ALESSE 100, 20 Microgram Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
LEVONORGESTREL ETHINYLESTRADIOL
Available from:
Pfizer Healthcare Ireland
INN (International Name):
LEVONORGESTREL ETHINYLESTRADIOL
Dosage:
100, 20 Microgram
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Authorization status:
Authorised
Authorization number:
PA0822/065/001
Authorization date:
0000-00-00

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PACKAGE LEAFLET

Package Leaflet: Information for the patient

ALESSE ®

100micrograms/20microgramsfilm-coated tablets

levonorgestrel/ethinylestradiol

Readallofthis leafletcarefully beforeyoustarttakingthismedicinebecauseit contains

importantinformationforyou.

- Keep this leaflet. You mayneed to read itagain.

- Ifyou have anyfurtherquestions, askyourdoctor,pharmacistornurse.

- This medicine has been prescribed foryouonly. Do notpass iton to others. Itmayharmthem, even if

theirsigns ofillness are the same as yours.

- Ifyou getanyside effects,talkto yourdoctor, pharmacistornurse. This includesanypossibleside

effects notlisted in this leaflet.See section 4.

Whatis inthisleaflet

1. WhatALESSE isand whatitis usedfor

2. Whatyou need to knowbefore you takeALESSE

3. Howto takeALESSE

4. Possible side effects

5. Howto store ALESSE

6. Contents ofthe packand otherinformation

1. WhatALESSEisand what it isused for

ALESSE isa combined oralcontraceptive pillforthe prevention ofpregnancy. Itcontains two different

female hormones, levonorgestreland ethinylestradiol.

Each ofthe 21 round pinktablets contains 100 micrograms oflevonorgestreland 20 micrograms

ethinylestradiol.

2. What you need to knowbefore youtake ALESSE

Before you can starttakingALESSE yourdoctorwillaskyou some questions around yourpersonalhealth

historyand thatofyourcloserelatives. Yourdoctorwillalso measure yourblood pressure and mayalso

carryoutsome othertests.

In thisleafletsome situations are described whereyou should stop usingALESSE or wherethe reliabilityof

ALESSE maybe decreased and there is ahigherriskofpregnancy. In such situations you should eithernot

have sex oryou should take extra non-hormonalcontraceptive precautions (e.g.usea condomorother

barriermethod). Do notusethe rhythmortemperature methods. These methods can become unreliable

because ALESSEalters the monthlychangesin bodytemperature and cervicalmucus.

ALESSElike other oralcontraceptive products doesnot protectagainstHIV infection (AIDS) orany

other sexually transmitted diseases

Do not takeALESSE:

Ifyouare allergicto eitherofthe active substances(levonorgestrelorethinylestradiol)oranyofthe

otheringredients ofthis medicine (listed in section 6)

Ifyou have, orhave everhad heartdisease ordiseasesofthe blood vessels, in particular;

a heartattack(myocardialinfarction), a heartrhythmdisorderora heartvalve disorder

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a blood clotincludingin thelegs (deep vein thrombosis)orin the lungs (pulmonaryembolism)

ora ruptured blood vesselin the brain (stroke), „mini-stroke‟ora generaltendencyto form

blood clots (venousorarterialthrombosis)

chestpain caused byangina pectoris

Ifyou have high blood pressure notstabilised bytreatment

Ifyou sufferfromcertain typesofmigraines(migraine with focalneurologicalsymptoms)

Ifyou have breastcancerorcancerofthe womb, ora type ofcancerthatis sensitive to female sex

hormones, oryou aresuspected ofhavinganyofthese cancers

Ifyou have vaginalbleedingofunknown cause

Ifyou have high levels ofsugarin yourblood (diabetes)associated with a disease ofthe blood vessels

Ifyou are pregnantorsuspectyou maybe pregnant

Ifyou haveorhave everhad abenign ormalignanttumourofthe liver, orifyou have recentlyhad liver

disease. In these casesyourdoctorwillaskyou to stop takingALESSE untilyourliveris working

properlyagain.

Warnings andprecautions

Talkto yourdoctor, pharmacistornursebefore takingALESSE.

In some situations you mayneed to take specialcare when takingALESSEoranyothercombined oral

contraceptive. Your doctorwillcheckyou regularly.Cigarette smokingincreases the riskofserious adverse

effects on the heartand blood vessels fromoralcontraceptive use. This riskincreases with age and withthe

extentofsmokingand is quite marked in women over35 years ofage. Women who use combined oral

contraceptivesshould notsmoke. Othermethods ofcontraception should be considered forthosewomen

over35 years old who smoke.

Ifanyofthe followingconditions appliesto you, you musttellyourdoctorbefore startingto take ALESSE.

Ifanyofthe conditions listed belowdevelops orgets worse whiletakingALESSE, you mustconsultyour

doctorso thattheycan decide whetherALESSE isstillsuitable foryou.

Tellyourdoctorif:

You have high blood pressure

You have high levels ofcholesterolorabnormallevels oflipids (fats)in the blood

(dyslipoproteinemia)-this is picked up in blood tests

You are obese

You have diabetes

You have adisease ofthe heartvalvesorheartrhythmdisorder(atrialfibrillation)

You ora closerelative (parent, brotherorsister) haseversuffered froma disease with atendencyto

develop blood clots (in the leg, lungorelsewhere in the bodyorhave ahistoryofheartattackor

stroke)

You have varicose veins orhave suffered frominflammation ofthe superficialveins in yourlegs

You experience anysudden unexplainedchangesin yourvision

You have gallstones, gallbladderdisease orhave problems caused bya blockage ofthe bile ducts

(cholestasis)-this maycauseintense itching

You develop migraine forthe firsttime orsufferworseningofexistingmigraine headaches

You have ordevelop liverdisease, jaundice, an inflamed pancreas orkidneydisease

You sufferfromdepression

You have alossofhearingdue to a disorderknown asotosclerosis

You have had duringa pregnancyorwhen usinganothercontraceptive pilla skin condition which

caused itching, red patches and blisters (herpesgestationnis)

You have had duringa pregnancytemporarybrown patches on yourskin (chloasma). The pillcan

make this recurso you should avoid strongsunlightorsunbeds while takingALESSE.

You sufferfroma disorderaffectingyourimmune system(systemic lupus erythematosus)

You sufferfroma disease known asSydenham‟s Chorea. The symptoms include irregular, sudden

invountarymovements.

You have everhad ablood disease associatedwith a kidneydisease (haemolytic uremic syndrome)

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You have everhad ablood disease called porphyria

You haveulcerative colitisorCrohn‟s disease(inflammation ofthe gutwhich causespain in the

abdomen, frequentdiarrhoeaand tiredness).

You have ablood disease called sickle celldisease

Ifyou have hereditaryangioedema, products containingoestrogensmay causeorworsen the symptoms of

angioedema. You should see yourdoctorimmediatelyifyou experience symptoms ofangioedema such as

swollen face, tongue and/orpharynx and/ordifficultyswallowing, orhivestogetherwith difficultyin

breathing.

ALESSEandthrombosis(bloodclots)

Venous thrombosis (blood clots)

The use ofanycombination pill, includingALESSE, increases awoman‟s riskofdevelopinga venous

thrombosis (formation ofa blood clotin vessels)compared with a woman who does nottake any

(contraceptive)pill.

The riskofvenousthrombosis in users ofcombined pills increases:

with increasingage

ifyou are overweight

ifone ofyourcloserelativeshasdeveloped ablood clotin a vesselatan earlyage

with prolonged immobilization (forexample, when you have yourlegorlegs in plasterorsplints), major

surgery, anysurgeryto the legs, majortrauma. In these situations itis betterto stop takingALESSE(if

the surgeryis planned you should stop atleastfourweeks beforehand)and notto startagain untiltwo

weeks afteryou are fullyon yourfeetagain.

Directlyaftergivingbirth, women are atan increased riskofblood clots so you should askyourdoctor

howsoon afterdeliveryyou can starttakinga combined pill.

Arterialthrombosis(blood clots)

The use ofcombination pills has been connected with an increaseofthe riskofarterialthrombosis

(obstruction ofan artery), forexample, in the blood vessels ofthe heart(heartattack)orthe brain (stroke).

