifyou arebreast-feeding.

Drivingand usingmachines

There is noevidence tosuggestthattakingCathate willaffectyourabilitytodrive ortooperate machinery.

Cathatecontains

Cathate tablets contain lactosemonohydrateand sucrose.Ifyou havebeen told byyourdoctorthatyou

havean intoleranceto somesugars, contactyourdoctorbeforetakingthismedicinalproduct.

3. HOW TOTAKE CATHATE

3.1Instructions forproper use

Ifyou havehad ahysterectomyyou arenotexpected to haveaperiod.However,ifyouhavenothada

hysterectomy,youmaybetakinganadditionalprogestogentabletfor12-14 dayseach month, and you will

probablyhavea"period", orwithdrawalbleed each month ataboutthetimeyoufinishtheadditional

progestogentablets. Thisiscaused bythehormonesin theHRTand isperfectlynatural. Somewomen

taking"combined HRT"(estrogen plustheadditionalprogestogen)mayexperienceagradualreduction in

withdrawalbleedinganditmayeventuallystop;thisisquitenormal. Ifyou haveheavyorirregular

bleedingyou should tellyourdoctor.

Dosage

Always takethismedicineexactlyas yourdoctor hastoldyou.Checkwith yourdoctororpharmacistif

you arenotsure.Yourdoctorwillaimto prescribethelowestdoseto treatyoursymptomforasshortas

necessary. Speakto yourdoctorifyou thinkthisdoseistoo strongornotstrongenough.

Therecommendeddose is one tabletperday, to beswallowed with adrinkofwater.

Youmaystartyourfirstpackatanyconvenienttime.

However, forwomen with auterusifyou aretransferringfromasequentialHRTproduct(anHRT

productthatgivesyou amonthlybleed),treatmentshould begin thedayfollowingcompletion ofthe

priorproductunlessinstructed otherwisebyyourdoctor.

Do notleaveabreakbetween packsunlessyourdoctortellsyou to. Do notstoptakingCathatewithoutfirst

discussingitwith yourdoctor.

Durationoftreatment

Thatreallydependson whyyou and yourdoctorhavedecided on acourseoftreatment. Ifyou aretaking

HRTtorelieve yourimmediate menopausalsymptoms like hotflushes andnightsweats,youmaybe

prescribedHRTfora relativelyshortperiod oftime.

If, however, you oryourdoctorareworried aboutosteoporosisyou maybeprescribed HRTforlonger.

3.2IfyoutakemoreCathatethanyoushould

Ifyou taketoo manytablets, do notworry, Cathatecontainsnaturalhormonesand itisunlikelythatserious

problemswilloccur. Ifin anydoubtconsultyourdoctororpharmacist.

Youmayfeelsome nausea (sickness),orexperience a shortperiodofvaginalbleeding(unless youhave had

a hysterectomy)ifyoutake toomanytablets.

3.3Ifyouforgetto takeCathate

Ifyou forgetto takeadose, takeitassoon asyou remember, then go on asbefore. Ifmorethan onetablet

hasbeenmissedtakethetabletforthe daythatyourememberandcontinue as normal.Do no takeextra

tabletstotrytomake upforthe missedtablets.

Missed pillsmaycausebreakthrough bleedingin women with auterus(womb).

3.4Ifyouneedto havesurgery

Ifyou aregoingto havesurgery, makesureyourdoctorand/oryoursurgeon knowsthatyou aretaking

Cathate. You mayneed to stop takingCathateabout4 to 6 weeksbeforetheoperation, to reducetherisk

ofablood clot(seesection 2.3-Blood Clotsin avein (thrombosis). Askyourdoctorwhen you can start

takingCathateagain.

Ifyou haveanyfurtherquestionson theuseofthismedicine, askyourdoctororpharmacist

4. POSSIBLE SIDE EFFECTS

Like allmedicines,thismedicinecancause side effects,although noteverybodygetsthem.

Thefollowing arereported moreoften in women usingHRTcompared to womennotusingHRT:

breastcancer

abnormalgrowth orcanceroftheliningofthewomb (endometrialhyperplasiaorcancer)

ovarian cancer

blood clotsin theveinsofthelegsorlungs(venousthromboembolism)

heartdisease

stroke

probablememoryloss(dementia)ifHRTis started overtheage of 65

For more information aboutthese sideeffects, see Section 2.

Inadditiontothosediscussedinsection2,thefollowingsideeffectshave beenreportedinwomentaking

HRT:

Common(may affectupto 1 in10 women)

breakthrough bleedingorspotting, vaginalinflammation

breasttenderness,swollenbreasts,nipple discharge,breastpain

depression

hairloss

muscle andjointaches,legcramps

weightchange (increase ordecrease)

changes inyourtriglyceride levels(fattysubstancesin theblood)

Uncommon(may affectupto 1 in100 women)

changesin menstrualflow, inflammation ofthevaginaresultingin discharge

thrush

nausea, bloating, abdominalpain

headache,migraine

dizziness

changesin mood includingnervousness/anxiety

changes inyourinterestinsex(increasedordecreasedlibido)

memoryloss (dementia)

visible swellingofthe face orankles

itchiness,acne

minoreye changes whichmaycause difficulties ifyouwearcontactlenses

gallbladderdisease (e.g.gallstones)

abnormalturningoutofthecervix

change incervicalmucus

increase inhairgrowth

discolorationofthe skinespeciallyofthe face orneckknownas “pregnancypatches” (chloasma)

