ARTHROTEC 75MG MODIFIED-RELEASE TABLETS

Main information

  • Trade name:
  • ARTHROTEC 75MG MODIFIED-RELEASE TABLETS
  • Dosage:
  • 75/ 0.2 Milligram
  • Pharmaceutical form:
  • Modified-release Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ARTHROTEC 75MG MODIFIED-RELEASE TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/114/002A
  • Authorization date:
  • 31-03-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Arthrotec75mgModified-ReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletconsistsofagastro-resistantcorecontaining75mgdiclofenecsodiumsurroundedbyanoutermantle

containing200microgramsmisoprostol.

Excipient:containslactose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Modified-releasetablet

ProductimportedfromItalyandtheUK:

White,round,biconvextabletsmarked‘Searle’and‘1421’ononesidewithfour‘A’sand‘75’ontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Arthrotec75isindicatedforpatientswhorequirethenon-steroidalanti-inflammatorydrugdiclofenactogetherwith

misoprostol.

ThediclofenaccomponentofArthrotec75isindicatedforthesymptomatictreatmentofosteoarthritisandrheumatoid

arthritis.ThemisoprostolcomponentofArthrotec75isindicatedforpatientswithaspecialneedfortheprophylaxisof

NSAID-inducedgastricandduodenalulceration.

4.2Posologyandmethodofadministration

Adults

Onetablettobetakenwithfood,twotimesdaily.Tabletsshouldbeswallowedwhole,notchewed.

Elderly/RenalImpairment/HepaticImpairment

Noadjustmentofdosageisnecessaryintheelderlyorinpatientswithhepaticimpairmentormildtomoderaterenal

impairmentaspharmacokineticsarenotalteredtoanyclinicallyrelevantextent.Neverthelesspatientswithrenalor

hepaticimpairmentshouldbecloselymonitored(seealsoSection4.8-UndesirableEffects).

Children

ThesafetyandefficacyofArthrotec75inchildrenhasnotbeenestablished

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.4).

4.3Contraindications

Arthrotec75iscontraindicatedin:

-PatientswithactivegastricorduodenalulcerationorwhohaveactiveGIbleedingorotheractivebleedingse.g.

cerebrovascularbleedings.

-Pregnantwomenandinwomenplanningapregnancy.

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-Patientswithaknownhypersensitivitytodiclofenac,aspirin,otherNSAIDs,misoprostol,otherprostaglandins,orany

otheringredientoftheproduct.

-Patientsinwhomattacksofasthma,urticariaoracuterhinitisareprecipitatedbyaspirinorothernon-steroidalanti-

inflammatoryagents.

-Historyofgastrointestinalbleedingorperforation,relatedtopreviousNSAIDstherapy.--Active,orhistoryof

recurrentpepticulcer/haemorrhage(twoormoredistinctepisodesofprovenulcerationorbleeding).

-Severeheartfailure.

4.4Specialwarningsandprecautionsforuse

ndesirableeffectsmaybeminimisedbyusingtheminimumeffectivedosefortheshortestdurationnecessaryto

controlthesymptoms(seesection4.2,andGIandcardiovascularrisksbelow)

TheuseofArthrotecmayimpairfemalefertilityandisnotrecommendedinwomenattemptingtoconceive.Inwomen

whohavedifficultiesconceivingorwhoareundergoinginvestigationofinfertility,withdrawalofArthrotecshouldbe

considered.

TheuseofArthrotecwithconcomitantNSAIDsincludingcyclooxygenase-2selectiveinhibitorsshouldbeavoided.

Elderly:TheelderlyhaveanincreasedfrequencyofadversereactionstoNSAIDsespeciallygastrointestinalbleeding

andperforationwhichmaybefatal(seesection4.2).

Gastrointestinalbleeding,ulcerationandperforation:GIbleeding,ulcerationorperforation,whichcanbefatal,hasbeen

reportedwithallNSAIDsatanytimeduringtreatment,withorwithoutwarningsymptomsoraprevioushistoryof

seriousGIevents.