The riskofarterialthrombosis in users ofcombined pills increases:

Ifyou smoke. You are strongly advised to stop smoking when youuseALESSE, especially ifyou

areolderthan35 years.

With increasingage even ifyou don‟tsmoke

ifyou have an increased fatcontentin yourblood (cholesterolortriglycerides)

ifyou are overweight

ifone ofyourcloserelativeshashad aheartattackorstroke ata youngage

ifyou havehigh blood pressure

ifyou have migraine

ifyou have aproblemwith yourheart(valve disorder, a disturbance ofthe heartrhythm)

Stop takingALESSEandconsultyour doctor immediately or go to the emergency departmentofthe

nearesthospitalifyou experiencepossiblesigns ofthrombosis, such as:

anyunusual, severe orlong-lastingheadache, ormore frequentorsevere migraine attack

an increasein blood pressure

severe pain and/orswellingin one ofyourlegs

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sudden severe pain in the chestwhich mayspread to the leftarm

difficultybreathing, sudden breathlessness

sudden unusualcough with no obvious cause

changesto youreyesight, partialorcomplete blindness, ordouble vision

difficultyin speaking, orinabilityto speak

sudden changesto yourhearing, senseofsmell, ortaste

dizziness orfainting

weakness, strange feeling, ornumbness in anypartofyourbody

sudden severe stomachache

ALESSEandcancer

Breastcancerhasbeen detected slightlymoreoften in women usingcombinedpills, butitis notknown

whetherthis is caused bythe pill. Itis possible thatthese women weresimplyexamined more thoroughly

and more frequently, meaningthatthe breastcancerwasdetected earlier.

In women usingcombinedpillsfora relativelylongtime, studieshave reported casesofcervicalcancer. Itis

currentlyunknown whetheritis caused bythe pillorconnected with sexualbehaviour(e.g. more frequent

changesofpartner)and otherfactors.

In rare cases, benign livertumours, and in even fewer cases malignantlivertumours have been reported in

pillusers. Contactyourdoctorifyou have unusuallysevere abdominalpain.

Bleeding betweenperiods

Duringthe firstfew months thatyou are takingALESSE, you mayhave unexpected bleeding(bleedingor

spottingoutside thetabletfreeweek). Ifthis bleedinglasts longerthan afew months, orifitbegins after

some months, yourdoctormustinvestigate the cause.

Whatto do ifno bleeding occurs inthetabletfreeweek

Ifyou have taken allthe tablets correctly, have nothad vomitingorsevere diarrhoeaand you have nottaken

anyothermedicines, itis highlyunlikelythatyou are pregnant.

Ifthe expected bleedingdoesnothappen twicein succession, you maybe pregnant. Contactyourdoctor

immediately. Do notstartthe nextblisterpackuntilyou are sure thatyou are notpregnant.

OthermedicinesandALESSE

Tellyourdoctororpharmacistifyou are takingorhave recentlytaken ormighttake anyothermedicines.

There are some medicinesthatmayinteractwith ALESSE.

Medicinescan sometimesinterfere with each other. Ifyou receive treatmentfromanyotherdoctor, nurseor

qualified healthcare professionalmake sure theyare aware thatyou areusingALESSE as acontraceptive.

Theycan adviseifitwillbe necessaryto take anyadditionalprecautions (e.g.usinga condomorother

barriercontraceptive)while you are takingothermedicineswhile you are takingALESSE.

SomemedicinescanmakeALESSElesseffectiveinpreventingpregnancy,orcancauseunexpected

bleeding. These include medicinesused fortreatmentof:

HIVinfections (ritonavir,nevirapine)

epilepsy(e.g. phenobarbital, phenytoin, primidone, felbamate,carbamazepine, oxcarbazepineor

topiramate)

infections(e.g. rifabutin, rifampicin, griseofulvin, ampicillineorotherpenicillinsortetracycline)

sleep disorders (modafinil)

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gout(phenylbutazone)

the herbalremedySt. John‟sWort(Hypericum perforatum), which is used to treatcertain typesof

depression

Ifyou have been told to take additionalcontraceptive precautions while takinganyofthe above medicines

followyourdoctor‟s instructions carefully. Ifyou need to take the medicine beyond the end ofyourcurrent

tabletpack, missyourtablet-freeweekand startthe nextpackstraightaway.

In some casesyou mayneed to continue to useadditionalbarriercontraception forseveralweeks afteryou

have stopped takingthe medicine.

Alessemayinterfere with the followingmedicines:

Cyclosporin (to reduce the body‟s immune response)

Lamotrigin (forepilepsy)

Takingan antibiotic medicine called troleandomycin mayincreasethe riskforintrahepatic cholestasis

(retention ofbile in the liver)while takingthe combined pill.

Takinga medicine called flunarazine used forpreventingmigraine mayincreasethe riskofgalactorrhoea.

This is acondition where yourbreasts spontaneouslyleakmilkwhen you have notbeen breastfeedingor

recentlyhad ababy.

Pregnancy

Do nottakeALESSEifyou are pregnant. Ifyou thinkyou mayhave become pregnantwhile

usingALESSEtellyourdoctorimmediately.

Breastfeeding

Itis notrecommended thatyou take the combined pillwhile you are breastfeedingasthe hormonescan

affectyourmilk. Ifyou wish to breastfeed, yourdoctorwillbe able to adviseyou on suitable alternative

methods ofcontraception.

Always askyourdoctor, nurse, orhealthcare professionalforadvicebefore takinganymedicine.

Driving andusing machines

The effectofAlesseon the abilityto drive oroperatemachineryhasnotbeen studied.Dizziness has been

reported as aside effect. Ifyou experience dizziness do notdrive oroperate machineryuntilithasresolved.

ALESSEcontainslactose

ALESSE contains lactose. Ifyou sufferfromintolerance to certain sugars you should consultyourdoctor

before takingALESSE.

3. Howto use ALESSE

Always take this medicine exactlyasyourdoctororpharmacisthastold you. Checkwith yourdoctoror

pharmacistifyou are notsure.

Each blisterstrip ofALESSE contains 21 tablets. Take yourfirsttabletfromthe blistershowingthe correct

dayofthe week. You musttake onetableteveryday, with waterifnecessary, atthe same time each dayuntil

the packis finished. You willthen have atabletfree-weekbefore you startyournextpackoftablets. You

willalways startyournextpackon the same dayofthe week.

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Duringthe tabletfreeweekyou willhave bleedingsimilarto a period. This bleedingwillusuallystartafter

two orthreedays, and maynotfinish before you startthe nextpackoftablets.

Ifthisis the firsttime you arestartingthe pillor you have not useda hormonalcontraceptive for the

pastmonth

Take the firsttableton the firstdayofyourperiod.

Startinglaterthan the firstdayofbleeding(fromdays 2-7 ofthe cycle)willmean you willhave to use

additionalbarriercontraception (e.g.condom)forthe first7 days.

Ifyou are changing fromanothercombinedcontraceptive pill

Changing frompills containing 21 tablets in each pack

Finish the packofthe currentpillbefore startingALESSE thenextdaywithouta break.

Changing from‘every day’pills containing 28 tablets in eachpack

Ifyourcurrentpillcontains anyinactive tablets (placebo tablets), do nottake these, and startALESSE

straightawaythe nextdaywithoutleavinganytablet-freebreak.

Ifyou are changing froma progestogen-onlypill, an injectablemethodor an implant

Whenchangingfromaprogestogen-onlypillyou can startALESSEatanytime duringyourmenstrual

cycle, the dayafterstoppingtheprogestogen-onlypill

When changingfroman implant,startALESSEthe dayafterthe implantis removed

Whenchangingfroman injectable contraceptive startALESSEon the dayafteryournextinjection was

due

In allcasesyou mustuse a barriercontraceptive methodduring the first7 days oftaking the pill.

Ifyou are starting ALESSEaftera termination thatoccurred during the firsttrimester(three

months)ofpregnancy

You can starttakingALESSEimmediatelybutshould followthe adviceofyourdoctorbefore doingso.No

additionalbarriercontraception is needed.