Rare(may affect upto 1 in1,000 women)

vomiting

changes inbreasttissue,milkysecretion fromthebreasts

allergic-like reactions

irritability

a worseningofglucose tolerance

aworseningofasthma

increasethegrowth ofexistingbenign meningioma(atumourofthemembranesaround thebrain or

spinalcord)

inflammationofthepancreas

inflammationofthe colon(partofthe intestine)whichmaypresentas lowerleftsidedabdominal

pain and/orbloodydiarrhoea

inflammation ofveinsjustundertheskin

worseningofepilepsy

heartattack

increasedsize offibroids

dysmenorrhoea(lowerbackorabdominalpain duringmenstruation)

Very rare(may affectupto 1 in10,000 women)

jaundice(e.g. yellowingoftheskin)

aworseningofchorea(an existingneurologicaldisordercharacterised byinvoluntaryspasmodic

movementsofthebody)

a worseningofhypocalcaemia (lowbloodlevels ofcalcium)in patientswho alreadyhaveaknown

riskoflowlevelsofcalciumintheirblood

enlargementoflivertumours

worseningofporphyria(a rare inheritedmetabolic disorder)

blood clotsin theveinsoftheeye

thickeningoftheliningoftheuterus

increasein blood pressure

painfulreddish skin nodules(erythemanodosum)

rashwithtarget-shaped reddeningorsores(erythemamultiforme)

These sideeffects are usuallytemporaryand should get betterovertime.

Reporting ofside effects

Ifyou getanysideeffects, talkto yourdoctor,pharmacistornurse. Thisincludesanypossibleside

effects notlisted in this leaflet. You can also reportsideeffects directly(see details below). Byreporting

sideeffectsyou can help providemoreinformation on thesafetyofthismedicine.

IRELAND:FREEPOST,Pharmacovigilance Section,Irish Medicines Board,Kevin O’MalleyHouse,

EarlsfortCentre,EarlsfortTerrace,Dublin 2, Ireland.

Tel:+353 1 6764971,Fax:+353 1 6762517,Website:www.imb.ie, email:imbpharmacovigilance@imb.ie

5. HOW TOSTORE CATHATE

Keepthis medicineoutofthesightandreachofchildren.

Do notuse this medicineaftertheexpirydatewhich isstated on thecarton andblisterafterEXP. The

expirydaterefersto thelastdayofthatmonth.

Do notstoreabove25 o C. Storein theoriginalcontainerto protectfrommoisture.

Do notusethismedicineifyou noticethepackhasbeen opened ordamaged andreturn itto your

pharmacist.

Do notthrowawayanymedicinesviawastewaterorhousehold waste. Askyourpharmacisthowtothrow

awaymedicines younolongeruse.These measures willhelpto protecttheenvironment.

6.CONTENTSOFTHEPACKAND OTHER INFORMATION

6.1WhatCathatecontains

The active substance is conjugatedestrogens.Each tabletcontains0.625 mgconjugated estrogens.

The otheringredients are:lactosemonohydrate, methylcellulose,magnesiumstearate,sucrose,

glycerylmono-oleate,Polyethyleneglycol20000,carnaubawax, calciumsulphateanhydrous,

microcrystalline cellulose,stearic acid,pharmaceuticalglaze(shellacsolution), titaniumdioxide

(E171)and edibleink(containsironoxideblack[E172], shellac, ethanol, n-butylalcohol,

propylene glycolandethylacetate).

WhatCathatelookslikeand contentsofthepack

Cathate0.625 mgcoated tabletsarewhiteovalshaped tabletsmarked with “0.625”in blackink.

Yourtablets are suppliedinacalendarpackcontainingonestrip of28 tablets.

MARKETINGAUTHORISATION HOLDER AND MANUFACTURER

TheMarketingAuthorisation Holderis:

PfizerHealthcare Ireland

9Riverwalk

National Digital Park

CitywestCampus

Dublin 24

Ireland

.

TheManufacturersare:

PfizerIrelandPharmaceuticals

LittleConnell

Newbridge

Co. Kildare

RepublicofIreland

Wyeth Laboratories

New Lane

Havant

Hants

PO9 2NQ

UK

This leafletwas lastrevisedinMM/YYYY.

Ref:CT4_2

Document Outline

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cathate0.625mgCoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Cathatetabletcontains0.625mgConjugatedEstrogens.

Excipients:ContainsLactoseMonohydrate91.8mgandsucrose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

CoatedTablet.

Awhite,oval,coatedtabletprinted“0.625”inblack.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Cathateisindicatedforhormonereplacementtherapy(HRT)forestrogendeficiencysymptomsinmenopausaland

postmenopausalwomen.

Preventionofosteoporosisinpostmenopausalwomenathighriskoffuturefractureswhoareintolerantof,or

contraindicatedfor,othermedicinalproductsapprovedforthepreventionofosteoporosis.

