CABERGOLINE 0.5 MILLIGRAM TABLETS 0.5 Milligram Tablets

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
CABERGOLINE
Available from:
Arrow Generics Limited
INN (International Name):
CABERGOLINE
Dosage:
0.5 Milligram
Pharmaceutical form:
Tablets
Prescription type:
Product subject to prescription which may not be renewed (A)
Authorization status:
Withdrawn
Authorization number:
PA1130/014/001
Authorization date:
2013-04-29

UK/H/955/01/DC

PACKAGE LEAFLET:INFORMATION FOR THE USER

Cabergoline 0.5mg Tablets

cabergoline

Read all of this leaflet carefully before you start taking this medicine.

- Keep this leaflet. You mayneed to read it again.

- If youhave anyfurtherquestions, ask your doctor orpharmacist.

- This medicine has been prescribed for you. Do not pass it on toothers. Itmayharmthem, even if their

symptoms are the sameasyours.

- If anyof the side effects gets serious, or ifyou noticeanyside effects not listed in this leaflet, please

tell your doctor or pharmacist.

In this leaflet:

1. What Cabergoline 0.5mg Tablets are and what theyare used for

2. Before youtake Cabergoline 0.5mg Tablets

3. How to take Cabergoline 0.5mg Tablets

4. Possible side effects

5. How to store Cabergoline 0.5mg Tablets

6. Further information.

1. WHAT CABERGOLINE0.5MG TABLETS AREAND WHAT THEYARE USED FOR

Cabergoline belongs to agroup ofmedicines knownas prolactin inhibitors. Cabergoline prevents lactation

(production of milk) bydecreasing the level of a hormone known as prolactin.

Cabergoline 0.5mg Tablets are also used to reduce abnormol quantities of the hormone prolactin in the

blood.

2. BEFORE YOU TAKECABERGOLINE 0.5MG TABLETS

Do not take Cabergoline 0.5mg Tablets

- ifyou are allergic (hypersensitive) to cabergoline orother ergot alkaloids medicines (e.g bromocriptine),

or to any of the other ingredients of Cabergoline 0.5mg Tablets

- if you haveuncontrolled highblood pressure

- ifyouhave swelling of thehands, feet and high blood pressure during or after pregnancy(pre-

eclampsia, eclampsia)

- ifyouhave ever suffered fromor are being treated for psychosis (currentlyor inthe past) or ifyou are at

risk of psychosis duringpregnancyor after childbirth

- ifyouhave ever been diagnosed in thepast withproblems described as fibrotic reactions affecting the

lungs, backofthe abdomen and kidneysor heart

- ifyou willbe treated with Cabergoline 0.5mg Tabletsfor a longperiod and have orhad fibrotic reactions

(scar tissue) affecting yourheart.

Take special care with Cabergoline 0.5mg Tablets

If youhave anyof the following healthproblems youmust informyour doctor before takingCabergoline

0.5mg Tablets as themedicinal productmaybe unsuitable foryou.

- impaired kidneyfunction

- impaired liver function

- cardiovascular disease

- low blood pressure

- Raynaud's syndrome (a painful condition where fingers ortoes turn white, then bluish and finally red on

exposure to cold or stress)

- stomach ulceror bleeding in the gastrointestinal tract (this cancause black faeces or vomitingwith

blood)

UK/H/955/01/DC

- ifyouhave orhad fibrotic reactions (scar tissue) affectingyour heart, lungsor abdomen. In case you are

treated with Cabergoline 0.5mg Tablets for a longperiod,your physician will check before starting

treatment whether your heart,lungs and kidneysare in good condition. He/she will also have an

echocardiogram(an ultrasoundtest of the heart) takenbefore treatment is started and at regular intervals

during treatment. If fibroticreactions occurtreatmentwill have to be discontinued.

Tell your doctor ifyou oryour family/carer notices thatyou are developing urges orcravings to behave in

waysthat are unusual foryou andyou cannot resist the impulse, drive or temptation to carryout certain

activities thatcould harmyourself or others. These are called impulse control disorders and can include

behaviours such as addictive gambling, excessive eatingor spending, an abnormally high sex drive or an

increase in sexual thoughtsor feelings.Your doctor may need to adjust or stop your dose.

Infertility can be reversed in women taking Cabergoline 0.5mg Tablets and pregnancycanoccur before the

menstrual cycle has normalized. Before you can start using cabergolineyouhave to exclude that you are

pregnant. Additionallyyou should takecare not becoming pregnant for at least one month once you have

stopped treatment with cabergoline.Suitablemeansof contraception should therefore be usedduring

treatment if necessary.

The safetyand efficacyofCabergoline 0.5mg Tablets has not been established in subjects less than 16years

of age.

