CYTOTEC

Main information

  • Trade name:
  • CYTOTEC Tablets 200 Microgram
  • Dosage:
  • 200 Microgram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CYTOTEC Tablets 200 Microgram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0936/022/001
  • Authorization date:
  • 11-04-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cytotec200microgramTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains200microgramsmisoprostol.

Excipients-ContainshydrogenatedCastorOil1.0mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

Whitetooff-white,flat,hexagonal-shapedtablets,scoredonbothsideswith‘SEARLE’over‘1461’ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthemanagementandprophylaxisofpepticulcersassociatedwithuseofnon-steroidalanti-inflammatorydrugs.In

theshort-termmanagementofgastricandduodenalulcer.

4.2Posologyandmethodofadministration

Adults

Healingofduodenalulcer,gastriculcerandNSAID-inducedpepticulcer:800microgramsdailyintwoorfour

divideddosestakenwithbreakfastand/oreachmainmealandatbedtime.

Treatmentshouldbegiveninitiallyforatleast4weeksevenifsymptomaticreliefhasbeenachievedsooner.Inmost

patientsulcerswillbehealedin4weeksbuttreatmentmaybecontinuedforupto8weeksifrequired.Iftheulcer

relapsesfurthertreatmentcoursesmaybegiven.

ProphylaxisofNSAID-inducedpepticulcer:200microgramstwicedaily,threetimesdailyorfourtimesdaily.

Treatmentcanbecontinuedasrequired.Dosageshouldbeindividualisedaccordingtotheclinicalconditionofeach

patient.

Elderly

Theusualdosagemaybeused.

Renalimpairment:Availableevidenceindicatesthatnoadjustmentofdosageisnecessaryinpatientswithrenal

impairment.

Hepaticimpairment:Cytotecismetabolisedbyfattyacidoxidisingsystemspresentinorgansthroughoutthebody.Its

metabolismandplasmalevelsarethereforeunlikelytobeaffectedmarkedlyinpatientswithhepaticimpairment.

Children

UseofCytotecinchildrenhasnotyetbeenevaluatedinthetreatmentofpepticulcerationorNSAID-inducedpeptic

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4.3Contraindications

Misoprostoliscontraindicatedinpatients:

Whoarepregnant,orinwhompregnancyhasnotbeenexcluded,orwomenplanningapregnancyasMisoprostol

increasesuterinetoneandcontractionsinpregnancywhichmaycausepartialorcompleteexpulsionoftheproductsof

conception(seeSections4.4,4.6and4.8)

Withaknownhypersensitivitytotheactivesubstance(misoprostol)anyotherprostaglandinsoranyoftheexcipients

ofCytotec.

4.4Specialwarningsandprecautionsforuse

Warnings

Useinpre-menopausalwomen(seealsoContraindications):

Cytotecshouldnotbeusedinpre-menopausalwomenunlessthepatientrequiresnonsteroidalanti-inflammatory

(NSAID)therapyandisathighriskofcomplicationsfromNSAID-inducedulceration.

InsuchpatientsitisadvisedthatCytotecshouldonlybeusedifthepatient:

takeseffectivecontraceptivemeasures

hasbeenadvisedoftherisksoftakingCytotecifpregnant(seeSection4.3,Contraindications).

Womenofchildbearingpotentialshouldnotbestartedonmisoprostoluntilpregnancyisexcluded,andshouldbefully

counselledontheimportanceofadequatecontraceptionwhileundergoingtreatment.

Ifpregnancyissuspectedtheproductshouldbediscontinued.(seeSections4.3,4.6and4.8)

Gastrointestinalbleeding,ulceration,andperforationhaveoccurredinNSAID-treatedpatientsreceivingmisoprostol.

Physiciansandpatientsshouldremainalertforulceration,evenintheabsenceofgastrointestinalsymptoms,and,

whereappropriate,endoscopyandbiopsyshouldbecarriedoutbeforeusetoensurethatmalignantdiseaseisabsent

intheuppergastrointestinaltract.Theseinvestigationsandanyothersconsiderednecessarybytheclinicianshouldbe

repeatedatappropriateintervalsforfollow-uppurposes.

Symptomaticresponsestomisoprostoldonotprecludethepresenceofgastricmalignancy.

Cautionisadvisedinconditionswherediarrhoeacanoccur,suchasulcerativecolitisandregionalileitis.Tominimize

theriskofdiarrhoea,misoprostolshouldbetakenwithfood,andmagnesium-containingantacidsshouldbeavoided

(seeSection4.5).

Theresultsofclinicalstudiesindicatethatmisoprostoldoesnotproducehypotensionatdosageseffectiveinpromoting

thehealingofgastricandduodenalulcers.Nevertheless,misoprostolshouldbeusedwithcautioninthepresenceof

diseasestateswherehypotensionmightprecipitateseverecomplications,e.g.,cerebrovasculardisease,coronaryartery

diseaseorsevereperipheralvasculardiseaseincludinghypertension.