(Seealsosection4.4)

4.2Posologyandmethodofadministration

CathateTabletsareanestrogenonlyHRTfororaluse.

Posology:

Adults

Cathate0.625-1.25mgdailyistheusualstartingdoseforwomenwithoutauterus.Continuousadministrationis

recommended.

Forinitiationandcontinuationoftreatmentofpostmenopausalsymptoms,thelowesteffectivedosefortheshortest

duration(seealsosection4.4)shouldbeused.Patientsshouldbere-evaluatedperiodicallytodetermineiftreatmentfor

symptomsisstillnecessary.

Vasomotorsymptoms:

0.625-1.25mgdailydependingontheresponseoftheindividual.

Atrophicvaginitis,kraurosisvulvae,atrophicurethritis:

0.625-1.25mgdailydependingontheresponseoftheindividual.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 01/11/2013 CRN 2134033 page number: 1

Theminimumeffectivedoseis0.625mgformostpatients.

Concomitantprogestogenuseforwomenwithauterus:

Unlessthereisapreviousdiagnosisofendometriosis,itisnotrecommendedtoaddaprogestogeninhysterectomised

women(seesection4.4)

Commencingtreatmentadvice:

Formostpostmenopausalwomen,therapymaybecommencedatanyconvenienttime.

Inwomenwhoarenottakinghormonereplacementtherapyorwomenwhoswitchfromacontinuouscombined

hormonereplacementtherapyproduct,treatmentmaybestartedonanyconvenientday.Inwomentransferringfroma

sequentialhormonereplacementtherapyregimen,treatmentshouldbeginthedayfollowingcompletionoftheprior

regimen.

Beforetherapycommencesitisrecommendedthatthepatientisfullyinformedofallthelikelybenefitsandpotential

risks.Sheshouldhaveacompletephysicalandgynaecologicalexaminationwithspecialemphasisonbloodpressure,

breasts,abdomenandpelvicorgansandanendometrialassessmentcarriedoutifappropriate.Follow-upexaminations

arerecommendedevery6-12months.

Forgottentablet:Ifatabletisforgotten,itshouldbetakenassoonasthepatientremembers;therapyshouldthenbe

continuedasbefore.Ifmorethanonetablethasbeenforgottenonlythemostrecenttabletshouldbetaken.

Missedpillsmaycausebreakthroughbleedinginwomenwithauterus.

Olderpeople:

Therearenospecialdosagerequirementsforolderpeople,butaswithallmedicinethelowesteffectivedoseshouldbe

used.

Paediatricpopulation:

Notrecommended.

4.3Contraindications

1.Known,pastorsuspectedbreastcancer.

2.Knownorsuspectedestrogen-dependentmalignanttumours(e.g.endometrialcancer).

3.Undiagnosedabnormalgenitalbleeding.

4.Untreatedendometrialhyperplasia.

5.Previousorcurrentvenousthromboembolism(deepvenousthrombosis,pulmonaryembolism).

6.Knownthrombophilicdisorders(e.g.proteinC,proteinS,orantithrombindeficiency,seesection4.4).

7.Activeorrecentarterialthromboembolicdisease(e.g.angina,myocardialinfarction).

8.Acuteliverdiseaseorhistoryofliverdiseasewheretheliverfunctiontestshavefailedtoreturntonormal.

9.Hypersensitivitytotheactivesubstanceortoanyoftheexcipientslistedinsection6.1.

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4.4Specialwarningsandprecautionsforuse

Forthetreatmentofpostmenopausalsymptoms,HRTshouldonlybeinitiatedforsymptomsthatadverselyaffectthe

qualityoflife.Inallcases,acarefulappraisaloftherisksandbenefitsshouldbeundertakenatleastannuallyandHRT

shouldonlybecontinuedaslongasthebenefitoutweighstherisk.

EvidenceregardingtherisksassociatedwithHRTinthetreatmentofprematuremenopauseislimited.Duetothelow

levelofabsoluteriskinyoungerwomen,however,thebalanceofbenefitsandrisksforthesewomenmaybemore

favourablethaninolderwomen.

1.Medicalexamination/follow-up

BeforeinitiatingorreinstitutingHRT,acompletepersonalandfamilymedicalhistoryshouldbetaken.Physical

(includingpelvicandbreast)examinationshouldbeguidedbythisandbythecontraindicationsandwarningsforuse.

Duringtreatment,periodiccheck-upsarerecommendedofafrequencyandnatureadaptedtotheindividualwomen.

Womenshouldbeadvisedwhatchangesintheirbreastsshouldbereportedtotheirdoctorornurse(see‘BreastCancer’

below).Investigations,includingappropriateimagingtools,e.g.mammography,shouldbecarriedoutinaccordance

withcurrentlyacceptedscreeningpractices,modifiedtotheclinicalneedsoftheindividual.