Before you are given Cabergoline 0.5mg Tablets yourdoctor will arrange foryou to have tests to assess the

condition ofyour heart. Your doctor will continuetomonitor yourmedical condition while taking

Cabergoline 0.5mg Tablets.

Taking other medicines

Certainmedicines used for reducing blood pressure and certain medicinal products (e.g phenothiazines,

butyrophenones or thioxanthenes) used for thetreatment of pyschological illness (schizophrenia or

psychoses), if taken at the sametime asCabergoline 0.5mg Tablets can interferewith the effects of

cabergoline. The treating doctor should thereforebe aware of all medicines you maybe taking.

There are othermedicinessuch as other ergot alkaloids,medicines to stopyou fromfeeling sick (such as

metoclopramide), and macrolide antibiotics (such aserythromycin) that mayaffect the activityand

tolerabilityofCabergoline 0.5mg Tablets.

Tell your doctor or pharmacist if you are taking orhave recentlytaken any othermedicinal products,

includingthose obtained without aprescription and natural medicalproducts/natural products.

Taking Cabergoline 0.5mg Tablets with food anddrink

Cabergoline 0.5mg Tablets should be taken bymouth, preferablywith meals. This will decrease the risk of

side effects like feeling sick.

The effect of alcohol on the tolerabilityof cabergoline is unknown and shouldbe avoided while you are

taking Cabergoline 0.5mg Tablets

Pregnancy and breast-feeding

Pregnancy

There is onlylimited experience of the use of cabergoline during pregnancy. Youshould therefore consult

your doctor ifyou are pregnant or plantobecome pregnant before the treatment is started. If you are being

treated with Cabergoline 0.5mg Tablets and becomepregnant during this time you shoulddiscontinue the

treatment and contact yourdoctor as soon as possible. Contraception should be continued forat least 4 weeks

after stoppingCabergoline 0.5mg Tablets.

Infertility can be reversed in women taking Cabergoline 0.5mg Tablets and pregnancycanoccur before the

menstrual cycle has normalized. Suitable means of contraception should therefore be used during treatment if

necessary.

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Breast Feeding

You should not take Cabergoline 0.5mg Tablets if you wish to continue breastfeeding as it willaffect

lactation (milk production).

Ask your doctor for advicebefore takingany medicine.

Driving andusing machines

Cabergoline 0.5mg Tablets can adversely affect the abilityto react in somepeople and this shouldbe

considered in cases wherea high level of alertness isrequired, e.g.driving a car and in precision work.

Cabergoline 0.5mg Tablets can cause somnolence (extremedrowsiness) and sudden sleep onset. Persons

affected bythis should therefore not drive or take part in activities in which reduced alertness could incur a

risk of serious harm(e.g. using machines), until suchrecurrent episodes and somnolence have resolved. If

affected, consultyour doctor.

Important information about someof theingredients of Cabergoline 0.5mg Tablets

Cabergoline 0.5mg Tablets contain lactose. If youhave beentoldbyyour doctorthatyouhavean intolerance

to somesugars, contact your doctor beforetaking thismedicinal product.

3. HOW TO TAKE CABERGOLINE 0.5MG TABLETS

Alwaystake Cabergoline 0.5mg Tablets exactlyas yourdoctor has toldyou. You should check withyour

doctor orpharmacist if youare not sure.

The tablets shouldbe taken with meals toreduce sideeffectssuch as nausea, vomiting and stomach pains.

Adults

The usual dose is as follows:

To prevent lactation (production of milk):

two tablets on the first day after givingbirth.

To reduce prolactin levels in other conditions:

Treatment is started with one tablet once a week inone or two doses (e.g. half a tablet on a Mondayand

half a tablet on a Thursday).The dose maythen beincreased gradually as directed byyourdoctor up toa

suitablemaintenance dose. The usual maintenance dose is from0.25 mgup to 2mgper week.

If you takemore Cabergoline 0.5mg Tablets than you should

It is important not totake too manytablets.Contact your nearest hospital Accident and Emergency

department or a doctor foradvice, if youhave taken too manytablets or ifyouthink a childhas swallowed

any.Symptoms of an overdose mayinclude nausea,vomiting, reduced bloodpressure, confusion/psychosis

or hallucinations (seeing things). Takethis leaflet and anytablets thatyou still have to show the doctor.

If you forgetto take Cabergoline 0.5mg Tablets

If you forget totake a dose at the right time, youcan take it as soon as you remember it.

If it is almost time to take the next dose,skipthe forgotten dose andtake the nextdose as usual.