TheriskofGIbleeding,ulcerationorperforationishigherwithincreasingNSAIDdoses,inpatientswithahistoryof

ulcer,particularlyifcomplicatedwithhaemorrhageorperforation(seesection4.3),andintheelderly.Thesepatients

shouldcommencetreatmentonthelowesedoseavailable.Combinationtherapywithprotectiveagents(e.g.

misoprostolorprotonpumpinhibitors)shouldbeconsideredforthesepatients,andalsoforpatientsrequiring

concomitantlowdoseaspirin,orotherdrugslikelytoincreasegastrointestinalrisk(seebelowand4.5)

PatientswithahistoryofGItoxicity,particularlywhenelderly,shouldreportanyunusualabdominalsymptoms

(especiallyGIbleeding)particularlyintheinitialstagesoftreatment.

Cautionshouldbeadvisedinpatientsreceivingconcomitantmedicationswhichcouldincreasetheriskofulcerationor

bleeding,suchasoralcorticosteroids,anticoagulantssuchaswarfarin,selectiveserotonin-reuptakeinhibitorsoranti-

plateletagentssuchasaspirin(seesection4.5).

WhenGIbleedingorulcerationoccursinpatientsreceivingArthrotec,thetreatmentshouldbewithdrawn.

NSAIDsshouldbegivenwithcaretopatientswithahistoryofgastrointestinaldisease(ulcerativecolitis,Chron’s

disease)astheirconditionmaybeexacerbated(seesection4.8–undesirableeffects).

Seriousskinreactions,someofthemfatal,includingexfoliativedermatitis,Stevens-Johnsonsyndrome,andtoxic

epidermalnecrolysis,havebeenreportedrarelyinassociationwiththeuseofNSAIDs(see4.8).Patientsappeartobe

athighestriskofthesereactionsearlyinthecourseoftherapy,theonsetofthereactionoccurringinthemajorityof

caseswithinthefirstmonthoftreatment.Arthrotecshouldbediscontinuedatthefirstappearanceofskinrash,mucoal

lesions,oranyothersignohhypersensitivity.

Cardiovascularandcerebrovasculareffects

Appropriatemonitoringandadvicearerequiredforpatientswithahistoryofhypertensionand/ormildtomoderate

congestiveheartfailureasfluidretentionandoedemahavebeenreportedinassociationwithNSAIDtherapy.

Clinicaltrialandepidemiologicaldatasuggestthattheuseofdiclofenac,particularlyathighdose(150mgdaily)andin

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myocardialinfarctionorstroke).

Patientswithuncontrolledhypertension,congestiveheartfailure,establishedischaemicheartdisease,peripheral

aerterialdisease,and/orcerebrovasculardiseaseshouldnotbetreatedwithdiclofenscaftercarefulconsideration.

Similarconsiderationshouldbemadebeforeinitiatinglonger-termtreatmentofpatientswithriskfactorsfor

cardiovascularevents(e.g.hypertension,hyperlipidaemia,diabetesmellitus,andsmoking).

Useinpre-menopausalwomen(seealsoContraindications)

Arthrotec75shouldnotbeusedinpre-menopausalwomenunlesstheyuseeffectivecontraceptionandhavebeen

advisedoftherisksoftakingtheproductifpregnant(seesection4.6).Thelabelwillstate:Notforusebypre-

menopausalwomenunlessusingeffectivecontraception.

Arthrotec75,incommonwithotherNSAIDs,maydecreaseplateletaggregationandprolongbleedingtime.Extra

supervisionisrecommendedinhaematopoieticdisordersorinconditionswithdefectivecoagulationorinpatientswith

ahistoryofcerebrovascularbleeding.

FluidretentionandoedemahavebeenobservedinpatientstakingNSAIDs,includingArthrotec75.Therefore,

Arthrotec75shouldbeusedwithcautioninpatientswithcompromisedcardiacfunctionandotherconditions

predisposingtofluidretention.

Inpatientswithrenal,cardiacorhepaticimpairmentcautionisrequiredsincetheuseofNSAIDsmayresultin

deteriorationofrenalfunction.InthefollowingconditionsArthrotec75shouldbeusedonlyinexceptional

circumstancesandwithcloseclinicalmonitoring:advancedcardiacfailure,advancedkidneyfailure,advancedliver

disease.

Similarlycautionisalsorequiredinpatientswithdiuretictreatmentorotherwiseatriskofhypovolaemia.Thedose

shouldbekeptaslowaspossibleandrenalfunctionshouldbemonitored.