2.Conditionswhichneedsupervision

Ifanyofthefollowingconditionsarepresent,haveoccurredpreviously,and/orhavebeenaggravatedduringpregnancy

orprevioushormonetreatment,thepatientshouldbecloselysupervised.Itshouldbetakenintoaccountthatthese

conditionsmayrecurorbeaggravatedduringtreatmentwithCathate,inparticular:

Leiomyoma(uterinefibroids)orendometriosis

Riskfactorsforthromboembolicdisorders(seebelow)

Riskfactorsforestrogendependenttumours(e.g.firstdegreeheredityforbreastcancer)

Hypertension

Liverdisorders(e.g.liveradenoma)

Diabetesmellituswithorwithoutvascularinvolvement

Cholelithiasis

Migraineor(severe)headaches

Systemiclupuserythematosus(SLE)

Ahistoryofendometrialhyperplasia(seebelow)

Epilepsy

Asthma

Otosclerosis

3.Reasonsforimmediatewithdrawaloftherapy

Therapyshouldbediscontinuedincaseacontraindicationisdiscoveredandinthefollowingsituations:

Jaundiceordeteriorationinliverfunction

Significantincreaseinbloodpressure

Newonsetofmigraine-typeheadache

Pregnancy

4.Endometrialhyperplasiaandcarcinoma

Inwomenwithanintactuterustheriskofendometrialhyperplasiaandcarcinomaisincreasedwhenestrogensare

administeredaloneforprolongedperiods.Thereportedincreaseinendometrialcancerriskamongestrogen-onlyusers

variesfrom2-to12-foldgreatercomparedwithnon-users,dependingonthedurationoftreatmentandestrogendose

(seesection4.8).Afterstoppingtreatmentriskmayremainelevatedforatleast10years.

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estrogen-progestogentherapyinnon-hysterectomisedwomenpreventstheexcessriskassociatedwithestrogen-only

HRT.

Fororaldosesofestradiol>2mg,conjugatedequineestrogens>0.625mgandpatches>50 µ

g/daytheendometrial

safetyofaddedprogestogenhasnotbeendemonstrated.

Breakthroughbleedingandspottingmayoccurduringthefirstmonthsoftreatment.Ifbreakthroughbleedingor

spottingappearsaftersometimeontherapy,orcontinuesaftertreatmenthasbeendiscontinued,thereasonshouldbe

investigated,whichmayincludeendometrialbiopsytoexcludeendometrialmalignancy.

Unopposedestrogenstimulationmayleadtopre-malignantormalignanttransformationintheresidualfociof

endometriosis.Therefore,theadditionofprogestogenstoestrogenreplacementtherapyshouldbeconsideredin

womenwhohaveundergonehysterectomybecauseofendometriosis,iftheyareknowntohaveresidualendometriosis.

5.Breastcancer

Theoverallevidencesuggestsanincreasedriskofbreastcancerinwomentakingcombinedestrogen-progestogenand

possiblyalsoestrogen-onlyHRT,thatisdependentonthedurationoftakingHRT.

TheWHItrialfoundnoincreaseintheriskofbreastcancerinhysterectomisedwomenusingestrogen-onlyHRT.

Observationalstudieshavemostlyreportedasmallincreaseinriskofhavingbreastcancerdiagnosedthatis

substantiallylowerthanthatfoundinusersofestrogen-progestogencombinations(seesection4.8).

Theexcessriskbecomesapparentwithinafewyearsofusebutreturnstobaselinewithinafew(atmostfive)years

afterstoppingtreatment.

HRT,especiallyestrogen-progestogencombinedtreatment,increasesthedensityofmammographicimageswhichmay

adverselyaffecttheradiologicaldetectionofbreastcancer.

6.OvarianCancer

Ovariancancerismuchrarerthanbreastcancer.Long-term(atleast5-10years)useofestrogen-onlyHRTproductshas

beenassociatedwithaslightlyincreasedriskofovariancancer(seeSection4.8).SomestudiesincludingtheWHItrial

suggestthatthelong-termuseofcombinedHRTsmayconferasimilar,orslightlysmaller,risk(seeSection4.8).

7.Venousthromboembolism

Hormonereplacementtherapy(HRT)isassociatedwitha1.3-3foldriskofdevelopingvenousthromboembolism

(VTE),i.e.deepveinthrombosisorpulmonaryembolism.Theoccurrenceofsuchaneventismorelikelyinthefirst

yearofHRTusethanlater(seeSection4.8).

PatientswithknownthrombophilicstateshaveanincreasedriskofVTEandHRTmayaddtothisrisk.HRTis

thereforecontraindicatedinthesepatients(seesection4.3).

GenerallyrecognisedriskfactorsforVTEincludeuseofestrogens,olderage,majorsurgery,prolonged

immobilisation,obesity(BodyMassIndex>30kg/m 2

),pregnancy/postpartumperiod,systemiclupuserythematosus

(SLE)andcancer.ThereisnoconsensusaboutthepossibleroleofvaricoseveinsinVTE.

Asinallpost-operativepatients,prophylacticmeasuresneedtobeconsideredtopreventVTEfollowingsurgery.If

prolongedimmobilisationistofollowelectivesurgery,temporarilystoppingHRT4to6weeksearlieris

recommended.Treatmentshouldnotberestarteduntilthewomaniscompletelymobilised.

InwomenwithnopersonalhistoryofVTEbutwithafirstdegreerelativewithahistoryofthrombosisatyoungage,

screeningmaybeofferedaftercarefulcounsellingregardingitslimitations(onlyaproportionofthrombophillicdefects

areidentifiedbyscreening).