If you stop taking Cabergoline 0.5mg Tablets

If you stop using Cabergoline 0.5mg Tablets the symptoms of your illnessmaybecomemoresevere andyou

shoulddiscuss with yourdoctor before youdiscontinue therapy. Cabergoline 0.5mg Tablets takemanydays

to be cleared fromthe bloodstreamand effectsmayworsen over a 2 week period.

If youhave anyfurtherquestions on theuse ofthis product, askyour doctoror pharmacist.

UK/H/955/01/DC

4.POSSIBLE SIDE EFFECTS

Like all medicines, Cabergoline 0.5mg Tablets can cause side effects, althoughnot everybodygets them.

You may experiencethefollowing side effects:

inabilitytoresist the impulse, drive or temptation toperforman action that could be harmful toyou or

others, which mayinclude:

¾Strong impulse to gamble excessivelydespite serious personal or familyconsequences.

¾Altered or increased sexual interest and behaviourofsignificant concern toyouor to others, for

example, an increased sexual drive.

¾Uncontrollable excessive shoppingor spending

¾binge eating (eating large amounts of food in a shorttimeperiod) or compulsive eating (eating more

food than normal andmore than is needed to satisfyyour hunger)

Tell your doctor if you experience any of these behaviours; they will discuss ways of managingor

reducing thesymptoms

The following side effectsmayalso occur:

Very common side effects (affecting more than 1 person in10):

Dizzinessand lightheadedness on standing, involuntary/uncontrolled movements, nausea and heart valve and

related disorders e.g. inflammation (pericarditis) or leaking of fluid in thepericardium(pericardial effusion).

The earlysymptomsmaybe one or more of the following: difficulty breathing,shortness of breath, chest or

back pain andswollen legs. If you experience any one of these symptoms you must tell your doctor

immediately.

Common side effects (affecting less than 1 person in10 but more than 1person in 100):

Vomiting, headaches, feeling tired or extreme drowsiness, digestive disturbances, inflammation of the

stomach lining (gastritis), stomach pain, constipation,redness of the skin, abnormalheart beat (palpitations),

chest pain (angina), depression, hallucinations confusion, crawling/prickling sensation in the body,swelling

in the extremities of the arms and legs, coughingorpain when breathing, drop inred blood cells and changes

in blood test results.

Uncommon side effects (affecting less than 1person in100 butmore than 1person in 1000):

Partial blindness (hemianopsia), nose bleeds, rednessand pain in the extremitiesof the arms and legs

(erythromelalgia)

Rare (affecting less than one person in 1,000but morethan one person in 10, 000):Episodesof sudden

sleepiness, fainting and cramp in the fingers or calves.

If any of the side effects becomesserious, or ifyou notice anysideeffects not listed in this leaflet, please tell

your doctor orpharmacist.

5. HOW TO STORE CABERGOLINE0.5MG TABLETS

Keep out of the reach and sight of children.

Do not use Cabergoline 0.5mg Tabletsafter the expirydate which is stated on the bottle after Exp. The

expirydate refers to the last dayof that month.

Do not storeabove 25 °C.Store in the original package to protect frommoisture.

Do not remove the package containingthe silica gel (desiccant) fromthe bottle, please refer tosection 6

“Further information”.

UK/H/955/01/DC

Medicines shouldnot bedisposed of viawastewateror household waste. Ask yourpharmacisthow to

dispose of medicines no longer required. Thesemeasures will help to protect theenvironment.

6. FURTHER INFORMATION

What Cabergoline 0.5mgTablets contains

- The active substance is cabergoline. Eachtablets contains 0.5mg cabergoline.

- The other ingredients are lactosemonohydrate and leucine.

What Cabergoline 0.5mg Tablets looks like and contents of the pack

Your medicine is in the formof a tablet.The tablets are white to off-white, capsule-shaped embossed with

‘C |5’ ononeside and ‘> partial score >’ on theotherside.

Cabergoline 0.5mg Tablets are packed inglass bottleswith a polypropylene screw cap. Within each bottleis

a package which contains silica gel (desiccant) which helps protect your tablets against moisture.

Each bottle contains 2,4,8, 20, 28, 30,40 & 80 tablets.

Not all pack sizesmaybemarketed.

Marketing AuthorisationHolder:

Arrow Generics Limited, Unit 2, Eastman Way, Stevenage, Herts, SG1 4SZ, U.K.

Manufacturer:

Juta PharmaGmbH, Gutenbergstrasse13, 24941, Flensburg, Germany

Arrow Pharma (Malta) Limited, 62 Hal FarIndustrial Estate, Birzebbugia BBG06, Malta

This leafletwas last revised in 10/2012.

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cabergoline0.5mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains0.5mgcabergoline.

Excipient:lactosemonohydrate75mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

Awhitetooff-white,capsule-shapedtablet,embossedwith‘C|5’ononesideand‘partialscore>’ontheotherside.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inhibitionoflactationformedicalreasons.