Ifyou are starting ALESSEaftergiving birth or aftera termination ofpregnancy that occurred

during the secondtrimester

As with anyothercontraceptive pill,ALESSEshould notbe started less than 28 days aftergivingbirth or

aftertermination ofa second trimesterpregnancybecause you are atan increased riskofblood clots.Ifyou

startlater, you are advised to usea barriercontraceptive method duringthe first7 days oftakingthe pill. If

you havehad sex before startingALESSEbe sure you are notpregnantorwaituntilyournextperiod.

Always askyourdoctorforadviceifyou are notsure.

Ifyou forgetto take ALESSE

Ifyou forgetto take a tabletthereis a risk you could become pregnant

Ifyou realiseyou have missed a tabletwithin 12 hoursofthe time younormallytake your tablet, take the

missed tabletimmediatelyand continue as normal, takingthe nexttabletatthe usualtime untilthe end of

the blisterpack.

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Ifyou realiseyou have missed a tabletmorethan12 hoursafteryou normally take it, there is ariskyou

could become pregnant. In this case:

take the lastmissed tabletimmediately, even ifthis means taking2 tablets on the same day

continue takingthetabletsuntilthe end ofthe blisterpack

in addition, usea barriermethod ofcontraception (e.g.condom)forthe next7 days

ifthis 7-dayperiod extendsbeyond the lasttabletin the pack, startthe nextblisterpackstraightaway

withouta tabletfree break. You mayhave some spottingorbleedingwhile takingthe second pack, this

is nothingto worryabout.

Ifyou have forgottenone ormore tabletsin ablisterpackand you do nothaveanybleedingin the tablet-free

week, you maybe pregnantand youshould askyourdoctorforadvice.

Ifyou have vomiting or diarrhoea

Vomitingorsevere diarrhoeawithin 4 hours oftakingthe pillis similarto ifyou forgetto takea tablet.

Aftervomitingordiarrhoea, you musttake anothertabletfroma reserve blisterpackassoon as possible. If

possible take itwithin 12 hoursofwhen you normallytake yourpill. Ifthis is notpossible or12 hours have

passed, you should followthe adviceabovegiven under“Ifyou realiseyou have missed a tabletmorethan

12 hours afteryou normally take it”.

Ifthese episodes ofvomitingorsevere diarrhoearecuroverseveraldays, you shouldusea barriermethod of

contraception (e.g.condom)untilthe beginningofthe nextblisterpack. Askyourdoctorforadvice.

Howtodelay a period

You can delayyourperiod bystartinganotherpackofALESSEwithoutanytablet-freeweek.You mayhave

some spottingorbleedingwhile takingthe second pack, this is nothingto worryabout.

You should have anormalbleed afterfinishingthe second courseoftablets.

IfyoutakemoreALESSEthanyoushould

IfyouaccidentallytakemoreALESSEthanyoushould,youmayhavesymptomsincludinggastrointestinal

problems(e.g.nausea,vomiting,abdominalpain),breasttenderness,dizziness,drowsiness/fatigueand

vaginalbleeding. These symptoms willreduce naturallyasyourbodydeals with the excesshormones.

Ifyou are worried askyourdoctorforadvice.

4. Possible side effects

Like allmedicines, this medicine can cause side effects, although noteverybodygets them. Ifanyofthe side

effects gets serious, orifyou noticeanyside effects notlisted in this leaflet, pleasetellyourdoctoror

pharmacist.

Ifyou experienceanyofthe following serious side effects, seek medicalhelp immediately:

Aseriousallergic reaction-itis notknown howfrequently thisoccurs

Symptoms include sudden wheeziness, difficultyin breathingordizziness, swellingofthe eyelids,

face, lips orthroat, skin rash, hives.

Ablood clotin the eye-itisnot known howfrequently thisoccurs

Symptoms includelossofvision, pain and swellingofthe eye especiallyifsudden.

Haemolytic uremic syndrome(a condition which affects yourblood and kidneys)–itis notknown

howfrequently thisoccurs

Symptoms include vomiting, diarrhoea(which maybe bloody), fever, feelingweak, passingless urine

than usual.

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Pancreatitis-itis notknown howfrequently thisoccurs

Symptoms includesevere upperabdominalpain which mayspreadtoyourback.

Erythema multiforme-itis notknown howfrequently thisoccurs

Symptoms include askin rash with pink-red blotches especiallyon palms ofhandsorsolesoffeetwhich

mayblister. You mayalso have ulcers in the mouth, eyesorgenitals and have afever.

Otherside effectsinclude:

Very common(mayaffectmore than 1 in 10 people)

Headache, includingmigraines

Breakthrough bleedingand spotting

Nausea

Abdominalpain

Painfulperiods

Common(mayaffectup to 1 in 10 people)

Vaginalirritation and infection, includingthrush

Mood changes, includingfeelingdepressed

Decreased sexualfeeling

Feelingnervous

Feelingdizzy

Vomiting

Diarrhoea

Feelingbloated

Acne(spots)

Skin rash

Noperiods (amenorrhoea)

Changesin the amountofblood lossand length ofperiods

Breastpain/tenderness orbreastenlargementordischarge fromthe nipple

Changesin yourcervix which mightgetpicked up duringa smeartest

Fluid retention (e.g.gettingswollen ankles)

Increases ordecreases in yourweight

Changesin levels offats in yourblood (picked up through blood tests)

Uncommon(mayaffectup to 1 in 100 people)

Increasedappetite

Decreased appetite

Hives(urticaria)

Unusualhairiness (hirsutism)

Hairloss

Darkpatches on yourskin (you mayhave had these in a previous pregnancy)

Increased blood pressure

Gallstones

Intolerance to a sugarcalled glucose

Aggravation ofvaricose veins

Rare(mayaffectup to 1 in 1,000 people)

Yellowingofthe skin oreyes(jaundicecaused byabnormalbile flowin the liver)

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Tenderred lumps underthe skin (erythema nodosum)

Notknown:frequencycannotbe estimated fromthe available data

Benign ormalignantcancerofthe liver

Worseningofan autoimmune condition called systemic lupus erythematosus

Worseningofan inherited blood condition called porphyria

Worseningofuncontrolled orjerkybodymovements (chorea)

Inflammation ofthe optic nerve (symptoms include blurred vision andmaylead to partialorcomplete

lossofsight)

Intolerance to contactlenses

Gallbladderdisease, orworseningofthis condition

Ischaemic orinflammatoryboweldisease-symptoms include abdominalcramps and pain, diarrhoea

(which maybe bloody), weightloss

Stomach cramps

Vaginaldischarge

Decreasein folate levels in the blood

Ifyou are atallworried aboutanynew symptomsorotheraspects ofyourhealth while takingALESSE,

pleasetellyourdoctor.

Reporting ofside effects

Ifyou getanyside effects, talkto yourdoctor,pharmacistornurse. This includesanypossible side effects

notlisted in this leaflet. You can also reportside effects directlyvia HPRAPharmacovigilance, Earlsfort

Terrace, IRL-Dublin 2;Tel:+353 1 6764971;Fax:+353 1 6762517. Website: www.hpra.ie ;E-mail:

medsafety@hpra.ie . Byreportingside effects you can help provide more information on the safetyofthis

medicine.

5. Howto storeALESSE

Keep this medicine outofthe sightand reach ofchildren.

Do notstore above 25

C

Do notusethis medicine afterthe expirydate stated on the blisterpackand the carton afterEXP.

The expirydate refers to the lastdayofthatmonth.

Ifyou stop takingALESSE:Do notthrowawayanymedicinesvia wastewaterorhousehold waste. Ask

yourpharmacisthowto throwawaymedicinesyou no longeruse. These measureswillhelp protectthe

environment.

6. Contentsof the packand otherinformation

What ALESSEcontains

The active substancesare 100 micrograms levonorgestreland 20 micrograms ethinylestradiol.

The otheringredients are :lactosemonohydrate, microcrystalline cellulose, polacrillin potassium,

magnesiumstearate, macrogol1450, hypromellose, titaniumdioxide (E171), synthetic red oxide (E172),

montanglycolwax.