Ifathrombophilicdefectisidentifiedwhichsegregateswiththrombosisinfamilymembersorifthedefectis

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Womenalreadyonchronicanticoagulanttreatmentrequirecarefulconsiderationofthebenefit-riskofuseofHRT.

IfVTEdevelopsafterinitiatingtherapy,thedrugshouldbediscontinued.Patientsshouldbetoldtocontacttheir

doctorsimmediatelywhentheyareawareofpotentialthromboembolicsymptoms(e.g.painfulswellingofaleg,

suddenpaininthechest,dyspnoea).

8.Coronaryarterydisease

Thereisnoevidencefromrandomisedcontrolledtrialsofprotectionagainstprotectionagainstmyocardialinfarctionin

womenwithorwithoutexistingCADwhoreceivedcombinedestrogens-progesteroneorestrogen-onlyHRT.

RandomisedcontrolleddatafoundnoincreasedriskofCADinhysterectomisedwomenusing

estrogen-onlytherapy.

9.Ischaemicstroke

Combinedestrogen-progestogenandestrogen-onlytherapyareassociatedwithanupto1.5-foldincreaseinriskof

ischaemicstroke.Therelativeriskdoesnotchangewithageortimesincemenopause.However,asthebaselineriskof

strokeisstronglyage-dependent,theoverallriskofstrokeinwomenwhouseHRTwillincreasewithage(seesection

4.8).

OtherConditions

10.Estrogensmaycausefluidretentionandthereforepatientswithcardiacorrenaldysfunctionshouldbecarefully

observed.Patientswithterminalrenalinsufficiencyshouldbecloselyobserved,sinceitisexpectedthatthelevelof

circulatingactiveingredientsinCathateisincreased.

11.Theuseofestrogenmayinfluencethelaboratoryresultsofcertainendocrinetestsandliverenzymes.

Estrogensincreasethyroidbindingglobulin(TBG),leadingtoincreasedcirculatingtotalthyroidhormone,asmeasured

byprotein-boundiodine(PBI),T4levels(bycolumnorbyradio-immunoassay)orT3levels(byradio-immunoassay).

T3resinuptakeisdecreased,reflectingtheelevatedTBG.FreeT4andfreeT3concentrationsareusuallyunaltered.

Patientsdependentonthyroidhormonereplacementtherapymayrequireincreaseddosesinordertomaintaintheirfree

thyroidhormonelevelsinanacceptablerange.

Otherbindingproteinsmaybeelevatedinserum,i.e.corticoidbindingglobulin(CBG),sex-hormone-bindingglobulin

(SHBG)leadingtoincreasedcirculatingcorticosteroidsandsexsteroids,respectively.Freeorbiologicalactive

hormoneconcentrationsareusuallyunchanged.Otherplasmaproteinsmaybeincreased(angiotensinogen/renin

substrate,alpha-I-antitrypsin,ceruloplasmin).

12.Atwo-tofour-foldincreaseintheriskofgallbladderdiseaserequiringsurgeryinwomenreceivingHRThasbeen

reported.

13.Aworseningofglucosetolerancemayoccurinpatientstakingestrogensandthereforediabeticpatientsshouldbe

carefullyobservedwhilereceivinghormonereplacementtherapy.

14.Estrogensshouldbeusedwithcautioninpatientswithdiseasethatcanpredisposetoseverehypocalcaemia.

15.Womenwithpre-existinghypertriglyceridemiashouldbefollowedcloselyduringestrogenreplacementorhormone

replacementtherapy,sincerarecasesoflargeincreasesofplasmatriglyceridesleadingtopancreatitishavebeen

reportedwithestrogentherapyinthiscondition.

16.HRTusedoesnotimprovecognitivefunction.Thereissomeevidenceofincreasedriskofprobabledementiain

womenwhostartusingcontinuouscombinedorestrogen-onlyHRTaftertheageof65.

17.Patientswithrarehereditaryproblemsofgalactoseorfructoseintolerance,theLapplactasedeficiency,glucose-

galactosemalabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethismedicine,astheexcipientsinthetablet

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Themetabolismofestrogensmaybeincreasedbyconcomitantuseofsubstancesknowntoinducedrug-metabolising

enzymes,specificallycytochromeP450enzymes,suchasanticonvulsants(e.g.phenobarbital,phenytoin,

carbamazepine)andanti-infectives(e.g.rifampicin,rifabutin,nevirapine,efavirenz).

Ritonavirandnelfinavir,althoughknownasstronginhibitors,bycontrastexhibitinducingpropertieswhenused

concomitantlywithsteroidhormones.

HotflushesandvaginalbleedinghavebeenreportedinpatientstakingHRTandSt.Johnswort(Hypericum

perforatum).St.John’swortmayinducehepaticmicrosomalenzymeswhichtheoreticallymayresultinreduced

efficacyofHRT.

CYP3A4inhibitorssuchascimetidine,erythromycinandketoconazolemayincreaseplasmaconcentrationsof17-

estradiolandmayresultinsideeffects.

Clinically,anincreasedmetabolismofestrogensandprogestogensmayleadtodecreasedeffectandchangesinthe

uterinebleedingprofile.