Hyperprolactimaemicdisorders.

Prolactinsecretingpituitaryadenomas.

Idiopathichyperprolactinaemia.

Itisrecommendedthatthemedicinalproductisinitiallyprescribedbyanappropriatespecialistorafterconsultinga

specialist.

4.2Posologyandmethodofadministration

Cabergolineistobeadministeredbytheoralroute.

Inordertoreducetheriskofgastrointestinalundesirableeffectsitisrecommendedthatcabergolinebepreferably

takenwithmealsforallthetherapeuticindications.

Treatmentofhyperprolactinaemicdisorders

Therecommendedinitialdosageofcabergolineis0.5mgperweekgiveninone(single0.5mg)ortwo(separate0.25

mg)doses(e.g.onMondayandThursday)perweek.

Theweeklydoseshouldbeincreasedgradually,preferablybyadding0.5mgperweekatmonthlyintervalsuntilan

optimaltherapeuticresponseisachieved.

Thetherapeuticdosageisusually1mgperweekandrangesfrom0.25mgto2mgcabergolineperweek.

Dosesofcabergolineupto4.5mgperweekhavebeenusedinhyperprolactinaemicpatients.Themaximumdailydose

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Theweeklydosemaybegivenasasingleadministrationordividedintotwoormoredosesperweekaccordingto

patienttolerability.Divisionoftheweeklydoseintomultipleadministrationsisadvisedwhendoseshigherthan1mg

perweekaretobegivensincethetolerabilityofdosesgreaterthan1mgtakenasasingleweeklydosehasbeen

evaluatedonlyinafewpatients.

Patientsshouldbeevaluatedduringdoseescalationtodeterminethelowestdosagethatproducesthetherapeutic

response.

Forinhibitionoflactation

Cabergolineshouldbeadministeredwithinthefirst24hourspost-partum.Therecommendedtherapeuticdosageis

1mgcabergolinegivenasadingledose.

Useinchildrenandadolescents

Thesafetyandefficacyofcabergolinehasnotbeenestablishedinsubjectslessthan16yearsofage.

Elderly

Asaconsequenceoftheindicationsforwhichthisstrengthofcabergolineispresentlyproposed,experienceinthe

elderlyisverylimited.Availabledatadonotindicateaspecialrisk.

RenalInsufficiency

Theassessmentofsafetyandefficacyofcabergolineislimitedinpatientswithrenaldisease.Nooveralldifferencesin

thepharmacokineticsofcabergolinewereobservedinmoderatetosevererenaldisease.Thepharmacokineticsof

cabergolinehasnotbeenstudiedinpatientshavingend-stagerenalfailure,orinpatientsonhaemodialysis;these

patientsshouldbetreatedwithcaution.

HepaticInsufficiency

Theassessmentofsafetyandefficacyofcabergolineislimitedinpatientswithhepaticdisease.Cabergoline

pharmacokineticsinpatientswithmildtomoderatedysfunction(Child-Pughscore<10)weresimilartothose

determinedinpreviousstudiesinsubjectswithnormalhepaticfunction.However,patientswiththemostsevere

dysfunction(Child-Pughscore>10)showedincreasedAUCvalues(>200%).Thesepatientsshouldbedosedwith

caution,anditisrecommendedthatthedoseshouldbelimitedtonomorethan1mg/day.

4.3Contraindications

Hypersensitivitytocabergoline,anyergotalkaloidortoanyoftheexcipients

Pre-eclampsia,eclampsia

Uncontrolledhypertension,post-partumhypertension

Historyofpulmonary,pleural,,pericardialandretroperitonealfibroticdisordersespeciallyifassociatedwiththe

useofdopamineagonists.

Evidenceofcardiacvalvulopathyasdeterminedbypretreatmentechocardiography.

Historyofpsychosisorriskofpostpartumpsychosis

4.4Specialwarningsandprecautionsforuse

General

Aswithotherergotalkaloids,cabergolineshouldbegivenwithcautiontosubjectswithcardiovasculardisease,

hypotension,Raynaud'ssyndrome,pepticulcerorgastrointestinalbleeding.

Theeffectsofalcoholontheoveralltolerabilityofcabergolinearecurrentlyunknown.

Hypotension

Symptomatichypotensioncanoccurwithcabergoline,particularlywhentakenconcomitantlywithothermedicinal

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Monitoringoftreatmentwithregularchecksofbloodpressureisrecommendedinthefirst3-4daysafterinitiationof

treatment.