ThereisnoevidencethatCytotechasadverseeffectsonglucosemetabolisminhumanvolunteersorpatientswith

diabetesmellitus.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Druginteractions

ConcomitantadministrationofNSAIDsandmisoprostolinrarecasescancauseatransaminaseincreaseandperipheral

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Cytotecispredominantlymetabolisedviafattyacidoxidisingsystemsandhasshownnoadverseeffectonthehepatic

microsomalmixedfunctionoxidase(P450)enzymesystem.Inspecificstudiesnoclinicallysignificant

pharmacokineticinteractionhasbeendemonstratedwithantipyrine,diazepam.Amodestincreaseinpropranolol

concentrations(meanapproximately20%inAUC,30%inCmax)hasbeenobservedwithmultipledosingof

misoprostol..InextensiveclinicalstudiesnodruginteractionshavebeenattributedtoCytotec.Additionalevidence

showsnoclinicallyimportantpharmacokineticorpharmacodynamicinteractionwithnonsteroidalanti-inflammatory

drugsincludingaspirin,diclofenac,ibuprofen,piroxicam,aspirin,naproxenorindomethacin.

Magnesium-containingantacidsshouldbeavoidedduringtreatmentwithmisoprostolasthismayworsenthe

misoprostol-induceddiarrhoea.

4.6Fertility,pregnancyandlactation

Pregnancy

Cytoteciscontraindicatedinwomenwhoarepregnantbecauseitincreasesuterinetoneandcontractionsinpregnancy

whichmaycausepartialorcompleteexpulsionoftheproductsofconception.Misoprostolisassociatedwithpremature

births.(SeeSection4.3ContraindicationsandSection4.4Specialwarningsandprecautionsforuse).Firsttrimester

exposuretomisoprostolisassociatedwithasignificantlyincreasedriskoftwobirthdefects;Möbiussequence,i.e.,

palsiesofcranialnervesVIandVII,andterminaltransverselimbdefects.Otherdefectsincludingarthrogryposishave

beenobserved.

Lactation

Misoprostolisrapidlymetabolisedinthemothertomisoprostolacid,whichisbiologicallyactiveandisexcretedin

breastmilk.Misoprostolshouldnotbeadministeredtonursingmothersbecausetheexcretionofmisoprostolacidcould

causeundesirableeffectssuchasdiarrhoeainnursinginfants.

4.7Effectsonabilitytodriveandusemachines

Cytoteccancausedizziness.Patientsshouldbecautionedaboutoperatingmachineryanddriving.

4.8Undesirableeffects

TheAdversereactiontermswerethencategorizedutilizingtheincidencerateasfollows:

VeryCommon: 1/10(>10%)

Common: 1/100and <

1/10,(>1%and<10%)

Uncommon: 1/1000and <

1/100,(>0.1%and<1%)

Rare: 1/10,000and <

1/1000,(>0.01%and<0.1%)

VeryRare: <

1/10,000,(<0.01%)

NotKnown

ImmuneSystemDisorder

NotKnown Anaphylacticreaction

NervousSystemDisorders

Common Dizziness,headache

GastrointestinalDisorders

Verycommon

Common Diarrhoea*

Abdominalpain*,constipation,dyspepsia,

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*Diarrhoeaandabdominalpainweredose-related,usuallydevelopedearlyinthecourseoftherapy,andwere

typicallyself-limiting.Rareinstancesofprofounddiarrhoealeadingtoseveredehydrationhasbeenreported.

Diarrhoeacanbeminimisedbyusingsingledosesnotexceeding200microgramswithfoodandbyavoidingtheuse

ofpredominantlymagnesiumcontainingantacidswhenanantacidisrequired.

Syncopehasbeeninfrequentlyreported.

ThepatternofadverseeventsassociatedwithCytotecissimilarwhenanNSAIDisgivenconcomitantly.

ClinicalTrials:

Inclinicaltrials,over15,000patientsandsubjectsreceivedatleastonedoseofmisoprostol.Adversereactions

involvedprimarilythegastrointestinalsystem.

Diarrhoeaandabdominalpainweredose-related,usuallydevelopedearlyinthecourseoftherapy,andweretypically

self-limiting.Rareinstancesofprofounddiarrhoealeadingtoseveredehydrationhavebeenreported.

Theprofileforadversereactionswith>1%incidencewassimilarforsubacute(fourtotwelveweeksduration)and

long-term(uptooneyear)clinicaltrials.

Thesafetyoflong-term(greaterthan12weeks)administrationofmisoprostolhasbeendemonstratedinseveralstudies

inwhichpatientsweretreatedcontinuouslyforuptooneyear.Thisincludesnoadverseorunusualchangeinthe

morphologyofgastricmucosa,asdeterminedbygastricbiopsy.