What ALESSElooks like andcontents ofthe pack

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ALESSE tablets are packed in aluminiumfoil/pvc blisterpacks containing21 round pinkbiconvex film

coated tablets with „W‟embossed on oneside and „912‟embossed on the other.

Blisterstrips are contained in an outercardboard carton orin a vinylwalletinsidea cardboard carton.

Each packmaycontain either:

1 x 21 tablets or

3 x 21 tablets or

6 x 21 tablets or

13 x 21 tablets.

Notallpacksizesmaybemarketed.

Marketing AuthorisationHolder

PfizerHealthcare Ireland

9 Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

Manufacturer

PfizerIreland Pharmaceuticals

Newbridge

Little Connell

Co Kildare

Ireland

For anyinformation aboutthis medicinalproduct, pleasecontactthe localrepresentative ofthe Marketing

AuthorisationHolder:

PfizerHealthcare Ireland

9 Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

Thismedicinal productis authorised in the Member Statesofthe EEAunder the following names:

Ireland ALESSE Filmcoated tablets

Spain LOETTE Filmcoated tablets

Denmark LOETTE

Thisleafletwas lastrevised inMM/YYYY.

Ref:AS5_2

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Alessefilmcoatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains100microgramlevonorgestreland20microgramethinylestradiol.

Forthefulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Filmcoatedtablets.

Roundpinkbiconvexfilmcoatedtabletswith“W”embossedononesideand“912”embossedontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Oralcontraception.

4.2Posologyandmethodofadministration

HowtotakeAlesse

Regulardailyintakeoftabletsfor21consecutivedaysisimportantforthepreservationofcontraceptiveefficacy.

Tabletsmustbetakenintheorderdirectedonthepackage,everyday,ataboutthesametime,withsomeliquidasneeded.

Onetabletistobetakendailyfor21consecutivedays.Eachsubsequentpackisstartedaftera7-daytablet-freeinterval,

duringwhichtimeawithdrawalbleedoccurs.Thisusuallystartsondays2-3afterthelasttabletandmaynothave

finishedbeforethenextpackisstarted.

HowtostartAlesse

Noprecedinghormonalcontraceptiveuse[inthepastmonth]

Tablet-takingshouldstartonday1ofthewoman’snaturalcycle(i.e.thefirstdayofhermenstrualbleeding).Startingon

days2-7isallowed,butduringthefirstcycleaback-upmethodofbirthcontrol[suchascondomsandspermicide]is

recommendedinadditionforthefirst7daysoftablet-taking.

Changingfromanothercombinedoralcontraceptive(COC)

ThewomanshouldstartAlessepreferablyonthedayafterthelastactivetabletofherpreviousCOC,butatthelateston

thedayfollowingtheusualtablet-freeorinactivetabletintervalofherpreviousCOC.

Changingfromaprogestin-onlymethod(progestin-onlypill,injection,implant)

Thewomanmayswitchanydayfromtheprogestin-onlypillandshouldbeginAlessethenextday.Sheshouldstart

Alesseonthedayafteranimplantremovalor,ifusinganinjectable,thedayafterthenextinjectionwouldbedue.Inall

ofthesesituations,thewomanshouldbeadvisedtoadditionallyuseaback-upmethodforthefirst7daysoftablet-taking.

Followingfirsttrimesterabortion

Thewomanmaystartimmediately.Whendoingso,sheneednottakeadditionalcontraceptivemeasures.

Followingdeliveryorsecond-trimesterabortion

Health Products Regulatory Authority

______________________________________________________________________________________________________________________

Date Printed 22/08/2014 CRN 2139090 page number: 1

shouldbestartednoearlierthanday28afterdeliveryorsecond-trimesterabortion.Thewomanshouldbeadvisedto

additionallyuseaback-upmethodforthefirst7daysoftablet-taking.However,ifintercoursehasalreadyoccurred,

pregnancyshouldbeexcludedbeforetheactualstartofCOCuse,orthewomanhastowaitforherfirstmenstrualperiod.

(Seesections4.4and4.6.)

Managementofmissedtablets

Contraceptivereliabilitymaybereducediftabletsaremissed,andparticularlyifthemissedtabletsextendthetablet-free

interval.Iftabletsweremissedinthefirstweekofthecycleandintercoursetookplaceintheweekbeforethetablets

weremissed,thepossibilityofapregnancyshouldbeconsidered.

Providedthattheuserislessthan12hourslateintakinganytablet,sheshouldtakeitassoonassheremembers,

andfurthertabletsshouldbetakenattheusualtime.

Ifsheismorethan12hourslateintakinganytablet,contraceptiveprotectionmaybereduced.

Theusershouldtakethelastmissedtabletassoonassheremembers,evenifthismeanstakingtwotabletsinone

day.Shethencontinuestotaketabletsatherusualtime.Inaddition,aback-upmethod,suchasthecondom,

shouldbeusedforthenext7days.

Ifthese7daysrunbeyondthelasttabletinthecurrentpack,thenextpackmustbestartedassoonasthecurrent

packisfinished;nogapshouldbeleftbetweenpacks.Thispreventsanextendedbreakintablet-taking,whichmay

increasetheriskofescapeovulation.Theuserisunlikelytohaveawithdrawalbleeduntiltheendofthesecond

pack,butshemayexperiencespottingorbreakthrough-bleedingontablet-takingdays.

Iftheuserdoesnothaveawithdrawalbleedattheendofthesecondpack,thepossibilityofpregnancymustbe

ruledoutbeforeresumingtablet-takingfromthenextpack.

Incaseofgastrointestinalupset

Theonsetofintercurrentdigestivedisorderswithinfourhoursaftertakingthetablet,suchasvomitingorsevere

diarrhoea,maycausetransientinefficacyofthemethodbyreducingCOChormoneabsorption,andsucheventsshouldbe

dealtwithinthesamewayasinthecasewhereatablethasbeenforgottenforlessthan12hours.Theextratabletshould

betakenfromaback-uppack.Iftheseepisodesrecuroverseveraldays,anonhormonalback-upcontraceptivemethod

shouldthenbeused(condom,spermicide,etc.)untilthebeginningofthenextblisterpack.

Howtodelayaperiod

Todelayaperiod,thewomanshouldcontinuewithanotherpackofAlessewithoutatablet-freeinterval.Theextension

canbecarriedonforaslongaswisheduntiltheendofthesecondpack.Duringtheextension,thewomanmay

experiencebreakthrough-bleedingorspotting.

RegularintakeofAlesseisthenresumedaftertheusual7-day,tablet-freeinterval.

Paediatricpopulation

Safetyandefficacywasevaluatedinsubjectsaged18yearsandabove.

4.3Contraindications

Combinedoralcontraceptives(COCs)shouldnotbeusedinwomenwithanyofthefollowingconditionslistedbelow.

ShouldanyoftheconditionsappearforthefirsttimeduringCOCusetheproductmustbestoppedimmediately:

Venousthrombosispresentorhistory(deepvenousthrombosis,pulmonaryembolism)orother

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thrombogenicrhythmdisorders(currentorhistory)

Arterialthrombosispresentorinhistory(e.g.myocardialinfarction)orprodromalconditions(e.g.

anginapectorisandtransientischaemicattack)

Presenceorhistoryofaprodromiofathrombosis(e.g.transientischaemicattack,anginapectoris)

Cerebrovascularaccidentpresentorinhistory

Thepresenceofasevereormultipleriskfactor(s)forvenousorarterialthrombosismayalso

constituteacontraindication(seesection4.4)

Knownorsuspectedcarcinomaofthebreast

Knownorsuspectedcarcinomaoftheendometriumorotherestrogen-dependentneoplasia

Undiagnosedvaginalbleeding

Severehepaticdisease,currentorprevious,aslongasliverfunctionvalueshavenotreturnedto

normal.