CNS

Somnolence:cabergolinehasbeenassociatedwithsomnolenceandepisodesofsuddensleeponset,particularlyin

patientswithParkinson’sdisease.Suddenonsetofsleepduringdailyactivities,insomecaseswithoutawarenessor

warningsigns,hasbeenreporteduncommonly.Patientsmustbeinformedofthisandadvisedtoexercisecautionwhile

drivingoroperatingmachinesduringtreatmentwithcabergoline.Patientswhohaveexperiencedsomnolenceand/oran

episodeofsuddensleeponsetmustrefrainfromdrivingoroperatingmachinesduringtreatmentwithcabergoline(see

section4.7).Further,areductionofdosageorterminationoftreatmentmaybeconsidered.

Impulsecontroldisorders

Patientsshouldberegularlymonitoredforthedevelopmentofimpulsecontroldisorders.Patientsandcarersshouldbe

madeawarethatbehaviouralsymptomsofimpulsecontroldisordersincludingpathologicalgambling,increasedlibido,

hypersexuality,compulsivespendingorbuying,bingeeatingandcompulsiveeatingcanoccurinpatientstreatedwith

dopamineagonists,includingcabergoline.Dosereduction/tapereddiscontinuationshouldbeconsideredifsuch

symptomsdevelop

Treatmentofhyperprolactinaemicdisorders

Sincehyperprolactinaemiawithamenorrhoeaandinfertilitymaybeassociatedwithpituitarytumours,theunderlying

causeofthehyperprolactinaemiashouldbeinvestigatedbeforetreatmentwithcabergolineiscommenced.

Monitoringofserumprolactinlevelsatmonthlyintervalsisadvisedsince,oncetheeffectivetherapeuticdosage

regimenhasbeenreached,serumprolactinnormalisationisusuallyobservedwithintwotofourweeks.

Aftercabergolinewithdrawal,recurrenceofhyperprolactinaemiaisusuallyobserved.However,persistentsuppression

ofprolactinlevelshasbeenobservedforseveralmonthsinsomepatients.

Fibrosisandcardiacvalvulopathyandpossiblyrelatedclinicalphenomena:

Fibroticandserosalinflammatorydisorderssuchaspleuritis,pleuraleffusion,pleuralfibrosis,pulmonaryfibrosis,

pericarditis,pericardialeffusion,cardiacvalvulopathyinvolvingoneormorevalves(aortic,mitralandtricuspid)or

retroperitonealfibrosishaveoccurredafterprolongedusageofergotderivativeswithagonistactivityattheserotonin

receptor,suchascabergoline.Insomecases,symptomsormanifestationsofcardiacvalvulopathyimproved

afterdiscontinuationofcabergoline.

Erythrocytesedimentationrate(ESR)hasbeenfoundtobeabnormallyincreasedinassociationwithpleural

effusion/fibrosis.Chestx-rayexaminationisrecommendedincasesofunexplainedESRincreasestoabnormalvalues.

Valvulopathyhasbeenassociatedwithcumulativedoses,therefore,patientsshouldbetreatedwiththelowesteffective

dose.Ateachvisit,theriskbenefitprofileofcabergolinetreatmentforthepatientshouldbereassessedtodeterminethe

suitabilityofcontinuedtreatmentwithcabergoline.

Beforeinitiatinglong-termtreatment:

Allpatientsmustundergoacardiovascularevaluation,includingechocardiogram,toassessthepotentialpresenceof

asymptomaticvalvulardisease.Itisalsoappropriatetoperformbaselineinvestigationsoferythrocytesedimentation

rateorotherinflammatorymarkers,lungfunction/chestX-rayandrenalfunctionpriortoinitiationoftherapy.

Inpatientswithvalvularregurgitation,itisnotknownwhethercabergolinetreatmentmightworsentheunderlying

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Duringlong-termtreatment:

Fibroticdisorderscanhaveaninsidiousonsetandpatientsshouldberegularlymonitoredforpossiblemanifestationsof

progressivefibrosis.

Therefore,duringtreatment,attentionshouldbepaidtothesignsandsymptomsof:

Pleuro-pulmonarydiseasesuchasdyspnoea,shortnessofbreath,persistentcoughorchestpain.

Renalinsufficiencyorureteral/abdominalvascularobstructionthatmayoccurwithpainintheloin/flankandlower

limboedemaaswellasanypossibleabdominalmassesortendernessthatmayindicateretroperitonealfibrosis.

Cardiacfailure;casesofvalvularandpericardialfibrosishaveoftenmanifestedascardiacfailure.Therefore,valvular

fibrosis(andconstrictivepericarditis)shouldbeexcludedifsuchsymptomsoccur.