CautionisrequiredinpatientssufferingfromulcerativecolitisorCrohn'sDisease.

NSAIDsmayprecipitatebronchospasminpatientssufferingfrom,orwithahistoryof,bronchialasthmaorallergic

disease.

Allpatientswhoarereceivinglong-termtreatmentwithNSAIDsshouldbemonitoredasaprecautionarymeasure(eg.

renal,hepaticfunction,bloodcountsandhaemocculttesting).

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Corticosteroids:increasedriskofgastrointestinalulcerationorbleeding(seesection4.4)

Anticoagulants:NSAIDsmayenhancetheeffectsofanti-coagulants,suchaswarfarin(seesection4.4)

Anti-plateletagentsandselectiveserotoninreuptakeinhibitors(SSRIs):increasedriskofgastrointestinalbleeding(see

section4.4)

NSAIDsmayattenuatethenatriureticefficacyofdiureticsduetoinhibitionofintrarenalsynthesisofprostaglandins.

Concomitanttreatmentwithpotassium-sparingdiureticsmaybeassociatedwithincreasedserumpotassiumlevels,

henceserumpotassiumshouldbemonitored.

Becauseoftheireffectonrenalprostaglandins,cyclo-oxygenaseinhibitorssuchasdiclofenaccanincreasethe

nephrotoxicityofcyclosporin.

Steadystateplasmalithiumanddigoxinlevelsmaybeincreasedandketoconazolelevelsmaybedecreased.

Pharmacodynamicstudieswithdiclofenachaveshownnopotentiationoforalhypoglycaemicandanticoagulantdrugs.

HoweverasinteractionshavebeenreportedwithotherNSAIDs,cautionandadequatemonitoringare,nevertheless

advised(seestatementonplateletaggregationinPrecautions).

BecauseofdecreasedplateletaggregationcautionisalsoadvisedwhenusingArthrotec75withanti-coagulants.

CautionisadvisedwhenmethotrexateisadministeredconcurrentlywithNSAIDsbecauseofpossibleenhancementof

itstoxicitybytheNSAIDasaresultofincreaseinmethotrexateplasmalevels

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4.6Fertility,pregnancyandlactation

Pregnancy

Arthrotec75iscontraindicatedinpregnantwomenandinwomenplanningapregnancyasmisoprostolmayincrease

uterinetoneandcontractionsinpregnancywhichcouldproducemiscarriage.Alsodiclofenacmaycausepremature

closureoftheductusarteriosus.

Lactation

Arthrotec75shouldnotbeadministeredduringbreastfeedingastherearenodataontheexcretionintobreastmilkfor

eithermisoprostolordiclofenac.

4.7Effectsonabilitytodriveandusemachines

PatientswhoexperiencedizzinessorothercentralnervoussystemdisturbanceswhiletakingNSAIDsshouldrefrain

fromdrivingoroperatingmachinery.

4.8Undesirableeffects

Gastro-intestinal:Themostcommonlyobservedadverseeventsaregastronintestinalinnature.Pepticulcers,

perforationorGIbleeding,sometimesfatal,particularlyintheelderly,mayoccur(seesection4.4).Nausea,vomiting,

diarrhoea,flatulence,constipation,dyspepsia,abdominalpain,melaaena,haematemesis,ulcerativestomatitis,

exacerbationofcolitisandhron’sdisease(seesection4.4–Specialwarningsandprecautionsforuse)havebeen

reportedfollowingadministration.Lessfrequently,gastritishasbeenobserved.

BullousreactionsincludingStevens-Johnsonsyndromeandtoxicepidermalnecrolysis(veryrare).

Common:

General:Headache,dizziness.

Gastrointestinal:Abdominalpain,diarrhoea,nausea,dyspepsia,flatulence,vomiting,gastritisandeructation.

DiarrhoeaisusuallymildtomoderateandtransientandcanbeminimisedbytakingArthrotec75withfoodandby

avoidingtheuseofpredominantlymagnesium-containingantacids.

Skin:Skinrashes.

Infrequent:

General:Tiredness,peripheraloedema.

Gastrointestinal:Pepticulcer,stomatitis,decreaseinhaemoglobinassociatedwithGIbloodloss,oesophageallesions.