Presenceorhistoryoflivertumours(benignormalignant)

Uncontrolledhypertension

Diabetesmellitusassociatedwithvascularinvolvement

Historyofmigrainewithfocalneurologicalsymptoms

Knownorsuspectedpregnancy

Hypersensitivitytotheactivesubstances(levonorgestrel,ethinylestradiol)ortoanyoftheexcipients

ofAlesselistedinsection6.1

4.4Specialwarningsandprecautionsforuse

Warnings

Ifanyoftheconditions/riskfactorsmentionedbelowispresent,thebenefitsofCOCuseshouldbeweighedagainstthe

possiblerisksforeachindividualanddiscussedwiththewomanbeforeshedecidestostartusingit.Intheeventof

aggravation,exacerbationorfirstappearanceofanyoftheseconditionsorriskfactors,thewomanshouldcontacther

physician.ThephysicianshouldthendecideonwhetherCOCuseshouldbediscontinued.

Cigarettesmokingincreasestheriskofseriouscardiovascularsideeffectsfromoral-contraceptiveuse.Thisriskincreases

withageandwiththeextentofsmokingandisquitemarkedinwomenover35yearsofage.Allwomenwhouseoral

contraceptivesshouldbestronglyadvisednottosmoke.Othermethodsofcontraceptionshouldbeconsideredforthose

womenover35yearsoldwhosmoke.

TheuseofCOCsisassociatedwithincreasedrisksofseveralseriousconditions,includingmyocardialinfarction,

thromboembolism,stroke,hepaticneoplasia,andhypertension.Theriskofmorbidityandmortalityincreasessignificantly

inthepresenceofotherunderlyingriskfactors,suchashypertension,hyperlipidemias,obesity,andparticularly,diabetes

withvascularinvolvement.

CirculatoryDisorders

EpidemiologicalstudieshaveshownthattheincidenceofVTEinusersoforalcontraceptiveswithlow

oestrogencontent(<50µgethinylestradiol)rangesfromabout20to40casesper100,000women-years,but

thisriskestimatevariesaccordingtotheprogestogen.Thiscompareswith5to10casesper100,000women-

yearsfornon-users.Theuseofanycombinedoralcontraceptivecarriesanincreasedriskofvenous

thromboembolism(VTE)comparedwithnouse.

TheexcessriskofVTEishighestduringthefirstyearawomaneverusesacombinedoralcontraceptive.This

increasedriskislessthantheriskofVTEassociatedwithpregnancy,whichisestimatedas60casesper100,000

pregnancies.

VTEisfatalin1-2%ofthecases.

Theoverallabsoluterisk(incidence)ofVTEforlevonorgestrelcontainingcombinedoralcontraceptiveswith30µg

ethinylestradiolisapproximately20casesper100,000women-yearsofuse.Epidemiologicalstudieshavealso

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forstroke.Atwotofourfoldincreaseinrelativeriskofpostoperativethromboemboliccomplicationshasbeenreported

withtheuseoforalcontraceptives.Therelativeriskofvenousthrombosisinwomenwhohavepredisposingconditions

istwicethatofwomenwithoutsuchmedicalconditions.

Extremelyrarely,thrombosishasbeenreportedtooccurinotherbloodvessels,e.g.hepatic,mesenteric,renal,retinal

veinsandarteries,incontraceptivepillusers.Thereisnoconsensusastowhethertheoccurrenceoftheseeventsis

associatedwiththeuseofhormonalcontraceptives.

Symptomsofvenousorarterialthrombotic/thromboemboliceventsorofacerebrovascularaccidentcaninclude:

unusualunilaterallegpainand/orswelling

suddenseverepaininthechest,whetherornotitradiatestotheleftarm

suddenbreathlessness

suddenonsetofcoughing

vertigo

collapsewithorwithoutfocalseizure

weaknessorverymarkednumbnesssuddenlyaffectingonesideoronepartofthebody

motordisturbances

‘acute’abdomen.

TheriskforvenousthromboemboliccomplicationsinCOCsusersincreaseswith:

increasingage

apositivefamilyhistory(venousthromboembolismeverinasiblingorparentatarelativelyearlyage).Ifa

hereditarypredispositionissuspected,thewomanshouldbereferredtoaspecialistforadvicebeforedeciding

aboutanyCOCuse.

prolongedimmobilisation,majorsurgery,anysurgerytothelegs,ormajortrauma.Inthesesituationsitis

advisabletodiscontinuethepill(inthecaseofelectivesurgeryatleastfourweeksinadvance)andnotto

resumeuntiltwoweeksaftercompleteremobilisation.

obesity(bodymassindexover30kg/m²).

thereisnoconsensusaboutthepossibleroleofvaricoseveinsandsuperficialthrombophlebitisintheonsetor

progressionofvenousthrombosis.

TheriskofarterialthromboemboliccomplicationsorofacerebrovascularaccidentinCOCusersincreaseswith:

increasingage

smoking(womenover35yearsshouldbestronglyadvisednottosmokeiftheywishtouseanCOC)

dyslipoproteinemia

hypertension

migraine

valvularheartdisease

atrialfibrillation

obesity(bodymassindexover30kg/m 2

Oralcontraceptiveshavebeenshowntoincreaseboththerelativeandattributablerisksofcerebrovascularevents

(transientischaemicattacks,thromboticandhemorrhagicstrokes),although,ingeneral,theriskisgreatestamongolder

>

35years),hypertensivewomenwhoalsosmoke.Hypertensionhasbeenfoundtobeariskfactorforbothusersand

nonusers,forbothtypesofstrokes,whilesmokingappearstoincreasetheriskforhemorrhagicstroke.

COCuserswithmigraine(particularlymigrainewithaura)maybeatincreasedriskofstroke.

Thepresenceofoneseriousormultipleriskfactors,dependingontypeandseverity,forvenousorarterialdisease,may

constituteanunacceptablelevelofrisk.

Theincreasedriskofthromboembolisminthepuerperiummustbeconsidered(seeSection4.6Pregnancyand

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Othermedicalconditionswhichhavebeenassociatedwithadversevasculareventsincludediabetesmellitus,systemic

lupuserythematosus,hemolyticuremicsyndromeandchronicinflammatoryboweldisease(Crohn'sdiseaseor

ulcerativecolitis)andsicklecelldisease.

Biochemicalfactorsthatmaybeindicativeofhereditaryoracquiredpredispositionforvenousorarterialthrombosis

includeActivatedProteinC(APC)resistance,hyperhomocysteinemia,antithrombin-IIIdeficiency,proteinC

deficiency,proteinSdeficiency,antiphospholipidantibodies(anticardiolipinantibodies,lupusanticoagulant).

Myocardialinfarction

Anincreasedriskofmyocardialinfarctionhasbeenattributedtooral-contraceptiveuse.Thisriskisprimarilyinsmokers

orwomenwithotherunderlyingriskfactorsforcoronary-arterydisease,suchashypertension,hypercholesterolemia,

morbidobesity,anddiabetes.

Smokingincombinationwithoral-contraceptiveusehasbeenshowntocontributesubstantiallytotheincidenceof

myocardialinfarctioninwomenintheirmid-thirtiesorolder,withsmokingaccountingforthemajorityofexcesscases.

Mortalityratesassociatedwithcirculatorydiseasehavebeenshowntoincreasesubstantiallyinsmokersovertheageof

35andnon-smokersovertheageof40amongwomenwhouseoralcontraceptives.

Carcinomaofthereproductiveorgans

Anincreasedriskofcervicalcancerinlong-termusersofCOCshasbeenreportedinsomeepidemiologicalstudies,but

therecontinuestobecontroversyabouttheextenttowhichthisfindingisattributabletotheconfoundingeffectsof

sexualbehaviorandotherfactorssuchashumanpapillomavirus(HPV).

Breastcancer

Ameta-analysisfrom54epidemiologicalstudiesshowedthatthereisaslightlyincreasedrelativerisk(RR=1.24)of

havingbreastcancerdiagnosedinwomenwhoarecurrentlyusingCOCs.Theincreasedriskgraduallydisappearsduring

thecourseofthe10yearsaftercessationofCOCuse.Becausebreastcancerisrareinwomenunder40yearsofage,the

excessnumberofbreastcancerdiagnosesincurrentandrecentCOCusersissmallinrelationtothelifetimeriskofbreast

cancer.Thesestudiesdonotprovideevidenceforcausation.Theobservedpatternofincreasedriskmaybeduetoan

earlierdiagnosisofbreastcancerinCOCusers,thebiologicaleffectsofCOCs,oracombinationofboth.Breastcancers

diagnosedinever-userstendtobelessadvancedclinicallythanthecancersdiagnosedinnever-users.