Clinicaldiagnosticmonitoringfordevelopmentoffibroticdisorders,asappropriate,isessential.Followingtreatment

initiation,thefirstechocardiogrammustoccurwithin3-6months,thereafter,thefrequencyofechocardiographic

monitoringshouldbedeterminedbyappropriateindividualclinicalassessmentwithparticularemphasisontheabove-

mentionedsignsandsymptoms,butmustoccuratleastevery6to12months.

Cabergolineshouldbediscontinuedifanechocardiogramrevealsneworworsenedvalvularregurgitation,valvular

restrictionorvalveleafletthickening(seeSection4.3).

Theneedforotherclinicalmonitoring(e.g.physicalexaminationincluding,cardiacauscultation,Xray,CTscan)

shouldbedeterminedonanindividualbasis.

Additionalappropriateinvestigationssuchaserythrocytesedimentationrate,andserumcreatininemeasurements

shouldbeperformedifnecessarytosupportadiagnosisofafibroticdisorder.

Other

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Precautions

Pharmacokineticinteractionswithothermedicinalproductscannotbepredictedbasedonavailableinformationabout

themetabolismofcabergoline.

NopharmacokineticinteractionswithL-dopaorselegilinehavebeenobservedinstudiesofpatientswithParkinson’s

disease.

Concomitantusenotrecommended

Elevatedplasmalevelsofbromocriptinehavebeenobservedincombinationwithmacrolideantibiotics(suchas

erythromycin).Effectsofmacrolideantibioticsoncabergoline’splasmalevelswhenadministeredsimultaneouslyhave

notbeenstudied.Thecombinationshouldbeavoided,asitmayresultinelevatedcabergolineplasmalevels.

Cabergolineactsthroughdirectstimulationofdopaminereceptors.Consequently,itshouldnotbecombinedwith

medicinalproductswithadopamineantagonisticeffect(suchasphenothiazines,butyrophenones,thioxanthenes,

metoclopramide)

Noinformationisavailableaboutpossibleinteractionsbetweencabergolineandotherergotalkaloids.Therefore,long-

termtreatmentwithcabergolineisnotadvisedincombinationwiththesemedicinalproducts.

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4.6Fertility,pregnancyandlactation

Pregnancy

Pregnancyshouldbeexcludedbeforecabergolineadministration,andshouldbepreventedforatleastonemonthafter

treatment.

Cabergolinehasbeenshowntocrosstheplacentainrats.Itisnotknownwhetherthisoccursinhumans.Dataona

limitednumberofpregnancies(n=100),generallytakenduringthefirst8weeksafterconception,donotindicate

cabergolinetobeassociatedwithanincreasedriskofabortion,prematuredelivery,multiplepregnancyorcongenital

abnormalities.Todate,nootherrelevantepidemiologicaldataareavailable.Animalstudiesindicatenodirector

indirectharmfuleffectswithrespecttopregnancy,embryonal/foetaldevelopment,parturitionorpost-natal

development.

Becauseofthelimitedexperienceoftheuseofcabergolineinpregnancy,cabergolineshouldbewithdrawnbeforea

plannedpregnancy.Ifthepatientbecomespregnantduringtreatment,cabergolineshallbeimmediatelywithdrawn.

Duringpregnancy,thesepatientsmustbecarefullymonitoredforanypregnancy-inducedpituitaryenlargement.

Cabergolinerestoresovulationandfertilityinwomenwithhyperprolactinaemichypogonadism:sincepregnancymight

occurpriortoreinitiationofmenses,pregnancytestingisrecommendedasappropriateduringtheamenorrhoeicperiod

and,oncemensesarereinitiated,everytimeamenstrualperiodisdelayedbymorethanthreedays.Whenstarting

dopaminergictreatment,womenmustbewarnedthatrestorationofovulationandfertilitymaybeimmediate(even

beforetheirfirstnormalmenstruation).Womennotseekingpregnancyshouldbeadvisedtouseeffectivenon-hormonal

contraceptionduringtreatmentandaftercabergolinewithdrawal.Becauseoflimitedexperienceonthesafetyoffoetal

exposuretocabergoline,itisadvisablethatwomenseekingpregnancyconceiveatleastonemonthaftercabergoline

discontinuationgiventhatovulatorycyclespersistinsomepatientsfor6monthsafterwithdrawal.Shouldpregnancy

occurduringtreatment,cabergolineistobediscontinued.Asaprecautionarymeasure,womenwhobecomepregnant

shouldbemonitoredtodetectsignsofpituitaryenlargementsinceexpansionofpre-existingpituitarytumoursmay

occurduringgestation.

Contraceptionshouldbecontinuedforatleast4weeksafterstoppingcabergoline.

Cabergolineshouldonlybeusedduringpregnancyifclearlyindicated.