Theresponsetometyraponemaybereduced.

4.6Fertility,pregnancyandlactation

Pregnancy:

Cathateisnotindicatedforuseduringpregnancy.

Forwomenwithauterus:

IfpregnancyoccursduringmedicationwithCathate,treatmentshouldbewithdrawnimmediately.Theresultsofmost

epidemiologicalstudiestodaterelevanttoinadvertentfoetalexposuretoestrogensindicatenoteratogenicorfoetotoxic

effects.

Lactation:

Cathateisnotindicatedduringlactation.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

4.8Undesirableeffects

Seealsosection4.4..

Adversedrugreactions(ADRs)

Theadversereactionslistedinthetablearebasedonpost-marketingspontaneousreportingrates,clinicaltrialsand

class-effects.

SystemOrgan

Class CommonADRs

(>1/100,<1/10) UncommonADRs

(>1/1000,<1/100) RareADRs

(>1/10000,<1/1000) VeryRareADRs

(<1/10000),isolated

reports

Infectionsand

infestations None Vaginitis,including

vaginalcandidiasis None None

Neoplasmsbenign

andmalignant None None Breastcancer;

Fibrocysticbreast Endometrialcancer;

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(includingcystsand

polyps) changes

Ovariancancer;

Growthpotentiation

ofbenign

meningioma hepatic

haemangiomas

Immunesystem

disorders None None Anaphylactic/

anaphylactoid

reactions,including

urticariaand

angioedema None

Metabolismand

nutritiondisorders None None Glucoseintolerance Exacerbationof

porphyria;

Hypocalcaemia(in

patientswithdisease

thatcanpredispose

tosevere

hypocalcaemia)

Psychiatricdisorders Depression Changesinlibido;

Mooddisturbances;

dementia Irritability None

Nervoussystem

disorders None Dizziness;Headache;

Migraine;Anxiety Stroke;Exacerbation

ofepilepsy; Exacerbationof

chorea

Eyedisorders None Intolerancetocontact

lenses None Retinalvascular

thrombosis

Cardiacdisorders None None Myocardial

infarction None

Vasculardisorders None Venousthrombosis Pulmonary

embolism;

Superficial

thrombophlebitis None

Respiratory,thoracic

andmediastinal

disorders None None Exacerbationof

asthma None

Gastrointestinal

disorders None Nausea;Bloating;

Abdominalpain Vomiting;

Pancreatitis;

Ischaemiccolitis None

Hepatobiliary

disorders None Gallbladderdisease None Cholestaticjaundice

Skinand

subcutaneoustissue

disorders Alopecia Chloasma/melasma;

Hirsutism;Pruritus;

Rash None Erythema

multiforme;

erythemanodosum

Musculoskeletal,

connectivetissue

andbonedisorders Arthralgias;Leg

cramps None None None

Reproductive

system&breast

disorders Breakthrough

bleeding/spotting;

breastpain,

tenderness,

enlargement,

discharge Changeinmenstrual

flow;Changein

cervicalectropionand

secretion Dysmenorrhoea;

Galactorrhoea;

Increasedsizeof

uterineleiomyomata Endometrial

hyperplasia

Generaldisorders

andadministration

siteconditions None Oedema None None

Investigations Changesinweight

(increaseor None None Increaseinblood

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Breastcancerrisk

Anupto2-foldincreasedriskofhavingbreastcancerdiagnosedisreportedinwomentaking

combinedestrogen-progestogentherapyformorethan5years.

Anyincreasedriskinusersofestrogen-onlytherapyissubstantiallylowerthanthatseeninusersofestrogen-

progestogencombinations.

Thelevelofriskisdependentonthedurationofuse(seesection4.4).

Resultsofthelargestrandomisedplacebo-controlledtrial(WHI-study)andlargestepidemiologicalstudy(MWS)are

presented.

MillionWomenstudy–Estimatedadditionalriskofbreastcancerafter5years’use

USWHIstudies-additionalriskofbreastcancerafter5years’use

‡WhentheanalysiswasrestrictedtowomenwhohadnotusedHRTpriortothestudytherewasnoincreasedrisk

apparentduringthefirst5yearsoftreatment:after5yearstheriskwashigherthaninnon-users.

*Takenfrombaselineincidenceratesindevelopedcountries

**WHIstudyinwomenwithnouterus,whichdidnotshowanincreaseinriskofbreastcancer

Endometrialcancerrisk

Postmenopausalwomenwithauterus

Theendometrialcancerriskisabout5inevery1000womenwithauterusnotusingHRT.

Inwomenwithauterus,useofestrogen-onlyHRTisnotrecommendedbecauseitincreasestheriskofendometrial

cancer(seesection4.4).

Dependingonthedurationofestrogen-onlyuseandestrogendose,theincreaseinriskofendometrialcancerin

epidemiologystudiesvariedfrombetween5and55extracasesdiagnosedinevery1000womenbetweentheagesof

50and65.