Liver:ElevationsofSGPT,SGOT,alkalinephosphataseorbilirubin

Femalereproductivesystem:Menorrhagia,intermenstrualbleedingandvaginalbleedinghavebeenreportedinpre-

menopausalwomenandvaginalbleedinginpost-menopausalwomen.

Rarelyorveryrarely:

Bloodsystem:Thrombocytopenia,leucopenia,agranulocytosis,haemolyticanaemia,aplasticanaemiaGastrointestinal:

Anorexia,drymouth,bleeding(haematemesis,melaena),perforatedulcer,glossitis,otherGIcomplaints(ulcerative

colitis,Crohn'sdisease),constipation.

Liver:Hepatitiswithorwithoutjaundice.

Skin/hypersensitivity:Urticaria,erythemamultiforme,photosensitivityreactions,Steven-Johnson'ssyndrome,Lyell's

syndrome(acutetoxicepidermalnecrolysis),hypersensitivityincludingbronchospasmandangioedema,purpura

includingallergicpurpuraandhairloss.

CNS:Drowsiness,paraesthesia,memorydisorders,disorientation,visualdisturbances,tinnitus,insomnia,irritability,

convulsions,depression,anxiety,nightmares,tremors,psychoticreactions,tastedisturbance.

Renal:AsaclassNSAIDshavebeenassociatedwithrenalpathologyincludingpapillarynecrosis,interstitialnephritis,

nephroticsyndromeandrenalfailure.

Other:Inisolatedcasesworseningofinflammationassociatedwithinfectionshavebeenreportedinassociationwith

NSAIDtreatment.

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Clinicaltrialandepidemiologicaldatasuggeststhatuseofdiclofenac,particularlyathighdoses(150mgdaily)andin

longtermtreatmentmaybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexample

myocardialinfarctionorstroke)(seesection4.4)

4.9Overdose

ThetoxicdoseofArthrotec75hasnotbeendeterminedandthereisnoexperienceofoverdosage.Intensificationofthe

pharmacologicaleffectsmayoccurwithoverdosage.ManagementofacutepoisoningwithNSAIDsessentiallyconsists

ofsupportiveandsymptomaticmeasures.Itisreasonabletotakemeasurestoreduceabsorptionofanyrecently

consumeddrugbyforcedemesis,gastriclavageoractivatedcharcoal.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Arthrotec75isanon-steroidal,anti-inflammatorydrugwhichiseffectiveintreatingthesignsandsymptomsof

arthriticconditions.

Thisactivityisduetothepresenceofdiclofenacwhichhasbeenshowntohaveanti-inflammatoryandanalgesic

properties.

Arthrotec75alsocontainsthegastroduodenalmucosalprotectivecomponentmisoprostolwhichisasynthetic

prostaglandinE

analoguethatenhancesseveralofthefactorsthatmaintaingastroduodenalmucosalintegrity.

5.2Pharmacokineticproperties

ThepharmacokineticprofilesofdiclofenacandmisoprostoladministeredasArthrotec75aresimilartotheprofiles

whenthetwodrugsareadministeredasseparatetabletsandtherearenopharmacokineticinteractionsbetweenthetwo

components.

5.3Preclinicalsafetydata

Inco-administrationstudiesinanimals,theadditionofmisoprostoldidnotenhancethetoxiceffectsofdiclofenac.The

combinationwasalsoshownnottobeteratogenicormutagenic.Theindividualcomponentsshownoevidenceof

carcinogenicpotential.

Misoprostolinmultiplesoftherecommendedtherapeuticdoseinanimalshasproducedgastricmucosalhyperplasia.

ThischaracteristicresponsetoE-seriesprostaglandinsrevertstonormalondiscontinuationofthecompound.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose

Microcrystallinecellulose

Maizestarch

PovidoneK-30

MethacrylicAcidCopolymerTypeC

SodiumHydroxide

TriethylCitrate

Hypromellose

Crospovidone

Magnesiumstearate

Hydrogenatedcasteroil

Colloidalanhydroussilica

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6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeintheoriginalpackageandkeeptheblisterintheoutercarton.

6.5Natureandcontentsofcontainer

Blisterpackcontaining30or60tablets.

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/114/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:31 st

March2004

Dateoflastauthorisation:31 st

March2009

10DATEOFREVISIONOFTHETEXT

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