Lactation

Cabergolineshouldnotbeadministeredtomotherswhoelecttobreast-feedtheirinfantssinceitpreventslactation.No

informationisavailableonexcretionoftheactivesubstanceinmaternalmilkbutinratscabergolineand/orits

metabolitesareexcretedinthemilk.

Breastfeedingshouldbeavoidedwhentakingcabergoline.

4.7Effectsonabilitytodriveandusemachines

Cabergolinereducesbloodpressure,whichmayimpairthereactionsofcertainpatients.Thisshouldbetakeninto

accountinsituationsrequiringintenseawareness,suchaswhendrivingacaroroperatingmachinery.

Patientsbeingtreatedwithcabergolineandpresentingwithsomnolenceand/orsuddensleepepisodesmustbe

informedtorefrainfromdrivingorengaginginactivitieswhereimpairedalertnessmayputthemselvesorothersatrisk

ofseriousinjuryordeath(e.g.operatingmachines)untilsuchrecurrentepisodesandsomnolencehaveresolved(see

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4.8Undesirableeffects

Theundesirableeffectsareusuallydose-dependent,andcanbereducedbydecreasingthedosegradually.

Inhibitionoflactation:

Approximately14%ofpatientsexperienceundesirableeffects.Themostcommonarelowbloodpressure(12%),

dizziness(6%)andheadaches(5%).Long-termtreatmentincreasesthefrequencyofundesirableeffectsto

approximately70%.

Post-marketingsurveillance(includingtreatmentwithdifferentstrengthsinParkinson’sDisease)

Fibroticreactions

Therehavebeenreportsoffibroticandserosalinflammatoryconditions,suchaspleuritis,pleuraleffusion,pleural

fibrosis,pulmonaryfibrosis,pericarditis,pericardialeffusion,cardiacvalvulopathyandretroperitonealfibrosis,in

patientstakingcabergoline(see‘Specialwarningsandspecialprecautionsforuse’).

Theincidenceofcardiacvalvulopathywithcabergolineisnotknown.Howeverbasedonrecentstudiesofthe

prevalenceofvalvularregurgitation(themostsensitiveechocardiogaphicmarkerforrestrictivevalvulopathy),the

prevalenceofregurgitation(virtuallyallcasesasymptomatic)potentiallyattributabletocabergolinemaybeintherange

of20%orgreater.Thereislimitedinformationavailableonthereversibilityofthesereactions.

Somnolence

Cabergolineisassociatedwithsomnolenceandhasbeenassociateduncommonlywithexcessivedaytimesomnolence

andsuddensleeponsetepisodes.

Impulsecontroldisorders

Pathologicalgambling,increasedlibido,hypersexuality,compulsivespendingorbuying,bingeeatingandcompulsive

eatingcanoccurinpatientstreatedwithdopamineagonistsincludingcabergoline(seesection4.4).

Thefollowingundesirableeffectshavebeenobservedduringtreatmentwithcabergolinewiththefollowing

frequencies:Verycommon(1/10),Common(1/100to<1/10),uncommon(1/1,000to<1/100),rare(1/10,000to

<1/1,000),veryrare(<1/10,000)includingisolatedreports

Investigations

Common Afallinhaemoglobinandhaematocrit

values,fallintheerythrocytecount,

increasesoftriglyceridesgreaterthan30%

abovetheupperlimitofthelaboratory

referencerange(mostlytransient)

Cardiacdisorders

Verycommon

Common

Orthostatichypotension(mainlyevidentin

thefirstweeksoftherapy).

Cardiacvalvulopathy(including

regurgitation)andrelateddisorders

(pericarditisandpericardialeffusion).

Angina,palpitations

Erythromelalgia

Nervoussystemdisorders

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4.9Overdose

Thereisnoclinicalexperienceofoverdosing,butobservationsfromanimalexperimentssuggestthatsymptoms

resultingfromoverstimulationofdopaminereceptorscanbeexpected,suchasnausea,vomiting,reducedblood

pressure,confusion/psychosisorhallucinations.Whereindicated,measuresmustbetakentorestorebloodpressure.In

addition,withpronouncedsymptomsfromtheCNS(hallucinations),administrationofadopamineantagonistcanbe

Common

Rare

Notknown(cannotbeestimatedfrom

theavailabledata) Drowsiness,Sleepdisorders/somnolence,

hallucinations,confusion,depression,

headache,fatigue,paresthesia

Suddensleeponsetepisodes

Pathologicalgambling,increasedlibidoand

hypersexuality,generallyreversibleupon

reductionofthedoseortreatment

discontinuation.

Eyedisorders

Uncommon Hemianopia

Respiratory,thoracicand

mediastinaldisorders

Common Symptomaticpleuraleffusion/pulmonary

fibrosis/pleuritis

Gastrointestinaldisorders

Verycommon

Common

Notknown(cannotbeestimatedfrom

theavailabledata) Nausea

Vomiting,dyspepsia,gastritis,constipation.