Addingaprogestogentoestrogen-onlytherapyforatleast12dayspercyclecanpreventthisincreasedrisk.Inthe

MillionWomenStudytheuseoffiveyearsofcombined(sequentialorcontinuous)HRTdidnotincreaseriskof

decrease);Increased

triglycerides

range

(years) Additionalcases

per1000never-users

ofHRT

overa5year

period* Riskratio&

95%CI# Additionalcasesper1000HRTusersover5

years

(95%CI)

estrogenonlyHRT

50-65 9-12 1.2 1-2(0-3)

Combinedestrogen-progestogen

50-65 9-12 1.7 6(5-7)

#Overallriskratio.Theriskratioisnotconstantbutwillincreasewithincreasingdurationon

Note:SincethebackgroundincidenceofbreastcancerdiffersbyEUcountry,thenumberof

additionalcasesofbreastcancerwillalsochangeproportionately.

Agerange

(yrs) Incidenceper1000women

inplaceboarmover5years Riskratio&95%CI Additionalcasesper1000HRT

usersover5years(95%CI)

CEEestrogen-only

50-79 21 0.8(0.7–1.0) -4(-6–0)**

CEE+MPAestrogen&progestogen‡

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Ovariancancer

Long-termuseofestrogen-onlyandcombinedestrogen-progestogenHRThasbeenassociatedwithaslightlyincreased

riskofovariancancer.IntheMillionWomenStudy5yearsofHRTresultedin1extracaseper2500users.

Riskofvenousthromboembolism

HRTisassociatedwitha1.3-3-foldincreasedrelativeriskofdevelopingvenousthromboembolism(VTE),i.e.deep

veinthrombosisorpulmonaryembolism.TheoccurrenceofsuchaneventismorelikelyinthefirstyearofusingHT

(seesection4.4).ResultsoftheWHIstudiesarepresented:

WHIStudies-AdditionalriskofVTEover5years’use

*Studyinwomenwithnouterus

Riskofcoronaryarterydisease

Theriskofcoronaryarterydiseaseisslightlyincreasedinusersofcombinedestrogen-progestogenHRTovertheage

of60(seesection4.4).

Riskofischaemicstroke

Theuseofestrogen-onlyandestrogen+progestogentherapyisassociatedwithanupto1.5foldincreasedrelativerisk

ofischaemicstroke.TheriskofhaemorrhagicstrokeisnotincreasedduringuseofHRT.

Thisrelativeriskisnotdependentonageorondurationofuse,butasthebaselineriskisstronglyage-dependent,the

overallriskofstrokeinwomenwhouseHRTwillincreasewithage,seesection4.4.

WHIstudiescombined-Additionalriskofischaemicstroke*over5years’use

*nodifferentiationwasmadebetweenischaemicandhaemorrhagicstroke.

Otheradversereactionsreportedinassociationwithestrogen/progestogentreatmentincludingCathate:

Estrogen-dependentneoplasmsbenignandmalignant,e.g.endometrialhyperplasia,endometrialcancer.

Venousthromboembolism,i.e.deeplegorpelvicvenousthrombosisandpulmonaryembolism,ismorefrequent

amonghormonereplacementtherapyusersthanamongnon-users.Forfurtherinformation,seesections4.3and4.4.

Retinalvascularthrombosis.

Myocardialinfarctionandstroke.

Increasesinbloodpressure.

Cholestaticjaundice.

Enlargementofhepaticheamangiomas.

Skinandsubcutaneousdisorders:erythemamultiforme,erythemanodosum;vascularpurpura.

Probabledementia(seesection4.4).

Exacerbationofchorea.

Agerange(years) Incidenceper1000

womeninplaceboarm

over5years Riskratioand95%CI Additionalcasesper

1000HRTusers

Oralestrogen-only*

50-59 7 1.2(0.6-2.4) 1(-3–10)

Oralcombinedestrogen-progestogen

50-59 4 2.3(1.2–4.3) 5(1-13)

Agerange(years) Incidenceper1000

womeninplaceboarm

over5years Riskratioand95%CI Additionalcasesper

1000HRTusersover5

years

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Exacerbationofhypocalcaemia.

Reportingofsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalareasktoreportanysuspected

adversereactionspreferablythroughtheonlinereportingoptionaccessiblefromtheIMBhomepage.Adownloadable

reportformisalsoaccessiblefromtheIMBwebsite,whichmaybecompletedmanuallyandsubmittedtotheIMBvia

‘freepost’.Alternatively,thetraditionalpost-paid‘yellowcard’optionmayalsocontinuetobeused.

FREEPOST

PharmacovigilanceSection

IrishMedicinesBoard

KevinO’MalleyHouse

EarlsfortCentre

EarlsfortTerrace

Dublin2

Tel:+35316764971

Fax:+35316762517

Website: http://www.imb.ie/

e-mail: imbpharmacovigilance@imb.ie

4.9Overdose

Numerousreportsofingestionoflargedosesofestrogencontainingoralcontraceptivesbyyoungchildrenindicatethat

acuteseriousilleffectsdonotoccur.Overdosageofestrogensmaycausenauseaandvomiting,andwithdrawal

bleedingmayoccurinfemales.Thereisnospecificantidoteandfurthertreatmentshouldbesymptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:G03CA57

ConjugatedEstrogens

Theactiveingredientsareprimarilythesulphateestersofestrone,equilinsulphatesand17/-estradiol.These

substituteforthelossofestrogenproductioninmenopausalwomen,andalleviatemenopausalsymptoms.Estrogens

preventbonelossfollowingmenopauseorovariectomy.