Hepaticneoplasia/liverdisease

Inrarecases,benignlivertumors,andevenmorerarely,malignantlivertumorshavebeenreportedinusersofCOCs.

Inisolatedcases,thesetumorshaveledtolife-threateningintra-abdominalhemorrhages.Ahepatictumorshouldbe

consideredinthedifferentialdiagnosiswhensevereupperabdominalpain,liverenlargementorsignsofintra-

abdominalhemorrhageoccurinwomentakingCOCs.

Studieshaveshownanincreasedriskofdevelopinghepatocellularcarcinomainlong-termoralcontraceptiveusers;

however,thesecancersareextremelyrare.

WomenwithahistoryofCOC-relatedcholestasisorwomenwithcholestasisduringpregnancyaremorelikelytohave

thisconditionwithCOCuse.IfthesepatientsreceiveaCOC,theyshouldbecarefullymonitored;andifthecondition

recurs,theCOCshouldbediscontinued.

OtherConditions

Carbohydrateandlipidmetaboliceffects

AlthoughCOCsmayhaveaneffectonperipheralinsulinresistanceandglucosetolerance,thereisnoevidencefora

needtoalterthetherapeuticregimenindiabeticsusinglow-doseCOCs.However,diabeticwomenshouldbecarefully

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Womenwithhypertriglyceridemia,orafamilyhistorythereof,maybeatanincreasedriskofpancreatitiswhenusing

COCs.

Asmallproportionofwomenwillhavepersistenthypertriglyceridemiawhileonthepill.Adeclineinserumhigh-density

lipoproteins(HDL)hasbeenreportedwithmanyprogestationalagents

Non-hormonalcontraceptionmaybeconsideredinwomenwithuncontrolleddyslipidemias.

Ocularlesions

Therehavebeencasereportsofretinalthrombosiswiththeuseoforalcontraceptives.Oralcontraceptivesshouldbe

discontinuedifthereisunexplainedpartialorcompletelossofvision,onsetofproptosisordiplopia,papilledema,or

retinalvascularlesions.

Gallbladderdisease

Anincreasedrelativeriskofgallbladderdiseaseinusersoforalcontraceptivesandestrogenshasbeenreportedinsome

studies.

Hypertension

AlthoughsmallincreasesinbloodpressurehavebeenreportedinmanywomentakingCOCs,clinicallyrelevant

increasesarerare.OnlyintheserarecasesanimmediatediscontinuationofCOCuseisjustified.If,duringtheuseofa

COCinpre-existinghypertension,constantlyelevatedbloodpressurevaluesorasignificantincreaseinbloodpressure

donotrespondadequatelytoantihypertensivetreatment,theCOCmustbewithdrawn.Whereconsideredappropriate,

COCusemayberesumedifnormotensivevaluescanbeachievedwithantihypertensivetherapy.

Womenwithahistoryofhypertension,hypertension-relateddiseases,orrenaldiseasesshouldbeencouragedtouse

anothermethodofcontraception.Ifwomenwithhypertensionelecttouseoralcontraceptives,theyshouldbemonitored

closely;andifsignificantelevationofbloodpressureoccurs,oralcontraceptivesshouldbediscontinued.

Headache

AnincreaseinfrequencyorseverityofmigraineduringCOCuse(whichmaybeprodromalofacerebrovascularevent)

maybeareasonforimmediatediscontinuationoftheCOC.Developmentofheadachewithanewpatternthatis

recurrent,persistentorsevererequiresdiscontinuationoftheCOCandinvestigationofthecause.

Bleedingirregularities

Reducedcyclecontrol

WithallCOCs,irregularbleeding(spottingorbreakthroughbleeding)mayoccur,especiallyduringthefirstmonthsof

use.Therefore,theevaluationofanyirregularbleedingisonlymeaningfulafteranadaptationintervalofaboutthree

cycles.

Ifbleedingirregularitiespersistoroccurafterpreviouslyregularcycles,thennon-hormonalcausesshouldbe

consideredandadequatediagnosticmeasuresareindicatedtoexcludemalignancyorpregnancy.Thesemayinclude

curettage.Ifpathologyhasbeenexcludedcontinueduseoftheoralcontraceptiveorachangetoanotherformulation

maysolvetheproblem.

Insomewomenwithdrawalbleedingmaynotoccurduringthetablet-freeinterval.IftheCOChasbeentaken

accordingtothedirectionsdescribedinsection4.2Posologyandmethodofadministrationitisunlikelythatthe

womanispregnant.However,iftheCOChasnotbeentakenaccordingtothesedirectionspriortothefirstmissed

withdrawalbleedoriftwowithdrawalbleedsaremissed,pregnancymustberuledoutbeforeCOCuseiscontinued.

Precautionsforuse

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Priortotheinitiationorreinstitutionofethinylestradiol/levonorgestrelacompletemedicalhistory(includingfamily

history)shouldbetakenandpregnancymustberuledout.Bloodpressureshouldbemeasuredandaphysical

examinationshouldbeperformed,guidedbythecontraindications(seesection4.3Contraindications)andwarnings

(seesection4.4SpecialWarningsandspecialprecautionsforuse').Thewomanshouldalsobeinstructedtocarefully

readtheuserleafletandtoadheretotheadvicegiven.Thefrequencyandnatureofexaminationsshouldbebasedon

establishedpracticeguidelinesandbeadaptedtotheindividualwoman.

WomenshouldbeadvisedthatoralcontraceptivesdonotprotectagainstHIVinfections(AIDS)andothersexually

transmitteddiseases.

Liverfunction

AcuteorchronicdisturbancesofliverfunctionmaynecessitatethediscontinuationofCOCuseuntiltheliverfunction

valuesreturntonormal.Recurrenceofcholestaticjaundiceand/orcholestasis-relatedprurituswhichoccurredduring

pregnancyorprevioususeofsexsteroidsnecessitatesthediscontinuationofCOCs.

Emotionaldisorders

Patientsbecomingsignificantlydepressedwhiletakingoralcontraceptivesshouldstopthemedicationandusean

alternatemethodofcontraceptioninanattempttodeterminewhetherthesymptomisdrug-related.Womenwithahistory

ofdepressionshouldbecarefullyobserved,andthedrugdiscontinued,ifdepressionrecurstoaseriousdegree.

Folatelevels

Serumfolatelevelsmaybedepressedbyoral-contraceptivetherapy.Thismaybeofclinicalsignificanceifawoman

becomespregnantshortlyafterdiscontinuingoralcontraceptives.

St.John’swort

Ifcombinedoralcontraceptives(COCs)andSt.John’swortareusedconcomitantly,anon-hormonalback-upmethodof

birthcontrolisrecommended(seeSection4.5).

Other

Reducedefficacy

TheefficacyofCOCsmaybereduced,intheeventofmissedtabletsvomitingordiarrheaorconcomitantmedication.

ThefollowingconditionshavebeenreportedtooccurordeterioratewithbothpregnancyandCOCuse,buttheevidence

ofanassociationwithCOCuseisinconclusive:jaundiceand/orpruritusrelatedtocholestasis,gallstones,porphyria,

systemiclupuserythematosus,haemolyticuraemicsyndrome,Sydenham´schorea,herpesgestationis,otosclerosis-related

hearingloss.

Inwomenwithhereditaryangioedemaexogenousestrogensmayinduceorexacerbatesymptomsofangioedema.

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,Lapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

WorseningofCrohn’sdiseaseandofulcerativecolitishasbeenreportedduringCOCuse.

Chloasmamayoccasionallyoccur,especiallyinwomenwithahistoryofchloasmagravidarum.Womenwitha

tendencytochloasmashouldavoidexposuretothesunorultravioletradiationwhilsttakingCOCs.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

InteractionsbetweenCOCsandotherdrugsmayimpairthecontraceptiveefficacyand/orleadtobreakthroughbleeding

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Womenontreatmentwithanyofthesedrugsshouldtemporarilyuseabarriermethodoranothermethodof

contraceptioninadditiontotheCOC.AfterdiscontinuationofsubstancesthatmayleadtodecreasedEEserum

concentrations,useofanonhormonalback-upmethodisrecommendedforatleast7days.Withliverenzymeinducing

drugs,thebarriermethodmustbeusedduringthewholetimeoftheconcomitantdrugtherapyandfor28daysafterits

discontinuation.