Gastricupsetappearedmorefrequentin

femalethaninmalepatients.

Retroperitionealfibrosis

Skinandsubcutaneoustissue

disorders

Common Facialredness

Musculoskeletal,connectivetissue

andbonedisorders

Rare Crampinfingersandcalves

Vasculardisorders

Uncommon

Rare Nosebleeding

Fainting

Generaldisordersand

administrationsiteconditions

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Prolactininhibitor

ATCcode:G02CB03

Cabergolineisasyntheticergotalkaloidandanergolinederivatewithlong-actingdopamineagonistandprolactin-

inhibitingproperties.AcentraldopaminergiceffectviaD2-receptorstimulationisachievedthroughhigherdosesthan

dosesthatreducethelevelsofserumprolactin.

Theprolactin-reducingeffectisdose-dependent,startingwithin3hoursandremainingfor2-3weeks.Thelong-acting

effectmeansthatasingledoseisgenerallysufficienttostoptheinitiationofmilksecretion.Intreatmentof

hyperprolactinaemia,theserumprolactinlevelsaregenerallynormalisedwithintwotofourweeksoftheoptimaldose

beingattained.Prolactincanstillbesignificantlyreducedseveralmonthsafterwithdrawalofthetreatment.

Withregardtotheendocrineeffectsofcabergolinenotrelatedtotheantiprolactinaemiceffect,availabledatafrom

humansconfirmtheexperimentalfindingsinanimalsindicatingthatthetestcompoundisendowedwithavery

selectiveactionwithnoeffectonbasalsecretionofotherpituitaryhormonesorcortisol.

Thepharmacodynamicactionsofcabergolinenotcorrelatedwiththetherapeuticeffectonlyrelatetobloodpressure

decrease.Themaximalhypotensiveeffectofcabergolineassingledoseusuallyoccursduringthefirst6hoursafter

activesubstanceintakeandisdose-dependentbothintermsofmaximaldecreaseandfrequency.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationcabergolineisrapidlyabsorbedfromthegastrointestinaltractasthepeakplasma

concentrationisreachedwithin0.5to4hours.

Fooddoesnotappeartoaffectabsorptionanddispositionofcabergoline.

Distribution

“In-vitro”experimentsshowedthatcabergolineatconcentrationsof0.1–10ng/mlis41-42%boundtoplasma

proteins.

Biotransformation

Inurine,themainmetaboliteidentifiedwas6-allyl-8-carboxy-ergoline,whichaccountedfor4-6%ofthedose.

Threeadditionalmetaboliteswereidentifiedinurine,whichaccountedoverallforlessthan3%ofthedose.The

metaboliteshavebeenfoundtobemuchlesspotentthancabergolineininhibitingprolactinsecretion“invitro”.

Elimination

Theeliminationhalf-lifeofcabergolineislong(63-68hoursinhealthyvolunteersand79-115hoursin

hyperprolactinaemicpatients.

Onthebasisoftheeliminationhalf-life,steadystateconditionsshouldbeachievedafter4weeks,asconfirmedbythe

meanpeakplasmalevelsofcabergolineobtainedafterasingledose(378pg/ml)andaftera4weekmultipleregimen

(10143pg/ml)for0.5mgcaberglinedose.

Tendaysafteradministrationabout18%and72%ofthedoseisrecoveredinurineandfaeces,respectively.

Unchangedcabergolineinurineaccountsfor2-3%ofthedose.

Linearity/Non-linearity

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5.3Preclinicalsafetydata

Almostallthefindingsnotedthroughouttheseriesofpreclinicalsafetystudiesareaconsequenceofthecentral

dopaminergiceffectsorthelong-lastinginhibitionofPRLinspecies(rodents)withaspecifichormonalphysiology

differenttoman.Preclinicalsafetystudiesofcabergolineindicatealargesafetymarginforthiscompoundinrodents

andinmonkeys,aswellasalackofteratogenic,mutagenicorcarcinogenicpotential.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Leucine

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackagetoprotectfrommoisture.

6.5Natureandcontentsofcontainer

TypeIIIamberglassbottleswithapolypropylenescrewcap.

Acylindricaltubeorsachetcontainingdesiccant(silicagel)isprovidedineachbottle.

Eachbottlecontains2,4,8,20,28,30,40&80tabletsandisenclosedinanoutercardboardcarton.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

ArrowGenericsLimited,

Unit2,EastmanWay,

Stevenage,

HertsSG14SZ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8 th

February2008

Dateoflastrenewal:13thMarch2012

10DATEOFREVISIONOFTHETEXT

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