Reliefofestrogen-deficiencysymptoms

InthefirstyearoftheHealthandOsteoporosis,ProgestinandEstrogen(HOPE)Study,atotalof2,805postmenopausal

women(averageage53.3±4.9years)wererandomlyassignedtooneofeighttreatmentgroups,receivingeither

placeboorconjugatedestrogens,withorwithoutmedroxyprogesteroneacetate.Efficacyforvasomotorsymptomswas

assessedduringthefirst12weeksoftreatmentinasubsetofsymptomaticwomen(n=241)whohadatleastseven

moderate-to-severehotflushesdaily,oratleast50moderate-to-severehotflushesduringtheweekbefore

randomisation.Withconjugatedestrogens0.625mgtablets,thereliefofboththefrequencyandseverityofmoderate-

to-severevasomotorsymptomswasshowntobestatisticallyimprovedcomparedwithplaceboatweeks4and12.

Preventionofosteoporosis

Estrogendeficiencyatmenopauseisassociatedwithanincreasingboneturnoveranddeclineinbonemass.Theeffect

ofestrogensonthebonemineraldensityisdose-dependent.Protectionappearstobeeffectiveforaslongastreatment

iscontinued.AfterdiscontinuationofHRT,bonemassislostataratesimilartothatinuntreatedwomen.

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progestogen–giventopredominantlyhealthywomen–reducestheriskofhip,vertebral,andotherosteoporotic

fractures.HRTmayalsopreventfracturesinwomenwithlowbonedensityand/orestablishedosteoporosis,butthe

evidenceforthatislimited.

After2yearsoftreatmentwithconjugatedestrogens0.625mgtablets,theincreaseinlumbarspinebonemineral

density(BMD)was2.46±0.37%(adjustedmean±SE).

Totalhipwasmeasuredbyfemoralneckandfemoraltrochanter.

After2yearsoftreatmentwithconjugatedestrogens0.625mgtablets,theincreaseinfemoralneckbonemineral

density(BMD)was1.82±0.45%(adjustedmean±SE).

After2yearsoftreatmentwithconjugatedestrogens0.625mgtablets,theincreaseinfemoraltrochanterbonemineral

density(BMD)was3.82±0.58%(adjustedmean±SE).

5.2Pharmacokineticproperties

Absorption

Conjugatedestrogensaresolubleinwaterandarewellabsorbedfromthegastrointestinaltractafterreleasefromthe

drugformulation.Theconjugatedestrogenstabletreleasesconjugatedestrogensslowlyoverseveralhours.

Distribution

Thedistributionofexogenousestrogensissimilartothatofendogenousestrogens.Estrogensarewidelydistributedin

thebodyandaregenerallyfoundinhigherconcentrationinthesexhormonetargetorgans.Estrogenscirculateinthe

bloodlargelyboundtosexhormonebindingglobulin(SHBG)andalbumin.

Metabolism

Exogenousestrogensaremetabolisedinthesamemannerasendogenousestrogens.Circulatingestrogensexistina

dynamicequilibriumofmetabolicinterconversions.Thesetransformationstakeplacemainlyintheliver.Estradiolis

convertedreversiblytoestrone,andbothcanbeconvertedtoestriol,whichisthemajorurinarymetabolite.Estrogens

alsoundergoenterohepaticrecirculationviasulphateandglucuronideconjugationintheliver,biliarysecretionof

conjugatesintotheintestine,andhydrolysisinthegutfollowedbyreabsorption.Inpostmenopausalwomena

significantproportionofthecirculatingestrogensexistsassulphateconjugates,especiallyestronesulphate,which

servesasacirculatingreservoirfortheformationofmoreactiveestrogens.

Excretion

Estradiol,estroneandestriolareexcretedintheurinealongwithglucuronideandsulphateconjugates.

5.3Preclinicalsafetydata

Long-termcontinuousadministrationofnaturalandsyntheticestrogensincertainanimalspeciesincreasesthe

frequencyofcarcinomasofthebreast,cervix,vaginaandliver.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore:

Lactosemonohydrate

Methylcellulose

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Coating:

Sucrose

GlycerolMono-oleate(60%Acylglycerol)

Polyethyleneglycol20000

Carnaubawax

Calciumsulphate

Shellacsolution

Microcrystallinecellulose

Stearicacid

Titaniumdioxide(E171)

Edibleprintingink(containingironoxideblack(E172),shellac,ethanol,n-butylalcohol,propyleneglycolandethyl

acetate)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Threeyears.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeintheoriginalcontainertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Polyvinylchloride(PVC)/AluminiumfoilblistersandpolypropyleneSecuritainers.

Blisterstripsof21or28tabletsandSecuritainersof100tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

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Date Printed 01/11/2013 CRN 2134033 page number: 12

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:19September1995

Dateoflastrenewal:19September2010

10DATEOFREVISIONOFTHETEXT

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Date Printed 01/11/2013 CRN 2134033 page number: 13

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