IfthedrugtherapyrunsbeyondtheendofthetabletsintheCOCpack,thenextCOCpackshouldbestartedwithout

theusualtablet-freeinterval.

Hepaticmetabolism:Interactionscanoccurwithdrugsthatinducehepaticmicrosomalenzymes,resultinginincreased

clearanceofsexhormones(e.g.phenytoin,barbiturates,primidone,phenylbutazone,carbamazepine,

oxycarbamazepine,rifampicin,rifabutin,modafinilandpossiblyalsooxcarbazepine,topiramate,felbamate,

griseofulvin,andproductscontainingtheherbalremedySt.John’swort(Hypericumperforatum)).Theinducingeffect

canpersistforatleast2weeksaftercessationoftreatmentwithStJohn’sWort.IfCOC’sandStJohn’sWortareused

concomitantly,anonhormonalbackupmethodofbirthcontrolisrecommended.

AlsoHIVprotease(e.g.ritonavir)andnon-nucleosidereversetranscriptaseinhibitors(e.g.nevirapine),and

combinationsofthem,havebeenreportedtopotentiallyincreasehepaticmetabolism.

Enterohepaticcirculation:Someclinicalreportssuggestthatenterohepaticcirculationofestrogensmaydecreasewhen

certainantibioticagents(e.g.penicillins,tetracyclins)aregivenatthesametime,whichmayreduceethinylestradiol

concentrationsinserum.Womenontreatmentwithantibioticsshoulduseabarriermethodduringtheuseofthe

antibioticsanduntil7daysaftertheirdiscontinuation.Womenontreatmentwiththeantibioticsrifampicinand

griseofulvinshouldfollowtheliverenzymeinducingdrugsrecommendationabove).

TroleandomycinmayincreasetheriskofintrahepaticcholestasisduringcoadministrationwithCOCs.

Oralcontraceptivesmayinterferewiththemetabolismofcertainotherdrugs.Increasedplasmaconcentrationsof

cyclosporinhavebeenreportedwithconcomitantadministrationofOCs.COCshavebeenshowntoinducemetabolism

oflamotrigineresultinginsub-therapeuticplasmaconcentrationsoflamotrigine.

CompetitiveinhibitorsforsulfationinthegastrointestinalwallmayincreaseserumEEconcentrations,suchas

ascorbicacid(vitaminC)andparacetamol

Inpatientstreatedwithflunarizine,useoforalcontraceptiveshasbeenreportedtoincreasetheriskofgalactorrhea.

Laboratorytests

Theuseofcontraceptivesteroidsmayinfluencetheresultsofcertainlaboratorytests,includingbiochemicalparameters

ofliver,thyroid,adrenalandrenalfunction,plasmalevelsof(carrier)proteins(e.g.,corticosteroidbindingglobulinand

lipid/lipoproteinfractions),parametersofcarbohydratemetabolismandparametersofcoagulationandfibrinolysis.

Changesgenerallyremainwithinthenormallaboratoryrange.

Note:Theprescribinginformationofconcomitantmedicationsshouldbeconsultedtoidentifypotentialinteractions.

4.6Fertility,pregnancyandlactation

Fertility

TherearenoclinicalsafetydataontheeffectsofAlesseonfertility.

Pregnancy

Alesseisnotindicatedduringpregnancy.

IfthewomanbecomespregnantwhileusingAlessefurtherintakemustbestopped.

However,extensiveepidemiologicalstudieshaverevealedneitheranincreasedriskofbirthdefectsinchildrenbornto

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earlypregnancy

Breastfeeding

LactationmaybeinfluencedbyCOCs,astheymayreducetheamountandchangethecompositionofbreastmilk,

therefore,theuseofCOCsshouldgenerallynotberecommendeduntilthenursingmotherhasweanedherchildoffbreast

milk.Smallamountsofcontraceptivesteroidsand/ormetaboliteshavebeenidentifiedinthemilkofnursingmothers.

Theseamountsmayaffectthechild.

4.7Effectsonabilitytodriveandusemachines

TheimpactofAlesseontheabilitytodriveandusemachineshasnotbeensystematicallyevaluated.Patientsshould

exercisecautionuntiltheyknowthatAlessedoesnotaffecttheseabilities.

4.8Undesirableeffects

ForseriousadverseeffectswhentakingCOCs,seesection4.4.Specialwarningsandprecautionforuse.Forvenous

andarterialthromboemebolicevents,lipiddisorders,gallbladderdiseases,breastcancer,hypertension,livertumours,

Crohn’sdisease,ulcerativecolitis,porphyria,systemiclupuserythematosus,herpesgestationis,Sydenham’schorea,

haemolyticuremicsyndrome,cholestaticjaundiceseealsosection4.4.

ThefrequencyofdiagnosisofbreastcancerisslightlyincreasedamongOCusers.Asbreastcancerisrareinwomen

under40yearsofagetheexcessnumberissmallinrelationtotheoverallriskofbreastcancer.CausationwithCOC

useisunknown.Forfurtherinformation,seesections4.3Contraindicationsand4.4Specialwarningsandprecautions

foruse.

Themostfrequently(greaterthan10%)reportedadverseeventsduringphaseIIIstudiesandpostmarketingsurveillance

inwomenusingAlesseareheadache,includingmigraines,dysmenorrhoea,abdominalpain,nausea,andbreakthrough

bleeding/spotting.

OtheradverseeventshavebeenreportedinwomentakingAlesse:

Systemorgan

class Frequencyofadverseevents

Common

(1/100to<1/10) Uncommon

(1/1,000to

<1/100) Rare

(1/10,000

to

<1/1,000) Frequencynot

known(cannotbe

estimatedfromthe

availabledata)

Infectionsand

infestations Vaginitis,

including

candidiasis

Neoplasms

benign,

malignantand

unspecified

(includingcysts

andpolyps) Hepaticneoplasm,

malignant,Hepatic

adenoma

Bloodand

lymphatic

system

disorders Haemolyticuraemic

syndrome

Immunesystem

disorders Anaphylactic/anaphylactoid

reaction,

angioedema***

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nutrition

disorders tolerance

impaired,

increased

appetite,

decreased

appetite

Psychiatric

disorders Moodaltered

including

depression;

nervousness,

changeinlibido

Nervoussystem

disorders Dizziness Opticneuritis*,

choreaaggravated

Eyedisorders Retinalvascular

thrombosis,contact

lensintolerance

Vascular

Disorders Aggravation

ofvaricose

veins

Gastrointestinal

disorders Vomiting,

diarrhoea,bloating Pancreatitis,colitis

ischaemic,

inflammatorybowel

disease(Crohn’s

disease,colitis

ulcerative)

abdominalcramps

Hepatobiliary

disorders Cholelithiasis Jaundice

cholestatic Gallbladder

disorder**

Skinand

subcutaneous

tissuedisorders Rash,acne Urticaria,

chloasma

whichmay

persist,

hirsutism,

alopecia Erythema

nodosum Erythema

multiforme

Musculoskeletal

andconnective

tissuedisorders Excerbationof

systemiclupus

erythematosus

Reproductive

systemand

breastdisorders Breastpain,breast

tenderness,breast

secretion,change

inmenstrualflow,

changeincervical

ectropionand

secretion,

amenorrhoea,

Vaginaldischarge

Congenital,

familialand

genetic

disorders Excerbationof

porphyria

General

disordersand Fluidretention,

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*mayleadtopartialorcompletelossofvision

**COC’smayworsenoraccelerategallbladderdisease

***Inwomenwithhereditaryangioedema,exogenousoestrogensmayinduceorexacerbatesymptomsofangioedema

Reportingofsuspectedadversereactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany

suspectedadversereactionsviaHPRAPharmacovigilance,EarlsfortTerrace,IRL-Dublin2;Tel:+35316764971;

Fax:+35316762517.Website: http://www.hpra.ie/ ;E-mail: medsafety@hpra.ie .