SpecialPopulations:

Therewerenosignificantdifferencesinthesafetyprofileofmisoprostolinpatientswhowere65yearsofageorolder,

comparedwithyoungerpatients.

Theuseofmisoprostolinchildrenhasnotyetbeenevaluated.

Anumberofsideeffectshavebeenreportedinclinicalstudiesorintheliteraturefollowinguseofmisoprostolfornon-

approvedindications.Theseincludeabnormaluterinecontractions,uterinehaemorrhage,uterinerupture/perforation,

retainedplacenta,amnioticfluidembolism,incompleteabortion,prematurebirth,foetaldeath,andbirthdefects.(See

Section4.3,Contraindications,Section4.6,PregnancyandLactationandSectionandSection4.4Specialwarningsand

SkinandSubcutaneousTissueDisorders

VeryCommon Rash

Pregnancy,puerperium,andperinatalconditions

NotKnown Amnioticfluidembolism,abnormaluterine

contractions,foetaldeath,incompleteabortion,

prematurebirth,retainedplacenta,uterinerupture,

uterineperforation

ReproductiveSystemandBreastDisorders

Uncommon

Rare

NotKnown Vaginalhaemorrhage(includingpostmenopausal

bleeding),intermenstrualbleeding,menstrual

disorder,uterinecramping

Menorrhagia,dysmenorrhoea

Uterinehaemorrhage

Congenital,FamilialandGeneticDisorders

NotKnown Birthdefects

GeneralDisordersandAdministrationSite

Conditions

NotKnown

Uncommon Chills

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4.9Overdose

SignsandSymptomsofOverdose

Thetoxicdoseofmisoprostolinhumanshasnotbeendetermined.Clinicalsignsthatmayindicateanoverdoseare

sedation,tremor,convulsions,dyspnea,abdominalpain,diarrhoea,fever,palpitations,hypotension,orbradycardia.

TreatmentofOverdose

Becausemisoprostolismetabolizedlikeafattyacid,itisunlikelythatdialysiswouldbeappropriatetreatmentfor

overdosage.Incasesofoverdose,standardsupportivemeasuresshouldbeadoptedasrequired.

Inclinicaltrialspatientshavetolerated1200microgramsdailyforthreemonthswithoutsignificantadverseeffects.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

CytotecisananalogueofnaturallyoccurringprostaglandinE1whichpromotespepticulcerhealingandsymptomatic

relief.AsaPGE

analogueitsharessomeatleast,ofthathormone’seffectsonsmoothmuscle.

Cytotecprotectsthegastroduodenalmucosabyinhibitingbasal,stimulatedandnocturnalacidsecretionandby

reducingthevolumeofgastricsecretions,theproteolyticactivityofthegastricfluid,andincreasingbicarbonateand

mucussecretion.

5.2Pharmacokineticproperties

Cytotecisrapidlyabsorbedfollowingoraladministration,withpeakplasmalevelsoftheactivemetabolite(misoprostol

acid)occurringafterabout30minutes.Theplasmaeliminationhalf-lifeofmisoprostolacidis20-40minutes.No

accumulationofmisoprostolacidinplasmaoccursafterrepeateddosingof400microgramstwicedaily.

5.3Preclinicalsafetydata

Insingleandrepeat-dosestudiesindogs,ratsandmiceatmultiplesofthehumandose,toxicologicalfindingswere

consistentwiththeknownpharmacologicaleffectsoftheE-typeprostaglandins,themainsymptomsbeingdiarrhoea,

vomiting,mydriasis,tremorsandhyperpyrexia.Gastricmucosalhyperplasiawasalsoobservedinthemouse,ratand

thedog.Intheratandthedogthehyperplasiawasreversibleondiscontinuationofmisoprostolfollowingoneyearof

dosing.Histologicalexaminationofgastricbiopsiesinhumanshasshownnoadversetissueresponseafteruptoone

year’streatment.Instudiesoffertility,teratogenicityandperi/post-nataltoxicityinratsandrabbitstherewerenomajor

findings.Adecreaseinimplantationsandsomepupgrowthretardationwasobservedatdosesgreaterthan100times

thehumandose.Itwasconcludedthatmisoprostoldoesnotsignificantlyaffectratpupsintheperi/post-natalperiod.

Misoprostolwasnegativeinabatteryof6invitroassaysandoneinvivotesttoassessmutagenicpotential.In

carcinogenicitystudiesintheratandmouseitwasconcludedthattherewasnoriskofcarcinogenichazard.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Sodiumstarchglycolate(TypeA)

Hydrogenatedcastoroil

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6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Cold-formedaluminiumblisterpacksof56,60112,120or140tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA936/22/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:11April1989

Dateoflastrenewal:11April2009

10DATEOFREVISIONOFTHETEXT

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