4.9Overdose

Therehavebeennoreportsofseriouseffectsfromoverdose.Symptomsthatmaybecausedbyoverdosearenausea,

vomiting,drowsiness/fatigue,andslightvaginalbleedinginyounggirls.Therearenoantidotesandthetreatmentis

symptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Progestin/estrogencombinedoralcontraceptive

ATCcode:G03A07

PearlIndex(excludingpregnanciesaftermissing3ormorepills)is0.93andPearlIndexformethodfailureis0.64

(26,554cycles).

ALESSEisacombinationoralcontraceptive(COC)containingethinylestradiol(EE)andlevonorgestrel.COCshave

beenshowntoexerttheireffectbydecreasinggonadotropinsecretiontosuppressovarianactivity,tosuppress

proliferationoftheendometriumandtocausethickeningofcervicalmucus.

5.2Pharmacokineticproperties

Pharmacokinetics

Absorption

NospecificinvestigationoftheabsolutebioavailabilityofAlesseinhumanshasbeenconducted.However,literature

indicatesthatlevonorgestrelisrapidlyandcompletelyabsorbedafteroraladministration(bioavailabilityabout100%)

andisnotsubjecttofirst-passmetabolism.Ethinylestradiolisrapidlyandalmostcompletelyabsorbedfromthe

gastrointestinaltract,but,duetofirst-passmetabolismingutmucosaandliver,thebioavailabilityofethinylestradiolis

between38%and48%.

AfterasingledoseofAlesseto22womenunderfastingconditions,maximumserumconcentrationsoflevonorgestrel

are2.8±0.9ng/mL(mean±SD)at1.6±0.9hours.Atsteadystate,attainedfromday19onwards,maximum

levonorgestrelconcentrationsof6.0±2.7ng/mLarereachedat1.5±0.5hoursafterthedailydose.Theminimum

administration

siteconditions

Investigations Weightincreased,

weightdecreased,

lipidsincreased

including

hypertriglyceridemia Blood

pressure

increased Bloodfolate

decreased(serum

folatelevelsmaybe

depressedbyCOC

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fromday1(singledose)todays6and21(multipledoses)by34%and96%,respectively.Unboundlevonorgestrel

concentrationsincreasedfromday1todays6and21by25%and83%,respectively.Thekineticsoftotal

levonorgestrelarenon-linearduetoanincreaseinbindingoflevonorgestreltosexhormonebindingglobulin(SHBG),

whichisattributedtoincreasedSHBGlevelsthatareinducedbythedailyadministrationofethinylestradiol.

Followingasingledose,maximumserumconcentrationsofethinylestradiolof62±21pg/mLarereachedat1.5±0.5

hours.Atsteadystate,attainedfromatleastday6onwards,maximumconcentrationsofethinylestradiolwere77±30

pg/mLandwerereachedat1.3±0.7hoursafterthedailydose.Theminimumserumlevelsofethinylestradiolat

steadystateare10.5±5.1pg/mL.Ethinylestradiolconcentrationsdidnotincreasefromdays1to6,butdidincrease

by19%fromdays1to21.

TableIprovidesasummaryoflevonorgestrelandethinylestradiolpharmacokineticparameters.

Distribution

LevonorgestrelinserumisprimarilyboundtoSHBG.Ethinylestradiolisabout97%boundtoplasmaalbumin.

EthinylestradioldoesnotbindtoSHBG,butinducesSHBGsynthesis.

Biotransformation

Levonorgestrel:Themostimportantmetabolicpathwayoccursinthereductionofthe4 -3-oxogroupand

hydroxylationatpositions2,1,and16,followedbyconjugation.Mostofthemetabolitesthatcirculateinthe

bloodaresulfatesof3,5-tetrahydro-levonorgestrel,whileexcretionoccurspredominantlyintheformof

glucuronides.Someoftheparentlevonorgestrelalsocirculatesas17-sulfate.Metabolicclearanceratesmaydiffer

amongindividualsbyseveral-fold,andthismayaccountinpartforthewidevariationobservedinlevonorgestrel

concentrationsamongusers.

Ethinylestradiol:CytochromeP450enzymes(CYP3A4)intheliverareresponsibleforthe2-hydroxylationthatisthe

majoroxidativereaction.The2-hydroxymetaboliteisfurthertransformedbymethylationandglucuronidationpriorto

urinaryandfecalexcretion.LevelsofcytochromeP450(CYP3A)varywidelyamongindividualsandcanexplainthe

variationinratesofethinylestradiol2-hydroxylation.Ethinylestradiolisexcretedintheurineandfecesas

TABLEI:MEAN(SD)PHARMACOKINETICPARAMETERSOFAlesse

OVERA21-DAYDOSINGPERIOD

---------------------------------------------Levonorgestrel-------------------------------------------

ng/mL T

h/mL CL/F

mL/h/kg V

L/kg SHBG

nmol/L

2.75(0.88) 1.6(0.9) 35.2(12.8) 53.7(20.8) 2.66(1.09) 57(18)

4.52(1.79) 1.5(0.7) 46.0(18.8) 40.8(14.5) 2.05(0.86) 81(25)

6.00(2.65) 1.5(0.5) 68.3(32.5) 28.4(10.3) 1.43(0.62) 93(40)

--------------------------------------UnboundLevonorgestrel--------------------------------------

pg/mL H pgh/mL L/h/kg L/kg fu%

51.2(12.9) 1.6(0.9) 654(201) 2.79(0.97) 135.9(41.8) 1.92(0.30)

77.9(22.0) 1.5(0.7) 794(240) 2.24(0.59) 112.4(40.5) 1.80(0.24)

103.6(36.9) 1.5(0.5) 1177(452) 1.57(0.49) 78.6(29.7) 1.78(0.19)

-----------------------------------Ethinylestradiol----------------------------------

pg/mL H pgh/mL mL/h/kg L/kg

62.0(20.5) 1.5(0.5) 653(227) 567(204) 14.3(3.7)

76.7(29.9) 1.3(0.7) 604(231) 610(196) 15.5(4.0)

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Excretion

Theeliminationhalf-lifeforlevonorgestrelisapproximately36±13hoursatsteadystate.Levonorgestrelandits

metabolitesareprimarilyexcretedintheurine(40%to68%)andabout16%to48%areexcretedinfeces.The

eliminationhalf-lifeofethinylestradiolis18±4.7hoursatsteadystate.

5.3Preclinicalsafetydata

Thetoxicityprofilesofethinylestradiolandlevonorgestrelaloneandincombinationarewellknown.Becauseof

markedspeciesdifferences,preclinicalresultspossessalimitedpredictivevaluefortheapplicationofestrogensin

humans.

Inexperimentalanimals,ethinylestradioldisplayedanembryotoxiceffect;malformationoftheurogenitaltractand

feminisationofmalefetuseswereobserved.

Levonorgestreldisplayedanembryotoxiceffectinanimalexperimentsavirilisingeffectonfemalefetuses.

Reproductiontoxicologystudiesinrats,miceandrabbitsprovidednootherevidenceofteratogenicity.

Preclinicaldatabasedonconventionalstudiesofrepeateddosetoxicity,genotoxicityandcarcinogenicpotential

revealednoparticularhumanriskbeyondthosediscussedinothersectionsoftheSmPC.However,itmustbebornein

mindthatsexsteroidscanpromotethegrowthofcertainhormone-dependenttissuesandtumours.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Lactosemonohydrate

Microcrystallinecellulose

Polacrilinpotassium

Magnesiumstearate

Filmcoatingmaterial:

Macrogol1450

Hypromellose

TitaniumdioxideE171

SyntheticredironoxideE172

Montanglycolwax.

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

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Primarycontainer

PVC/aluminiumfoilblisterpack

Secondarycontainer

Cardboardcartonorvinylwalletincardboardcarton

Presentation

Packcontaining1x21,3x21,6x21and13x21tablets.Notallpacksmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA822/65/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:24January2003

Dateoflastrenewal:07December2008

10DATEOFREVISIONOFTHETEXT

Health Products Regulatory Authority

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Date Printed 22/08/2014 CRN 2139090 page number: 14

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